NERVOUS SYSTEM Flashcards
What are the components of the central nervous system (CNS)?
Brain and spinal cord
The CNS serves as the integrative and control center of the body.
What does the peripheral nervous system (PNS) consist of?
Cranial nerves and spinal nerves
The PNS provides communication lines between the CNS and the rest of the body.
What is the function of the sensory (afferent) division of the PNS?
Conducts impulses from receptors to the CNS
It includes somatic and visceral sensory nerve fibers.
What is the role of the motor (efferent) division of the PNS?
Conducts impulses from the CNS to effectors (muscles and glands)
This includes somatic and autonomic nervous systems.
What is the somatic nervous system responsible for?
Conducts impulses from the CNS to skeletal muscles (voluntary)
It is part of the motor division of the PNS.
What does the autonomic nervous system (ANS) control?
Visceral motor (involuntary) functions
It conducts impulses from the CNS to cardiac muscles, smooth muscles, and glands.
What is the function of sympathetic division of the ANS?
Mobilizes body systems during activity
It prepares the body for ‘fight or flight’ responses.
What is the function of parasympathetic division of the ANS?
Conserves energy and promotes housekeeping functions during rest
It is often referred to as the ‘rest and digest’ system.
What are neuroglia?
Supportive cells in the nervous system
They include astrocytes, microglia, ependymal cells, and oligodendrocytes.
What is the role of astrocytes?
Most abundant, versatile, and highly branched glial cells
They cling to neurons, synaptic endings, and capillaries.
What function do microglia serve?
Monitor neurons and migrate toward injured neurons
They can transform to phagocytize microorganisms and neuronal debris.
What is the role of ependymal cells?
Line the central cavities of the brain and spinal column
They may be ciliated and help circulate cerebrospinal fluid (CSF).
What do oligodendrocytes do?
Form insulating myelin sheaths around CNS nerve fibers
Their processes wrap around thicker nerve fibers.
What are the unique features of neurons?
- Do not divide
- Do not change once matured
- Do not repair if damaged
- High metabolic rate
Neurons conduct impulses and have extreme longevity.
What is the resting membrane potential?
Approximately -70 mV
It is the voltage across a neuron’s membrane at rest.
What is the Nernst equation used for?
To calculate the equilibrium potential for an ion
It considers the concentration gradients of ions across the membrane.
What are the key ions involved in resting membrane potential?
- Na+
- K+
- Cl-
- Anions
Their concentration gradients contribute to the resting potential.
What is the role of the Na+/K+ ATPase?
Maintains ionic gradients across the cell membrane
It pumps Na+ out and K+ into the cell, using ATP.
What is an action potential?
A major mechanism of neuronal communication
It travels down the axon to trigger neurotransmitter release.
What is the difference between graded potentials and action potentials?
- Graded potentials: short distance
- Action potentials: long distance
Graded potentials can vary in amplitude and duration.
What is the peak of an action potential also known as?
Overshoot
It is followed by a phase known as afterhyperpolarization (AHP).
What does depolarization refer to?
A decrease in membrane potential, making it less negative
It occurs when Na+ ions enter the neuron.
What are ion channels?
Proteins that allow ions to pass through the cell membrane
They can be voltage-gated, ligand-gated, or mechanically gated.
What is the term for the decrease in a quantity over time?
decrement
Decrement is often used in contexts such as signal processing or memory allocation.
What triggers the release of neurotransmitters in neurons?
Trigger
Triggers are often action potentials or changes in membrane potential.
What is the role of a transmitter in the nervous system?
transmitter
Transmitters are chemical messengers that carry signals across synapses.
What is the term for the electrical signal that travels along a neuron?
Action potential
Action potentials are essential for neuronal communication.
What occurs at the peak of an action potential?
overshoot
This is the phase where the membrane potential becomes positive.
What is the afterhyperpolarisation also known as?
AHP
AHP occurs following the action potential and results in a temporary increase in negativity.
What phase of the action potential is characterized by Na+ influx?
Rising phase
This phase is crucial for the depolarization of the neuron.
What percentage of Na+ is involved in the rising phase of action potential according to Hodgkin and Katz 1949?
33% Na+
This percentage indicates the contribution of sodium ions during depolarization.
What is the resting potential of a neuron?
~ -70 mV
This value represents the stable state of a neuron when it is not transmitting signals.
What happens to Na+ channels during depolarization?
open
Open Na+ channels allow for the influx of sodium ions, leading to depolarization.
What is the concentration of Na+ inside and outside the neuron at rest?
Inside: 12 mM, Outside: 120 mM
This gradient is essential for the movement of Na+ during action potentials.
What is the driving force for Na+ movement into the neuron?
concentration gradient + electrical gradient
Both gradients contribute to the net movement of sodium ions during depolarization.
What initiates the opening of voltage-gated Na+ channels?
Synaptic transmission: EPSPs
Excitatory postsynaptic potentials are crucial for neuronal activation.
What is the effect of Na+ channel opening during an action potential?
regenerative depolarisation
This leads to a rapid increase in membrane potential.
What is the term for the phase when the neuron returns to resting potential?
repolarisation
Repolarization is necessary to prepare the neuron for the next action potential.
What is the absolute refractory period?
Neurone cannot be re-stimulated
During this period, Na+ channels are inactivated and cannot reopen.
What is the relative refractory period?
Greater stimulation required to trigger action potential
Some Na+ channels may be inactive, but K+ channels remain active.
What is the resting membrane potential of a neuron?
~ -70 mV
This is the baseline electrical state of a neuron at rest.
Making the membrane potential more negative is called _______.
Hyperpolarising
Hyperpolarization occurs when K+ ions flow out of the neuron.
Making the membrane potential more positive is called _______.
Depolarising
Depolarization is crucial for the generation of action potentials.
What is a reflex arc?
A neural pathway that controls a reflex action
Reflex arcs involve sensory neurons, interneurons, and motor neurons.
What condition is most likely to cause demyelination?
Auto-immune disease
Conditions like Multiple Sclerosis can lead to demyelination.
What is the role of voltage-gated channels?
Activated by changes in voltage (depolarisation)
These channels are crucial for the propagation of action potentials.
What does the Peripheral Nervous System (PNS) consist of?
Nerves that extend from the brain and spinal cord, including spinal nerves (31 pairs) and cranial nerves (12 pairs)
The PNS is considered separate in structure and function from the CNS.
What are the two functional divisions of the Peripheral Nervous System?
Sensory (afferent) division and Motor (efferent) division
The sensory division conveys impulses to the CNS, while the motor division transmits impulses from the CNS to effector organs.
What is the role of the Somatic Nervous System?
Conducts impulses from the CNS to skeletal muscles, allowing voluntary control
It is often referred to as the voluntary nervous system.
What does the Autonomic Nervous System regulate?
Smooth muscle, cardiac muscle, and glands
It is known as the involuntary nervous system.
What are the two subdivisions of the Autonomic Nervous System?
Sympathetic and Parasympathetic
These subdivisions work in opposition to each other.
Fill in the blank: The sympathetic nervous system is associated with _______.
Fight or Flight
Fill in the blank: The parasympathetic nervous system is associated with _______.
Rest and Digest
What is the transmitter used in the Autonomic Nervous System?
Acetylcholine (ACh)
ACh is the primary neurotransmitter for the parasympathetic division.
What characterizes the ganglia of the parasympathetic nervous system?
They lie close to the target site and often within the tissue of the target organ
This anatomical arrangement allows for a localized response.
What are pre-ganglionic and post-ganglionic neurons?
Pre-ganglionic neurons are the first neurons in the autonomic pathway, while post-ganglionic neurons are the second neurons that synapse in an autonomic ganglion.
True or False: Post-ganglionic nerves in the sympathetic nervous system are myelinated.
False
Post-ganglionic nerves in the sympathetic system are not myelinated.
What is the main physiological effect of α1-adrenoceptors?
Constrict blood vessels
This leads to an increase in blood pressure.
What is the main physiological effect of β2-adrenoceptors?
Relaxation of smooth muscle
This includes dilation of bronchi and relaxation of the GIT.
What is a characteristic effect of adrenergic agonists on the heart?
Increase heart rate and force of contraction
This is primarily mediated by β1-adrenoceptors.
What happens to skeletal muscle under the influence of β2-adrenoceptors?
Increased peripheral vasodilation
This effect facilitates increased blood flow to the muscles.
What is the effect of α2-adrenoceptors on neurotransmitter release?
Decrease release of norepinephrine
This is a presynaptic effect that provides negative feedback.
What is Myasthenia gravis?
A condition where circulating antibodies block ACh at nicotinic receptors at the neuromuscular junction
This leads to muscle weakness.
What are the two main types of cholinergic receptors?
Nicotinic and Muscarinic receptors
Fill in the blank: The _______ nervous system is responsible for involuntary actions.
Autonomic
What is the role of hemicholinium in cholinergic transmission?
Blocks the re-uptake of choline
This affects the synthesis of acetylcholine.
What is the function of vesamicol in cholinergic nerve terminals?
Blocks the uptake of ACh into vesicles
What are the two main types of receptors that cholinergic transmitters act on?
Nicotinic and muscarinic receptors
What type of receptor is the nicotinic receptor?
IONOTROPIC
How many subunits does a nicotinic receptor have?
Five (2α, β, δ, ε)
Where are nicotinic receptors found?
At neuromuscular junctions and in autonomic ganglia
What is the effect of depolarising blockers on nicotinic receptors?
They activate the nicotinic receptor and produce an initial contraction of muscle fibers
What do non-depolarising blockers do at the neuromuscular junction?
They act as competitive antagonists, reducing end-plate potential
What can reverse the effects of non-depolarising blockers?
An increase in acetylcholine concentration, e.g., by administration of anticholinesterases
What is the duration of action for Pancuronium?
1-2 hours
What are ganglion blocking drugs known to cause?
Widespread effects including hypotension and dry mouth
What is hexamethonium?
A direct channel blocker that competitively blocks ganglionic nicotinic receptors
What is the primary characteristic of muscarinic receptors?
They are members of the G-protein-coupled receptor family
How many muscarinic receptor subtypes have been cloned?
Five (M1-M5), with three well characterized
What is the primary action of M2 muscarinic receptors?
Inhibit adenylate cyclase and open K+ channels
Name an agonist that acts on muscarinic receptors.
Bethanechol
What are the main functional types of muscarinic receptors?
M1 (Neural), M2 (Cardiac), M3 (Glandular/Smooth Muscle)
What is the cellular effect of M1 receptors?
Increase IP3 and DAG
Fill in the blank: Muscarinic receptors have _______ transmembrane segments.
Seven
True or False: Non-depolarising blockers can produce a propagated action potential.
False
What is a common effect of succinylcholine?
Produces bradycardia and potassium efflux
What are the effects of excessive nicotine?
May produce a depolarising block at the ganglion
What is the duration of action for succinylcholine?
10 minutes
What type of activity does Pancuronium have?
Some antimuscarinic activity
What is the effect of M3 receptors on smooth muscle?
Stimulate calcium release and contraction
What is the primary function of M2 receptors in the heart?
Cardiac inhibition
What type of action do agonists have on muscarinic receptors?
They stimulate the receptors
Name an antagonist that acts on muscarinic receptors.
Atropine
What happens when a person has a ganglionic blockade?
They may experience dry mouth and tachycardia
What percentage of total body mass does the adult human brain constitute?
2%
The brain consumes approximately 20% of the body’s resting energy.
What is the primary energy substrate for the brain?
Glucose
The brain also requires nutrients such as amino acids, monocarboxylates (e.g., lactate, pyruvate), and vitamins.
What is the approximate length of cerebral blood vessels in the adult human brain?
650 km
85% of these vessels are capillaries.
What is the average inter-capillary distance in the brain?
40 μm
Ensures that neurons are 8-20 μm from blood vessels.
What are the primary components of neuronal communication?
Ions, neurotransmitters, neuromodulators, neuropeptides
Neurons communicate using electrical signals (synaptic and action potentials).
What is the main function of the Blood Brain Barrier (BBB)?
To maintain the homeostasis of the brain
It acts as a physical, metabolic, and immunological barrier.
Who provided early evidence for the existence of the Blood Brain Barrier?
Ehrlich and Lewandosky
They demonstrated that certain dyes did not stain the brain when injected intravenously.
What are the principal barrier-forming components of the BBB?
Brain capillary endothelial cells (BCECs)
Other cell types such as pericytes, astrocytes, and neuronal cells also contribute.
What prevents paracellular transport of compounds from blood to brain in the BBB?
Tight junctions
These junctions are formed by brain capillary endothelial cells.
What type of pumps serve to transport materials across the BBB?
Drug efflux pumps
They transport materials from within the brain to BCECs or from BCECs into the systemic circulation.
What is the role of pericytes in the BBB?
They have phagocytotic activity that contributes to the BBB’s properties.
What types of compounds are typically expelled by efflux pumps in the BBB?
Xenobiotics/drugs
These transporters recognize a wide diversity of substances.
What is the significance of lipophilicity in drug transport across the BBB?
Lipophilicity determines passive diffusion through the BBB
A molecule must be lipophilic to cross the hydrophobic phospholipid bilayer.
What is the ideal log P range for BBB permeability?
1.5–2.5
What is the molecular weight threshold for small-molecule drugs to cross the BBB?
Under 400 to 500 Da
Molecules above this threshold have significantly reduced permeability.
True or False: Approximately 98% of new small molecule drugs penetrate the BBB effectively.
False
Poor BBB penetration applies to approximately 98% of new small molecule drugs.
What strategies are used to deliver drugs across the BBB?
Trojan horse strategy, nanomedicine
These methods involve coupling substances that can cross the BBB with those that cannot.
What is receptor-mediated transcytosis in the context of the BBB?
A process where essential nutrients and carrier proteins cross the BBB via receptors on BCECs.
What is the role of transferrin receptor (TfR) in drug delivery?
It carries iron across the BBB and is explored for delivering protein therapeutics.
What is one method being researched to bypass the BBB?
Focussed ultrasound
This method can generate microbubbles that transiently open tight junctions.
What creates a significant barrier to drug permeation into the brain?
Continuous tight junctions of endothelial cells in brain capillaries
This contrasts with capillaries in other organs that have small pores.
What are the main topics covered in Pharmacy 202?
Anxiety, Depression, Bipolar Disorder
These topics were previously taught in Pharmacy 302.
List the learning objectives for sessions 1-3.
- List symptoms of depression
- Discuss diagnostic criteria for depression using ICD-10 and DSM-V
- Discuss pharmacology and clinical use of common antidepressants
- Explain treatment options for depression
- Select appropriate treatment based on guidelines
- Identify pharmaceutical care issues for patients
These objectives aim to equip students with necessary skills in managing depressive disorders.
What is depression?
An affective disorder characterized by depressed mood and/or loss of pleasure in most activities
Anhedonia refers to the loss of pleasure.
According to WHO (2017), what characterizes depression?
Persistent sadness and loss of interest in activities for at least two weeks
This includes an inability to carry out daily activities.
What is the difference between depression and simply feeling unhappy?
Depression is more than just feeling unhappy or fed up for a few days
It involves significant functional impairment.
What are some other names for depression?
- Melancholia
- ‘the blues’
- Living with/having ‘the black dog’
These terms reflect various cultural perceptions of depression.
What characterizes Major Depressive Disorder according to DSM-V?
Depressed mood and/or loss of pleasure for at least 2 weeks
This includes irritability in children.
What is Persistent Depressive Disorder previously called?
Dysthymia
Characterized by a depressed mood for most of the time for at least two years.
How is the severity of depression determined?
By the number and severity of symptoms plus the degree of functional impairment
This can classify Major Depression as mild, moderate, or severe.
What is psychotic depression?
A rare form of severe major depression with psychotic symptoms like delusions or hallucinations
It is associated with significant disability.
What is the global prevalence of depression?
More than 300 million people worldwide suffer from depression
It is the leading cause of disability globally.
What is the ‘Rule of Halves’ related to depression?
- Half of people with depression do not seek help
- Half of those who seek help are not correctly diagnosed
- Half of those diagnosed receive treatment
- Half of those receiving treatment do not complete it
This highlights the challenges in diagnosis and treatment adherence.
What are some biological factors contributing to depression?
- Genetics
- Personality
- Early environment
- Precipitating factors
- Monoamine hypothesis
These factors may increase the risk of developing depression.
What does the Monoamine Hypothesis suggest?
Depression is related to reduced levels of biogenic amines (monoamines)
This includes neurotransmitters like serotonin and noradrenaline.
What is the role of genetic factors in depression?
Increased risk in first-degree relatives and higher concordance in monozygotic twins
It suggests a polygenic inheritance pattern.
What are significant life events in relation to depression?
Events that can act as precipitating factors for depressive episodes
Social vulnerability factors can increase risk.
What is the median duration of a depressive episode?
16-23 weeks
About 12% of individuals do not achieve full remission.
True or False: More women are affected by depression than men.
True
This pattern is observed worldwide.
Fill in the blank: Depression is frequently associated with significant _______.
disability
It is often under-recognized.
What is serotonin?
A neurotransmitter that plays a key role in mood regulation
Serotonin is often linked to feelings of well-being and happiness.
What are MAOIs?
Monoamine oxidase inhibitors, a class of antidepressants
MAOIs work by preventing the breakdown of neurotransmitters like serotonin.
What are SNRIs?
Serotonin-norepinephrine reuptake inhibitors, a class of antidepressants
SNRIs increase levels of serotonin and norepinephrine in the brain.
What do TCAs stand for?
Tricyclic antidepressants
TCAs are an older class of antidepressants that affect neurotransmitter levels.
What is the effect of antidepressants on self-harm?
Antidepressants can increase the risk of self-harm and suicidal thoughts
This is particularly important in the early stages of treatment.
What is self-harm?
Deliberate pain or damage caused to one’s own body
It can be either suicidal or non-suicidal in intent.
Why do people self-harm?
To relieve or express distressing feelings, thoughts, or memories
Other reasons may include feelings of guilt or shame.
True or False: Most people who self-harm are trying to kill themselves.
False
Most individuals who self-harm do not intend to end their lives.
What percentage of suicide burden occurs in males?
Approx 75%
This statistic highlights the gender disparity in suicide rates.
What is the rate of suicide among males per 1000 population?
8.7 per 1000 population
This is significantly higher compared to females, who have a rate of 2.9.
What age groups have the highest rates of suicidal thoughts and behaviors?
25-34 years, 15-24 years, and 35-44 years
These age groups show the highest prevalence of suicidal behaviors.
What are the risk factors for depression?
Combination of recent events, personal factors, and genetic predisposition
Depression is usually multifactorial.
What are the core features of depression?
Persisting low mood and anhedonia
Anhedonia refers to the inability to feel pleasure.
List the psychological symptoms of depression.
- Hopelessness
- Low mood
- Anhedonia
- Negative thinking/pessimism
- Worthlessness
- Guilt
These symptoms often overlap and can vary in intensity.
What is the average length of a depressive episode?
6 months
This duration can vary significantly between individuals.
What is the purpose of diagnostic criteria for depression?
To standardize care and interpretation of trials and studies
These criteria help in consistent diagnosis and treatment.
What are some treatment options for depression?
- Psychoeducation
- Psychosocial interventions
- Pharmacotherapy
- Physical therapy such as ECT
Lifestyle changes can also significantly impact treatment outcomes.
What is the recommended approach to sleep hygiene?
- Establish regular sleep and wake times
- Avoid stimulants before bed
- Create a proper sleep environment
Good sleep hygiene is crucial for managing depression.
What is cognitive behavioral therapy (CBT)?
A psychological therapy that helps patients identify unhelpful thoughts and behaviors
CBT teaches patients to view challenging situations more clearly.
What is the difference between mild, moderate, and severe depression according to DSM-5?
Mild: Few symptoms; Moderate: Symptoms between mild and severe; Severe: Several symptoms with significant impairment
Severity is determined by the number of symptoms and their impact on functioning.
Fill in the blank: The exact cause of depression is ______.
[unknown]
Depression is typically multifactorial.
What is the focus of Cognitive Behavioural Therapy (CBT)?
Helping patients to identify unhelpful or distorted thoughts, emotions, and behaviours.
CBT teaches patients to view challenging situations more clearly and respond effectively.
What does Interpersonal Therapy (IPT) aim to address?
Helping patients to identify and understand interpersonal problems contributing to their condition.
IPT often focuses on areas of grief, interpersonal disputes, deficits, and role transitions.
What is the goal of Problem Solving Therapy?
Helping the patient to articulate personal problems and develop solutions from which they can systematically select the most appropriate solution.
What does Behavioural Activation Therapy focus on?
Helping patients to reconnect with sources of positive reinforcement by scheduling activities to increase pleasant activities.
What is Nondirective Supportive Therapy also known as?
Counselling.
In this therapy, patients discuss concerns and receive empathy.
What does Short-term Psychodynamic Therapy help patients understand?
Repetitive internal struggles and conflicts by examining past experiences and conflicts.
What is Electroconvulsive Therapy (ECT)?
A physical therapy used in severe cases of depression.
What is the NICE CG90 stepped-care model used for?
To guide treatment options for depression based on severity and complexity.
What interventions are included in STEP 4 of the NICE stepped-care model?
Medication, high-intensity psychological interventions, electroconvulsive therapy, crisis services, combined treatments, multiprofessional and inpatient care.
What should be done after a patient experiences symptom resolution?
Continue treatment for at least 6 months after symptom resolution to reduce the risk of relapse.
What is the recommended duration for continued antidepressant treatment after remission?
At least 6 months, and possibly up to 2 years or longer based on risk factors.
What are the types of antidepressants?
- TCA (Tricyclic antidepressants)
- SSRI (Selective serotonin reuptake inhibitors)
- SNRI (Serotonin and noradrenaline reuptake inhibitors)
- MAOI (Monoamine oxidase inhibitors)
- RIMA (Reversible inhibitor of MAO-A)
- NARI (Noradrenaline reuptake inhibitors)
- NASSA (Noradrenaline and specific serotonin antidepressants)
What is the mechanism of action of SSRIs?
Inhibition of the serotonin transporter (SERT) pre- and post-synapse.
True or False: Antidepressants are addictive.
False.
Antidepressants are not associated with addiction, though stopping abruptly may increase withdrawal symptoms.
What are potential side effects of SSRIs?
- Nausea
- Parkinsonian side effects
- Sexual dysfunction
- Prolonged QTc (for Citalopram)
- Discontinuation syndrome (for Paroxetine)
What is a significant concern with Tricyclic Antidepressants (TCAs)?
Cardiotoxicity, especially in overdose.
TCAs also have a range of adverse effects due to their action on various receptors.
What is the washout period required for MAOIs?
More than 2 weeks.
What is the effect of Mirtazapine compared to other antidepressants?
Comparable efficacy to TCA and SSRI in moderate to severe depression.
What is the role of Lithium in depression treatment?
Limited effect for monotherapy but increased effect when added to antidepressant therapy.
What is the expected clinical response rate to antidepressants?
70-80% may report a marked improvement after one month.
Fill in the blank: The acronym TCA stands for _______.
Tricyclic antidepressant.
What is the recommended approach for patients with multiple episodes of depression?
Consider lifelong treatment for multiple episodes.
What factors should be considered when deciding on maintenance treatment for depression?
- Age
- Comorbid conditions
- Other risk factors
What type of depression does Fluphenthixol show some effects for?
Psychotic depression
What is the effect of Lithium in monotherapy for depression?
Limited effect
How much does Lithium increase symptom control when added to antidepressant therapy?
50%
What is the symptom control percentage with placebo?
30%
What herbal remedy is proposed to have MAOI effect?
St John’s Wort
What is Hypericum evidence for?
Benefit in mild to moderate depressive episodes compared to placebo
What type of preparations does St John’s Wort come in?
Unstandardised preparations
What are some interactions of St John’s Wort?
- Oral contraceptive pill
- Theophylline
- Ciclosporin
What syndrome can occur when switching between antidepressants?
Serotonin Syndrome
What are some symptoms of Serotonin Syndrome?
- Shivering
- Sweating
- Autonomic instability
- Tachycardia
- Agitation
- Confusion
- Delirium
- Tremor
- Myoclonus
What is the cost of avoidable non-adherence to treatment?
£100 million
What percentage of rates of non-adherence with antidepressants is reported?
30-60%, up to 75%
What are the four key principles in managing medication adherence?
- Explore
- Educate
- Empower
- Enable
What are common symptoms of Discontinuation Syndrome?
- Flu-like
- Paraesthesia
- Electric shock sensation
- Insomnia
- Headache
- Excessive dreaming
- Agitation
What is a recommended approach to avoid Discontinuation Syndrome?
Dose reduction at end of treatment period
Which antidepressants are more prevalent for Discontinuation Syndrome due to shorter half-life?
- Paroxetine
- Venlafaxine
What factors influence the choice of pharmacological treatment for depression?
- Efficacy
- Tolerability
- Cost-effectiveness
- Guidelines
What are some patient factors to consider when choosing treatment?
- Allergy
- Drug history
- Medical history/Co-morbidities
- Previous response
- Social history
- Overdose risk
- Patient choice and understanding
What is a significant risk factor for poor adherence in depression?
Depression itself
What should be offered to all women with perinatal depression?
Psychological therapy
What is usually preferred for treating major depression during pregnancy?
SSRIs (not paroxetine)
What is the preferred SSRI for use during pregnancy?
Sertraline
What should be avoided in breastfeeding due to high concentrations in breast milk?
Fluoxetine
What is the preferred initial management for mild major depression in children?
Active monitoring
What should moderate-severe major depression in children initially be managed with?
CBT or IPT
What is a concern when using pharmacotherapy in young people?
Susceptibility to suicidal thoughts and activation symptoms
What factors should be considered for major depression in older people?
- Falls risk
- Renal and hepatic function
- Bleeding risk
- SIADH
- QT prolongation
- Sensitivity to SADRs
- Polypharmacy
What is the primary resource for guidelines on treating depression with antidepressants?
BAP Consensus Guidelines
What is the global prevalence of anxiety disorders?
About 7%
This figure represents the estimated prevalence of anxiety disorders in the general population.
What percentage of people with anxiety disorders receive treatment?
~25%
This indicates that a significant number of individuals do not seek or receive appropriate treatment for their anxiety.
What are some common symptoms associated with anxiety disorders?
Some common symptoms include:
* Excessive worry
* Restlessness
* Fatigue
* Difficulty concentrating
* Irritability
* Muscle tension
* Sleep disturbance
Symptoms can vary based on the specific type of anxiety disorder.
True or False: Anxiety is always considered a pathological condition.
False
While anxiety is a natural response to stress, it becomes pathological when excessive or interfering with normal functioning.
What are the three components of anxiety?
The three components of anxiety are:
* Physiological
* Cognitive
* Behavioral
Each component represents a different aspect of the anxiety experience.
List some recognized risk factors for anxiety disorders.
Some recognized risk factors include:
* Family history
* Life events causing emotional stress
* Personality traits like perfectionism and shyness
* Childhood adversity
* Being female
* Social isolation
* Unemployment or poverty
These factors can contribute to the development of anxiety disorders.
What is the role of GABA in anxiety disorders?
GABA is an important inhibitory neurotransmitter that regulates excitability and is linked to fear and anxiety responses.
Even mild attenuation of GABA transmission can lead to increased anxiety and related symptoms.
What are some secondary causes of anxiety?
Some secondary causes include:
* Neurologic conditions (e.g. Parkinson’s Disease)
* Endocrine disorders (e.g. Cushing’s disease)
* Cardiovascular issues (e.g. Angina)
* Inflammatory diseases (e.g. RA)
* Gastrointestinal disorders (e.g. IBS)
* Chronic infections (e.g. HIV)
Understanding these secondary causes is essential for accurate diagnosis and treatment.
Fill in the blank: The DSM-5 is used for _______ of anxiety disorders.
diagnosis
The DSM-5 provides criteria and guidelines for diagnosing various mental health disorders, including anxiety.
What is Generalized Anxiety Disorder (GAD)?
GAD is characterized by excessive anxiety and worry about multiple life circumstances occurring more days than not for over 6 months.
It is the second most common psychiatric disorder after depression.
What is the incidence rate of Generalized Anxiety Disorder (GAD)?
1-5%
This rate reflects the proportion of the population affected by GAD.
True or False: Anxiety disorders are only associated with psychological symptoms.
False
Anxiety disorders can also present with physical symptoms, which may lead individuals to seek medical help for physical rather than psychological issues.
What neurotransmitters are involved in the regulation of anxiety?
Key neurotransmitters involved include:
* Serotonin
* Noradrenaline (norepinephrine)
* Dopamine
* Glutamine
* Neurokinin
Dysregulation of these neurotransmitters is linked to the development of anxiety disorders.
What is the impact of anxiety on healthcare resources?
Failure to diagnose anxiety disorders is associated with overuse of healthcare resources and increased morbidity and mortality.
This highlights the importance of accurate diagnosis and effective treatment.
What are some common types of anxiety disorders?
Types of anxiety disorders include:
* Generalized Anxiety Disorder (GAD)
* Obsessive Compulsive Disorder (OCD)
* Panic Disorder
* Post-Traumatic Stress Disorder (PTSD)
* Phobic Disorders
* Social Anxiety Disorder
Each type has distinct features and diagnostic criteria.
What are the three or more symptoms associated with Generalized Anxiety Disorder (GAD)?
- Restlessness or feeling on edge
- Easily fatigued
- Difficulty concentrating or mind going blank
- Irritability
- Muscle tension
- Sleep disturbance
Symptoms must be present for at least 6 months for diagnosis.
What is the primary pathophysiological factor in Generalized Anxiety Disorder?
Neurotransmitter dysregulation in the basal ganglia, cortex, thalamus, and limbic system
Includes NA overactivity, 5HT receptor dysregulation, and reduced BZD binding sites on GABA.
What is considered the first-line therapy for Generalized Anxiety Disorder?
Psychological intervention, specifically Cognitive Behavioral Therapy (CBT)
CBT is more efficacious than anxiety management therapy alone.
Name one pharmacotherapy option for Generalized Anxiety Disorder.
- SSRIs
- Venlafaxine
- Duloxetine
- Imipramine
- Buspirone
- Benzodiazepines
SSRIs are often recommended as first-line pharmacological treatment.
What is the prevalence of Obsessive Compulsive Disorder (OCD) in adults?
Up to 2.5% in adults
The prevalence in children is about 0.5%.
What are the two main types of symptoms in Obsessive Compulsive Disorder?
- Obsessions
- Compulsions
Obsessions are unwanted thoughts, while compulsions are repetitive behaviors or mental acts.
What is the DSM-V criteria for diagnosing OCD?
Symptoms must:
* Create marked distress
* Consume more than 1 hour per day
* Significantly affect normal function
* Not be related to medications or other conditions
This ensures that the diagnosis is specific to OCD.
What is the recommended drug therapy for OCD?
- SSRIs
- Clomipramine
Therapeutic response generally increases over 6-12 weeks.
What characterizes Panic Disorder?
Recurrent, unexpected panic attacks associated with intense cardiac and nervous symptoms
Patients often fear losing control or dying.
What is a common co-morbidity associated with Panic Disorder?
Major depressive episode (50-60% risk)
Panic Disorder often co-occurs with agoraphobia.
What is the first-line treatment for Panic Disorder?
Psychological intervention, particularly education and CBT
SSRIs and Venlafaxine are first-line pharmacotherapy.
What are the three symptom clusters of Post-Traumatic Stress Disorder (PTSD)?
- Intrusive phenomena (recollections, nightmares, flashbacks)
- Hyperarousal phenomena (exaggerated startle responses, irritability, anger)
- Avoidance of reminders/emotional numbing
These clusters help in identifying PTSD symptoms.
What is a notable characteristic of the pathophysiology of PTSD?
NA overactivity and dysregulation of α2-AR and 5HT
Cortisol secretion dysregulation is also present.
What is the recommended treatment for phobias?
Psychological intervention, specifically Cognitive Behavioral Therapy (CBT)
Pharmacotherapy is not generally recommended.
What is Social Anxiety Disorder characterized by?
Marked and persistent fear and avoidance of social situations
This condition often leads to embarrassment or humiliation.
What is the treatment of choice for Social Anxiety Disorder?
Cognitive Behavioral Therapy (CBT) incorporating exposure-based therapy
SSRIs or Venlafaxine may also be used.
Fill in the blank: The therapeutic response for OCD drug therapy typically increases over ______ weeks.
6-12
Some improvement may be seen within the first month.
True or False: The onset of Panic Disorder typically occurs in late adolescence to mid-30s.
True
Age of onset is crucial for diagnosis.
What symptoms suggest Sara may be experiencing an anxiety disorder?
Trouble falling asleep, fitful sleep, waking up early, constant worry, inability to concentrate, and forgetfulness
Symptoms began after her daughter was diagnosed with health issues.
What is cognitive behavioural therapy (CBT)?
Psychological treatment aimed at modifying thinking and behaviours
What does eCBT stand for?
Computer-assisted and internet-based therapy
Name two classes of pharmacological therapies for anxiety disorders.
- Antidepressant agents
- Benzodiazepines
What are selective serotonin reuptake inhibitors (SSRIs)?
A common class of antidepressant agents used for anxiety disorders
What is the recommended duration for continuing antidepressants after symptom resolution?
6 months
What lifestyle interventions are suggested for anxiety treatment?
- Reduction in alcohol/smoking
- Moderate exercise
- Engagement in hobbies/activities
What is an anxiolytic?
A group of medications with anxiety-relieving effects
What is the primary neurotransmitter that benzodiazepines act on?
GABA (gamma aminobutyric acid)
What are some common side effects of benzodiazepines?
- Sedation
- Cognitive impairment
- Difficulty concentrating
- Problems with balance/coordination
True or False: Benzodiazepines were considered safe and effective when first introduced.
True
What are the main effects of benzodiazepines?
- Reduction in anxiety
- Induction of sleep
- Muscle relaxation
- Anticonvulsant effects
What is the significance of the half-life of benzodiazepines?
It influences their duration of action and clinical use
What is the primary action of benzodiazepines on GABA receptors?
They potentiate inhibitory action by binding to benzodiazepine receptors
What are the risks associated with benzodiazepine use in older adults?
- Higher risk of falls
- Increased risk of CNS side effects
Fill in the blank: Benzodiazepines are metabolized and excreted as _______.
glucuronide conjugates
What can cause tolerance to benzodiazepines?
Changes to the GABA A receptor
What are some contraindications for benzodiazepine use?
- Respiratory depression
- Severe hepatic impairment
- Myasthenia gravis
What is the role of pharmacies in mental health care?
Provide individualized and respectful care, develop trustworthy relationships with consumers
What are the effects of benzodiazepines on driving ability?
Associated with a 60-80% increase in risk of traffic accidents
What is buspirone?
An anxiolytic with minimal sedation
What are ‘Z’ drugs?
Hypnotics with minimal anxiolytic effects, e.g., zolpidem and zolpiclone
What is the primary reason for the decrease in benzodiazepine usage?
Evidence of their addictive nature and the development of alternative treatments
What is the effect of longer exposure to benzodiazepines (BZDs)?
Difficult to demonstrate in humans.
May occur but is debated.
What is dependence in the context of benzodiazepines?
A complex condition including BZD addiction and abuse.
What is Substance Use Disorder according to DSM-5?
A cluster of behavioural, cognitive, and physiological changes ranging from mild to severe.
What are withdrawal syndromes?
Severity of symptoms is variable.
What characterizes pharmacological dependence?
Not a preoccupation and craving for BZDs, generally no adverse social consequences.
What percentage of people experience withdrawal symptoms when using BZDs for insomnia after 4-6 weeks?
Approximately 15-30%.
What factors are related to the occurrence of withdrawal symptoms?
High dosage and long-term use.
What are common withdrawal symptoms from benzodiazepines?
- Anxiety
- Insomnia
- Irritability
- Paraesthesia
- Tinnitus
- Headaches
- Dizziness
- Poor memory
- Poor concentration
- Perceptual distortions
- Menstrual disturbances
- Nausea
- Depression
- Ataxia
- Rarely psychosis and seizures.
How can withdrawal effects be reduced?
By tapering the dose gradually over a period of at least 2-3 weeks.
What is the risk associated with short and intermediate-acting BZDs?
Greater risk of rebound and withdrawal.
What is the typical onset time for rebound anxiety and insomnia?
Hours to days.
What is the average daily BZD intake estimation method?
Calculate an equivalent dose of diazepam and substitute.
What are the common side effects of Zolpidem?
- Diarrhoea
- Dizziness (common)
- Hallucinations
- Acute rage
- Agitation (rare)
What are the contraindications for Zolpidem?
- Myasthenia gravis
- Concomitant alcohol intake
- Acute/severe pulmonary insufficiency.
What is the main action of Buspirone?
Acts at specific serotonin (5HT1A) receptors.
What is the dependence potential of Buspirone?
Low.
What are the therapeutic options for managing acute mania?
- Mood stabiliser
- Olanzapine
- Adjunctive therapy (antipsychotics, benzodiazepines).
What characterizes Bipolar I disorder?
At least 1 full manic episode and 1 full major depressive episode.
What is the lifetime prevalence of Bipolar II disorder?
0.5-1%, more common in women.
What is the neurochemical basis for Bipolar affective disorder (BPAD)?
Unclear, but involves structural abnormalities in the amygdala, basal ganglia, and prefrontal cortex.
What exacerbates mania in BPAD?
Drugs that increase catecholamine levels.
What distinguishes a manic episode from hypomania?
Severity and duration.
What are the signs of a manic episode?
- Elevated mood
- Increased motor activity
- Accelerated thoughts and speech
- Irritability
- Decreased sleep
- Increased or decreased appetite
- Distractibility
- Grandiose ideas.
What is the pharmacological option that is most widely used for BPAD?
Lithium.
What is the pharmacokinetic profile of Lithium?
Almost completely absorbed from GIT, peak effect in 2-4 hours, half-life of 18-24 hours.
What is the role of adjunctive therapy once a manic phase resolves?
Slowly taper off adjunctive therapy.
What does lithium inhibit the release of?
DA release
DA stands for dopamine.
What does lithium enhance the release of?
5HT release
5HT stands for serotonin.
What is the peak effect time for lithium?
2-4 hours
What is the half-life (t½) of lithium?
18-24 hours
How long does it take to reach steady-state levels of lithium with regular dosing?
5-7 days
Does lithium have protein binding?
No
How is lithium excreted from the body?
Unchanged in the urine
What percentage of lithium is reabsorbed in the proximal tubule?
~80%
What can cause lithium to accumulate in the elderly?
t½ typically 25% longer
What is the ideal blood level of lithium for acute mania?
0.6-1.0 mmol/L
What is the ideal blood level of lithium for prophylaxis?
0.6-0.8 mmol/L
What blood level of lithium is associated with side effects?
> 1.2 mmol/L
What blood level of lithium is associated with serious toxicity?
> 2.0 mmol/L
Is therapeutic drug monitoring (TDM) compulsory for patients on lithium?
Yes
When should lithium levels be monitored after stabilisation?
q3-6m
What are early acute signs of lithium toxicity?
1.2-1.5 mmol/L
What are severe signs of lithium toxicity?
> 2 mmol/L
What are common signs of lithium toxicity?
- GI (N&V, diarrhea)
- Cardiac (ECG changes, arrhythmias, prolonged QT interval)
What are signs of chronic lithium intoxication?
- Ataxia
- Confusion
- Tremor
- Cardiac symptoms
- Renal impairment
What are the most common causes of lithium toxicity?
- Drug interactions
- Renal impairment
- Dehydration
- Reduced fluid intake
- Persistent vomiting/diarrhea
- Excessive sweating
What are some drugs that reduce lithium clearance?
- Thiazides (up to 50%)
- NSAIDs (20-60%)
- ACEI/calcium channel blockers
What should be done if lithium toxicity occurs?
Cease lithium therapy
What is recommended for lithium levels <3 mmol/L?
Saline infusion to induce diuresis
What is the recommendation for lithium levels >3 mmol/L?
Renal dialysis
What are common side effects of lithium?
- Metallic taste
- Nausea
- Diarrhea
- Polydipsia
- Polyuria
- Cognitive impairment
- Tremor
What are non-dose related side effects of lithium?
- Diabetes
- Hypothyroidism
- Hypercalcemia
- Weight gain
- Maculopapular rash
What are some precautions for lithium use?
- Acute hyponatraemia
- Psoriasis
- Concurrent serotonin-enhancing drugs
- Renal impairment
- Surgery
- Elderly
What are contraindications for lithium use?
- Severe renal impairment
- Breastfeeding
What is the teratogenic risk associated with lithium during pregnancy?
Malformation of heart and large vessels
What is the preferred treatment for BPAD during pregnancy?
Antipsychotics or antidepressants
What is the recommended monitoring for patients on lithium?
- TDM
- ECG
- Renal function test
- Thyroid function test
What should patients be educated about regarding lithium therapy?
Do not stop taking suddenly
What is recommended regarding sodium intake while on lithium?
Maintain normal diet with standard amounts of sodium & fluid intake
What can be used as alternatives to lithium in BPAD?
- Olanzapine
- Lamotrigine
- Carbamazepine
- Sodium Valproate
- Gabapentin
- Topiramate
When is sodium valproate indicated in BPAD?
When lithium therapy has failed or is contraindicated
What are the common side effects of sodium valproate?
- GI disturbance
- Weight gain
- Sedation
- Tremor
What are rare but serious side effects of sodium valproate?
- Acute pancreatitis
- Hypersensitivity syndrome
- Thrombocytopenia
- Hepatotoxicity
What are contraindications for sodium valproate?
- Valproate hypersensitivity
- Severe hepatic dysfunction
- Pancreatic dysfunction
- Porphyria
- Urea cycle disorders
What is the recommended patient counselling for sodium valproate?
Take with/after food
When is carbamazepine indicated in BPAD?
When lithium therapy has failed or is contraindicated
What is the pharmacological action of carbamazepine?
Stabilises hyperexcited nerve membranes
What are common side effects of carbamazepine?
- Drowsiness
- Vertigo
- Ataxia
- Diplopia
- Blurred vision
What should be monitored in patients taking carbamazepine?
- Renal function
- Liver function tests
- Electrolytes
- Full blood count
What is the recommendation for duration of treatment in BPAD?
Highly variable; maintenance therapy recommended after two episodes
What should be included in the ‘Stay Well’ plan for BPAD patients?
- Daily mood chart
- Medication adjustments
- Education and counselling
What common reason might lead to non-compliance in BPAD treatment?
Perceived inefficacy
What are common reasons for non-compliance in treatment?
Perceived inefficacy, S/Es, belief that medication is no longer necessary
S/Es refers to side effects.
What is central to good management of BPAD?
Education of both the individual with BPAD and their family
BPAD stands for Bipolar Affective Disorder.
What is a ‘Stay Well’ plan?
A strategy to maintain mental health, may include a daily mood chart
A daily mood chart helps identify triggers.
What can a daily mood chart help identify?
Triggers
Triggers can include various lifestyle factors.
Name some triggers for mood fluctuations.
- Overseas travel
- Excessive coffee
- Recreational drugs
- Life events
- Disrupted sleep pattern
These factors can significantly affect mood stability.
How can the effects of medication be established?
More easily through a daily mood chart
Tracking mood can clarify the impact of medication.
What is suggested about the response of patients to mood stabilizers?
About 1/3 of patients will respond to a single mood-stabilizer, 1/3 will respond to multiple mood-stabilizers, and 1/3 will have a problematic course
This indicates the varying effectiveness of treatments.
What is common for patients who have a problematic course with medications?
Frequent medication adjustments
Adjustments may be necessary to find effective treatment.
What two main types of neural cells compose the nervous system?
Neurones and glial cells
Neurones transmit messages; glial cells support neurones.
What is the role of microglia in the nervous system?
Destroy invading microorganisms, remove cell debris, and promote tissue repair
Microglia are a type of glial cell.
What are oligodendrocytes and Schwann cells classified as?
Macroglia
They have supportive functions in the nervous system.
What is the function of the cell body of a neurone?
Contains the cellular machinery that keeps the neurone alive
Includes the nucleus.
What does the myelin sheath do?
Increases the transmission speed of an action potential along the axon
Myelinated axons are wrapped in myelin.
What are axon terminals?
Regions at the end of an axon that release neurotransmitters
They facilitate communication between neurones.
What is the function of dendrites?
Receive information from other neurones
Each neurone typically has multiple dendrites.
What is the role of the thalamus?
Relay station for all sensory information (except smell) from the PNS to the cerebral cortex
It plays a crucial role in sensory processing.
What is the function of the hypothalamus?
Regulates internal body functions such as eating, drinking, and sleep cycles
It also influences motivation and reward behaviors.
What is the cerebrum known as?
The ‘seat of intelligence’
It is divided into two hemispheres.
What does the cerebellum coordinate?
Posture, head and eye movements, and fine-tuning of muscle movements
It is crucial for learning motor skills.
What does the brainstem control?
Involuntary functions such as blood pressure and breathing
It is located between the spinal cord and the cerebrum.
What are gyri and sulci?
Gyri are raised ridges of tissue; sulci are shallow grooves
They characterize the surface of the cerebral cortex.
What is the difference between grey matter and white matter?
Grey matter consists of neuronal cell bodies and dendrites; white matter consists of glial cells and myelinated axons
Grey matter is involved in processing, while white matter relays messages.
What are the main regions of the cerebrum?
Cerebral cortex, underlying white matter, and several subcortical structures
The basal ganglia are part of the subcortical structures.
What is an action potential?
A signal generated by a neurone that transmits information
It is transmitted through the nervous system via axons.
What occurs at the synapse?
Neurotransmitters are released and bind to receptors on the postsynaptic neurone
This process is crucial for communication between neurones.
What is the role of neurotransmitters?
Excite or inhibit the generation of action potentials
They can also induce other biochemical processes.
How are neurotransmitters cleared from the synaptic cleft?
Reuptake into the presynaptic neurone, removal by astrocytes, diffusion, or breakdown by enzymes
These processes ensure neurotransmitter availability and action.
What are the subtypes of GABA receptors?
GABA A, GABA B, and GABA C
GABA is the major inhibitory neurotransmitter in the brain.
What is glutamate’s primary function in the CNS?
It is the principal excitatory neurotransmitter
Glutamate is an amino acid produced from glutamine.
What neurotransmitter receptor subtypes are associated with serotonin?
5-HT receptors (5-HT 1A-F, 5-HT 2A-C, 5-HT 3-7)
Serotonin is involved in mood regulation and other functions.
Fill in the blank: Glutamate is removed from the synapse by transporters on specialized neurones, metabolized to _______.
glutamine
This process allows for the recycling of glutamate.
True or False: Neurones physically touch each other at the synapse.
False
There is a gap known as the synaptic cleft.
What is GABA?
GABA is an ionotropic chloride channel and a major inhibitory neurotransmitter in the brain.
GABA is involved in many inhibitory synapses, with a significant number utilizing it.
What is the primary precursor for GABA?
Glutamate
Glutamate is an excitatory neurotransmitter that is converted into GABA.
Which other neurotransmitter is considered a major inhibitory neurotransmitter alongside GABA?
Glycine
Glycine is primarily found in the spinal cord and acts as a co-factor on NMDA receptors.
How is GABA removed from the synapse?
By specific transporters
These transporters ensure that GABA is recycled and prevents prolonged inhibitory signaling.
What is serotonin also known as?
5-HT
Serotonin is a neurotransmitter found throughout the body, especially in the CNS.
Where are high concentrations of serotonin found?
CNS, platelets, and certain cells in the gastrointestinal tract
These areas are crucial for various physiological functions.
What is the origin of serotonergic neurons in the brain?
Raphe nuclei of the brainstem
These neurons project widely throughout the brain.
True or False: Serotonergic projections to the spinal cord may regulate pain.
True
Pain regulation is one of the roles of serotonergic projections.
What role does serotonin play in the forebrain?
Regulates sleep and wakefulness
Serotonin is crucial for maintaining circadian rhythms.
What is the function of noradrenergic projections to the cerebellum?
Mediates motor movements, especially tremor
This highlights the importance of noradrenaline in motor control.
What does the noradrenergic projection to the brainstem control?
Blood pressure
This indicates the role of noradrenaline in autonomic functions.
What are the functions of noradrenergic projections to the prefrontal cortex?
Regulate mood and mediate attention
These functions link noradrenaline to cognitive processes.
What is the principal function of the locus coeruleus?
Prioritize competing incoming stimuli
This includes focusing attention on threats or pain.
What neurotransmitter is produced in the locus coeruleus?
Noradrenaline (norepinephrine)
This neurotransmitter is crucial for arousal and attention.
What is dopamine involved in?
Movement control, motivation, reward, and reinforcement
Dopamine is affected by many addictive substances.
What is the precursor molecule for dopamine?
DOPA (dihydroxyphenylalanine)
DOPA is converted into dopamine by DOPA decarboxylase.
How is dopamine removed from the synapse?
By specialized dopamine transporters
It is also catabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).
What is the mesocortical pathway associated with?
Influencing perception, cognition, and social behavior
This pathway links dopamine to higher cognitive functions.
What is the nigrostriatal pathway’s role?
Control of fine movements and initiation of movement
This pathway is critical for motor function.
What does the tuberoinfundibular pathway normally inhibit?
Release of prolactin
Prolactin is important for lactation and reproductive health.
What is the mesolimbic pathway involved in?
Emotion, memory, pleasurable sensations, and reward
It is also associated with psychotic symptoms like delusions and hallucinations.
What is the termination point of the spinal cord?
Conus medullaris
The conus medullaris is the tapered end of the spinal cord.
What is the function of the filum terminale?
Fibrous extension of conus covered with pia mater, anchors spinal cord
The filum terminale extends to the coccyx.
What are denticulate ligaments?
Extensions of pia mater that secure cord to dura mater
Name the three layers of meninges.
- Dura mater
- Arachnoid mater
- Pia mater
What is meningitis?
Inflammation of meninges
True or False: During meningitis, the integrity of the blood-brain barrier is disrupted.
True
What are the bones of the skull made up of?
22 individual bones, 14 facial and 8 cranial bones
What is the primary function of the meninges?
Cover and protect CNS, protect blood vessels, and enclose venous sinuses
What are ventricles in the brain?
Continuous central hollow cavities filled with cerebrospinal fluid (CSF)
How many lateral ventricles are there?
2 paired C-shaped ventricles
What is the role of the brain stem?
Controls automatic behaviors necessary for survival
What does the reticular formation regulate?
Awakening/sleeping cycle and filtering incoming stimuli
What is the basic function of the cerebellum?
Coordinate movements, maintain posture and equilibrium
What type of information does the cerebellum receive?
- Equilibrium information
- Proprioceptive information
- Cerebral cortex input
What is the function of cerebrospinal fluid (CSF)?
- Gives buoyancy to CNS structures
- Reduces weight by 97%
- Protects CNS from trauma
- Nourishes brain and carries chemical signals
What is the normal volume of cerebrospinal fluid?
Approximately 150 ml
What condition is caused by obstruction of CSF circulation?
Hydrocephalus
What is the epidural space?
Cushion of fat and network of veins in space between vertebrae and spinal dura mater
What is the function of the pia mater?
Delicate vascularized connective tissue that clings tightly to the brain
What does the choroid plexus do?
Produces cerebrospinal fluid (CSF) at a constant rate
What is the role of arachnoid villi?
Return cerebrospinal fluid to the dural sinus
What are the two layers of the dura mater?
- Periosteal layer
- Meningeal layer
What does the falx cerebri do?
Separates the two cerebral hemispheres in the longitudinal fissure
What is the main function of the epithalamus?
Forms the roof of the third ventricle and regulates sleep-wake cycles
What hormone does the pineal gland secrete?
Melatonin
What is the function of the hypothalamus?
Controls the autonomic nervous system and regulates various bodily functions
What regulates sleep-wake cycles?
Suprachiasmatic nucleus
Known as the biological clock.
What system does the hypothalamus control?
Endocrine system
It controls secretions of the anterior pituitary gland.
What hormones does the hypothalamus produce?
Posterior pituitary hormones
What does the hypothalamus regulate in the autonomic nervous system?
Blood pressure, rate and force of heartbeat, digestive tract motility, pupil size
What physical responses does the hypothalamus influence?
Emotional responses such as pleasure, fear, and rage
How does the hypothalamus regulate body temperature?
Through sweating and shivering
What does the hypothalamus regulate in terms of hunger?
Hunger and satiety in response to nutrient blood levels or hormones
What balance does the hypothalamus regulate?
Water balance and thirst
What are the six divisions of the adult CNS evident in the fetus by day 50 of gestation?
Cerebrum, cerebellum, brainstem, spinal cord, diencephalon, basal ganglia
What is found in the epidural space?
Cushion of fat and network of veins
What is the site of lumbar puncture?
Subarachnoid space
The spinal cord is absent there.
What separates the hemispheres of the brain?
Median longitudinal fissure
What does the transverse cerebral fissure separate?
Cerebral hemisphere from the cerebellum
What imaging techniques provide detailed anatomical structure and 3D images?
MRI and CT
What do PET and functional MRI measure?
Blood flow or glucose utilization in the brain
What is the primary role of the thalamus?
Gateway to the cortex
What are the three groups of white matter fibers classified by their connections?
- Commissures
- Association fibers
- Projection fibers
What does the prefrontal cortex involve?
Complex cognitive behavior, decision making, social behavior, personality expression
What is the function of the basal ganglia?
Regulate intensity of voluntary movements
What does the primary motor cortex control?
Conscious control of precise, skilled, skeletal muscle movements
What is the primary visual cortex responsible for?
Visual processing
Located at the extreme posterior tip of the occipital lobe.
What area evaluates sounds?
Auditory association area
What does the primary somatosensory cortex allow?
Conscious awareness of overall somatic sensation
What does the premotor cortex do?
Involved in planning movements
What does Broca’s area control?
Speech production
What is the term used for first generation (typical) antipsychotics?
Neuroleptic
The term neuroleptic is derived from their ability to produce neurolepsis.
What are the key characteristics of neurolepsis?
- Psychomotor slowing
- Affective indifference
- Emotional quieting
What do antipsychotics originally lack?
Extrapyramidal side effects
This is currently under debate as newer antipsychotics show varied side effects.
What are the two main classifications of symptoms in schizophrenia?
- Positive symptoms
- Negative symptoms
What are positive symptoms of schizophrenia?
- Delusions
- Hallucinations
- Bizarre behavior
What are negative symptoms of schizophrenia?
- Decline in normal function
- Reduced speech
- Flattened affect
- Loss of motivation
- Social withdrawal
- Anhedonia
What is the dopamine hypothesis of schizophrenia?
Overactivity of the mesolimbic pathway is involved in positive symptoms, while underactivity in the mesocortical pathway is linked to negative symptoms.
Which pathway is associated with extrapyramidal symptoms?
Nigrostriatal pathway
Antagonism of D2 receptors in this pathway increases the risk of extrapyramidal symptoms.
What are the four dopamine pathways affected in schizophrenia?
- Mesolimbic pathway
- Mesocortical pathway
- Nigrostriatal pathway
- Tuberoinfundibular pathway
What is the function of the tuberoinfundibular pathway?
Regulation of prolactin hormone release
What are common toxicities associated with antipsychotic drugs?
- Chlorpromazine
- Clozapine
- Haloperidol
- Thioridazine
- Ziprasidone
What is tardive dyskinesia?
A condition resulting from long-term use of antipsychotic medications, characterized by repetitive, involuntary movements.
What is the diagnostic criteria for schizophrenia according to DSM-5?
More than 1 positive symptom and 1 negative symptom present most of the time for at least 1 month.
What are positive symptoms in the context of schizophrenia diagnosis?
- Hallucinations
- Delusions
- Thought disorders
What are negative symptoms in the context of schizophrenia diagnosis?
- Emotional apathy
- Social withdrawal
- Poverty of speech
- Loss of motivation
- Self-neglect
- Severely disorganized or catatonic behavior
What is the significance of the mesocortical pathway in schizophrenia?
Dysfunction is associated with cognitive impairments and disturbances of emotions and affect.
What is the common mechanism of action for antipsychotics?
Postsynaptic D2 receptor antagonism
What is the relationship between dopamine and prolactin levels?
Dopamine inhibits prolactin release; D2 blockade increases prolactin levels.
Fill in the blank: Antipsychotics are primarily used to manage _______.
[psychosis]
True or False: Negative symptoms are easier to treat with antipsychotic drugs than positive symptoms.
False
What do all antipsychotics have in common?
They block dopamine receptors
What is a common side effect of high doses of first-generation antipsychotics?
Secondary negative symptoms and cognitive effects
What are the implications of blocking the mesocortical pathway?
Potential cognitive effects and exacerbation of negative symptoms.
What factors contribute to the aetiology of schizophrenia?
- Genetic vulnerability
- Environmental influences
- Viral infections
- Early life stress
- Obstetric complications
- Substance use (e.g., alcohol, cannabis)
What are common presenting symptoms of schizophrenia?
Apathy, withdrawal, reduced care in appearance, agitation, sleep disturbance, decline in function, incoherent or paucity of speech, hallucinations, delusional thoughts
Symptoms can also include trauma, financial worries, abuse, isolation, physical health triggers, depression/anxiety, transient/attenuated psychotic symptoms, drug or alcohol use, PTSD, and family history of schizophrenia.
What investigations should be considered in primary care for suspected schizophrenia?
FBC, U+Es, LFT, TFT, B12, urine drug testing, HIV, syphilis, anti-NMDA receptors (if neurological features present), BMI, waist circumference, CVD risk screen, prolactin level, ECG if CVD risk is high, echo for those with cardiac problems
These investigations help rule out organic causes.
What is the role of GPs in the management of schizophrenia?
Identification, referral, and supporting long-term health needs
GPs should not start antipsychotics without consultant psychiatric advice.
How long should antipsychotic medication be continued to reduce the risk of relapse?
At least 2 years
This is important for effective management of schizophrenia.
What are common side effects of antipsychotic medication?
Weight gain, extrapyramidal effects, cardiovascular problems, hormonal imbalance (prolactin rise)
Side effects vary by antipsychotic class.
What distinguishes typical from atypical antipsychotics?
Typical (first-generation) antipsychotics are more likely to cause extrapyramidal side effects, while atypical (second-generation) are less likely but have a higher risk of metabolic adverse effects
Atypical antipsychotics are also known for their lower risk of tardive dyskinesia.
Name two commonly used second-generation antipsychotics.
Aripiprazole, Clozapine
Other examples include Olanzapine, Paliperidone, Quetiapine, and Risperidone.
What is the importance of early diagnosis of schizophrenia?
Leads to better outcomes
Early identification of symptoms can improve management and prognosis.
What should be assessed during an annual review for schizophrenia management?
CVD risk, smoking cessation, adherence to medication plan, relapse prevention plan, carer support
This review helps in ongoing management and support.
Fill in the blank: Second-generation antipsychotics are also known as _______.
atypical antipsychotics
This term reflects their lower risk of extrapyramidal effects compared to first-generation.
What are the key features of second-generation antipsychotics?
5HT2A receptor antagonism, rapid dissociation from D2 receptors
These mechanisms contribute to their therapeutic effects and side effect profiles.
True or False: First-generation antipsychotics are also known as dopamine-serotonin antagonists.
False
First-generation antipsychotics are primarily dopamine antagonists, while second-generation are known as dopamine-serotonin antagonists.
List some adverse effects of first-generation antipsychotics.
- Extrapyramidal side effects (EPS)
- Sedation
- Orthostatic hypotension
- Weight gain
- Hormonal changes (amenorrhea, galactorrhea)
- Gynaecomastia
- Tardive dyskinesia
- Neuroleptic Malignant Syndrome (NMS)
These side effects can significantly impact patient quality of life.
What is the dopamine hypothesis in relation to schizophrenia?
The hypothesis suggests that increased dopaminergic activity is linked to the positive symptoms of schizophrenia
This is a foundational concept in understanding the pathophysiology of the disorder.
What are the four dopamine pathways affected by first-generation antipsychotics?
- Mesolimbic
- Mesocortical
- Nigrostriatal
- Tuberoinfundibular
Blocking D2 receptors in these pathways influences both therapeutic and adverse effects.
What are serotonin-dopamine antagonists?
They are drugs that block serotonin receptors.
This is a key feature of their mechanism of action.
What is the primary mechanism of action for second generation antipsychotics?
They act as 5HT2A antagonists and dissociate rapidly from D2 receptors.
Which was the first second generation antipsychotic?
Clozapine.
What is significant about the affinity of Clozapine?
It has a very high affinity for 5HT2A and lower D2 affinity than Haloperidol.
What hypothesis explains the differential antipsychotic effect of Clozapine?
The 5HT2A/D2 hypothesis.
How does 5HT2A antagonism affect extrapyramidal symptoms?
It can increase dopaminergic neurotransmission in the nigrostriatal pathway, reducing the risk of extrapyramidal symptoms.
What potential benefits could 5HT2A antagonism have in schizophrenia?
It could theoretically improve negative and cognitive symptoms by increasing dopamine release in the prefrontal cortex.
What is the chemical structure of Olanzapine similar to?
Clozapine.
List some indications for Olanzapine treatment.
- Schizophrenia
- Bipolar disorder
What are some side effects of Olanzapine?
- Weight gain
- Hypertriglyceridemia
- Hypercholesterolemia
- NMS
- Somnolence
- EPS
- Hyperprolactinemia
- VTE
- Hyperglycemia
- DKA
- Diabetic coma
- Seizures
What conditions is Risperidone used to treat?
- Schizophrenia (including adolescent schizophrenia)
- Schizoaffective disorder
- Bipolar disorder
- Autism
What are common side effects of Risperidone?
- Somnolence
- Agitation and anxiety
- Headache
- Tachycardia
- Orthostatic hypotension
- NMS
- Hyperprolactinemia
- Gynaecomastia (in children)
- Dyspepsia
- Nausea
- Vomiting
- Seizures
- DM type 2
- TTP
- Agranulocytosis
What type of drug is Risperidone classified as?
An atypical antipsychotic and a partial D2 agonist.
What is a functional selective drug?
A drug whose effects depend on the anatomical location and cell-type expressing the D2-type receptor.
What is the current example of a drug that achieves reduction of dopaminergic transmission via partial D2 agonism?
Aripiprazole.
What is the typical dose-response relationship for drugs?
It shows differences in potency and efficacy.
How does Aripiprazole function at D2 receptors?
It can stimulate D2 receptors where synaptic DA levels are limited or decrease dopaminergic activity when dopamine concentrations are high.
What clinical evidence supports the partial DA agonist properties of Aripiprazole?
A reduction in serum prolactin levels.
What receptors does Aripiprazole partially agonize?
- D2
- D3
- 5-HT1A
- 5-HT2C
What are the main differences between typical and atypical antipsychotics?
They rest on receptor profile, incidence of extrapyramidal side effects, and efficacy in treatment-resistant patients.
Which medications belong to the first generation of antipsychotics?
_________
Provide specific examples in context.
Which medications belong to the second generation of antipsychotics?
_________
Provide specific examples in context.
Which antipsychotic drug could be considered for depot intramuscular injectable preparation based on its chemical scaffold?
_________
Indicate based on the drug’s structure.
What aspect of a drug’s structure allows it to be used as a long-acting injectable antipsychotic?
_________
Indicate the specific substituent or region of the drug.
What should be reflected upon regarding schizophrenia and smoking?
Pharmacology, genetics, and clinical implications of smoking in people living with schizophrenia.
What is the lifetime prevalence of schizophrenia?
About 1%
Schizophrenia is a severe, chronic, disabling brain disorder.
At what ages does the onset of schizophrenia typically occur in men and women?
Men: 15-24 years; Women: 25-34 years
Men usually experience an earlier onset than women.
What are the three symptom clusters of schizophrenia?
- Positive
- Negative
- Cognitive
True or False: There is one essential symptom required for a diagnosis of schizophrenia.
False
Patients experience different combinations of the main symptoms.
How is schizophrenia characterized?
Disintegration of thought processes and emotional responsiveness
Common manifestations include auditory hallucinations and bizarre delusions.
What are the types of schizophrenia identified?
- Catatonic Type
- Disorganized Type
- Paranoid Type
- Residual Type
- Undifferentiated Type
What distinguishes Early Onset Psychosis from Later Onset Schizophrenia?
- Rare
- Poorer prognosis
- Similar gender ratio
- No gender difference in age of onset
List the categories of symptoms in schizophrenia.
- Positive Symptoms
- Negative Symptoms
- Cognitive Symptoms
What are positive symptoms of schizophrenia?
- Disturbances of thought processes
- Delusions
- Hallucinations
- Erratic emotions
- Disorganized speech and behavior
What are negative symptoms of schizophrenia?
- Lack of interest/enjoyment
- Low energy/motivation
- Blank facial expression
- Difficulty initiating activities
- Social isolation
What is the Dopamine Hypothesis in relation to schizophrenia?
Disturbed functioning in the dopamine system, particularly excess dopamine activity at certain synaptic sites
Supportive evidence includes the effects of phenothiazines and L-Dopa.
What are the five dopamine pathways relevant to schizophrenia?
- Mesolimbic pathway
- Tuberoinfundibular pathway
- Nigrostriatal pathway
- Mesocortical pathway
- D2 subtype
What is the primary role of antipsychotics in the management of schizophrenia?
Diminish positive symptoms and prevent relapses
There is no clear drug of choice; clozapine is noted as the most effective.
Fill in the blank: Delusions of _______ refer to the belief that one is a famous or powerful person.
Grandeur
What type of hallucinations are most common in schizophrenia?
Auditory hallucinations
They may include hearing voices that comment on one’s behavior.
What is anhedonia in the context of negative symptoms?
Inability to feel pleasure or lack of interest in activities
It is a common negative symptom associated with schizophrenia.
What are the challenges associated with diagnosing schizophrenia?
Physical and lab exams rule out other disorders; diagnosis is commonly made from history and mental status exam.
Currently, there are no reliable biomarkers for diagnosis.
What is the DSM-V criterion for the duration of symptoms in schizophrenia?
At least 6 months
This includes social/occupational dysfunction and exclusion of schizoaffective and mood disorders.
What are the potential side effects of dopamine receptor blockade?
- Extrapyramidal side effects (EPS)
- Tardive dyskinesia
True or False: Negative symptoms of schizophrenia are generally more responsive to treatment than positive symptoms.
False
Positive symptoms are generally more responsive to treatment.
What is the role of NMDA receptors in schizophrenia according to non-dopamine theories?
Excitatory amino acids like glutamate could play a role; NMDA antagonists can induce psychotic symptoms
Increased NMDA receptors have been observed in post-mortem studies of schizophrenic brains.
What is the relationship between the amount and type of disability and the individual’s illness?
The amount and type of disability is related to the symptoms of the individual’s illness and how responsive these symptoms are to treatment.
What is the main role of antipsychotics in managing schizophrenia?
Antipsychotics diminish the positive symptoms and prevent relapses.
What is the most effective medication for schizophrenia but not recommended as first-line therapy?
Clozapine.
What types of psychosocial treatments are essential for schizophrenia management?
- Social skills training
- Cognitive-behavioral therapy
- Cognitive remediation
- Social cognition training
True or False: Nearly all patients on antipsychotic medications will experience some burden from side effects.
True.
What are the two major types of antipsychotics?
- Conventional
- Atypical
What is the mechanism of action for antipsychotics?
Antagonise dopamine receptors, resulting in anti-psychotic effects.
What are the two types of typical antipsychotics?
- Phenothiazines
- Thioxanthenes
What are the common side effects of conventional antipsychotics?
- Parkinsonism
- Dystonia
- Akathisia
- Tardive dyskinesia
What is the first tricyclic antihistamine that was developed into an antipsychotic?
Chlorpromazine.
What are the main challenges associated with Olanzapine?
- Sedation
- Weight gain
What is the primary benefit of long-acting injectable antipsychotics?
Enhance adherence.
What are the general concerns associated with long-acting injectable antipsychotics?
- Associated with worse side effects?
- Patients’ acceptance?
- Reduced patient autonomy?
- Nursing involvement?
What are some manifestations of extrapyramidal symptoms (EPS)?
- Drowsiness
- Lethargy
- Mental confusion
- Parkinson’s syndrome
- Acute akathisia
- Acute dystonia
What is a potential serious complication of antipsychotic use related to muscle rigidity and fever?
Neuroleptic Malignant Syndrome (NMS).
What are the common cardiovascular side effects of antipsychotics?
- Orthostatic hypotension
- Increased heart rate
- Dizziness
Fill in the blank: Atypical antipsychotics exhibit _______ action.
multireceptor
What is hyperprolactinemia and how is it related to antipsychotic use?
Could result in amenorrhea, menstrual cycle disorders, breast enlargement, galactorrhea, sexual effects.
Which antipsychotic has the highest risk of agranulocytosis?
Clozapine.
What is the recommended duration of antipsychotic treatment after an acute episode?
At least 6 months.
What is the effect of serotonin on dopamine release in the nigrostriatal pathway?
Serotonin opposes the release of dopamine.
True or False: Atypical antipsychotics are less likely to induce extrapyramidal side effects (EPSE).
True.
What is the significance of the D2 receptor blockade in antipsychotic action?
Dopamine blockade in the ‘limbic system’ and in mesocortical areas is responsible for the antipsychotic actions.
What are the adverse effects of clozapine?
- Agranulocytosis
- Weight gain
- Sedation
What is a key consideration when prescribing antipsychotics to the elderly?
Start low & go slow, titrate over longer periods.
What are the potential neonatal adverse effects of antipsychotic use during pregnancy?
Observed neonatal adverse effects include developmental issues.
What is the relationship between weight gain and metabolic syndrome in antipsychotic treatment?
Weight gain is a precursor to metabolic syndrome.
What are the first-generation (typical) antipsychotics?
Chlorpromazine, levomepromazine, promazine, pericyazine, pipothiazine, trifluoperazine, fluphenazine, haloperidol, benperidol, flupentixol, zuclopenthixol, pimozide, fluspirilene, sulpiride, amisulpride
These drugs are primarily used to treat schizophrenia and other psychotic disorders.
Name at least five second-generation (atypical) antipsychotics.
Aripiprazole, Clozapine, Olanzapine, Paliperidone, Quetiapine, Risperidone, Sertindole
Atypical antipsychotics are considered to have a different side effect profile compared to typical antipsychotics.
Which antipsychotic drug is shown to be more effective than others for refractory schizophrenia?
Clozapine
Clozapine is particularly effective in patients who do not respond to other treatments.
What factors influence the choice of antipsychotic medication?
Previous response to a drug, co-morbid illness, potential for drug interactions, potential for side effects, prescriber, patient or carer preference
Patient choice is important as it can affect treatment adherence.
What is the general principle of prescribing antipsychotics?
Use lowest possible dose, dose increase only after 2 weeks of assessment, use of a single antipsychotic recommended
In exceptional circumstances, augmentation with another antipsychotic may be acceptable.
What are some strengths of antipsychotic medications?
- 70% of patients respond, achieving partial or complete remission
- Familiar drugs with predictable side effects
- Multiple formulations available
- Reduce relapse in most patients
- Mostly inexpensive
- Wide choice of drugs
The choice of drug often depends on the side effect profile.
What are some weaknesses of antipsychotic medications?
- Generally ineffective against negative and cognitive symptoms
- Low efficacy in many people
- Slow response (up to 6-8 weeks)
- Not liked by patients due to many side effects
Side effects include extrapyramidal symptoms (EPSE), anticholinergic effects, and endocrine problems.
What is the mechanism of action of atypical antipsychotics?
D2 and 5-HT2A antagonism
This antagonism helps reduce the risk of extrapyramidal side effects.
True or False: Most people will experience sedation as a side effect of antipsychotics.
True
Sedation is commonly observed, especially in the first few months of treatment.
Fill in the blank: The primary action of antipsychotics is to block _______ receptors.
[dopamine]
Dopamine receptor antagonism is crucial for their therapeutic effects.
What are extrapyramidal side effects (EPSE)?
Acute or tardive motor symptoms caused by D2 antagonism in the striatum
Symptoms include tremor, rigidity, bradykinesia, dystonia, akathisia, and dyskinesia.
What is hyperprolactinaemia and what causes it?
Increased prolactin secretion due to D2 antagonism in the tuberoinfundibular pathway
It can lead to menstrual disturbances, reduced bone mineral density, and sexual dysfunction.
List some common side effects of antipsychotic medications.
- Extrapyramidal symptoms (EPSE)
- Weight gain
- Sedation
- Dry mouth
- Constipation
- Tachycardia
Monitoring for these side effects is essential for patient safety.
What is the role of lifestyle changes in managing antipsychotic-induced weight gain?
Dietary advice, lifestyle changes, and/or treatment with statins
Monitoring baseline weight and regular assessments are important for managing weight.
How often should long-acting injections of antipsychotics be administered?
Every 1 to 4 weeks
These injections are indicated for patients with poor compliance.
What formulations are available for long-acting injections?
- Flupentixol decanoate
- Fluphenazine decanoate
- Haloperidol decanoate
- Pipotiazine palmitate
- Zuclopenthixol decanoate
- Olanzapine pamoate
- Paliperidone palmitate
- Risperidone
These formulations may differ in their base and administration requirements.
What are the most common types of seizures?
Generalized seizures, focal seizures, absence seizures, tonic-clonic seizures, myoclonic seizures.
What limits the duration and frequency of the action potential?
Refractory period and ion channel inactivation.
What are EPSP?
Excitatory postsynaptic potentials.
What are IPSP?
Inhibitory postsynaptic potentials.
Define a paroxysmal depolarizing shift (PDS)
A sudden and intense depolarization of a neuron that can lead to seizure activity.
What is the difference between seizures and epilepsy?
Seizures are transient events; epilepsy is a disorder characterized by recurrent seizures.
Give a definition of Epileptogenesis.
The process by which a normal brain develops epilepsy.
List possible anti-epileptic drugs (AED).
- Phenytoin
- Carbamazepine
- Lamotrigine
- Valproic acid
- Ethosuximide
- Gabapentin
- Felbamate.
What role does the voltage-gated Na+ channel play in normal neuronal function?
Action potential upstroke and repetitive action potential firing.
What is the possible role of the voltage-gated Na+ channel in epilepsy?
Repetitive action potential firing.
What is the role of voltage-gated K+ channels in neuronal function?
Action potential downstroke.
What can abnormal action potential repolarization indicate?
Possible epilepsy.
What is the function of Ca2+-dependent K+ channels?
Sets refractory period and limits repetitive firing.
What is the role of voltage-gated Ca2+ channels?
Transmitter release and carries depolarizing charge.
What is the function of non-NMDA receptors (e.g., AMPA)?
Initiates fast EPSP.
What is the function of NMDA receptors?
Maintains PDS and activates intracellular processes.
What is the role of GABA-A receptors?
Limits excitation.
What is the role of GABA-B receptors?
Prolonged IPSP; limits excitation.
What is the role of electrical synapses?
Ultrafast excitatory transmission and synchronization of neuronal firing.
What does the Na+-K+ pump do?
Restores ionic balance and prevents K+-induced depolarization.
What are the conditions associated with altered neuronal circuits leading to epilepsy?
- Cerebral dysgenesis
- Post-traumatic scar
- Mesial temporal sclerosis.
What is the significance of pyridoxine (vitamin B6) dependency?
Decreased GABA synthesis; B6 is a co-factor for GAD.
What can lead to excess glycine and activation of NMDA receptors?
Nonketotic hyperglycinemia.
What are the mechanisms of pharmacotherapy for focal seizures?
- Enhance inhibition
- Prevent spread of synchronous activity.
Which antiepileptic drugs act on GABAA receptors?
- Barbiturates
- Benzodiazepines.
How do Na+ channel inhibitors prevent rapid neuronal firing?
By prolonging Na+ channel inactivation.
What is the cause of absence seizures?
Self-sustaining cycle of activity between thalamic and cortical cells.
What do T-type calcium channel inhibitors do?
Prevent burst activity of thalamic relay neurons.
What is the definition of epilepsy as per the ILAE?
A disorder characterized by an enduring predisposition to generate epileptic seizures.
How many seizures are typically required for a diagnosis of epilepsy?
Two or more seizures.
What is the historical belief about curing epilepsy in ancient Rome?
Drinking a slain gladiator’s blood could cure epilepsy.
What was a common belief about the causes of epilepsy in the mid-1800s?
- Fear
- Masturbation
- Drunkenness.
What is the oldest known record of epilepsy?
The Sakikku, a Babylonian cuneiform medical text from 1067–1046 BC.
What are the most common types of seizures?
Focal seizures, Generalized seizures
Seizures can be classified based on their origin and spread.
What is a cortical homunculus?
A pictorial representation of the anatomical divisions of the primary motor cortex and the primary somatosensory cortex
It represents the movement and exchange of sensory and motor information in the brain.
What neurotransmitters regulate action potential traffic?
GABA and Glutamate
GABA is inhibitory, while Glutamate is excitatory.
What role does GABA play in the nervous system?
Stops action potentials
GABA is an inhibitory neurotransmitter that helps regulate neuronal excitability.
What is the function of Glutamate?
Starts action potentials or keeps them going
Glutamate is an excitatory neurotransmitter critical for synaptic transmission.
What is an epileptic focus?
Groups of neurons, e.g., cortical pyramidal cells, firing trains of action potentials
This abnormal activity can lead to seizures.
What is a paroxysmal depolarizing shift (PDS)?
A sustained depolarization characterized by a train of action potentials
It is observed in neurons within the epileptic focus.
What are the two broad classifications of seizures?
Focal seizures and Generalized seizures
This classification is based on the site of origin and pattern of spread.
What are the symptoms associated with focal seizures?
Related to the function ordinarily subserved by the area of the brain where they arise
Symptoms can vary based on the specific brain region affected.
What characterizes primary generalized seizures?
Begins simultaneously in both hemispheres
They often display a bilateral synchronous spike-wave pattern on EEG.
What types of seizures are included in the generalized category?
- Absence epilepsy
- Tonic
- Clonic
- Tonic-clonic
- Atonic
- Myoclonic
Generalized seizures can involve loss of consciousness.
Fill in the blank: A normal action potential is generated by voltage-dependent _______ channels.
sodium ion
These channels are critical for the propagation of action potentials.
What can cause a higher proportion of seizures in the elderly?
Brain Tumours and Strokes
These conditions are more prevalent in older populations.
What is Epileptogenesis?
The sequence of events that turns a normal neuronal network into a hyperexcitable network
This process can lead to the development of epilepsy.
What are some genetic factors associated with epilepsy?
- Single gene mutations
- Multiple genes + environment
Genetic disorders such as Down syndrome and Dravet syndrome can increase the risk of epilepsy.
What is the significance of the corpus callosum in seizure spread?
Contributes to rapid bilateral synchrony
It facilitates communication between the two hemispheres of the brain.
What are common underlying causes of seizures in children?
- Birth Traumas
- Infections (e.g., Meningitis)
- Congenital abnormalities
- High fevers
These factors can trigger seizures in pediatric populations.
What is the role of domoic acid in the development of seizures?
Activates glutamate receptors leading to neurotoxicity
Domoic acid can cause excessive glutamate release, resulting in neuronal degeneration.
What is the difference between simple and complex focal seizures?
Simple: no loss of consciousness; Complex: impairment of consciousness
This distinction is crucial for diagnosis and treatment.
What is a neuron?
A basic unit of the nervous system that transmits signals.
What is the role of an axon?
It conducts electrical impulses away from the neuron’s cell body.
What is a terminal in the context of a neuron?
The end part of an axon where neurotransmitters are released.
What are the key aspects of managing seizures and epilepsy?
- Treatment of a single seizure by specialists
- Treatment of underlying abnormalities
- Consideration of precipitating factors
What factors should be considered in the treatment of a single seizure?
Precipitating factors such as drug abuse (e.g., cocaine) and sleep deprivation.
What is the impact of epilepsy on driving?
Epilepsy can affect driving eligibility as assessed by DVLA.
What are the considerations for treating epilepsy?
- Sleep hygiene
- Diet
- Stress management
What is the basis for selecting antiepileptic drugs (AEDs)?
- The type of seizure or epilepsy syndrome
- The side effect profile of AEDs
- Vigilance about drug-drug interactions
What should be monitored in the treatment for recurrent seizures?
- Serum anticonvulsant levels
- Patient counselling
- Acute problems (e.g., infection)
What should be considered when seizures seem refractory to treatment?
Evaluation of appropriate doses of anticonvulsants.
What action sites are relevant for AEDs?
- Voltage-gated Na+ Channels
- HVA Ca2+ Channels
- LVA Ca2+ Channels
- Voltage-gated K+ Channels
- GABA A receptor
- GABA Turnover
- Glutamate receptor
- Synaptic vesicle protein 2A
Name some examples of antiepileptic drugs.
- Phenytoin
- Ethosuximide
- Carbamazepine
- Lamotrigine
- Levetiracetam
True or False: The mechanism of action of AEDs can involve voltage-gated Na+ Channels.
True
Fill in the blank: The mechanism of action of AEDs may include _______.
[GABA A receptor]
What additional reading resources are mentioned for epilepsy management?
- Nature Reviews Neurology
- Foye’s Principles of Medicinal Chemistry
- Essentials of Human Physiology for Pharmacy
What are voltage-gated channels associated with AEDs?
- Na+ Channels
- Ca2+ Channels
- K+ Channels
What is the definition of a seizure?
A seizure is a brief, temporary disturbance in the electrical activity of the brain.
What characterizes epilepsy?
Epilepsy is a disorder characterized by recurring seizures.
What are the common causes of epilepsy in 30% of cases?
- Head trauma
- Brain tumor and stroke
- Lead poisoning
- Infection of brain tissue
- Heredity
- Prenatal disturbance of brain development
What is the cumulative incidence of epilepsy by the age of 75 years?
3400 per 100,000 men (3.4%) and 2800 per 100,000 women (2.8%).
What is the global prevalence of epilepsy?
Around 60 million people have epilepsy.
What percentage of people will have a seizure in their lifetime?
Up to 5%.
What is the incidence of epilepsy approximately per year?
Approximately 45/100,000.
What are the common triggers for photosensitivity epilepsy?
- Flashing lights
- Stress
- Alcohol
- Not taking medication
What percentage of people with epilepsy have photosensitivity epilepsy?
5%.
What is the risk of premature death in people with epilepsy compared to the general population?
2-3 times higher.
What is the prognosis for people who develop epilepsy?
- 70-80% will eventually become seizure free
- 50% will successfully withdraw medication
- 20-30% may develop chronic epilepsy
What percentage of epilepsy patients report restricted daily activities?
56%.
What are the types of focal-onset seizures?
- Simple (no loss of consciousness)
- Complex (consciousness impaired)
- With or without aura
- With or without automatisms
What are generalized seizures characterized by?
Apparent start over wide areas of the brain.
What is a tonic-clonic seizure also known as?
Grand mal seizure.
What occurs during a tonic-clonic seizure?
- Loss of consciousness
- Sudden stiffness
- Rhythmical shaking
- Possible temporary cessation of breathing
What is the incidence of seizures approximately per year?
Approximately 80/100,000.
What are the key symptoms of myoclonic seizures?
Sudden, brief, involuntary muscle contractions.
What are the common causes for the first seizure?
- Head injury
- Alcohol withdrawal
- Drugs
- Metabolic disturbance
- Stroke
What mechanisms are involved in the pathophysiology of seizures?
- Abnormal discharges spread to other parts of the brain
- Imbalance between excitatory and inhibitory forces in cortical neurons
True or False: The majority of causes of epilepsy are known.
False.
What is the impact of epilepsy on cognition and memory?
46% report difficulties.
What is the term for seizures that start in one location of the brain?
Focal-onset seizures.
What characterizes absence seizures?
Brief lapses in consciousness.
Fill in the blank: A seizure results when a sudden imbalance occurs between the _______ and _______ forces within the network of cortical neurons.
[excitatory], [inhibitory]
What are the key population considerations for epilepsy?
Considerations include age, gender, and comorbid conditions.
What is the term for seizures characterized by sudden loss of muscle tone?
Atonic seizures.
What type of seizure is characterized by rhythmic shaking and loss of consciousness?
Tonic-clonic seizure.
What is the role of GABA neurons in the pathophysiology of seizures?
Defective activation can lead to decreased inhibition.
What is a seizure characterized by loss of consciousness, sudden stiffness, and rhythmical shaking?
Convulsion
May also include temporary breathing cessation and cyanosis.
What type of seizure involves sudden, brief, involuntary muscle jerks?
Myoclonic seizure
Can vary in intensity and may affect only part of the body.
What defines an absence seizure?
Momentary lapse in awareness
Often involves staring or blinking and is more common in children.
What is the primary aim of seizure diagnosis?
Differentiate between events that mimic epileptic seizures
Examples include syncope, vertigo, migraine, and psychogenic non-epileptic seizures.
What is the goal of epilepsy management?
Achieve complete seizure control with a single drug
Ideally taken once or twice daily without side effects.
What factors affect the choice of antiepileptic medication?
- Type of seizure or epilepsy syndrome
- Pharmacokinetic profile
- Interactions/other medical conditions
- Efficacy & safety
- Treatment cost
What is the recommendation regarding the sudden cessation of antiepileptic drugs (AEDs)?
Never stop AEDs suddenly
A minimum of 2 seizure-free years is required in patients without risk factors.
What should be done if seizures continue despite maximum tolerated dose of AED?
Review the diagnosis
Consider adding another first-line drug while withdrawing the first one.
What is Carbamazepine primarily used for?
Partial and generalized tonic-clonic seizures
It is an enzyme-inducing drug and can interact with other medications.
What is a significant side effect of Sodium Valproate?
Teratogenic effects causing spina bifida
Especially important to avoid in women of child-bearing age.
What is Lamotrigine effective against?
Absence seizures
It is safer for women of child-bearing age compared to other AEDs.
What is Ethosuximide used for?
First-line treatment for absence seizures
Can be used as monotherapy or adjunctive treatment.
What are common side effects of older antiepileptic drugs?
- Sedation
- Drug interactions
- Narrow therapeutic range
What is a major risk associated with Phenytoin?
Potent enzyme inducer
It has a narrow therapeutic range and can cause serious side effects.
What are newer antiepileptic drugs primarily used for?
Focal seizures with or without secondary generalization
Examples include Gabapentin and Pregabalin.
What non-pharmacological approach is based on findings that starvation has an antiepileptic effect?
Ketogenic diet
High in fat and low in carbohydrates and protein.
What is the role of benzodiazepines in the context of seizures?
Used as adjuvants in emergency cases
Particularly for uncontrolled seizures like status epilepticus.
What should be monitored during the treatment with older AEDs?
Blood disorders and sedation levels
Particularly important for drugs like Phenobarbital and Phenytoin.
What is the primary dietary approach used to treat severe childhood epilepsy?
High fat, low carbohydrate and protein intake
This dietary approach is known as the ketogenic diet.
What is the mechanism of action for Vagus Nerve Stimulation (VNS)?
Delivers electrical stimulation to the vagus nerve in the neck
This method relays impulses to widespread areas of the brain to control seizures.
What types of seizures is Vagus Nerve Stimulation (VNS) used to treat?
Partial seizures
Used when medication does not work.
What are some non-pharmacological approaches to epilepsy treatment?
- Behavioral therapy (Biofeedback, Relaxation, Positive reinforcement)
- Cognitive therapy
- Aromatherapy
What hormonal changes can affect seizure frequency in women?
- Puberty
- Menopause
- Monthly cycle
What is the teratogenic risk associated with antiepileptic drugs during pregnancy?
All antiepileptic drugs carry teratogenic risks
Polytherapy increases this risk.
What is the recommended folic acid dosage for pregnant women with epilepsy?
5 mg
This is advised to help mitigate risks.
How do neonates and children metabolize antiepileptic drugs compared to adults?
They tend to metabolize the drugs faster than adults.
What adjustments are needed for elderly patients receiving antiepileptic drugs?
Lower initial and maintenance doses
Due to slowed hepatic metabolism and decreased renal clearance.
Which anticonvulsants have been associated with acute hepatic injury?
- Phenytoin
- Carbamazepine
- Valproic acid
- Felbamate
What factors can lead to possible recurrence risk after AED withdrawal?
Drug-drug interactions caused by hepatic enzyme induction or inhibition.
Fill in the blank: Birth control pills may be less effective in women with _______.
Polycystic ovary syndrome
True or False: Most pregnancies in mothers with epilepsy produce abnormal children.
False
Most produce normal children despite risks.
What are the normal features of the aging process that affect antiepileptic drug dosing in elderly patients?
- Slowed hepatic metabolism
- Decreased renal clearance
- Decreased volumes of distribution
What should be considered in patients with renal insufficiency when prescribing antiepileptic drugs?
Dose adjustments for drugs like Gabapentin, pregabalin, levetiracetam, and lacosamide.
What types of drugs can provoke seizures by reducing the seizure threshold?
- Anti-depressants
- Antipsychotics
- Antimalarial
What is ADHD?
Attention Deficit Hyperactivity Disorder
What are the core symptoms of ADHD?
Excessive activity, inattention, and impulsivity
What is the primary brain region involved in planning and action realization?
Prefrontal Cortex
Which brain region is responsible for impulse control?
Basal Ganglia
What is the role of the Corpus Callosum?
Communication between the two brain hemispheres
Which brain region manages emotions?
Anterior Cingulate
List the main brain regions affected in ADHD.
- Frontal lobe
- Temporal lobe
- Limbic system
- Cerebellum
What factors are believed to contribute to the aetiology of ADHD?
- Genetic factors
- Environmental factors
What are common genetic associations with ADHD?
Genotypes affecting serotonin and dopamine pathways
What are some environmental factors associated with ADHD?
- Maternal alcohol and substance abuse
- Low birth weight
- Nutritional deficiencies
- Environmental toxin exposure
- Early psychosocial adversity
What are the three types of ADHD?
- Inattentive Type
- Hyperactive-Impulsive Type
- Combined Type
What is the minimum age for ADHD symptoms to be present for diagnosis?
Before age 7 years
What are the aims of drug treatment for ADHD?
- Reduce symptoms
- Improve academic performance
- Improve quality of life
What symptoms must persist for at least 6 months for Inattentive Type ADHD?
- Lack of attention to details
- Lack of sustained attention
- Poor listener
- Failure to follow through on tasks
- Poor organization
- Easily distracted
- Forgetful
What symptoms must persist for at least 6 months for Hyperactive-Impulsive Type ADHD?
- Fidgeting or squirming
- Leaving seat
- Difficulty with quiet activities
- Excessive talking
- Blurting answers
- Can’t wait turn
What are secondary effects of ADHD?
- Low self-esteem
- Low school performance
- Social disability
What is the prevalence of sleep disorders in children with ADHD?
Around 50%
What is the percentage of children with ADHD that may have a mood disorder?
20%
What is the role of stimulants in ADHD treatment?
Increase synaptic concentration of Noradrenaline and Dopamine
What is the Biochemical Hypothesis of ADHD focused on?
Dopamine and Noradrenaline dysregulation
What are the main functions of monoamines in the brain?
- Mood
- Anxiety
- Attention
- Motivation
- Cognition
What role does the Dopamine Transporter Protein (DAT1) play?
Regulates dopamine clearance from the synaptic cleft
What is the significance of Monoamine Oxidase A (MAO-A)?
It is responsible for the catabolism of Dopamine
What should be considered in differential diagnosis for ADHD?
- Mood and Anxiety disorders
- Specific learning disabilities
- Iron deficiency anemia
What regulates dopamine clearance from the synaptic cleft?
Dopamine Transporter Protein (DAT1), Monoamine Oxidase A (MAO-A), Catechol-O-Methyl-Transferase (COMT)
DAT1 is responsible for rapid uptake of dopamine, while MAO-A and COMT are involved in dopamine catabolism.
Which neurotransmitters are studied in relation to ADHD in the prefrontal cortex?
Noradrenaline (NA) and Dopamine (DA)
Genetic studies of ADHD have focused on candidate genes coding for elements of dopamine metabolism.
What area of the brain is sensitive to noradrenaline and dopamine in regulating working memory?
Dorsolateral prefrontal cortex (PFC)
Studies in non-human primates have shown its sensitivity to NA and DA.
What is the role of noradrenaline in the prefrontal cortex?
Acts on post-synaptic Alpha-2 receptors
The A subtype of alpha-2 receptors is most important for noradrenaline action in the PFC.
How does noradrenaline affect executive operations in the prefrontal cortex?
Dampens noise, enhances executive operations, increases inhibition
This modulation helps focus on preferred or relevant inputs.
What is the hypothesized function of prefrontal cortical α2A and D1 receptors?
In cognitive performance and the treatment of ADHD
Their activity is thought to be an inverted U-shaped function in relation to catecholaminergic systems.
What are the aims of drug treatment for ADHD?
Reduce symptoms, improve academic performance, improve quality of life
Drug treatment should be initiated by qualified healthcare professionals.
What should drug treatment for ADHD be based on?
Comprehensive assessment and diagnosis
Continued prescribing may be performed by general practitioners under shared care arrangements.
In which cases is drug treatment not recommended for ADHD?
For preschool children, as first-line treatment for all school-age children and young people
It should be reserved for those with severe symptoms or moderate impairment who refuse non-drug interventions.
What are the first-line pharmacotherapy options for ADHD?
Stimulants like Methylphenidate or dextroamphetamine
These increase levels of dopamine and noradrenaline in the prefrontal cortex.
What is the mechanism of action of Atomoxetine?
Selective inhibition of noradrenaline reuptake
Atomoxetine is a non-stimulant option for ADHD.
What are common side effects of Methylphenidate?
Dry mouth, loss of appetite, weight loss, slower growth, sleep disturbance
These side effects were reported in various studies.
What are the therapeutic effects of Methylphenidate linked to?
Amplification of extracellular dopamine in the basal ganglia
Variability in responses may be due to differences in dopamine tone between individuals.
What should be considered when prescribing Methylphenidate for children?
Modified-release preparations
They improve adherence and reduce stigma associated with taking medication at school.
What should parents be warned about regarding Atomoxetine?
Potential for suicidal thinking and liver damage
Symptoms include abdominal pain, unexplained nausea, malaise, dark urine, or jaundice.
What limited evidence exists for unlicensed melatonin products?
May reduce sleep onset
Evidence comes from small randomized controlled trials.
What is the primary use of unlicensed melatonin products?
They may reduce sleep onset latency in children with sleep onset insomnia and ADHD by approximately 20 minutes.
Unlicensed melatonin products have shown potential in short-term use for specific sleep issues.
How much may melatonin improve average sleep duration?
15 to 20 minutes.
This improvement was noted in children with sleep onset insomnia.
What is the limitation of the studies on unlicensed melatonin products?
They are small, and longer-term efficacy is unclear.
Only two small RCTs and one follow-up study were referenced.
What form of melatonin is currently licensed in the UK?
Prolonged-release tablets for the short-term treatment of primary insomnia in adults aged 55 years or over.
Circadin is the only licensed form mentioned.
What was not robustly demonstrated in relation to unlicensed melatonin?
Improvement in ADHD-related behaviour, cognition, or quality of life.
The evidence did not support significant behavioral benefits.
How well was unlicensed melatonin tolerated in the short to medium term?
It appeared well tolerated with only transient mild to moderate adverse effects reported.
This indicates a favorable safety profile.
What is the recommendation regarding TV usage for children?
Consider reduction of TV usage to less than two hours a day and none for children under 2.
This is part of behavioral recommendations for managing ADHD.
Is the elimination of artificial coloring and additives from the diet recommended for children with ADHD?
No, it is not recommended as a generally applicable treatment.
This reflects the current stance on dietary interventions.
What abnormalities have been implicated in individuals with Autism Spectrum Disorders (ASD)?
Abnormalities in melatonin physiology and the circadian rhythm.
These abnormalities may affect sleep patterns in individuals with ASD.
What differences in melatonin concentrations were found in individuals with ASD compared to controls?
Lower nighttime melatonin concentrations.
This may relate to sleep issues commonly seen in ASD.
What did a recent meta-analysis of melatonin supplementation in ASD report?
Significant improvements in total sleep duration and sleep onset latency with large effect sizes.
This indicates the potential effectiveness of melatonin supplementation.
What are the characteristics of ADHD?
Attention, hyperactivity, and impulsivity.
These symptoms can lead to various functional impairments.
What is the estimated worldwide prevalence of ADHD?
3% to 7%.
This prevalence highlights the commonality of the disorder.
What factors often contribute to the etiology of ADHD?
Genetic factors.
Genetics plays a significant role in the development of ADHD.
What have neuroimaging studies demonstrated about individuals with ADHD?
Significant differences in their brains compared to those without ADHD.
These differences are often linked to specific brain circuits controlling attention and behavior.
Which brain areas are affected in individuals with ADHD?
Cortical-striatal-thalamic-cortical circuit.
This circuit is crucial for controlling attention, motoric output, impulsivity, and executive functions.
What is drug misuse?
Use of a drug in an inappropriate, but perhaps well-intentioned, way.
Often used interchangeably with drug abuse, but implies a lack of intentional harm.
What is drug abuse?
Deliberately using a drug outside of its license to achieve an inappropriate aim.
This term is often associated with intentional harm or disregard for the consequences.
Define addiction.
Not having control over doing, taking, or using something to the point where it could be harmful.
Addiction can involve physical and psychological dependence.
What are the risk factors for addiction?
Varied and can include genetic, environmental, and psychological factors.
Specific risk factors can vary widely among individuals.
List three classes of controlled drugs under the Misuse of Drugs Act 1971.
- Class A
- Class B
- Class C
These classes are based on penalties for possession, supply, or manufacture.
What is the Misuse of Drugs Act 1971?
Legislation that classifies controlled drugs and establishes rules for their legal supply and possession.
It also provides penalties for violations.
What percentage of people aged 16 to 59 have taken an illegal drug in the past year?
Around 8%.
This statistic highlights the prevalence of drug misuse in the population.
Fill in the blank: The Psychoactive Substances Act was introduced in _______.
[2016].
What substances can be abused?
- Alcohol
- Tobacco
- Illicit drugs
- OTC medicines
- Prescription drugs
- Non-drug products
This includes a wide range of substances across various categories.
What are New Psychoactive Substances (NPS)?
Substances not controlled under the Misuse of Drugs Act.
They may mimic the effects of illegal drugs but are not classified as such.
What is detoxification in the context of substance misuse treatment?
The process of discontinuing substance use and managing withdrawal symptoms.
This is often the first step in treatment.
What challenges do patients face in drug misuse therapy?
- Relapse is common
- Patients may remain in a community of drug users
- Side effects from treatment
- Illicit use of prescribed substances
These challenges can complicate recovery efforts.
What are the aims of treatment for substance misuse?
- Reducing harm
- Discontinuation of substance use
- Addressing social issues
- Reintegration into societal roles
Treatment is holistic and addresses multiple aspects of a patient’s life.
What is the role of the Advisory Council on Misuse of Drugs (ACMD)?
To provide advice to the government on drug misuse issues.
Established as part of the Misuse of Drugs Act 1971.
What is a common pattern found in drug use among nightclub visitors?
Use of any Class A drug was around 10 times higher among people who had visited a nightclub at least 4 times in the past month.
This suggests a correlation between nightlife activities and drug use.
What is the significance of the Misuse of Drugs Regulations 2001?
It outlines specific regulations regarding the supply and management of controlled drugs.
This legislation complements the Misuse of Drugs Act 1971.
What are the common side effects of substance misuse treatment?
- Constipation
- Sweating
- Withdrawal symptoms
These side effects can affect compliance with treatment.
What is the relationship between drug misuse and social issues?
Drug misuse can lead to a range of social issues, including homelessness, unemployment, and family breakdown.
Addressing these issues is a critical component of rehabilitation.
What is meant by ‘tolerance’ in the context of drug use?
A person’s diminished response to a drug, occurring with repeated use.
This can lead to increased consumption to achieve the same effect.
What is supervised consumption?
A service where medication is administered under the supervision of a healthcare professional.
What are needle exchange schemes?
Programs that provide sterile injecting equipment and facilitate the safe disposal of used equipment.
Define drug misuse and abuse.
The inappropriate use of drugs, either by taking them in a manner not prescribed or taking substances for non-medical purposes.
What services are provided for people who misuse or abuse drugs?
- Supervised consumption
- Needle exchange services
- Counseling and support programs
What is the purpose of supervised consumption?
To reduce street diversion, aid compliance, improve control/safety, and prevent harm to others.
Fill in the blank: The _______ of Drugs Regulations 2001 governs the legal framework for controlled substances.
[Misuse]
What is the role of pharmacies in needle exchange programs?
- Provision of sterile injecting equipment
- Disposal of used injecting equipment
- Provision of advice on safer injecting
What information is required on a methadone dispensing prescription?
- Size of instalments
- Instructions for pharmacy closed days
- Management of missed doses
True or False: Endorsing the FP10MDA is a legal requirement for dispensing.
False
List the medical complications associated with injecting.
- Soft tissue infections
- Septicaemia and endocarditis
- Pulmonary complications
- Blood borne viruses
What is the FP10MDA?
A prescription form specifically for controlled drugs.
What is the purpose of the Medicines, Ethics and Practice document?
To provide guidance on the ethical and legal aspects of medication dispensing.
What should be done if three or more consecutive days of the prescription have been missed?
Consult the prescriber.
What does the term ‘instalment dispensing’ refer to?
The method of providing medication in specified doses over a period of time.
Fill in the blank: Community pharmacies provide a three-way partnership between prescriber, pharmacy, and _______.
[client]
What is a key reference for drug misuse legislation in the UK?
The Misuse of Drugs Regulations 2001.
What is included in the 1ml RED pack for injecting?
- 10 x 1ml combined needle & syringe
- 10 x cooking spoons
- 10 x citric acid sachets
What is the significance of the Intoxicating Substances (Supply) Act 1985?
It regulates the supply of substances that can be misused.
What are the prescribing information requirements for methadone?
- Normal CD requirements
- Size of instalments
- Instructions for supply
What should be done with daily doses of methadone if the collection day has been missed?
Dispense the amount for any remaining days of that instalment.
What does the Crime and Disorder Act 1998 pertain to?
It addresses issues related to drug trafficking and related offenses.
What is addiction?
A chronic progressive behavioral disorder characterized by compulsive drug use despite adverse consequences.
Addiction involves alterations in the brain’s reward systems due to chronic drug use.
What are the DSM-5 criteria for a mild substance use disorder diagnosis?
A minimum of 2-3 criteria is required for a mild substance use disorder diagnosis.
Criteria include taking larger amounts than intended, wanting to cut down but unable to, and spending a lot of time obtaining the substance.
What is craving in the context of substance use?
A strong urge to use the substance or a strong desire that one cannot think of anything else.
It includes difficulty resisting the urge to use.
What are the key components of the brain’s reward pathway?
The reward pathway is activated by food, water, sex, and drugs/alcohol.
It is involved in reinforcing behaviors that promote survival.
What percentage of people who use drugs are employed?
70% of people who use drugs are employed.
Drug use can lead to workplace deaths, absenteeism, and reduced productivity.
What is the role of the pharmacist in addiction treatment?
Pharmacists support substance addiction treatment by ensuring medication management and patient counseling.
What is the significance of tolerance in substance use disorders?
Tolerance involves needing markedly increased amounts to achieve intoxication or a diminished effect with continued use.
In older adults, tolerance may involve using less to achieve the same effect.
What is the function of the anterior cingulate cortex (ACC) in addiction?
The ACC is involved in decision-making based on reward values and generates new actions based on past rewards/punishments.
Fill in the blank: The primary neurotransmitter involved in the brain’s reward pathway is _______.
Dopamine.
What are common comorbidities in people with substance use disorder?
Common comorbidities include mental health disorders, chronic pain, and other substance use disorders.
True or False: All diagnostic criteria in the DSM-V for addiction are pharmacological.
False.
Eight of the ten diagnostic criteria in DSM-V are behavioral.
What is the impact of addiction on social interactions?
Addiction can lead to failure to fulfill role obligations and continued use despite social or interpersonal problems.
What are the effects of alcohol on traffic fatalities?
Alcohol is involved in 40% of traffic fatalities.
What is the relationship between addiction and the limbic system?
The limbic system is involved in emotional responses and is critical in the development and maintenance of addictive behaviors.
What is the role of the insular cortex (IC) in addiction?
The IC is important for emotional awareness and interceptive representation, impacting craving and addiction denial.
What is the key feature of addiction behavior according to DSM-V?
Impaired control over substance use.
List some dopamine-releasing compounds associated with addiction.
- Alcohol
- Opiates/Opioids
- Cocaine
- Amphetamines
- Cannabinoids
- Nicotine
- Caffeine
Fill in the blank: The strong desire to use a substance that one cannot resist is known as _______.
Craving.
What is the effect of chronic drug use on the reward pathway?
Chronic drug use hijacks the brain’s reward circuits.
What factors are considered when treating an addiction?
Factors include the type of substance, the severity of the disorder, and the presence of comorbidities.
What are the two principal aspects of motivational processes?
Pleasure and pain
These aspects arise in the Limbic areas of the brain.
What are the two states of stress managed by the hypothalamus?
Eustress (positive) and Distress (negative)
These states are controlled by the hypothalamic structures.
What does the hypothalamus control?
Hunger, thirst, reproductive drive, temperature, blood pressure
It maintains hormonal balance.
Which neurotransmitter is primarily involved in the reward pathway?
Dopamine
Dopamine projections occur from the Ventral Tegmental Area (VTA) to the nucleus accumbens (Nac).
What are the serotonin receptors relevant for addiction?
5HT2A and 5HT2C
Functions include mood, impulsivity, anxiety, sleep, and cognition.
What are the receptors for opioid peptides?
Kappa, Mu, Delta
Their function is related to pain management.
How do stimulants like cocaine and amphetamines affect dopamine levels?
Cocaine blocks reuptake, while amphetamines facilitate DA release
Both increase levels of dopamine in the nucleus accumbens.
What is the heritability rate for substance dependence?
Around 50%
This is similar to rates found in asthma, hypertension, and diabetes.
What is the Single Alcohol Screen Question for men?
How many times in the past year have you had 5 or more drinks on one occasion?
For women, the question is about having 4 or more drinks.
What are some common risk factors for addiction?
- Aggressive behavior in childhood
- Lack of parental supervision
- Poor social skills
- Drug experimentation
- Availability of drugs at school
- Community poverty
These factors contribute to the development of addiction.
What are protective factors against addiction?
- Good self-control
- Parental monitoring and support
- Positive relationships
- Academic competence
- School anti-drug policies
- Neighborhood pride
These factors can mitigate the risk of developing addiction.
What is the assessment for withdrawal state in addiction?
Should include assessment of objective signs and subjective symptoms
For nicotine, consider likelihood of withdrawal; for alcohol, use CIWA-Ar; for opioids, use COWS.
What are the symptoms of acute alcohol withdrawal?
- Tremor
- Nausea
- Sweating
- Vomiting
- Agitation
- Headache
- Insomnia
Severe dependence can lead to seizures and delirium tremens.
What is Wernicke’s encephalopathy caused by?
Thiamine deficiency
It is a progressive neurological condition often seen in alcoholics.
What is the aim of treating opioid addiction?
Maintenance, detoxification, and abstinence
Individual regimens are required based on symptoms.
What is the function of nicotine in addiction?
Activates α4β2 and α7 nicotinic receptors, leading to dopamine release
This mechanism contributes to the reinforcing effects of nicotine.
What is the main action of nicotine in the brain?
Nicotine activates α4β2 and α7 nicotinic receptors, leading to dopamine release
This activation contributes to the reinforcing effects of nicotine.
What happens to nicotinic receptors after prolonged nicotine use?
They become desensitised, resulting in a temporary loss of function
This desensitisation contributes to cravings and withdrawal symptoms.
What is the role of nicotine replacement therapy (NRT)?
Delivers nicotine by alternate routes to reduce cravings without receptor upregulation
It helps mitigate withdrawal symptoms during cessation.
What is bupropion (Zyban) used for?
It is a noradrenaline and dopamine reuptake inhibitor used as an antidepressant and for smoking cessation
It increases dopamine in the nucleus accumbens, satisfying cravings.
What are common adverse drug reactions (ADRs) associated with bupropion?
Dry mouth, headaches, insomnia
There is also a warning for seizure risk and suicide risk.
What is varenicline (Champix) and how does it work?
A selective α4β2 nicotinic receptor partial agonist that stabilises the nicotinic channel partially open without desensitisation
This mechanism helps reduce cravings for nicotine.
What are the common ADRs of varenicline?
Dry mouth, headaches, insomnia
It also carries warnings for seizures, suicide risk, and myocardial infarction.
What is the mechanism of action of alcohol in the brain?
Alcohol enhances inhibition at GABA synapses and reduces excitation at glutamate synapses
This results in a euphoric relaxation effect.
What is chlordiazepoxide (Librium) used for?
A benzodiazepine that enhances GABA transmission
It is often used for managing alcohol withdrawal symptoms.
What is the dosing regimen for chlordiazepoxide in severe alcohol withdrawal?
Doses may start at 30mg QDS and taper down
The regimen is based on local protocol and CIWA-Ar.
What does acamprosate (Campral) do?
Stimulates GABAergic neurotransmission and antagonises glutamate
It helps restore balance after chronic alcohol use.
What is the effect of disulfiram (Antabuse)?
Irreversible inhibition of aldehyde dehydrogenase, causing unpleasant reactions with alcohol
Side effects include headache, tachycardia, and hypotension.
What is nalmefene (Selincro) used for?
An opioid antagonist that blocks the dopamine reward pathway
It is used for risk reduction rather than immediate abstinence.
What is naltrexone (Adepend)?
An opioid antagonist thought to block the dopamine reward pathway
It is also used for risk reduction rather than immediate abstinence.
What is buprenorphine and how is it administered?
An opioid partial agonist given sublingually
It has a long duration of action, allowing for once-daily dosing.
What are the risks associated with methadone?
Risk of fatal overdose increases with alcohol and benzodiazepines
It also has a long half-life and can lead to QTc prolongation.
What is the initial dosing strategy for methadone?
Start with 5-10mg and monitor withdrawal syndrome
Adjustments can be made based on patient response.
What are common prescription medications that can cause euphoric effects?
Anticholinergics (e.g., procyclidine), antihistamines (e.g., cyclizine), gabapentinoids
Healthcare professionals should be vigilant for misuse.
Is it illegal to drive under the influence of legal or illegal drugs?
Yes, it is illegal to drive if unfit due to drug use
This includes both legal substances like alcohol and illegal drugs.
What is the role of a pharmacist in substance addiction treatment?
Provide information about laws and drug-driving risks, and monitor for side effects
They should direct patients to proper resources.
What is the definition of pain according to the IASP?
Pain is a subjective experience that includes sensory discriminative, affective (emotional), and cognitive components
Pain is not merely a stimulus but an experience interpreted by the brain.
What are the two main types of pain identified in modern research?
- Nociceptive pain
- Neuropathic pain
What activates nociceptors?
- Physical trauma
- Chemicals
- Excessive heat or cold
- Stretching beyond normal range
- Ischaemia
What is nociception?
The neural process of encoding noxious stimuli triggered by harmful stimuli acting on specialized peripheral nerve endings
Nociception does not always result in the perception of pain.
What are the types of nociceptors?
- Mechanical nociceptors
- Thermal nociceptors
- Chemical nociceptors
What are the characteristics of first and second pain?
- First pain: sharp and brief, carried by myelinated Aδ neurons
- Second pain: delayed and dull, carried by unmyelinated C fibers
What happens when nociception arrives in the spinal cord?
- Triggers reflex activity
- Conveys information to the brain regarding location and intensity
Which areas of the brain are involved in pain perception?
- Somatosensory cortex: sensory discrimination
- Limbic system: affective-motivational function
- Prefrontal cortex: cognitive evaluation
What is the role of the somatosensory cortex in pain perception?
Localizes the site, quality, and intensity of the stimulus
What is the concept of pain modulation?
Pain modulation refers to the processes that influence the perception of pain, often through the interaction between peripheral and central nervous systems
It is more complex than a simple relationship between these systems.
True or False: Pain and suffering are the same.
False
What is the main takeaway about pain pathways?
The sensory nervous system prioritizes information about potentially harmful stimuli.
Fill in the blank: Nociceptors are usually activated by stimuli that can be _______.
[harmful]
What is the Cartesian model of pain?
A simplistic view that does not fully explain the complexities of pain perception and experience.
What is neuroplasticity in the context of pain?
The ability of the brain to adapt and change in response to pain experiences.
What is the significance of the descending pain modulation pathways?
They influence the perception of pain from the brain to the spinal cord.
What are the major features of the pain experience?
- Subjective experience
- Influenced by context
- Not solely a physiological response
What does the term ‘transduction’ refer to in nociception?
The process by which nociceptive neurons convert harmful stimuli into electrical signals.
What is the role of the limbic system in pain perception?
It processes the emotional aspects of pain and influences attention and memory of pain.
What is the importance of specialist input in pain management?
Specialist input is crucial due to the complexity of pain management.
What is the significance of the ‘hand on the hotplate’ example?
It illustrates the immediate reflexive response to nociceptive stimuli.
What is the relationship between mood and pain perception?
An individual’s mood can influence how pain is perceived and interpreted.
What is the difference between pain and suffering?
Pain and suffering are not the same.
What does the Cartesian model of pain fail to explain?
It does not explain the whole story; things are more complex.
What is the Gate Theory of Pain?
It proposes that C-fibre nociceptor signals are inhibited at the spinal cord level by large nerve fibres before being transmitted to the brain.
What is a practical application of the Gate Theory of Pain?
Transcutaneous Electrical Nerve Stimulator (TENS) is used for pain management.
What types of therapies are based on the Gate Theory?
- Physical therapies
- Spinal cord stimulators
- Heat
- Cold
- Massage
- Manipulation
- Acupuncture
What role do descending nerve pathways play in pain modulation?
They inhibit or facilitate nociceptive signals in the spine.
What neurotransmitters are involved in descending modulation of pain?
- Opioids
- Serotonin (5HT)
- Noradrenaline
- Gamma Amino Butyric Acid (GABA)
What is the modern concept of pain related to?
It involves cognition, mood, experience, and attention.
What is the definition of pain according to the IASP?
An unpleasant sensory and emotional experience with actual or potential tissue damage.
What percentage of people will need medical advice for acute pain in their lifetime?
More than 50%.
What is nociceptive pain?
Pain that arises from the activation of nociceptors due to noxious stimuli.
What types of pain fall under nociceptive pain?
- Somatic
- Visceral
What is neuropathic pain?
Pain resulting from damaged sensory nerves.
What are the classifications of pain based on duration?
- Acute
- Chronic
- Persistent
What are the different therapeutic modalities for pain control?
- Aspirin and other NSAIDs
- Morphine and other opioids/cannabinoids
- Transcutaneous Electrical Nerve Stimulation (TENS)
- Deep brain stimulation
- Placebo
- Acupuncture
- Hypnosis
What is the primary afferent pathway in pain perception?
Primary afferent neuron -> dorsal root ganglion -> second order neurons -> to brain stem and thalamus.
What does the WHO Pain Ladder include?
- Non-opioid drugs (e.g., paracetamol, NSAIDs)
- Opioids (pure mu agonist and agonist-antagonist drugs)
- Adjuvant analgesics
What is the benefit of using a multimodal approach to pain pharmacotherapy?
It matches the multi-sources of pain and perception in our neurobiology.
What is sensitization in relation to pain?
It refers to an increased responsiveness of nociceptive neurons to their normal input.
What is hyperalgesia?
An increased sensitivity to painful stimuli.
What is allodynia?
Pain due to a stimulus that does not normally provoke pain.
What are the types of non-migraine headaches?
- Acute muscle contraction (tension) headache
- ‘Ice-cream’/’ice-pick’ headache
- Chronic daily headache
- Cluster headache
- Sinister headache
What is the most common cause of headache?
Tension headache
Thought to be due to muscle spasm in neck/scalp.
How is tension headache characterized?
- Mild to moderate pain
- Non-throbbing, vice-like
- Feeling of tightness or squeezing
- Usually affects both sides of the head
How does migraine pain differ from tension headache pain?
- Moderate to severe pain
- Usually unilateral
- Pulsating
- Aggravated by normal activity
What is the management for tension headache?
- OTC analgesic
- Non-drug interventions (Relaxation, Massage, Hot bath)
What triggers an ‘ice-cream’ headache?
Eating cold food or drinks
What defines chronic daily headache?
Occurs for more than 4 hours on more than 15 days in a month
What characterizes cluster headache?
- Excruciating severe unilateral headache
- Accompanied by red eye, lacrimation, nasal congestion
- Sudden onset, may wake the patient from sleep
- Duration: between 10 mins to 3 hours
What is the management for cluster headache?
- Prophylactic treatment if attacks are frequent
- Options include: 100% Oxygen, Sumatriptan S/C, High-dose verapamil
What are some sinister causes of headache?
- Meningitis
- Subarachnoid haemorrhage
- Temporal arteritis
- Trigeminal neuralgia
- Depression
- Glaucoma
- Raised intracranial pressure
When should a headache be referred?
- Unresponsive to analgesics
- In children under 12 years with stiff neck or skin rash
- Lasted for more than 2 weeks
- Accompanied by nausea and vomiting without classical migraine symptoms
What are red flag symptoms of a headache?
- Sudden, disabling onset
- Accompanying symptoms (loss of consciousness, rash, neck stiffness)
- Worsening pattern on awakening
What are the phases of migraine?
- Prodrome
- Aura
- Headache
- Postdrome
What are the symptoms of migraine?
- Lateralized and pulsating headache
- Associated with nausea and vomiting, photophobia, phonophobia
What are the trigger factors for migraine?
- Foods (alcohol, caffeine, chocolate)
- Hormonal changes (HRT, contraceptive pill)
- Emotional and environmental factors
What characterizes the diagnosis of migraine according to the International Headache Society?
Repeated attacks of headaches lasting 4-72 hours with specific features
What are the new treatment options for preventing migraine?
- Galcanezumab (Injection)
- Fremanezumab (Injection)
- Erenumab (Injection)
- Rimegepant (Oral)
What should be offered as first-line treatment for acute migraine?
- Simple analgesics
- Oral triptan (sumatriptan) alone or with NSAID or paracetamol
What is the recommended management for acute migraine if vomiting restricts oral treatment?
Consider a non-oral formulation such as zolmitriptan nasal spray or subcutaneous sumatriptan
What is the role of anti-emetics in migraine treatment?
Consider adding an anti-emetic even in the absence of nausea and vomiting
What are the recommended acute anti-emetic preparations?
- Metoclopramide
- Domperidone
- Prochlorperazine
What is the maximum daily dosage of aspirin for acute monotherapy?
900 mg every 4–6 hours up to a maximum of 4 g daily
What is the maximum duration for metoclopramide treatment?
5 days
What is the recommended maximum dosage for domperidone?
10 mg three times a day
What age group is indicated for the use of sumatriptan?
18-65 years old
What should be done if vomiting restricts oral treatment?
Consider a non-oral anti-emetic preparation
What are common side effects of triptans?
- Tiredness
- Dizziness
- Heaviness on chest and throat
True or False: Ergotamine is recommended for use in acute migraine treatment.
False
What condition can result from taking medication too often for tension-type headaches or migraines?
Medication overuse headache
What is a key strategy for preventing medication overuse headache?
Limit painkillers for headache to <15 days/month
What is the treatment for medication overuse headache?
Stop current therapy
What does the term ‘prophylaxis’ in headache treatment refer to?
Preventing headaches before they occur
What should be monitored to evaluate the effectiveness of prophylactic treatment?
Headache diaries
Name a first-line prophylactic agent for migraine treatment.
- Topiramate
- Propranolol
What is a significant risk associated with topiramate?
Risk of foetal malformations
What is the mechanism of action for Botox in migraine treatment?
Relaxes muscles and blocks pain feedback
What are the three monoclonal antibodies recommended for preventing migraine?
- Galcanezumab
- Fremanezumab
- Erenumab
What is the criteria for recommending monoclonal antibodies for migraine prevention?
4 or more migraine days a month and at least 3 preventive drug treatments have failed
What role do pharmacists play in migraine management?
- Raise awareness of migraine
- Signpost patients for improved management
- Identify OTC analgesic overuse
- Help doctors with management strategies
- Educate patients on realistic expectations
Fill in the blank: Triptans are _______ agonists.
5-HT1
What is the protocol for taking a second dose of sumatriptan?
Wait two hours before the 2nd dose
What is the time frame for effectiveness of prophylactic treatments for migraines?
6-12 months
What should be done if a patient has a period of stability in headache frequency?
Taper or discontinue therapy
What type of medication is rimegepant classified as?
CGRP receptor antagonist
What is insomnia?
Difficulty getting to sleep or staying asleep, early morning wakening, non-restorative sleep, and daytime functioning impairment.
What are the symptoms necessary for the diagnosis of insomnia?
At least one of the following symptoms:
* Difficulty getting to sleep
* Difficulty staying asleep
* Early morning wakening
* Non-restorative sleep
* Daytime functioning impairment.
What is normal sleep?
A restorative physiological process characterized by alterations in brainwave activity.
What characterizes sleep as a physiological process?
Alteration in brainwave activity, as shown via an electroencephalograph (EEG).
What is the Ascending Reticular Activating System (ARAS)?
Arousal system of the brain that is continuously stimulated by impulses, maintaining wakefulness.
What happens to ARAS activity during sleep?
Endogenous neurochemical factors reduce the activity of ARAS.
What are the two main groups of neurotransmitters relevant to sleep?
- Inhibitory:
* GABA - Excitatory:
* Glutamate
What is the role of GABA in sleep?
An inhibitory neurotransmitter that stops action potentials.
What neurotransmitter is known for its role in wakefulness?
Orexin (Hypocretin).
What regulates the release of orexin?
The body’s internal circadian biological clock (CBC) and hunger/satiety signals.
What is the circadian rhythm?
An endogenous cycle of around 24 hours influenced by melatonin and environmental cues.
What accumulates to increase sleep pressure?
Adenosine levels in the pre-frontal cortex.
Fill in the blank: Sleep pressure is governed by _______.
adenosine levels.
What are the stages of orthodox sleep?
Four stages:
* N1: Light sleep
* N2: Deeper, memory-forming sleep
* N3: Deep, restorative sleep
* REM: Rapid eye movement sleep.
What percentage of sleep is orthodox sleep?
75%.
What is paradoxical sleep?
Characterized by rapid eye movement (REM) and accounts for 25% of sleep time.
What is the definition of insomnia according to NICE?
Difficulty in getting to sleep, difficulty staying asleep, early wakening, or non-restorative sleep, despite adequate time and opportunity to sleep.
Who does insomnia affect?
About 1/3 of the UK population; prevalence in primary care is estimated between 10% and 50%.
How do sleep requirements change with age?
Sleep requirements reduce with age, but older people report poorer sleep.
What is cognitive behavioral therapy for insomnia (CBT-i)?
A structured program that helps individuals identify and replace thoughts and behaviors that cause or worsen sleep problems.
What are common pitfalls in managing insomnia?
Misunderstanding patient expectations and reliance on sedative prescriptions.
When should a patient with insomnia be referred?
When initial management strategies fail or when there are underlying medical conditions.
What percentage of the UK population is affected by insomnia?
About 1/3 of the UK population.
Insomnia prevalence in primary care is estimated between 10% and 50%.
What is insomnia?
Difficulty getting to sleep or staying asleep, early wakening, or non-restorative sleep despite adequate time to sleep.
Significant insomnia results in impaired daytime functioning.
What are the two main types of insomnia?
Primary insomnia and Secondary (Comorbid) insomnia.
Primary insomnia (15-20% of cases) has no associated comorbidity, while secondary insomnia (80%) is associated with other conditions.
What are common causes of secondary insomnia?
- Anxiety and depression
- Chronic pain
- Physical health conditions (e.g., CVD, thyroid disorders)
- Other sleep disorders
- Circadian rhythm disorders
- Environmental factors
- Situational stress
- Drug and substance misuse
What are some drugs that contribute to insomnia?
- Antidepressants (SSRIs, SNRIs)
- Antiepileptics (lamotrigine, phenytoin)
- Antihypertensives (beta-/calcium-channel blockers)
- NSAIDs
- Hormones (corticosteroids, thyroid hormones)
- Stimulants (methylphenidate, modafinil)
- Sympathomimetics (salbutamol, theophylline)
- Substance misuse (alcohol, caffeine, nicotine)
What is the normal sleep onset latency considered to be?
Less than 30 minutes.
Variability in sleep patterns exists with age.
What are some consequences of chronic insomnia?
- Reduced quality of life
- Increased risk of mental health conditions (e.g., depression, anxiety)
- Poor work performance
- Increased risk of CVD and diabetes
What is the first-line treatment for chronic insomnia?
Cognitive Behavioral Therapy for Insomnia (CBT-I).
CBT-I is the most effective and lasting treatment.
What are some recommendations for sleep hygiene?
- Regular sleep schedule
- Creating a comfortable sleep environment
- Limiting screen time before bed
- Reducing caffeine and alcohol intake
Fill in the blank: Insomnia often follows __________ triggered by short-term difficulty.
acute insomnia
What is a potential risk of using hypnotic drugs for insomnia?
Tolerance and dependence may develop.
Withdrawal can lead to anxiety, depression, and impaired concentration.
True or False: Melatonin has been proven effective in improving sleep in dementia patients.
False.
No difference was found between melatonin and placebo groups for sleep efficiency.
What is the typical duration of short-term insomnia?
1 to 4 weeks.
What behavioral patterns may contribute to chronic insomnia?
- Excessive time spent in bed
- Irregular sleep schedules
- Daytime napping
What is the recommended duration for prescribing hypnotics?
Not longer than 2 weeks.
Only consider if daytime impairment is severe.
What is the purpose of a sleep diary?
To establish patterns and identify useful behavioral targets for change.
What are Z-drugs used for?
They are used as hypnotics to treat insomnia.
Examples include zopiclone and zolpidem.
Fill in the blank: Chronic insomnia is associated with __________ beliefs about sleep.
dysfunctional
What may be a significant impact of overcoming sleep difficulties?
Improving quality of life.
What is insomnia?
A sleep disorder characterized by difficulty falling asleep, staying asleep, or waking up too early
List three common symptoms of insomnia.
- Difficulty falling asleep
- Waking up frequently during the night
- Feeling tired upon waking
True or False: Insomnia can lead to daytime fatigue and mood disturbances.
True
Fill in the blank: Insomnia is often associated with _______.
stress or anxiety
What are two common types of insomnia?
- Acute insomnia
- Chronic insomnia
What is the recommended first-line treatment for insomnia?
Cognitive Behavioral Therapy for Insomnia (CBT-I)
True or False: Dependence-forming medications are a long-term solution for insomnia.
False
What is one potential consequence of using dependence-forming medications for insomnia?
Withdrawal symptoms or rebound insomnia
List three non-pharmacological strategies to cope with insomnia.
- Sleep hygiene practices
- Relaxation techniques
- Stimulus control therapy
Fill in the blank: The Sleep Council provides resources for improving _______.
sleep quality
What is the primary focus of the RCGP resource regarding medications?
To inform about the risks of dependence-forming medications
What is Alzheimer’s disease (AD)?
A degenerative brain disorder and the most common form of dementia.
What cognitive skills decline in Alzheimer’s disease?
Memory, language, problem-solving, and other cognitive skills.
What leads to neuron loss in Alzheimer’s disease?
Loss of neurons, especially pyramidal cells, in brain regions responsible for cognitive function.
What are the basic functions impaired by Alzheimer’s disease as it progresses?
Walking and swallowing.
How long does short-term memory hold information?
For seconds to a minute.
What is the capacity of short-term memory?
Limited capacity.
What does long-term memory store?
Vast information for a lifetime.
What are the two types of explicit memory?
- Semantic: Facts & general knowledge
- Episodic: Personal experiences.
What is the difference between implicit and explicit memory?
Implicit memory is unconscious; explicit memory is conscious.
What are the types of implicit memory?
- Procedural: Motor & cognitive skills
- Priming: Enhanced object/word recognition
- Classical Conditioning: Learned associations.
What brain regions are involved in semantic memory?
Specific to each task, e.g., tools and the motor cortex.
What mediates episodic memory?
Entorhinal cortex and hippocampus.
What is the early impact of Alzheimer’s disease on memory?
Early loss in episodic and semantic memory.
What remains preserved in Alzheimer’s disease?
Implicit perceptual memory.
What are key hallmarks of Alzheimer’s disease?
- Amyloid plaques: Dystrophic neurites around amyloid core
- Neurofibrillary tangles: Abnormal tau protein filaments in neurons.
What structural changes occur in the brain due to Alzheimer’s disease?
- Enlarged ventricles
- Neocortex shrinkage
- Extreme hippocampal atrophy.
What types of neurons are lost in Alzheimer’s disease?
- Pyramidal
- Cholinergic
- Noradrenergic
- Serotonergic.
When is a definitive diagnosis of Alzheimer’s disease possible?
Only postmortem.
What is the prodromal phase of Alzheimer’s disease?
Presents as amnesic mild cognitive impairment.
Which region is first affected in Alzheimer’s disease?
Entorhinal cortex.
What is the final stage of Alzheimer’s disease characterized by?
Loss of GABAergic interneurons leading to widespread dysfunction.
What is the goal of Alzheimer’s drug discovery?
Develop treatments to slow or stop neurodegeneration.
What are the key targets for Alzheimer’s drug therapies?
- Anti-Aβ monoclonal antibodies
- Enzyme inhibitors (β- and γ-secretase)
- Tau-targeted therapies.
What does the Amyloid Hypothesis suggest?
Aβ deposits drive AD progression.
What does the Tau Hypothesis propose?
Hyperphosphorylated tau destabilizes microtubules and forms NFTs.
What is motor neurone disease (MND)?
A neurodegenerative condition affecting the brain and spinal cord, leading to the degeneration of motor neurones and resulting in progressive weakness of limb or bulbar muscles while sensory function remains largely unaffected.
What is the prevalence of motor neurone disease?
4-7/100,000.
At what age does motor neurone disease typically present?
Between ages 50–60.
What percentage of motor neurone disease cases are genetic?
10–15%.
List some risk factors for motor neurone disease.
- High levels of physical activity
- Recurrent concussive or cervical trauma.
What is the typical diagnostic delay for motor neurone disease?
10–16 months.
What are key features of motor neurone disease?
- Progressive muscular weakness
- Muscle wasting
- Focal weakness
- Dysarthria and dysphagia.
What is amyotrophic lateral sclerosis (ALS)?
The commonest type of motor neurone disease characterized by progressive weakness and muscle wasting.
What are the symptoms of ALS?
- Progressive weakness
- Muscle atrophy
- Spasticity.
What is the survival rate for ALS patients?
3 to 5 years from onset for most cases.
Fill in the blank: Early diagnosis of MND allows for __________.
[multidisciplinary team (MDT) specialist support].
True or False: Most cases of ALS are inherited.
False.
What is the anatomical basis of amyotrophic lateral sclerosis?
Degeneration of upper and lower motor neurons.
What is the clinical significance of recognizing motor neurone disease early?
It allows for timely referrals and interventions that can improve quality of life.
What does the term ‘lateral sclerosis’ refer to?
The scarred appearance of the spinal cord caused by loss of lateral corticospinal tract neurons.
What is the role of primary care in recognizing motor neurone disease?
Recognizing early, unexplained muscular weakness and making timely referrals to neurology.
What clinical signs are associated with bulbar symptoms in MND?
- Dysarthria
- Dysphagia.
What is primary lateral sclerosis (PLS)?
A type of motor neurone disease characterized by upper motor neuron degeneration without lower motor neuron involvement.
What is the difference between upper motor neuron (UMN) and lower motor neuron (LMN) signs?
UMN signs include spasticity; LMN signs include muscle atrophy.
What is the definition of a clinical syndrome?
The group of signs and symptoms produced by a specific disease process.
What is the significance of the RNA/DNA binding protein TDP-43 in ALS?
About 95% of ALS patients feature abnormalities in TDP-43.
What percentage of ALS patients survive for 10 or more years?
10%.
Fill in the blank: Symptoms of MND often go __________ or misattributed.
[unrecognized].
What is the common presentation of limb symptoms in MND?
70% present with limb symptoms such as focal weakness and muscle wasting.
What is the relationship between smoking and ALS?
Those who smoke are at higher risk for developing ALS.
What are the two parts of the motor system?
- Upper motor neurons
- Lower motor neurons.
What is the difference between a sign and a symptom?
A sign is an objective manifestation of a disease, whereas a symptom is a subjective manifestation of a disease.
What is a clinical syndrome?
The group of signs and symptoms produced by a specific disease process.
What percentage of MND cases present with limb weakness at onset?
65%.
What are the symptoms associated with bulbar onset MND?
Dysarthria, dysphagia.
What are the respiratory symptoms at onset for MND?
Shortness of breath, orthopnoea, sleep disruption, early morning headaches, daytime somnolence.
What cognitive symptoms may occur with MND?
Behavioral change, emotional lability, memory impairment, dementia.
What is axial weakness in MND?
Head drop, posture.
What are the signs of lower motor neurone (LMN) involvement in MND?
Wasting, fasciculation, reduced tone, depressed reflexes, weakness (focal).
What are the signs of upper motor neurone (UMN) involvement in MND?
Increased tone, brisk reflexes, jaw jerk, weakness (pyramidal).
What does LMN signify in MND diagnosis?
Anterior horn cell death, muscle wasting (amyotrophy).
What does UMN signify in MND diagnosis?
Corticospinal tracts, lateral sclerosis or gliosis in spinal cord (and motor cortex).
What is the most common form of MND?
Amyotrophic lateral sclerosis (ALS).
What is the prevalence of LMN-predominant MND?
5-15%.
What characterizes progressive muscular atrophy (PMA)?
Pure form of MND with no/little UMN signs clinically.
What is primary lateral sclerosis (PLS)?
Pure form of MND with no wasting after 4 years.
What does ‘amyotrophic’ in ALS refer to?
Muscle wasting/lack of nourishment.
What is the diagnostic method for ALS?
Clinical diagnosis based on history and physical examination, supported by electrophysiological findings.
What tests are included in the investigations for MND?
Blood tests, NCS/EMG, MRI, lumbar puncture.
What are the common blood tests for MND diagnosis?
FBC, U, E & Cr, LFTs, Ca, B12, folate, SEP, CK.
What is the role of NCS/EMG in MND diagnosis?
To show normal motor & sensory nerve conduction, fibrillation & fasciculation potentials, reduced motor unit potentials.
What genetic cause accounts for the majority of familial cases of MND?
C9ORF72.
What percentage of MND cases have a genetic cause?
Up to 10%.
What is the role of superoxide dismutase 1 (SOD1) gene in MND?
Accounts for 20% of familial and 2% of sporadic MND, associated with autosomal dominant inheritance.
What are the proposed mechanisms underlying neurodegeneration in ALS?
Excitotoxicity, protein aggregation, axonal transport breakdown, reduced ATP production, neuroinflammation, triggering of cell death pathways.
True or False: Riluzole is the only licensed drug for MND in the UK.
True.
What are the three mechanisms by which Riluzole prevents glutamate transmission?
- Inhibition of voltage-dependent Na+ presynaptic neuron * Increase in glutamate re-uptake in astrocytes.
What is the purpose of a multidisciplinary team in MND management?
To provide comprehensive care and a single point of contact for patients.
What psychological support is essential for individuals with MND?
Support groups, online forums, referral to counselling/psychological services, provision of respite care.
What should be considered when planning end-of-life care for MND patients?
Patient’s communication ability, cognitive status, and mental capacity.
Fill in the blank: The most common presentation of MND is _______.
limb features.
What is the significance of the DS1500 form in MND management?
It may be appropriate for social care needs.
What are antimuscarinics used for?
Problematic saliva
Antimuscarinics are medications that help reduce saliva production.
What features should be looked for in motor neurone disease (MND)?
Progressive, asymmetrical features
Commonly limb or bulbar features.
What is the most common presentation of MND?
Limb features
Weakness and wasting without sensory symptoms indicate MND.
If considering MND as a diagnosis, what should be done?
Refer directly to neurology and specifically query the diagnosis
Care should be provided by a specialist MND multidisciplinary team.
What is a first-line treatment for muscle spasms in MND?
Quinine
Quinine can be used effectively for muscle spasms.
List some first-line treatments for muscle spasticity, stiffness, or increased tone.
- Baclofen
- Dantrolene
- Tizanidine
- Gabapentin
These medications help manage muscle tone issues.
Why is advanced care planning important in MND?
It is crucial for managing the progressive nature of the disease
Helps ensure appropriate care and resources are in place.
What does the internal structure of the spinal cord consist of?
Gray and white matter
Gray matter contains neuronal cell bodies, while white matter consists of myelinated axons.
What are the main components of the motor system?
- Corticospinal (upper) motor neurons in the motor cortex
- Bulbar and spinal (lower) motor neurons
These components innervate skeletal muscle.
What does lateral sclerosis refer to?
Gliosis (scarring)
This describes the scarring seen in the lateral columns of the spinal cord.
What occurs in the posterior-lateral columns of the spinal cord in MND?
Degeneration and disappearance of myelin replaced by gliosis
This leads to atrophy and decreased volume of the spinal cord.
What is the significance of the cortico-spinal tracts?
They are projections originating from the motor neurons
Located in the posterior columns of the spinal cord.
True or False: Bulbar onset is a presentation of MND.
True
Bulbar onset refers to symptoms starting in the bulbar region.
Fill in the blank: The spinal cord is atrophic and the volume is ______.
decreased
This atrophy is associated with degeneration in MND.
What is a sign in the context of disease?
An objective manifestation of a disease.
What is a symptom in the context of disease?
A subjective manifestation of a disease.
What is a clinical syndrome?
The group of signs and symptoms produced by a specific disease process.
What are the four courses that Multiple Sclerosis (MS) can take?
- Relapsing-remitting MS (RRMS)
- Primary-progressive MS (PPMS)
- Secondary-progressive MS (SPMS)
- Progressive-relapsing MS (PRMS)
What is the main aim of drug treatment in MS?
To reduce neuroinflammation by restraining the activity of immunoreactive cells and/or enhancing immune tolerance.
What is the target of the autoimmune attack in Multiple Sclerosis?
The protein in myelin produced by oligodendrocytes in the CNS.
What is optic neuritis?
A condition that should lead a person diagnosed by an ophthalmologist to be referred to a neurologist for assessment.
What is neuromyelitis optica?
An autoimmune condition characterized by optic neuritis and transverse myelitis.
List some common symptoms of Multiple Sclerosis.
- Fatigue
- Numbness
- Headache
- Coordination problems
- Bladder and bowel problems
- Vision problems
- Dizziness
- Sexual dysfunction
- Pain
- Cognitive dysfunction
- Emotional changes
- Spasticity
True or False: Depression is more common in MS patients than in the general population.
True.
What complicates the diagnosis of MS?
Symptoms are similar to several other disorders.
What diagnostic criteria must be met for a diagnosis of MS?
Lesions in at least two areas of the CNS or optic nerves.
What does the presence of oligoclonal bands in the CSF indicate?
Inflammatory processes.
What tests are used to assess evoked potentials?
Tests for demyelination/myelination of the optic nerve.
What is the recommended follow-up time after a diagnosis of MS?
Within 6 weeks of diagnosis.
What are modifiable risk factors for relapse or progression in MS?
- Smoking
- Exercise
- Flu jab
- Pregnancy
What is the relationship between vitamin D and MS?
Vitamin D is thought to be protective against MS.
What are disease-modifying drugs (DMDs) for MS known for?
They vary in efficacy and offer modest reductions in rates of relapse.
What is the annual treatment cost range for DMDs?
From £6000 to £35,000.
Fill in the blank: MS is primarily considered an _______ disorder.
[autoimmune]
What must be ruled out when diagnosing MS?
- Viral infections
- Toxic chemicals
- Vitamin B12 deficiency
- Guillain-Barré syndrome
What is the role of a neurologist in the diagnosis of MS?
Diagnosis should ALWAYS be made by a neurologist.
List some treatment options for spasticity in MS.
- Baclofen
- Benzodiazepines
- Dantolene
- Gabapentin
- Tizanidine
- Botulinum toxin
- Sativex
What is the significance of corticosteroids in MS management?
They may be required during a relapse.
What is the effect of exercise on MS patients?
Encouraged, especially aerobic exercise for those with mobility problems/fatigue.
What is the impact of flu immunization in relapsing-remitting MS?
There is a risk of relapse after flu immunization.
What is the importance of multidisciplinary care in MS?
Care should be provided by a multidisciplinary team.
What are some treatment options for emotional lability in MS?
Amitriptyline.
What are the symptoms that may indicate a relapse in MS?
- Loss of vision in one eye with painful eye movements
- Double vision
- Ascending sensory disturbance and/or weakness
- Problems with balance or clumsiness
- Altered sensation when bending forward
What is the significance of reviewing cases of MS diagnosis that do not meet full criteria?
It helps ensure the accuracy of diagnosis and treatment.
What is the definition of highly-active relapsing MS?
A severe form of multiple sclerosis characterized by frequent relapses and significant disability progression
Highly-active relapsing MS often requires aggressive treatment options.
Which drugs are licensed in the UK for treating MS?
The drugs licensed in the UK include:
* Ocrelizumab
* Interferon beta (1a and 1b)
* Glatiramer acetate
* Mitoxantrone
* Natalizumab
* Fingolimod
* Teriflunomide
These drugs vary in effectiveness and safety profiles.
What is the role of disease-modifying treatments in MS?
They reduce the frequency and severity of relapses and accumulation of lesions.
How does Interferon beta function in MS treatment?
It increases suppressor T-cell function, maintaining tolerance to self-antigens and decreasing self-attack.
What is Glatiramer acetate and its mechanism of action?
A synthetic protein that simulates myelin protein and may work by blocking T cells.
What is the function of Mitoxantrone in MS treatment?
It suppresses components of the immune system, including T cells, B cells, and macrophages.
What type of drug is Natalizumab?
A monoclonal antibody that hampers the movement of T cells across the blood-brain barrier.
What does Fingolimod do in MS treatment?
It is a sphingosine 1-phosphate receptor modulator that causes retention of lymphocytes in lymph nodes.
What is the mechanism of action for Teriflunomide?
It is a pyrimidine synthesis inhibitor that inhibits the function of specific immune cells.
What are corticosteroids used for in MS treatment?
They are used to treat acute exacerbations affecting ability to perform at home or work.
What are common side effects of corticosteroids?
Side effects include:
* Stomach irritation
* Elevated blood sugar
* Water retention
* Insomnia
* Mood swings
What types of medications are used to manage MS symptoms?
Medications include:
* Antidepressants
* Pain medications
* Drugs for bladder and bowel dysfunction
What is Dalfampridine and its potential side effects?
A potassium channel blocker used to treat walking dysfunction, with side effects including risk of seizures.
What non-drug treatments are available for MS?
Non-drug treatments include:
* Physical therapy
* Occupational therapy
* Speech/language therapy
* Cognitive rehabilitation
* Assistive devices
What is a key take-home message regarding MS?
If you suspect MS, refer the patient to a multi-professional team.
Why is recognizing relapses in MS important?
Recognizing relapses is crucial as some require treatment while others do not.
What should be ruled out before diagnosing a relapse in MS?
Always rule out other causes, especially urinary and respiratory infections.
Who typically uses disease-modifying treatments in MS?
Disease-modifying treatments are used by secondary care.
What is Parkinson’s disease (PD)?
A movement disorder characterized by a combination of hypo and hyperactive movements, including slowness, dyskinesia, and tremor.
What is the prevalence of Parkinson’s disease?
Increases with age, predominantly affecting individuals over 70, though some cases occur in those under 50.
What is the pathophysiology of Parkinson’s disease?
Neurodegeneration of dopamine-producing neurons in the substantia nigra leads to motor dysfunction when there is significant neuron loss.
What percentage of neuron loss in the substantia nigra is required for Parkinson’s disease symptoms to manifest?
50% loss in substantia nigra reticulata and 80% loss of dopamine in the striatum.
What are Lewy bodies, and why are they significant in Parkinson’s disease?
Inclusion bodies containing alpha-synuclein, significant for PD pathology and associated with non-motor symptoms.
Where is the aetiological origin of Parkinson’s disease believed to begin?
In the gut, with the aetiological agent ascending via the vagus nerve to the substantia nigra.
What are the three cardinal clinical features of idiopathic Parkinson’s disease?
- Slowness (bradykinesia) * Stiffness (rigidity) * Shaking (resting tremor)
What does the presence of early imbalance and falls indicate regarding Parkinson’s disease?
It goes against the diagnosis of idiopathic Parkinson’s disease.
What are the red flag signs that indicate an alternative pathology to idiopathic Parkinson’s disease?
- Early imbalance * Difficulty swallowing * Early memory problems * Autonomic failure * Poor eye movements * Early hallucinations
What is the main role of dopamine in the brain?
Facilitates normal motor activity by acting on dopamine receptors in the striatum.
What happens to dopamine receptors in Parkinson’s disease?
They remain intact but develop abnormal responses as the disease progresses.
What is levodopa’s role in the treatment of Parkinson’s disease?
It provides more dopamine into the terminals to improve motor function.
What are the two enzymes that degrade dopamine in the synaptic cleft?
- Monoamine oxidase B (MAOB) * Carboxy-o-methyl transferase (COMT)
What type of tremor is associated with Parkinson’s disease?
Resting tremor that improves with posture and action.
What is the significance of the SPECT / DAT scan in Parkinson’s disease diagnosis?
Reveals dopaminergic degeneration by showing reduced re-uptake of pre-synaptic dopamine.
What are some conditions that show abnormal SPECT / DAT scans similar to Parkinson’s disease?
- Multi-system atrophy (MSA) * Progressive supranuclear palsy (PSP) * Cortico-basal degeneration (CBD)
What is the main value of MRI in parkinsonism?
To identify alternative causes of parkinsonian syndrome.
What is the impact of non-motor symptoms on Parkinson’s disease patients?
They significantly affect the quality of life and are often present before motor symptoms.
What are some common non-motor symptoms of Parkinson’s disease?
- Cognitive impairment * Depression * Gastrointestinal issues (constipation) * Autonomic dysfunction * Sleep disorders
What are the Hoehn and Yahr stages of Parkinson’s disease?
- Stage 1: Unilateral disease * Stage 2: Bilateral disease * Stage 3: Impaired balance * Stage 4: Motor complications * Stage 5: Total dependence
What is Parkinsonism?
Clinical features of Parkinsonian syndrome not due to idiopathic PD, including conditions like Parkinson’s plus syndromes.
What are the challenges in managing Parkinson’s disease?
- Early detection * Disease modification * Effective symptom control * Preventing complications
What is the purpose of early detection in Parkinson’s disease?
To attempt to prevent the onset of motor disorder through preventive measures.
What is the current status of disease modification research in Parkinson’s disease?
No confirmed advances have been made in altering the course of the disease.
What is the mainstay of managing Parkinson’s disease symptoms?
Levodopa, which is rapid acting and effective for symptom control.
What are the adverse effects related to long-term use of levodopa?
Fluctuations and dyskinesia.
What is the main action of Levodopa (LD) in the brain?
Converted into dopamine by dopa-decarboxylase in the brain
How quickly do patients typically feel the benefits of Levodopa?
Within a few days
What are the typical adverse effects associated with long-term use of Levodopa?
Fluctuations and dyskinesia
What factors increase the risk of complications when using Levodopa?
- Dose of LD
- Timing and fragmentation of dose
- Low body weight
- Weight loss
- Female gender
- Genetic factors
What percentage of patients develop complications related to Levodopa after ten years?
Up to 80%
How does Levodopa compare to other medications in terms of symptom control?
More effective for symptom control
What is the impact of slow release Levodopa formulations like Madopar CR?
Does not necessarily prolong the effect of medication
What is the role of MAOB inhibitors in relation to Levodopa?
Reduce degradation of dopamine in synaptic cleft
Which MAOB inhibitor was introduced in the early 80s?
Selegiline
What is the main advantage of Rasagiline over Selegiline?
Does not lead to a rise in nor-adrenaline
What is the first COMT inhibitor introduced and why was it withdrawn?
Tolcapone due to severe and fatal hepato-toxicity
What is the main advantage of Entacapone?
Can be administered with each dose of levodopa
What are the current dopamine agonists (DAs) in use?
- Ropinirole
- Pramipexole
- Rotigotine
What are some significant adverse effects of dopamine agonists?
- Hallucinations
- Confusion
- Psychosis
- Impulse compulsive disorders
What is the purpose of Amantadine in Parkinson’s disease treatment?
Reduces LD induced dyskinesia and helps with fluctuations
What is the method of administration for Apomorphine?
Subcutaneous route
What are the indications for Deep Brain Stimulation (DBS)?
- Advanced PD
- Early PD with drug intolerance
- Dyskinesia
- Intolerance to oral medications and apomorphine
What are the limitations of Deep Brain Stimulation?
- Not suitable for older patients
- Complications related to procedure
- May lead to cognitive impairment
What is DuoDopa?
Levodopa gel treatment infused directly into jejunum
What is the first choice option for initial therapy in early Parkinson’s Disease?
No single drug of choice
What medication is used for managing dementia in Parkinson’s disease?
Acetylcholinesterase inhibitors or memantine
Fill in the blank: Levodopa is associated with a high risk of _______.
Dyskinesia
True or False: Dopamine agonists have been proven to provide disease modification in Parkinson’s disease.
False
What is the primary focus of the educational content?
An overview of Parkinson’s disease including pathology, diagnosis, pharmacology, motor symptoms, and non-motor symptoms.
Define movement disorder.
Abnormal movements in the absence of weakness or spasticity.
What are the two types of excessive movements in movement disorders?
- Hyperkinesia * Dyskinesia
What are the types of paucity of movements?
- Bradykinesia * Akinesia * Hypokinesia
What characterizes Parkinson’s disease?
Clinical and neuropathological entity characterized by bradykinesia, rigidity, and tremor.
How does Parkinson’s disease onset typically present?
Usually asymmetric and responsive to dopaminergic treatment.
What is Parkinsonism?
Any bradykinetic-rigid syndrome that is not Parkinson’s disease.
What is the pathogenesis of Parkinson’s disease?
Dopamine-containing nerve cell bodies within the nigrostriatal and mesocorticolimbic pathways are selectively and progressively destroyed.
What happens when approximately 80% of striatal dopamine and 50% of nigral neurons are lost?
Clinical signs of Parkinson’s disease become evident.
What structures comprise the basal ganglia?
- Caudate nucleus * Lentiform nucleus * Putamen * Globus pallidus * Substantia nigra * Subthalamic nucleus
What is the role of tyrosine in dopamine synthesis?
Tyrosine is a precursor that is converted to L-Dopa by tyrosine hydroxylase.
What is the most common and easily recognized clinical symptom of Parkinson’s disease?
Rest tremor.
What is bradykinesia?
Difficulty with planning, initiating, and executing movements.
What characterizes rigidity in Parkinson’s disease?
Increased resistance, often associated with the ‘cogwheel’ phenomenon.
What are common postural deformities in Parkinson’s disease?
- Flexed neck and trunk posture * Flexed elbows and knees
What is postural instability?
Loss of postural reflexes, generally a manifestation of the late stages of Parkinson’s disease.
What is required to assess postural instability?
The pull-test.
What are the essential diagnostic criteria for Parkinson’s disease according to the UK Parkinson’s Disease Society Brain Bank?
- Bradykinesia * Rigidity * Rest tremor * Postural instability not caused by other dysfunctions
What features suggest alternative diagnoses in Parkinson’s disease?
- Prominent postural instability in the first 3 years * Freezing phenomenon in the first 3 years * Hallucinations unrelated to medications in the first 3 years * Dementia preceding motor symptoms
What is the criterion for definite Parkinson’s disease?
All criteria for probable Parkinson’s are met and histopathological confirmation is obtained at autopsy.
What is the significance of a substantial and sustained response to levodopa?
It is necessary for the diagnosis of probable Parkinson’s disease.
What is levodopa?
A medication used to treat Parkinson’s disease by replenishing dopamine levels
Levodopa is often used in combination with other treatments.
What are the criteria for possible Parkinson’s Disease (PD)?
At least two of the four features in group A are present, at least one is tremor or bradykinesia, and either none of the features in group B is present or symptoms have been present for 3 years with none of the features in group B present
Group B features may include atypical symptoms.
What is freezing in Parkinson’s Disease?
A form of akinesia that occurs in ~47% of patients, affecting legs during walking
Freezing can also affect arms and eyelids.
What are the five subtypes of freezing?
- Start hesitation
- Turn hesitation
- Hesitation in tight quarters
- Destination hesitation
- Open space hesitation
Episodes may be more severe in the OFF state.
True or False: Freezing can lead to falls in Parkinson’s patients.
True
It has substantial social and clinical consequences.
What are some non-motor features of Parkinson’s Disease?
- Autonomic dysfunction
- Cognitive and neurobehavioural abnormalities
- Sleep disorders
- Sensory abnormalities
These symptoms are often underappreciated.
What cognitive issues are associated with Parkinson’s Disease?
Cognitive decline in 84% of patients and dementia in 48%
Neuropsychiatric comorbidities may include depression, apathy, and anxiety.
What are common sleep disorders in Parkinson’s Disease?
- REM behavior disorder
- Insomnia
- Excessive daytime sleepiness
Sleep fragmentation may contribute to fatigue.
What is the impact of α-synuclein pathology in Parkinson’s Disease?
It is thought to be associated with the evolution of PD
Staging of this pathology may help in understanding the disease progression.
What are the motor symptoms of Parkinson’s Disease?
- Tremor
- Bradykinesia
- Rigidity
- Postural instability
These are cardinal features for diagnosis.
What are the major types of parkinsonism?
- Idiopathic Parkinson’s Disease
- Symptomatic parkinsonism
- Atypical parkinsonism
Atypical forms include Multiple System Atrophy and Progressive Supranuclear Palsy.
What is the differential diagnosis of parkinsonian disorders?
Includes drug-induced parkinsonism, vascular disease, and neurodegenerative disorders
Examples of drug-induced causes include neuroleptics and antidepressants.
What is the significance of olfactory function in diagnosing Parkinson’s Disease?
It differentiates PD (reduced olfaction) from other parkinsonian syndromes (preserved olfaction)
This can aid in early diagnosis.
What are the common diagnostic errors associated with Parkinson’s Disease?
Diagnostic error is common, with rates of 10% in Movement Disorder clinics and 50% in primary healthcare
NICE guidelines recommend timely referral to specialists.
What are some common complications associated with Parkinson’s Disease?
- Motor fluctuations
- Dyskinesias
- Cognitive impairment
- Hallucinations and delirium
These complications can significantly affect quality of life.
What does the term ‘Parkinsonism’ refer to?
A collection of symptoms present in PD and other disorders, collectively called parkinsonian conditions
It can be idiopathic, genetic, or environmental.
What are the stages of Parkinson’s Disease?
- Early stage
- Motor complication period
- Cognitive decline period
Each stage presents unique challenges and symptoms.
What is the importance of timely diagnosis in Parkinson’s Disease?
Increased diagnostic accuracy through the use of standard criteria can lead to better management and outcomes
Early intervention is crucial for effective treatment.
What are the primary forms of Parkinson’s Disease?
- Idiopathic PD
- Genetic forms
- Environmental forms (e.g. caused by toxins)
- Other atypical forms including:
- Progressive supranuclear palsy
- Multiple systems atrophy
- Corticobasal degeneration
References to forms of Parkinson’s Disease based on etiology.
What are the therapeutic challenges in managing Parkinson’s Disease?
- Early detection in pre-motor stage
- Disease modification
- Diagnosis
- Effective motor control
- Symptomatic treatment
- Delay of motor complications
- Managing motor problems
- Managing non-motor complications
Various therapeutic challenges faced in Parkinson’s Disease management.
What types of therapy are involved in the treatment of Parkinson’s Disease?
- Physiotherapy
- Pharmacotherapy
- Neurosurgical therapy
- Psychosocial measures
- Orthopaedics
- Psychologic support
- Creation of support/understanding by family
- Patient-support groups
- Stereotactic interventions
- Implantation of pacemakers
Different therapeutic approaches to manage Parkinson’s Disease.
What are the main pharmacological treatments for Parkinson’s Disease?
- L-Dopa
- Dopa decarboxylase inhibitor
- MAO-B inhibitor
- COMT inhibitor
- Dopamine agonists:
- Ergolinics: bromocriptine, pergolide, cabergoline
- Non-ergolinics: pramipexole, ropinirole, rotigotine
Overview of pharmacological treatments targeting dopamine metabolism.
What is the role of L-Dopa in Parkinson’s Disease treatment?
Restores depleted dopamine and prolongs the duration of L-Dopa’s effects.
L-Dopa is considered the ‘gold standard’ treatment for Parkinson’s symptoms.
What is the function of MAO-B inhibitors in Parkinson’s Disease therapy?
Enhances the effect of endogenous dopamine in the central nervous system and prolongs the effect of dopamine derived from L-Dopa.
MAO-B inhibitors play a critical role in preserving dopamine availability.
True or False: Dopamine agonists have a shorter half-life than L-Dopa.
False
Dopamine agonists generally have a longer half-life and duration of action than L-Dopa.
What are the first-line treatment options for early Parkinson’s Disease according to NICE recommendations?
- Levodopa
- Dopamine agonists
- MAO-B inhibitors
- Anticholinergics (lack of evidence)
- Beta-blockers (lack of evidence)
- Amantadine (lack of evidence)
NICE recommendations for treating early-stage Parkinson’s Disease.
Fill in the blank: The mainstay treatment for Parkinson’s Disease symptoms and disability is _______.
Levodopa
Levodopa’s role as a primary treatment option for managing Parkinson’s Disease.
What are the pros and cons of using Levodopa as monotherapy?
Pros:
* Effective at preventing slow movements and stiffness
* Reduces tremor
Cons:
* Efficacy reduction over time
* Common side effects include:
* Dyskinesia
* Nausea/vomiting
* Low blood pressure on standing
* Sleepiness
* Hallucinations
* Vivid dreams
* Prolonged use may be linked to weight loss
Summary of advantages and disadvantages of Levodopa therapy.
What factors determine the initial choice of drug treatment for Parkinson’s Disease?
- Relative drug efficacy
- Adverse effects
- Comorbidity
- Patient preference
Factors influencing the selection of initial pharmacotherapy in Parkinson’s Disease management.
What is the significance of Rasagiline in Parkinson’s Disease treatment?
Long-lasting effect due to irreversible inhibition of MAO-B, prolongs the effect of dopamine derived from L-Dopa.
Rasagiline’s role in enhancing dopamine availability in patients.
What are the currently licensed MAO-B inhibitors?
Rasagiline (Azilect®), Safinamide, Selegiline (Eldepryl®), Fast dissolving tablet (Zelapar®)
These drugs are used in the treatment of Parkinson’s disease.
What are the pros of using MAO-B inhibitors in monotherapy?
- Useful in early treatment
- Delay the need for levodopa
- Once daily administration
- Can be used in combination with levodopa
- May protect brain cells and slow disease progression
- Generally well tolerated
These benefits make MAO-B inhibitors an essential option in managing Parkinson’s disease.
What are the common side effects of MAO-B inhibitors?
- Headache
- Nausea
- Constipation
- Dry mouth
- Sleeping disorders
- Low blood pressure on standing
Monitoring for these side effects is crucial in patients receiving MAO-B inhibitors.
What is the role of COMT inhibitors in Parkinson’s disease treatment?
Blocking COMT prevents the conversion of LD to 3-O-methyldopa, allowing more LD to enter the brain
This prolongs the duration of levodopa action but does not increase its peak effect.
What is the significance of the ‘wearing-off’ phenomenon in Parkinson’s disease?
It refers to the gradual diminishing response to levodopa, leading to fluctuations in PD symptoms before the next scheduled dose
This phenomenon can significantly affect patient quality of life.
What non-motor fluctuations are recognized in Parkinson’s disease?
- Mood changes
- Anxiety
- Fatigue
- Pain
- Cognitive and sensory problems
These fluctuations are now acknowledged as important in the overall management of Parkinson’s disease.
What does the term ‘ADL’ stand for in the context of Parkinson’s disease?
Activities of Daily Living
ADL assessment is crucial in evaluating the impact of Parkinson’s disease on patient quality of life.
What is the NICE clinical guideline regarding the treatment of suspected Parkinson’s disease?
People with suspected PD should be referred quickly and untreated to a specialist
This guideline emphasizes the importance of early diagnosis and treatment initiation.
What are the forms of dopamine agonists available for monotherapy?
- Ropinirole (ReQuip®)
- Pramipexole (Mirapexin®)
- Rotigotine (Neupro® - adhesive skin patch)
- Apomorphine (Apo-Go® - injection)
- Cabergoline (Cabaser®)
- Bromocriptine (Parlodel®)
- Pergolide (Celance®)
These formulations help manage motor symptoms in Parkinson’s disease.
What are the pros of using dopamine agonists in monotherapy?
- Useful in early stages
- Can be used in combination with levodopa
- Fewer dyskinesias and ON-OFF fluctuations than levodopa in the first 5 years
These advantages make dopamine agonists a valuable option in the early treatment of Parkinson’s disease.
What are the side effects associated with dopamine agonists?
- Nausea/vomiting
- Low blood pressure on standing
- Confusion and hallucinations
- Dyskinesia
- Constipation
- Oedema
- Vivid dreams
- Fatigue
- Compulsive disorders
Awareness of these side effects is important for patient management.
What does the term ‘Dopamine Agonist Withdrawal (DAW)’ refer to?
Acute withdrawal symptoms similar to those seen in cocaine addicts, causing significant distress, affecting 1 in 3 patients
Understanding DAW is crucial for managing treatment in patients on dopamine agonists.
What is the significance of the CALM-PD study?
It compared Pramipexole vs Levodopa in motor function, showing that Levodopa is more effective for control of motor symptoms
This highlights the effectiveness of Levodopa as a primary treatment.
What is the importance of early treatment initiation in Parkinson’s disease?
Early treatment improves quality of life and may have some neuromodulation efficacy
Studies like ADAGIO support the benefits of starting treatment soon after diagnosis.
What are the key findings from the ADAGIO trial?
Early-start Azilect group experienced significantly less deterioration compared to delayed-start group
This trial emphasizes the benefits of early intervention in Parkinson’s disease management.
What are the severe symptoms associated with dopamine agonist withdrawal?
Severe physical and psychological symptoms
Correlate with DA withdrawal and cause clinically significant distress or social/occupational dysfunction
What percentage of patients experience recurrence of hyperprolactinemia?
Affects 1 in 5 patients
What is Amantadine and its primary function?
An antiviral drug with mild symptomatic benefit that acts as an NMDA receptor inhibitor
In which type of patients does Amantadine show better results?
Better in akinetic-rigid syndrome patients
What can abrupt withdrawal from Amantadine lead to?
Dyskinesia
What is the effect of chronic levodopa therapy in Parkinson’s disease?
Diminished motor response as the disease advances
What does the incidence of dyskinesia correlate with in the context of levodopa treatment?
Dyskinesia threshold and magnitude of response
What is the significance of body weight changes in Parkinson’s disease?
Weight losers are at increased risk of dyskinesia, higher mortality, and reduced quality of life
Fill in the blank: The time to develop dyskinesias was significantly longer in the ______ group.
ropinirole-initiated
How does the efficacy of dopamine agonists compare in early vs late disease?
Early disease: DA > placebo; Late disease: DA < Levodopa
What is the primary benefit of using small doses of different drugs in Parkinson’s treatment?
Prevents complications from using too much of one drug
What is the purpose of deep brain stimulation in advanced Parkinson’s disease?
Targets thalamus, globus pallidus, and subthalamic nucleus to disrupt pathologic network
True or False: Pulsatile stimulation in healthy brains causes significant variations in dopaminergic receptor stimulation.
False
What are some potential benefits of continuing dopaminergic stimulation?
- May prevent or reverse motor complications
- May improve sleep quality
- May reduce gastric dysfunction
What is the aim regarding levodopa dosage in Parkinson’s disease management?
Use the minimum dose of levodopa per kilogram body weight to achieve a desired clinical response
What is the correlation between levodopa-induced changes in synaptic dopamine levels and disease duration?
Positively correlated; identical doses cause larger changes as PD progresses
What are the common problems to look for in Parkinson’s disease patients?
- Motor fluctuations
- Dyskinesia
- Confusion
- Falls
- Non-motor issues
What is the diagnostic and therapeutic value of apomorphine in Parkinsonian patients?
Effective treatment in select patients with motor complications
What is the effect of dopamine agonist withdrawal on patients?
Acute withdrawal symptoms similar to those seen in cocaine addicts
What is the role of MAO-B inhibitors in Parkinson’s disease therapy?
They provide additional benefit when combined with other medications
Fill in the blank: ‘Wearing off’ affects ______ of patients within five years of starting levodopa therapy.
30% – 50%
What are the primary targets for deep brain stimulation (DBS)?
Thalamus, Globus pallidus, Subthalamic nucleus
DBS is used to treat various neurological conditions, particularly Parkinson’s disease.
How does deep brain stimulation work?
Hyperpolarization of cell membrane, Reduced excitability, Disruption of pathologic network
It essentially ‘jams’ signal flow in the targeted brain areas.
What are the benefits of deep brain stimulation?
Reversible, Adjustable, Can be removed, Turned off, Reduces drug cost in long term
Despite its effectiveness, DBS is an expensive procedure.
What is the site for DBS electrode placement for thalamic stimulation?
Posterior commissure
This placement is critical for effective stimulation.
What is thalamotomy and its effectiveness?
Effective for the relief of tremor, significant risk of complications, only used rarely in current practice
Thalamotomy has largely fallen out of favor due to risks.
What is pallidotomy and its primary use?
Targeting the globus pallidus internus, widely indicated for relief of symptoms related to Parkinson’s disease
It can lead to relief of tremor, rigidity, bradykinesia, motor fluctuations, dyskinesia, and uncoordination.
What symptoms can subthalamotomy improve?
Several symptoms associated with Parkinson’s disease
This option is viable in regions where DBS is not available.
What is the principle for drug recommendations for fluctuations in Parkinson’s disease?
- Increase bioavailability of levodopa - COMTi, MAO-B I
- Enhance receptor stimulation with continuous dopaminergic stimulation - Dopamine agonists
- Combination of all options usually needed
This multi-faceted approach helps manage symptoms effectively.
What non-levodopa responsive problems dominate in long-term follow-up?
Choking, Dyskinesia, Urinary incontinence, Post hypotension, Depression, Hallucinations, Dementia, Cognitive decline, Fractures, Falls
These issues can significantly impact quality of life.
What is a common recommendation for a patient with Parkinson’s disease experiencing fluctuations?
Increase levodopa CR Madopar, Add COMT inhibitor, Add a Dopamine agonist, Add MAO-B inhibitor, Add Amantadine
These adjustments can help manage worsening symptoms.
What is rasagiline and its role?
MAO-B inhibitor, Prolongs effect of endogenous dopamine, Long-lasting effect (irreversible inhibition)
It is used to enhance the effects of L-DOPA in Parkinson’s treatment.
True or False: Pallidotomy is commonly used in current practice.
False
Due to significant risks, it is rarely performed.
Fill in the blank: The primary site for thalamic stimulation in DBS is the _______.
posterior commissure
What are the major symptoms that pallidotomy can relieve?
Tremor, Rigidity, Bradykinesia, Motor fluctuations, Dyskinesia, Uncoordination
Pallidotomy is particularly effective for Parkinson’s disease symptoms.
What is the typical drug regimen for a patient with Parkinson’s disease experiencing dyskinesia and fluctuations?
Increase Neupro, Add MAO-B I - Rasagiline vs Selegiline
Adjustments in medication can help manage these symptoms.
What is the mechanism of action of levodopa?
Levodopa is converted to dopamine in the brain, helping to alleviate symptoms of Parkinson’s disease.
Levodopa is often administered with a peripheral dopa decarboxylase inhibitor to prevent its conversion to dopamine outside the brain.
What are the strengths of levodopa?
Levodopa is effective in reducing motor symptoms and is considered the most effective treatment for Parkinson’s disease.
It significantly improves quality of life for many patients.
What are the limitations of levodopa?
Long-term use can lead to decreased effectiveness and side effects such as dyskinesia and motor fluctuations.
Patients may experience a phenomenon known as ‘wearing-off’.
What does ‘wearing-off’ refer to in the context of levodopa treatment?
‘Wearing-off’ refers to the gradual loss of effectiveness of levodopa, leading to a return of symptoms before the next dose.
This can occur as the disease progresses.
What are dyskinesia and motor fluctuations?
Dyskinesia refers to involuntary movements, while motor fluctuations are variations in the ability to move.
Both can be side effects of long-term levodopa use.
List some other medications used in the treatment of Parkinson’s disease.
- Dopamine agonists
- MAO-B inhibitors
- COMT inhibitors
- Anticholinergics
- Amantadine
Each class of medication works differently to manage symptoms.
What is the role of holistic medicine in Parkinson’s disease treatment?
Holistic medicine focuses on treating the whole person and may include complementary therapies alongside conventional treatment.
A multi-disciplinary approach is often beneficial.
How can exercise benefit individuals with Parkinson’s disease?
Exercise can improve mobility, balance, and overall quality of life.
Regular physical activity is recommended as part of a comprehensive treatment plan.
What are the treatment principles in the advanced stages of Parkinson’s disease?
Treatment focuses on symptom management, maintaining quality of life, and considering palliative care options.
Advanced care may involve a multi-disciplinary team.
What is deep brain stimulation?
Deep brain stimulation is a surgical treatment that involves implanting electrodes in specific brain areas to alleviate symptoms.
It is typically considered for patients with advanced Parkinson’s disease.
Where are the common targets for deep brain stimulation?
- Globus pallidus pars interna (GPi)
- Subthalamic nucleus (STN)
The choice of target depends on individual patient needs and symptoms.
What is the clinical efficacy of deep brain stimulation?
Deep brain stimulation can significantly improve motor symptoms and quality of life for patients with Parkinson’s disease.
It can also reduce the need for medication.
