neuropyschopharmacology Flashcards
What is Bipolar 1
at least 1 manic episode, impairment functioning, duration 1 week
What is Bipolar 2
at least 1 hypomanic episode, no severe impairment, duration 4 days
what is the criteria for mania?
1 week elevated/irritable mood, 3+(grandiosity, decr sleep, racing thoughts, distractibility, agitation etc), impaired functioning
what is involved in bipolar disorder with psychotic symptoms
hallucinations, delusions, grandiose/depressed mood, formal thought disorder
what is the epidemiology of bipolar
1% (adult)
what is the gender distribution of bipolar
equal in men and women
half of bipolar patients are diagnosed before what age?
25
what are the causes of bipolar
environmental and genetic- polygenetic
what are some diseases coexisting with bipolar?
substance abuse, ADHD, anxiety, thyroid disease, migraine, heart disease etc
What would you use antidepressant alongside?
mood stabiliser as need to be taken with caution
what drugs can be used prophylactically to prevent relapse
lithium, valproate, carbamazepine, olanzapine, risperidone
how does lithium work?
affects cation transport, monoaminergic transmission, cholinergic transmission, affects second messengers, has some neuroprotective functions
how does lithium affect cation transport?
increase Na+/K+ ATPase pump, neurotransmitter release
how does lithium affect NA and 5HT function
increases their functions
How does lithium affect cholinergic activity
increases it
what Is the effect of lithium on second messengers in the brain
inhibits cAMP, limits IP3 formation
How does lithium lead to neuroprotection
increased neuronal growth factors, makes neurones more resilient to stress
side effects of lithium
early- polyuria, dry mouth, weak; late- fine tremor, hair loss, thyroid enlargement; toxic- nausea, vomiting, confusion, convulsions
what do you need to monitor in lithium treatment
plasma monitoring- therapeautic window; TFTs; u and es
what is the problem with lithium and pregnancy
teratogen
what else is used in the treatment of bipolar (psychosocial)
CBT, psychoeducation
what is the definition of psychosis?
mental state dysfunction of behaviour, perception and thought processes
what is the definition of delusions
abnormality in the content of thought, not explained by cultural background
definition of hallucination
false perception without external stimulus present
what is the difference between true hallucinations and illusions?
illusions are the misperception of an external stimulus whereas hallucinations don’t have an external stimulus
what are the disorganised symptoms associated with schizophrenia
symptoms of the thought process- impairment to think properly, making up words, altered sense of self, changes in emotion and movements and behaviour
what is needed for the diagnosis of schizophrenia (at least one)
delusions of thought, delusions of control, voices in 3rd person, persistent delusions completely impossible
what is needed for the diagnosis of schizophrenia (at least 2)
persistent hallucination, formal thought disorder, catatonic behaviour, negative symptoms, change in overall quality of behaviour
what are the positive symptoms of schizophrenia
delusions, hallucinations, thought disorder
what are the negative symptoms of schizophrenia
decrease reactivity/range of emotions, poverty of speech/thought, apathy
what is the most reported symptom in schizophrenia
lack of insight (95%), then auditory hallucinations (74%)
how is the onset of schizophrenia
gradual
how is the outcome of schizophrenia
1/3s- good, intermediate, poor
what is a common clinical feature of schizophrenia
depression
what is the lifetime risk of having schizophrenia
1%
what is the peak age group of schizophrenia
20-24 (males), 25-29 (female)
what is enlarged in schizophrenia
lateral ventricles
what is a hypothesis in schizophrenia
dopamine hypothesis- mesolimbic dopamine overactivity
what is a limitation of the dopamine hypothesis in schiz
doesn’t explain the negative symptoms
what are the alternate hypotheses
glutamate, serotonin, and non neurochemical hypotheses
what are short term and long term medical treatments of schiz
short term- tranquilisers. long term- antipsychotics
how long is the delay of the antipsychotics in schizop
2-4 weeks
what are the 4 pathways associated with dopamine?
mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular
what is the key action of antipsychotics but why are they ‘dirty’
blockade of D2 receptor. dirty as they bind other receptors- cholinergic, histaminic, adrenergic
what are the problems with conventional antipsychotics
extra pyramidal side effects
which conventional antipsychotics have more EPSEs?
high potency (low potency have less EPSE)
example of high potency conventional antipsych
haloperidol
example of low potency conventional antipsych
chlorpromazine, thioridazine
what are some side effects of conventional antipsychs
hyperprolactinaemia, tardive dyskinesia (involuntary movements), neuroleptic malignant syndrome, nigrostriatal blockade- EPSE, parkinsonism, rigidity, tremor, bradykinesia, acute dystonia, akathisia (inner restlessness)
what are the advantages of newer atypical antipsychotics
don’t cause EPSEs, less D2 blockade
examples of atypical antipsychotics
clozapine, olanzapine, risperidone, quetiapine
what are other side effects of atypical antipsych
weight gain, lipid, diabetes
what is the annual prevalence of unipolar depression
3-10% (lifetime 10-20%)
what classifies as a major depressive ep
> 5 of following- depressed mood; diminished interest; insomnia/hypersomnia; retardation; feeling worthless; suicidal; loss concentration
what are the biological symptoms of depression
mood worse in mornings, sleep disturbance, loss libido, appetite changes, psychomotor agitation
what is decreased (neurotransmitters) in depression
decrease 5HT and NA. (monoamine hypothesis of depression)
what endocrine abnormalities are associated with depression
hypercortisolaemia
what % of depressions are heritable
30%-males, 40%- females
what is hyperactive in depression
hypothalamic- pituitary- adrenal axis
what does hypercortisolaemia lead to
shrinkage of the hippocampus
what drugs are used in the treatment of depression
SSRIs (fluoxetine, citalopram); TCA (imipramine); MAOI (phenelzine); SNRIs (serotonin noradrenaline reuptake inhibitors- venlafaxine)
what are the causes of dementia
alzheimers (50%), vascular dementia (25%), mixed alzheimers/vascular dementia (25%), Lewy body (15%), others- frontotemporal,subcortical, secondary causes eg lesions (5%)
what is aphasia
difficulty in speech, communication, writing
what is agnosia
loss of ability of recognition
what is apraxia
can’t execute motor actions even though have ability in the muscles
what protein is involved in alzheimers
apolipoprotein E4
brain volume reduces but where is there more atrophy in the brain in alzheimers
in frontoparietal and temporal lobes
what pathology is found in alzheimers
neuritic plaques (amyloid B); neurofibrillary tangles (phosphorylated tau)
what are the main neurotransmitters in alzheimers
ach and glutamate
what happens to cholinergic innervation in alzheimers
loss of neurones from the nucleus of Meynert (cholinergic nucleus). neocortical cholinergic innervation lost due to amyloid plaque.
what is glutamate involved in and what happens in alzheimers
main of neocortical and hippocampal pyramidal neurones. involved in higher functions such as cognition and memory. die due to the neurofibrillary tangles
what treatments are used in alzheimers and examples
ACHEIs (donezepil, rivastigmine) and NMDA receptor antagonist (memantine)
when are ACHEIs used in alzheimers
mild to moderate. (NMDA antagonist used in moderate to severe)
what are the 3 symptoms in dementia with Lewy Bodies
fluctuating cognitive impairment; parkinsonism; visual hallucinations
what is the pathology in Lewy Body dementia
cortical atrophy, ventricular enlargement, Lewy bodies in cortex
what neurochem abnormalities are present in Lewy Body
cholinergic, disruption dopaminergic input to striatum
what does vascular dementia co exist with?
multi infarct dementia (problem in blood supply to the brain), small vessel disease (leading to subcortical changes), subtypes include post stroke dementia
what is the onset of multi infarct dementia
abrupt onset
what occurs in multi infarct dementia
emotional and mood changes, insight may be retained for longer, epilepsy more common
what is a common history for someone with multi infarct dementia
prev strokes and TIA
how many people with dementia develop at least one behavioural and psychological symptom of dementia (BPSD)
90% (85% of these are serious)
what are the main 3 syndromes associated with BPSD
agitation, psychosis, mood disorders
what pharmacological treatments are given to those with dementia
antidepressants, anticonvulsants, antipsychotics
what is the volume of distribution calculated by
total amount of drug/concentration in plasma
what is the rate of elimination calculated by?
clearance x concentration in the blood
why would you need to give drugs at a higher concentration
if they undergo first pass metabolism
is lithium metabolised?
no, relies entirely on excretion
what can affect the excretion of lithium
dehydration/overhydration; alcohol; diuretics; renal insufficiency; polyuria
what are the dopamine tracts and associated conditions
nigrostriatal (parkinsons); mesocortical and mesolimbic (schizophrenia); and tuberoinfundibular (prolactin release control)
what is the precursor of serotonin and enzymes involved
trytophan (tryptophan hydroxylase)
what is the precursor of dopamine and enzymes involved
tyrosine (tyrosine hydroxylase)
precursor of NA and enzyme involved
dopamine. dopamine B oxidase
precursor of Ach metabolised by what enzyme
choline. choline acetylcholinesterase
what is NA involved in
attention
what is involved in alzheimers
Ach
where are amino acid neurotransmitters contained (GABA, glutamate)
astrocytes and interneurones
what is a benzo commonly used in anxiety
alprazolam, lorazepam
what benzo is used in insomnia
temazepam
what benzos are not metabolised in the liver and so can be considered in liver failure
LOT- lorazepam, oxazepam, temazepam
what are the types of adrenoceptors and which are excitatory
alpha and beta. alpha 1- excitatory. alpha-2 inhibitory. b1,2,3 stimulatory
what blocks muscarinic ACHRs
atropine
what effects do muscarinic ACHrs have
increase sweating, decrease HR,bp; bronchoconstriction, contraction of pupils; increase motility of GI
what effects do nicotinic ACHRs have
symp and para effects
what are the side effects of anti cholinergic
tachycardia, dry mouth, blurred vision, urinary retention
what are the side effects of anti adrenergic
hypotension, arrhythmia, tachycardia
what are effects of dopamine blockade
EPSE- tardive dyskinesia, akithesia, acute dystonia, hyperprolactinaemia, anhedronia
anti histaminic side effects
sedation, weight gain
is glutamate increased or decreased in mood disorders, shizophrenia
increased
is GABA increased or decreased in mood disorders, schizo, epilepsy
decreased
