Overview 2 Flashcards
Loss of cells occurs where causing PD
Subsantia nigra pars compacta
What forms in the brain in a patient with PD?
Lewy bodies
What are Lewy bodies composed of?
Protein alpha-synuclein
What cells are lost in PD?
Dopaminergic cells
Where are dopaminergic cells lost in a patient with PD?
Substantia nigra pars compacta
What are the three main features/presentations of PD?
Resting tremor
Bradykinesia
Rigidity
Gradual development of what condition develops with PD?
Microphagia
Give five non-motor presentations of PD
Olfactory dysfunction Depression Dementia Sleep disturbance Autonomic disturbance
Non-motor presentations of PD can occur how much earlier than the motor symptoms?
Up to 12-15 years
Loss of dopaminergic cells in PD causes an imbalance in which two pathways?
Direct and indirect pathways of basal ganglia
What is meant by a score of 100% in the Schwab and England Activities of Daily living?
Patient is completely independent
How can the brain be imaged for dopaminergic cells in PD?
Dopamine transporter imaging
PD more common in males or females?
Males
MPTP has what effect on PD?
Can result in very advanced PD
Why can MPTP cause advanced PD?
Transformed into MPP+ which is neurotoxic to dopaminergic neurones
MPTP causes dysfunction of which organelle?
Mitochondria
What is the main enzyme causing oxidative stress in PD?
MAOb
Which of the dopaminergic pathways of the CNS is involved in PD?
Nigrostriatal pathway
Which of the dopaminergic pathways of the CNS is involved in PD?
Nigrostriatal pathway
What are the two groups of dopamine receptors?
D1
D2
D1 dopamine receptor groups consists of which dopamine receptors?
D1 and D5
D2 dopamine receptor groups consists of which dopamine receptors?
D2, D3, D4
Stages of metabolism of dopamine?
Dopamine to DOPAC to homovanillic acid
What is the role of MAO in dopamine metabolism?
Dopamine to DOPAC via MAO
What is the role of COMT in dopamine metabolism?
DOPAC to homovanillic acid via COMT
What type of receptor is the dopamine receptor?
G-protein coupled receptors
L-dopa can be used to treat dopamine because?
Pre-cursor - will be converted into dopamine
L-dopa should be given to a patient along with what?
Peripherally acting DOPA decarboxylase inhibitor
Name two other drug groups used for the treatment of PD? x2
MAOb inhibitors
Anticholinergic compounds
COMT inhibitors
Why are anticholinergic compounds used to treat PD?
Dopamine loss leads to hyperactivity of cholinergic cells
What is the role of amantadine in PD treatment? x2
Inhibits dopamine reuptake and increases dopamine release
What is apomorphine?
Dopamien agonist used as infusion for major motor fluctuations
What is rotigotine?
Dopamine agonist - transdermal patch
What is carbidopa?
Peripherally acting DOPA decarboxylase inhibitor
What is ropinerole?
Dopaminergic agonist
What is rasagiline?
MAOb inhibitor
What is benserazide?
Peripherally acting DOPA decarboxylase inhibitor
What is entacapone?
COMT inhibitor
What is tolcapone?
COMT inhibitor
What is tolcapone?
COMT inhibitor
Give 5 non-motor effects of L-DOPA
Nausea/vomiting Postural hypertension Psychosis Impulse-control disorders Excessive day-time sleepiness
Give four motor complications of L-dopa therapy
On-off effect
Wearing off
Dyskinesia/dystonia
Three types of therapy that should be offered to patients with PD?
Physiotherapy
Speech and language therapy
Occupational therapy
What is Huntington’s chorea?
Involuntary jerky movements
Cause of Huntington’s chorea?
Mutation on huntington protein of chromosome 4
Mutation involved with Huntington’s chorea is?
Abnormal number of repeats of glutamine (CAG)
Inheritance of Huntington’s chorea is?
Autosomal dominant
Four pathological changes in the brain seen in Huntington’s chorea?
Cortical atrophy
Striatal degneration
Loss of medium spiny neurones
Intranuclear inclusions of huntington
Main drug used to treat Huntington’s chorea?
Tetrabenazine
Main drug used to treat Huntington’s chorea?
Tetrabenazine
Two types of stroke are?
Ischaemic
Haemorrhagic
Main cause of intercerebral bleed is?
Hypertension
Four secondary causes of intercerberal haemorrhages?
Trauma
Tumour
Venous thrombosis
Drug usage
Four complications of ICH?
Local damage
Local mass effect/herniation
Raised ICP
Hydrocephalus
Three medical conditions that are risk factors for stroke are?
Hypertension
Hypercholesterolaemia
Diabetes
Cardiac condition that is a risk factor for stroke is?
AF
Deficit occurring from left hemisphere stroke is?
Reading and writing deficits
Prognosis for stroke?
1/3 - do well
1/3 - die
1/3 - poor prognosis
Prognosis for stroke?
1/3 - do well
1/3 - die
1/3 - poor prognosis
Three common symptom of MS?
Sensory/motor problems - numbness of the limbs/tingling sensation
Vision problems - blurriness/loss/diplopia
Progressive motor deficits
Three uncommon symptoms of MS
Bladder dysfunction
Heat intolerance
Dementia
What is MS?
Demyelinating, degenerative and inflammatory condition
What imaging is used for MS type conditions?
MRI
MRI signs of MS? x2
Lesion in corpus callosum
Areas of inflammation and brain atrophy
Non-imaging investigation used for MS?
Lumbar puncture
Three stages of MS disease progression?
Relapsing-remitting
Primary progressive
Secondary progressive
Lumbar puncture for MS - looking for what?
Presence of neurofilaments - oligoclonal bands
Four diagnostic criteria for MS?
Neurological deficits
Dissemination in space
Dissemination in time - damage occurred at two points in time
Exclusion of other causes
How many areas of the CNS must be damaged to diagnose MS?
At least two separate areas
Life expectancy of those with MS is reduced by what amount?
10-15 years
Loss of which cells occur in MS?
Oligodendrocytes
Loss of which cells occur in MS?
Oligodendrocytes
Oligodendrocytes produce what?
Myelin sheath
Four features of an MS lesion?
Astrocytic scar
Demyelination
Activated microglia
Oligodendrocyte loss
Cells involved in the demyelination of MS are?
Macrophages
Pathological hallmark of an MS lesion is?
Demyelinated axons
Infiltration of what cells occurs in MS?
T cells
T cells involved in MS are known as?
Autoreactive lymphocytes
T cells can enter brain in MS because?
BBB is damaged
Weighting of MRI for MS diagnosis?
T1
Differential diagnosis for MS? x4
Cerebrovascular disease
Syphilis
B12 deficiency
Lyme disease
Typical age of diagnosis of MS?
20s/30s
What comes first in MS - inflammation or degeneration?
We do not know
Relation of smoking to MS?
Smoking can cause MS
Four stages of MS treatment
Anti-inflammatory
Neuroprotection
Remyelination
Neuro-restoration
First line teatment for MS? x2?
IFNb
Natalizumab
Second line treatment for MS? x3
Fingolimod
Natalizumab
Alemtuzumab
Anatomical location of lumbar puncture?
Between L3 and L4 into subarachnoid space
Anatomical location of lumbar puncture?
Between L3 and L4 into subarachnoid space
Four physiological stages in the mechanism of pain?
Transduction
Transmission
Perception
Modulation
Transduction of pain involves what?
Noxious stimuli into electrical activity at sensory nerve endings
Endings of nociceptors are free or capsulated?
Free
Nociceptive channel that opens in response to heat thermal stimuli is?
TRPV1
Nociceptive channel that opens in response to cold thermal stimuli is?
TRPM8
Noxious fibres lost in diabetic neuropathy are?
C fibres
C fibres/a-delta fibres - which are myelinated?
A-delta
C fibres/a-delta fibres - which are fast conducting?
A-delta
C fibres/a-delta fibres - which is first and which is second pain?
A-delta - first, immediate pain
C - second, emotional pain
Resulting action from activation of a-delta fibres is?
Reflex withdrawal
Two classes of C fibres are?
Peptidergic c-fibres
Peptide-poor c fibres
Peptidergic C fibres release what? x2
Substance P
CGRP
Receptor of peptide poor c fibres is?
P2X3 - peptide poor C fibres
C fibre classes - which involves ATP receptors?
Peptide poor
A delta fibres project to which laminae?
I and V
C fibres project to which laminae?
I and II
What projects to lamina I?
All nociceptors
Gene responsible for the development of nociceptors is?
trkA
A-beta fibres enter/innervate which lamina?
V
What are projection neurones?
Second order neurones
What are VPL and VPM?
Nuclei:
Ventral posterior lateral
Ventral posterior medial
VPL and VPM project to where?
Primary somatosensory cortex
A-delta fibres mainly run into which spinal tract?
Anterior spinothalamic
Function of anterior spinothalamic tract is?
Regulates immediate need to withdraw arm from pain
A-delta fibres innervate which nuclei? x4
VPL
VPM
VPI (inferior)
CL (central lateral)
C-fibres mainly run into which spinal tract?
Lateral spinothalamic tract
C-fibres innervate which nucleus? x2
Posterior thalamus
Mediodorsal nucleus
Function of the lateral spinothalamic tract?
Regulation of punishing aspects of pain - prevent repetition
Lateral spinothalamic tract projects to where?
Anterior cingulate cortex (limbic system)
Rostral insular cortex
Anterior spinothalamic tract projects to where?
Primary and secondary somatosensory cortex
Lateral spinothalamic associated with which pain pathway?
Periaqueductal grey PAG
PAG pathway located where?
Midbrain
Lateral spinothalamic projects to which three specific areas?
PAG
Reticular formation
Parabrachial nucleus
Four signs of inflammation?
Calor - heat
Rubor - redness
Dolor - pain
Tumor - swelling
Inflammation results in what type of sensitisation?
Peripheral sensitiation
Three hallmarks of sensitisation?
Hyperalgesia
Allodynia
Spontaneous pain
Hyperalgesia is?
Abnormally heightened sensitivity to pain
Allodynia is?
Sensation of pain from non-noxious stimuli
Two features of peripheral sensitisation?
Reduced activation threshold
Increased responsiveness
NaV1.8 is?
Sodium channel
NaV1.9 is?
Sodium channel
Arachidonic acid released via what enzyme?
Phospholipase A2
Arachidonic acid converted to what?
Prostaglandins
Arachidonic acid converted to prostaglandins via what enzymes?
COX1
COX2
COX1 present what?
Normally present in all tissues at low levels
COX2 present when?
COX-2 induced during inflammation
Prostaglandins sensitise which pain fibres?
C-fibres
Prostaglandins are targeted by which pain relieving drug specifically?
NSAIDs
Central sensitisation caused by?
Prolonged nociceptive input
Central sensitisation results in what?
Modified response - low level inputs produce repsonse
Neurotransmitter involved in central sensitisation development?
Glutamate
Neuropathic pain is?
Pain due to injury/dysfunction in the PNS or CNS
Gate control theory of pain is?
Endogenous modulation e.g. acupuncture e.g. DNIC
Neurones responsible for pain modulation are?
Interneurones in lamina II
DNIC works how? - which fibres and pain pathway are activated?
Diffuse noxious inhibitory control
Activation of a-delta fibres
Stimulation of PAG pathway
PAG pathway involves which two neurotransmitters?
Serotonin
Noradrenaline
PAG pathway involves which other mediator, other than the neurotransmitters?
Opioids
MS lesions are located where?
Periventricular
Three types of pain are?
Nociceptive - acute
Inflammatory - chronic
Neuropathic - chronic maladaptive
What are enkephalines?
Endogenous opioids used in the PAG pathway
Transmitters from NRM to dorsal horn in the PAG pathway are? x2
5-HT
Enkephalines
Transmitter from LC to Dorsal horn in PAG pathway is?
Noradrenaline
Opioids have action at which sites of the PAG pathway? X3
PAG
NRPG
Dorsal horn
Six factors that influence pain perception are?
Cognition Mood Chemicals and structure Context Genetics Injury
Enkepahline are short or long peptides?
Short
Enkephalines are derived from?
Proenkephalin
Opioid receptors are what type of receptor?
G protein coupled receptor
Three opioid/opiate receptors are?
Mu 1, 2, 3
Delta 1, 2
Kappa 1, 2, 3
Mu opioid receptors are located where?
All over the body
Morphine works on what channels? x2
Increased at K+ channel
Decreased at Ca2+ channel
Overall effect of morphine is?
Decreased excitability
Increased release of neurotransmitters
What is naloxone?
Opiate antagonist
Half life of naloxone is long or short?
Short
What is opioid switch?
Patient becomes tolerant to one particular opioid drug - switch them to another
Strongest side effect associated with kappa opioid receptors is?
Dysphoria
Three side effects associated with opioid medication?
Respiratory depression
Sedation
Reduced GI motility - constipation
Three stages of analgesic ladder?
Non-opioids and adjuvant drugs
Moderate efficacy opioids
High efficacy opioids
Function of paracetamol in pain management?
Reduces Cox-2 levels
Analgesic and antipyretic
Function of NSAIDs in pain management?
Cox 1 and Cox 2 inhibitors
Two side effects of NSAIDs?
Nausea
GI bleeding
Amitriptyline is?
Tricyclic antidepressant
Indication for amitriptyline in pain management is? x2
Neuropathic pain
Cancer
Indication for anticonvulsant drugs in pain management is? x2
Neuropathic pain
Trigeminal neuralgia
Carbamazepine is?
Anticonvulsant - sodium channel
Sodium valproate is?
Anticonvulsant - sodium channel
Pregabalin is?
Anticonvulsant - calcium channel
Pregabalin works on which part of the calcium channel?
alpha 2 delta
Anaesthetics work via what mechanism?
Blockage of sodium channels
Cause of trigeminal neuralgia?
Compression/stretching of trigeminal nerve root
Artery that tends to compress trigeminal nerve in trigeminal neuralgia is? x2
AICA or PICA
Treatment for trigeminal neuralgia? x3
Carbamazepine
Baclofen
Phenytoin
The most common site of chronic pain in the UK is?
Back pain
CBT programme for management for pain lasts how long?
12 weeks
Four types of pain behaviours are?
Negative affect Facial/audible expression of distress Distorted posture Avoidance of activity e.g. work
Seizures in epilepsy are described as? x2
Recurrent and unprovoked
Seizures are?
Abnormal paroxysmal changes in electrical activity of the brain
Epileptogenesis is?
Development of epilepsy in a normal brain
Prevalence of epilepsy in the UK?
1%
Status epilepticus is?
Form of epilepsy where seizures last more than 5 minutes/more than one seizure in the space of 5 minutes
Is status epilepticus a medical emergency?
Yes
Five stages of tonic-clonic seizure?
Premonition Pre-tonic-clonic phase Tonic phase Clonic phase Postictal period
What happens in the premonition stage?
Vague sense that seizure is immunent
What happens in the pre-tonic-clonic phase?
Few myoclonic jerks/brief clonic seizures
What happens in the tonic phase?
Contraction of axial muscles
Upward eye deviation
Epileptic cry
Respiratory muscle contraction
What happens in the clonic phase?
Jerks of increasing amplitude
May have sphincter opening
What happens in the postictal period?
Generalised lethargy
Decreased muscle tone
Headaches
Sore
A person may wet themselves in which stage of a tonic clonic seizure?
Clonic
You may hear a person cry out in which stage of a tonic-clonic seizure?
Tonic
Someone may smell a burning smell that is not apparent to anyone else around them in which stage of a tonic-clonic seizure?
Premonition - this may be their aura
Diagnostic criteria for epilepsy diagnosis?
Occurence of two or more seizures
Witness account essential
Reorganisation of what particular region occurs in temporal lobe epilepsy?
Hippocampus
What happens to the hippocampus in temporal lobe epilepsy?
Becomes sclerotic
What may happen to fibres in the temporal lobe in temporal lobe epilepsy?
May have a sprouting of new fibres
Why is a sprouting of new fibres problematic?
Can lead to development of aberrant circuits
Sprouting of new fibres in temporal lobe epilepsy typically occurs from which cells?
Granule cells
What cells are typically lost in epilepsy?
Chandelier cells
What are chandelier cells?
Inhibitory GABAeric interneurones
Chandelier cells synapse where?
On axon initial segment of pyramidal cells
Chandelier cells control activity of what?
Cortical pyramidal cells
Loss of chandelier cells results in what?
Increased risk of abnormal excitatory activity
Three causes of secondary epilepsy?
Stroke
Brain tumour
CNS infection
Three cellular mechanisms resulting in the development of epilepsy are?
Increased excitation - glutamate dependent
Decreased inhibition - GABA dependent
Abnormal neuronal excitability - ion channels
What are the receptors involved in the paroxysmal depolarising shift of a seizure?
NMDA glutamate receptor
Abnormalities/mutations of what cell may be involved in development of epilepsy?
Glial cells
Role of glial cells with glutamate neurotransmitter?
Glial cells - glutamate transport and clearance
Two pathways that may be involved in the development of epilepsy?
mTOR
REST
Phenytoin has an effect on what channel?
Sodium
Phenytoin should not be used in what type of seizure?
Absence
Carbamazepine works on what channel?
Sodium
Phenytoin has what order kinetics?
Zero
Carbamazepine should not be used in what type of seizure?
Absence seizure
Lamotrogine works at what two channels?
Sodium
Calcium
Lamotrogine has what effect?
Presynaptic inhibition of glutamate release
What drug should be used in absence seizures?
Ethosuxomide
Ethosuxomide targets what channels?
T-type calcium channels
Gapapentin/pregabalin targets what channels?
Alpha2delta subunit of calcium channels
Tiagabine has what effect and what target?
Inhibits GABA uptake
GAT-1 transporter
Vigabatrin has what effect?
Inhibits GABA metabolism
Which two anti-epileptic drugs increases hepatic levels of their own enzymes?
Phenytoin
Carbamazepine
Treatment for status epilepticus?
IV diazepam
Three potential treatments for epilepsy? (non pharmacological)
DBS
Vagal nerve stimulation
Ketogenic diet
Three types of primary headaches?
Tension-type
Migraine
Cluster headache
Treatment of cluster headache?
Provision of 100% O2
Pathophysiology of migraine revolves around what?
Cortical spreading depression
What types of brains are subject to migraines?
Excitable brains
What is heightened during a migraine?
Senses - smell, light, sounds, touch
Four factors that could result in the onset of a migraine?
Hormones
Lack of food
Dehydration
Lack of sleep
Migraine with/without aura - which is more common?
Without aura
What part of the brain plays a major role in the onset of a migraine?
Hypothalamus
A migraine aura comes from what part of the brain?
Visual cortex - occipital lobe
Cortical spreading depression occurs in which region of the brain?
Visual cortex - occipital lobe
Effect of cortical spreading depression on arteries?
Swelling of arteries - increased inflammation
What type of inflammation occurs from cortical spreading depression?
Neurogenic inflammation
Via what activation does cortical spreading depression result in the onset of pain?
Trigeminal ganglion activation leads to peripheral sensitisation
Swelling of what arteries occurs during a migraine?
Meningeal arteres
Trigeminal nerve conveys pain impulses to where in a migraine?
Trigeminal nucleus caudalis in the brainstem
What must you never give to a patient suffering from a migraine?
Codeine
Function of vestibular system? x3
Maintenance of balance, posture and spatial orientation
Three receptors systems to the vestibular system are?
Eyes
General proprioception - muscles, joints, tendonds
Vestibular apparatus in inner ear
Three components of the inner ear are?
Labyrinth
Vestibular apparatus
Cochlea
Two parts of the vestibular apparatus?
Vestibular part
Auditory part
What are the two solutions in the labyrinth?
Endolymph
Perilymph
Which part of the vestibular system is the membranous part?
Labyrinth
Where is the endolymph located?
Inner solution
Endolymph electrolyte balance?
High K+ and low Na+
Perilymph electrolyte balance
Low K+ and High Na+ (CSF)
Where is the perilymph located?
Surrounds the labyrinth
Components of the labyrinth are known as what?
Semicircular ducts
What moves around in the semicircular ducts?
Endolymph
What is on the surface of vestibular cells?
Cilia - hair cells
Function of the cilia on vestibular cells?
These are mechanoreceptors
Activation of cilia results in what in vestibular cells?
Depolarisation of the cell
Cilia on the vestibular cells are known as what?
Stereocilia
Function of the semi-circular ducts? x2
Provides kinetic sensitivity i.e. awareness of movement of the head
Provides information about angular acceleration
What are utricles?
Cilia on hair cells are angled towards the striola
What are saccules?
Cilia on hair cells are angled away from striola
What is Meniere’s disease?
Mixing of the endolymph and the perilymph
Cause of Meniere’s disease?
Overproduction of endolymph
Most common symptom of Meniere’s disease?
Tinnitis
What is Kinnetosis?
Motion sickness
Hallpike maneuver tests for what?
Benign paroxysmal positional vertigo
Mental state examination tests what?
Someone’s mindset
Mini mental state examination tests what?
Someone’s cognition
What is psychopathology?
The study of all abnormal experiences, cognition and behaviour
What is penomenology?
The study of subjective psychological evetns
Six components of the mental state examination?
Appearance and behaviour Speech and form of thought Mood Perceptions Cognition Insight
What is classical conditioning?
Paring of two stimuli
Neutral stimulus elicits biological response e.g. dogs and bell
What is operant conditioning?
Association between a behaviour and its consequence
One main region of the brain where operant conditioning occurs?
Nucleus accumbens
Role of nucleus accumbens in operant conditioning?
Release of dopamine after e.g. sex, exercise
What is social learning?
People do what other people do - see them as role models
MS is a disease of which cells in the CNS?
Oligodendrocytes
Neurodegeneration of MS is most visible where?
Ventricles
Three core symptoms of MS?
Pain
Tremor
Spasms
Two cannabinoid receptors found in the body?
CB1 and CB2
CB1 found where?
Abundant in adult CNS:
Brain Adipose tissue Muscle Liver GI tract Pancreas
CB2 found where?
Restricted to the immune system
CB1 is what type of receptor?
G-protein coupled receptor
Function of cannabinoids in the body?
Regulation of synaptic neurotransmission
Define addiction?
Chronic disease characterised by drug seeking use that is compulsive/difficult to control DESPITE harmful consequences
What is drug abuse?
Drug use in amounts/methods that is directly or indirectly harmful to themselves or others
What is drug dependence?
Adaptive state developing after repeated drug use - results in withdrawal symptoms upon cessation
What is drug tolerance?
Diminishing effect of a drug following repeated admission at a set dose
What is psychological dependence?
Dependence involving emotional-motivational symptoms e.g. depression, restlessness, anhedonia
What is physical dependence?
Dependence resulting in significant physical-somatic withdrawal symptoms e.g. fatigue, nausea
Ethanol has an action at which receptors? x2
GABAa
NMDA
Hallucinogens has action at which receptor?
5-HT2
Three factors that determine the development of addiction?
Environment
Drug-induced effects
Genes
Where is the projection of dopamine in the brain that is most important for drug dependence? (x2 regions)
From ventral tegmental area to the
Nucleus accumbens
Three stages of the addiction cycle?
Binge/intoxication
Withdrawal/negative affect
Preoccupation/anticipation
What is released upon multiple uses of drug consumption?
GABA
What is the effect of GABA release upon multiple drug use?
Attempts to dampen down the dopamine release from the drug - drug tolerance
Drug tolerance is mediated via which neurotransmitter?
GABA
Drug addicts have reduced numbers of which receptors in the brain?
D2 dopamine
Lack of self-control, emotional regulation, motivation, attention, decision making, working memory etc in drug addicts is due to damage in which region of the brain?
Pre-frontal cortex
Where is the ventral tegmental area/ventral tegmentum located?
Floor of the midbrain - near the midline
Alcohol has an effect on which receptors?
NMDA - excitatory
GABAa - inhibitory
Alcohol abuse involves drinking over how many units per day - men?
5
Alcohol abuse involves drinking over how many units per day - women?
3
General effect of alcohol abuse on the brain?
Shrinking of grey matter
Loss of what percentage of grey matter occurs in alcohol abuse?
12%
Ecstasy is also known as?
NMDA
Five receptors of MDMA are?
5-HT 5-HT2 Dopamine Histamine H2 Alpha-2 adrenergic
Loss of what innervation pathways occurs when you take NMDA?
5-HT
Cannabis acts on what receptor? x2
CB1
CB2
CB1 receptors are located where?
CNS
CB2 receptors are located where? x2
Peripheral organs
Immune system
Cannabinoids are inhibitory or excitatory?
Inhibitory
What type of receptor are CB1 and CB2?
G protein coupled receptor
Five methods for drug addiction management
Detoxification - eliminate from the body Psychological support - counselling Medication Treatment for mental health Long term follow up
What is nalmefene?
Opioid antagonist
Function of nalmefene in treatment drug addiction?
Reduction of alcohol consumption
Use of antibiotic ceftriaxone in treatment of drug addiction?
Attenuate cocaine relapse after cessation
Treatment for rhabdomyelosis?
Dantrolene
Monoaminergic theory for depressions states that?
Reduced levels of monoamines is responsible for the development of depression
Two monoamines outlined in the monoaminergic theory of depression?
Serotonin
Noradrenaline
Patients with depression have decreased rates of metabolism where in the brain?
Subgenual prefrontal cortex
Sign of depression in grey matter is?
Decreased cortical thickness
What is meant by ‘default mode network’ in teh brain?
Network of brain regions that are active whilst the brain is at wakeful rest
Pathway for rumination?
Negative stimulus activates amygdala and hippocampus
Activates subgenual cingulate cortex
Prefrontal cortex normally stops pathway here
Effect of depression on rumination?
Prefrontal cortex does not have the desired effect to stop the rumination pathway
Function of tricyclic antidepressants?
Inhibition of monoamine reuptake - increase levels of monomines
SO three theories to explain development of depression?
Monoamine theory
Reduced dopamine level theory
Reduced grey matter theory
Adverse effects of tricyclic antidepressants? x3
Dry mouth
Blurred vision
Loss of libido
Main adverse effect of MAOb inhibitors?
Cheese effect
Cheese effect involves foods containing what compound?
Tyramine
Main disadvantage of TCAs?
Have widespread selectivity at different receptors e.g. histamine receptor
The most selective SSRI is?
Citalopram
Advantages of using SSRIs? x2
Similar efficacy to tricyclic antidepressants
No selectivity for other receptors
What is moclobemide?
Reversible monoamine oxidase inhibitor
Advantage of moclobemide? x3
Increased selectivity of MAOa
Not irreversible
No cheese effect
Why is there a delay of action of antidepressant drugs?
Action of autoreceptors - these then become desensitised
What is antidepressant drug discontinuation syndrome?
Symptoms occurring following sudden cessation of antidepressant medication
Gradual decrease in antidepressant medication over how long to avoid the onset of antidepressant drug discontinuation syndrome?
6 months
Drug used in treatment of bipolar disorder?
Lithium
What is bipolar disorder?
Cycles of depression and mania
Function of which two organs should be checked prior to lithium treatment?
Thyroid
Renal
Four non-pharmacological treatments for depression?
Electrocompulsive therapy
CBT
Vagal nerve stimulation
DBS
Disadvantage of ECT?
Long lasting cognitive effects
Advantage of CBT in treatment of depression?
Can augment pharmacological effects
Indication for use of vagal nerve stimulation for treatment fo depression?
Chronic depresson
DBS in which area for treatment of depression?
Area 25 - subcallosal cingulate cortex
Indication for use of ECT for treatment of depression?
Severe and treatment resistant depression
Neuronal loss occurs specifically where in the brain with depression?
Hippocampus
Depression - increase in levels of what in the brain? x2
Cortisol
IL6
Three symptom types in schizophrenia are?
Positive
Negative
Cognitive
Positive symptoms of schizophrenia are?
Hallucinations, delusions - things people would not normally experience
Negative symptoms of schizophrenia are?
Introversion, apathy, low self-esteem - things mentally stable may experience
Cognitive symptoms of schizophrenia are?
Poor memory, attention deficit
Diagnostic criteria for schizophrenia?
Two or more of the outlines symptoms each present for a significant portion of time during a one month period
Four genes associated with the development of schizophrenia?
BDNF
COMT
DAOA
Neuregulin 1
Function of BDNF?
Neurotrophic factor that has an effect on long term memory
Function of COMT?
Dopaminergic transmission
Function of DAOA?
Glutaminergic transmission
Function of neuregulin 1?
Neuroplasticity
Treatment for schizophrenia are generally used for the management of which symptoms?
Positive symptoms
Normally - what is seen in MRI of schizophrenia patient?
Normally see no change
What might be seen in MRI of schizophrenia patient? x2
Larger ventricles
Smaller mesial temporal lobe structures
Changes in cerebral perfusion in schizophrena? x3
Decreased perfusion in the prefrontal cortex
Increased perfusion in the thalamus and cerebellum
Kraepelinian definition of a poor outcome for schizophrenia is?
Progressive deteriorating course
Involvement of which dopaminergic pathways in schizophrenia? x2
Mesolimbic pathway
Mesocortical pathway
Changes in the dopaminergic pathways in schizophrenia are?
Hyperactivity in the mesolimbic pathway
Hypoactivity in the mesocortical pathway
Nigrostriatal dopaminergic pathway is involved in what condition?
PD
D1 type receptors are?
D1, D2
D2 type receptors are?
D2, D3, D4
First medication available for treatment of schizophrenia was?
Chlorpromazine
What is chlorpromazine?
Typical antipsychotic
Typical vs. atypical antipsychotics?
Atypicals also have an effect at 5-HT receptors SO on cognitive and negative symptoms
Typicals vs. atypicals - which is the first line treatment for schiz?
Atypicals
Clozapine is?
Atypical antipsychotic
Clozapine has significant action at which receptor?
D4
Use of antipsychotic drugs (typicals and atypicals) restuls in an increase in which hormone?
Prolactin
Usage of atypicals results in which metabolic adverse effects? x3
Weight gain
Dyslipidaemia
Type 2 diabetes
Extrapyramidal effects of antypsychotic drug use? x3
Dystonia
Parkinsonism
Tardive dyskinesia
Two antipsychotics that can be used as depot IM injections for slow release are?
Fluphenazine
Haloperidol
Why might depot IM injection be used for treatment of schiz?
High levels of non-compliance
Antipsychotic drug used in drug resistance in treatment of schiz?
Clozapine
Percentage of schiz patients that do not respond to treatment is?
30%
Adverse effect of clozapine?
Agranulocytosis
Two non-phamacological treatments for schiz?
CBT
Family therapy
Can non-pharmacological treatments replace the pharmacological treatments in schiz?
No
Schiz associated with decreased levels of which neurotransmitter and receptor?
Glutamate NMDA
