L9 Introduction to Neuropharmacology Flashcards
What are ‘psychiatric’ or ‘mental’ illnesses?
These disorders involve disturbances of psychological functions, such as:
- fear or anxiety disturbance of mood, e.g. depression
- development of abnormal, bizarre ideas
- impairment in memory or concentration
How can psychiatric or mental disturbances be difficult to assess and measure?
–they describe their symptoms to you or
–someone else thinks their behaviour has become unusual
Both of these mechanisms are open to considerable subjectivity and do not lend themselves easily to objective measurement.
Nb these other conditions are easier
–anaemia: patient looks pale, has low RBC count, has low haemoglobin
–pneumonia: patient appears short of breath, may have ↑ temperature, shadowing on X-ray
–Parkinson’s disease: patient has slow movements and tremor, muscle tone feels increased
How are psyciatric disorders diagnosed?
Diagnosis is based on the presence of pathology -most often abnormal psychological process
Groups of signs and symptoms are brought together in psychiatric syndromes
A person may not complain (eg mania)
Be careful not to diagnose on basis of presence of “deviant” behaviour/appearance/speech
What is the hierarchical classification of psyciatric illness?
(in increasing severity)
Personality disorders
Anxiety Disorders
Mood Disorders
Psychoses
Organic Disorders
Need to work from the top of the pyramid down to rule our the most serious conditions
What are examples of ORGANIC DISORDERS
Parkinson’s
Alzheimer’s
Dementia
Symptoms resulting from many physical illnesses eg endocrine disease, brain tumour, head injury
Dementias, Delirium
Acute drug induced symptoms, e.g. Delirium Tremens from alcohol withdrawal; LSD intoxication
What is Parkinson’s Disease?
An Organic Disorder
A disorder with obvious neurological signs:
- tremor, increased muscle tone and stiffness, dysarthria, clumsiness, shuffling gait, motor slowness
Also has psychological symptoms:
- depression of mood
- cognitive impairment
What is the cause of Parkinson’s Disease?
Loss of pigmented neurones in the s.nigra
Loss of dopaminergic function
What is Dementia?
Global term - a set of symptoms with evidence of decline in memory and thinking which impairs functioning in daily living and is present for 6 months or more.
Associated with changes in behaviour, motivation and personality
What sorts of symptoms will someone with Dementia have?
Obvious impairment of higher cortical function.
- orientation
- thinking and judgement
- memory
- capacity to learn new information
May also have neurological signs:
- impairments of language
- dysphasia, dyspraxia
Give examples of some types of Dementia
- Alzheimer’s disease-most common
- Vascular dementia (mini strokes in brain)
- Lewy body dementia
- Frontotemporal dementia
- Dementia of Parkinson’s disease and Huntingdons disease
- Creutzfeldt-Jacob disease (mad cow disease)
How does a patient with Alzheimer’s Disease present?
- Early = slight changes in mood or memory
- Short term memory becomes more affected, other features will appear
- Loss of ability to do more complex tasks (eg finance)
- Disorientation, concentration difficulties
- BPSD - Behavioural and Psychological Symptoms are common later in the disease
What is the clinical course of Alzhiemer’s Disease?
- Profound memory loss
- Frequent BPSD symptoms
- Loss of ability to perform basic activities of daily living
- Mobility affected
- Patient become dependent
What are the 4 domains of the caregiver burden?
Global Function
Cognitive Function
Activities of Daily Living
Behavioural Disturbances
What is Psychosis?
- Loss of contact with reality- demonstrated by presence of delusions (abnormal beliefs) and hallucinations (a percept without an object)
- Lack of insight- that is do not accept/believe they are ill/require treatment (insight is often “partial”)
What are delusions?
- A false fixed belief which is out of keeping with ones educational, social, cultural and religious background
- It is unshakeable by argument
(Not just one that you disagree with)
(If a belief is in keeping with a person’s social/cultural group it is unlikely to be delusional)
Give examples of some Psychotic Illnesses
Schizophrenia
Schizoaffective disorder
Persistent delusional disorders
What is ‘perception’?
- Perceiving the outside world relates to a complex neuropsychological process
- Sense organs collect and modulate raw data
- Brain decodes and produces an internal neural representation of the outside world
What is a Hallucination?
A hallucination is a perception in the absence of external stimulus that has qualities of real perception.
- Hallucinations are vivid, substantial, and located in external objective space.
- Hallucinations can occur in any sensory modality —visual, auditory, olfactory, gustatory, tactile, proprioceptive, equilibrioceptive, nociceptive, thermoceptive and chronoceptive.
What are some examples of Mood Disorders?
Mania
Depression
Unipolar depressive illness
Bipolar disorder: episodes of mania and depression
What is depression?
the pathological state of sadness.
A syndrome, with associated symptoms (including loss of appetite, weight loss, sleep disturbance, suicidal thoughts)
Diagnosis of depressive illness: presence of depressed mood or loss of interest, plus four other symptoms, for at least two weeks
What are the symptoms of Mania / Hypomania
- Increased Energy
- Over activity
- Irritability
- Disinhibition
- Increased Libido
- Grandiosity
Give examples of Anxiety Disorders
Anxiety disorders, e.g. generalised anxiety disorder, panic disorder, phobias
Obsessive-compulsive disorder
Hypochondriasis
Maladaptive behaviour
Abnormal illness behaviour
What are some SOMATIC symptoms of anxiety?
- Butterflies
- Tremor
- Sweating
- Dry mouth
- Giddiness
- Choking
- Blushing
- Vertigo
- Shortness of Breath
- Palpitations
- Headaches
- Chest Pains
- Diarrhoea
- Nausea
- Tinnitus
- Tingling
What are some PSYCHIC symptoms of anxiety?
- Worry
- On edge
- Exhaustion/Fatigue
- Restlessness
- Hypersensitive to noise
- Anxious Foreboding
- Irritable
- Poor concentration
What are obsessions?
Recurrent, persistent, forceful thoughts, impulses or images which the patient feels are senseless but recognises as his own.
They feel compelled to resist them.
What are some themes associated with obsession?
- Dirt and contamination
- Aggression
- Orderliness
- Religious
- Sexual
- Illness
Can be accompanied by compulsive acts:
–Hand washing
–Complicated rituals
Give examples of Personality Disorders?
Personality disorders, e.g. psychopathy, dependent, anankastic, borderline,
cyclothymic, narcissitic,
anxious
What are the criteria for a neurotransmitter?
- Present in nerve terminals in the area where it is thought to act.
- Stimulation of the appropriate nerves should evoke a measurable release.
- The proposed neurotransmitter must produce post-synaptic effects identical physiologically and pharmacologically to those produced by neuronal stimulation.
- Enzymes present for its synthesis and a means of inactivation available.
- Non-uniform distribution in the brain.
What are the major CNS Transmitters?
(receptors in the picture)
Glutamate
GABA
Glycine
Acetylcholine (Ach)
Serotonin (5HT)
Noradrenaline
Dopamine
Draw neurotransmitter release
What are the 4 main types of neutransmitter receptors?
Type 1 – ligand gated ion channels (ionotropic)
Type 2 – G-protein coupled receptors (metabotropic)
[Type 3 – kinase linked receptors]
[Type 4 – nuclear receptors]
What receptors are the main targets for current drugs targeting the CNS/
Type 1 – ligand gated ion channels (ionotropic)
Type 2 – G-protein coupled receptors (metabotropic)
Describe the Neurotransmitter synthesis, metabolism, and inactivation of dopamine
- CAT choline acetyl-transferase
- Acetyl-CoA acetyl co-enzyme A
- MAO monoamine oxidase
- COMT catechol-O-methyltransferase
- HVA homovanillic acid
- DOPA dihydroxyphenylalanine
- DOPAC dihydroxyphenylacetic acid
- DBH dopamine beta-hydroxylase
- MHPG 3-methoxy-4-hydroxy-phenylethyleneglycol
- VMA vanillylmandelic acid
- 5-HIAA 5-hydroxy-indoleacetic acid
- PCPA para-chloro-phenylalanine
How is dopamine locally regulated?
- CAT choline acetyl-transferase
- Acetyl-CoA acetyl co-enzyme A
- MAO monoamine oxidase
- COMT catechol-O-methyltransferase
- HVA homovanillic acid
- DOPA dihydroxyphenylalanine
- DOPAC dihydroxyphenylacetic acid
- DBH dopamine beta-hydroxylase
- MHPG 3-methoxy-4-hydroxy-phenylethyleneglycol
- VMA vanillylmandelic acid
- 5-HIAA 5-hydroxy-indoleacetic acid
- PCPA para-chloro-phenylalanine
How is neurotransmitter release dampened?
The long-loop feedback process
(autoreceptors create this process)
- CAT choline acetyl-transferase
- Acetyl-CoA acetyl co-enzyme A
- MAO monoamine oxidase
- COMT catechol-O-methyltransferase
- HVA homovanillic acid
- DOPA dihydroxyphenylalanine
- DOPAC dihydroxyphenylacetic acid
- DBH dopamine beta-hydroxylase
- MHPG 3-methoxy-4-hydroxy-phenylethyleneglycol
- VMA vanillylmandelic acid
- 5-HIAA 5-hydroxy-indoleacetic acid
- PCPA para-chloro-phenylalanine
What are the EXITATORY Amino Acid Neurotransmitters?
–glutamate
–aspartate
–(NMDA, AMPA, kainate)
What are the INHIBITORY Amino Acid Neurotransmitters?
–GABA (gamma amino butyric acid)
–glycine (spinal cord grey matter; blocked by strychnine; no therapeutically useful drugs)
Where is glutamate stored?
Do any drugs interfere with its metabolism?
What happens after release?
When is there excessive release?
- Glutamate is stored in vesicles
- No clinically useful drugs interfere with its metabolism
- Following release, there is re-uptake into terminals and astrocytes (like GABA)
- Excessive release in ischaemia causes neuronal damage and death.
What is used to treat dementia?
Nootropic drugs
What is used to treat Parkinson’s Disease?
Anti-parkisonian drugs
What is used to treat epilepsy?
Anti-convulsant drugs
What is used to treat psyciatric disorders?
- Psychosis
- Depression and mania
- Anxiety
- OCD
Treatment of psychiatric disorders – psychotropic drugs:
- Psychosis - antipsychotics
- Depression and Mania – antidepressants and mood stabilisers
- Anxiety - antidepressants
- Obsessive-compulsive disorder - antidepressants
What are the Potential mechanisms for drug action
- Stimulate synthesis
- Stimulate release
- Receptor agonist
- Receptor antagonist
- Re-uptake blocker
- Enzyme inhibitor
- L-dopa in Parkinson’s
- Stimulate release amphetamine
- bromocriptine
- antipsychotic drugs
- SSRI antidepressants
- MAOI antidepressants
Discuss the Dopamine NT function
and pathway
Control of movement
Cognition/Emotional Expression
Hormone Secretion
Nigrostriatal
Mesolimbic
1.Hypothalamic-pituitary
Treatment of clearly definable ‘organic’ brain disorders, such as Parkinson’s disease or Alzheimer’s disease, involves what?
Treatment of epilepsy involves what?
‘replacement’ in some way of the neurochemical deficit.
drugs designed to control the electrical hyper-excitability.
What is the noradrenaline pathway involved in?
limbic system
REM sleep
reward mechanisms
hypothalamic fn
autonomic functions
What is the Serotonin Pathway involved in?
sleep
pain & temp control
aggression
sexual behaviour
hormone control
punishment
Discuss the acetylcholine neuronal pathways
and their function
- septo-hippocampal
- nucleus basalis
- s.nigra – thalamus
- striatal interneurons
memory arousal
learning movement
What are the general principles for medication in
- Depression
- Psychosis
- Dementia
For most psychiatric meds the aim is to increase levels of whatever brain chemical (or neurotransmitter) is thought to be low or lacking
- serotonin and adrenaline
- dopamine
- acetylcholine
Often symptons are treated by meds instead
What can antidepressants be used to treat?
What can mood stabilisers also be used to treat?
anti-anxiety and anti-pain
epilepsy
What are the difficulities with under and over prescribing?
What is the correct balance between psychological therapies, medication and doing nothing?
