MECHANISM OF PSYCHOTROPIC DRUG ACTION Flashcards
what are 4 strategies to help alleviate mental illness?
lifestyle
social support
psychotherapy
antidepressants
what are the 4 dopamine pathways?
mesolimbic
mesocortical
nigrostriatal
tuberoinfundibular
what is the function of the nigrostriatal pathway?
initiation and control of movement
what is the function of the mesolimbic pathway?
reward and reinforcement
what is the function of the mesocortical pathway?
cognition, planning and motivation
what is the function of the tubero-infundibular pathway?
Inhibits the release of prolactin hormone from the pituitary gland
what behaviour does noradrenaline influence?
sleep
wakefulness
attention
feeding behaviour
where is noradrenaline most commonly released from?
neurones originating from the locus coeruleus in the brainstem
where is serotonin released from?
neurones originating from the Raphe nuclei in the brainstem
what does serotonin influence?
mood, emotional behaviour, sleep and the feeling of being satisfied
where is GABA released from?
inhibitory neurones throughout the CNS
what is GABAs mechanism of action?
It binds to a GABA-A receptor, which allows an influx of Cl- across the post-synaptic membrane which hyper polarises the neurone
what are positive schizophrenic symptoms?
hallucinations
delusions
thought disorder
what is the aim of treatment for positive symptoms?
To decrease dopamine transmission as they’re associated with the mesolimbic pathway.
what are negative schizophrenic symptoms?
lack of motivation, reduced speech, reduced emotion, social withdrawal
what is the aim of treatment for the negative schizophrenic symptoms?
To increase dopamine transmission as they are associated with the mesocortical pathway.
what is the cause of schizophrenia?
unknown
what is the dopamine hypothesis of schizophrenia?
hyperactivity of dopamine D2 receptor neurotransmission in subcortical and limbic brain regions contributes to positive symptoms of schizophrenia, whereas negative and cognitive symptoms of the disorder can be attributed to hypofunctionality of dopamine D1
what are some arguments for the dopamine hypothesis?
Antipsychotics block dopamine receptors
Drugs that increase dopamine cause psychosis
PET and SPECT scans show increased brain Dopamine activity when people have Schizophrenia
what are some arguments against the dopamine hypothesis?
Neurotransmitter effects are immediate, but antipsychotics take 2+ weeks to work on symptoms
Other transmitters appear to be involved with psychosis –Glutamate, 5HT2, 5HT1A
Critical potential role for environmental factors during brain development
Neurodegeneration associated with worsening symptoms. Linked to glutamate induced excitotoxicity
what are antipsychotics mechanism of action?
antagonizes D2 receptors in the mesolimbic system
what can antipsychotics be used to treat?
delusions, hallucinations, thought disorder, mania, delirium
what’s the different between first and second generation antipsychotics?
1st- target D1 and D2
2nd- target D2 mostly and a little D1
what is the effect of antipsychotics acting on the nigrostriatal pathway?
extrapyramidal side effects e.g. Parkinsonism, acute dystonia, dyskinesia
what is the effect of antipsychotics acting on the tubuloinfundibular pathway?
excess prolactin
leads to galactorrhea, amenorrhoea, infertility
what are some long term side effects of antipsychotics?
weight gain, diabetes, raised cholesterol
what are some factors of depression?
persistent low mood/self esteem reduced enjoymnt fatigue sleep/appetite/weight/concentration changes loss of consciousness indecisiveness guilt hopelessness suicidal thoughts
what is the monoamine theory of depression?
Depression is a result of a deficiency in brain monoamine neurotransmitters
what are the 4 monoamine transmitters?
serotonin
noradrenaline
adrenaline
dopamine
what are arguments for MOA hypothesis?
Antidepressants increase the availability of monoamines at synapses
People with depression can have lower levels of monoamine precursors/metabolites in their CSF or blood
what are arguments against MOA hypothesis?
Neurotransmitter effects of antidepressants are immediate, but they take 2+ weeks to work on symptoms
Cocaine and amphetamine mimic NA and 5-HT but do not act as antidepressants
Iprindole is an antidepressant which does not affect NA or 5-HT reuptake (5-HT2 antagonist)
what are some antidepressant types?
tricyclic antidepressants
selective serotonin reuptake inhibitors
monoamine oxidase inhibitors
serotonin noradrenaline reuptake inhibitors
what are tricyclic antidepressants mechanism of action?
block reuptake of noradrenaline and serotonin which allows it to have an elongated effect. However, they do not have an effect on Ach reuptake.
what are the side effects of tricyclic antidepressants?
sedation, dry mouth, blurred vision, constipation, urinary retention, postural retention, can cause drug interactions, potentiates effects of alcohol and anaesthetics.
what is the mechanism of selective serotonin re-uptake inhibitors?
Block re-uptake of serotonin from synaptic cleft to give it longer to work.
what are the side effects of selective serotonin re-uptake inhibitors?
nausea and vomiting, sexual dysfunction, withdrawal reaction, can inhibit metabolism of other drugs.
what is the mechanism of monoamine oxidase inhibitors?
Inhibit monoamine oxidase so serotonin and noradrenaline can’t be broken down. This allows the continuation of the neurotransmitter activity in the synaptic cleft.
what are side effects of monoamine oxidase inhibitors?
postural hypotension, insomnia, weight gain, potential drug interactions.
what is the theory about why antidepressants take 2 weeks to work?
Initially the increased 5HT in synapses is cancelled out by auto-receptors reducing 5HT release and more reuptake of the extra 5HT in the synapses. But after a couple of weeks, the auto-receptors desensitise, and the blocked reuptake transporters get internalised. So eventually there really is increased 5HT in the synapses
what are symptoms of anxiety disorders?
nervousness foreboding agitation palpitations sweating bowel upset
what are some benzodiazepines?
diazepam
lorazepam
temazepam
what are benzodiazepines used for?
anxiety
seizures
increased muscle tone
what are side effects of benzodiazepines?
drowsiness, confusion, forgetfulness, impaired motor control, tolerance, dependence, respiratory depression
