Pharmacology of Antipsychotic Drugs Part B Flashcards
what is the MOA for atypical antipsychotics?
still have some activity as D2 antagonists( primarily mesolimbic system)
also act as 5HT2a antagonists (in some cases more so than D2 antagonists) pharmacology also determined by binding to other receptors
What are the clinical features of atypical antipsychotics?
effective in controlling positive symptoms some offer better management of negative symptoms compared to typical drugs. lower risk of EPS some cause metabolic problems (weight gain increased risk of diabetes) in general typical drugs more variability in terms of mechanism and SE)
Why do atypical drugs have lower risk for EPS?
presynaptic 5-HT2a receptors on dopaminergic neurons projecting from the substantia nigra pars compacta to the striatum play a key role. in the presence of an atypical antipsychotic the post synaptic D2 receptors are blocked but the drugs antagonism of 5-HT2a receptors leads to greater dopamine release into the synapse partially offsetting the D2 antagonism (5HT-2A receptor is blocked so can’t reduce dopamine levels)
what happens in the absence of drug (control)?
in the absence of drug the binding of serotonin to presynaptic 5-HT2a receptors reduces the amount of dopamine released by nigral dopaminergic neurons into the synapse
what do typical drugs do?
in the presence of a typical antipsychotic, post-synaptic D2 receptors are blocked and serotonin again acts on presynaptic 5-HT2a receptors to reduce the amount of dopamine released into the synapse. the blocking leads to movement disorders (dopamine inhibits motor pathways so less dopamine=more movement)
what is Clonzapine (Clozaril)?
the 1st atypical antipsychotic drug. high efficacy(especially for positive symptoms but also may improve negative symptoms) lower d2 potency so reduced risk EPS. SE anticholinergic, sedation, orthostatic hypotension. metabolic SE weight gain risk of diabetes,
agranulocytosis-serious SE involoving a drop in neutrophil counts weekly blood monitoring needed) prolings QTc interval
What is olanzipine (zyprexa)?
similar clinical features as clozapine(low EPS risk) similar SE profile as clozapine-anticholinergic sedation orthostatic hypotension weight gain diabetes risk but generally less severe.Risk of DRESS but no agranulocytosis risk)
What is Quetiapine (seroquel)
similar clinical features as clozapine and olanzapine it antagonizes D2 5HT2a with low EPS risk
SE similar to olanzapine sedation orthostatic hypotension low antimuscarinic activity metabolic SE weight gain and diabetes risk prolongs QTc metabolite has antidepressant activity (target NET and SERT)
What is Asenapine (saphris)
similar clinical features as quetiapine antagonizes D2 5HT2a with a low risk EPS similar SE profile as quetiapine orthostatic hypotension weight gain lower sedation antimuscarinic activity compared to quetiapine prolongs QTc interval
what is risperidone (risperidol)
rationally designed to be a combined D2 and 5HT2a antagonist low risk of EPS when administered at <8mg/day SE:similar to quetiapine sedation orthostatic hypotension low antimuscarinic activity weight gain and risk of diabetes
What is Ziprasidone (Geodon/Zeldox)
similar clinical features as risperidone similar SE profile as risperidone sedation orthostatic hypotension weight gain diabetes risk but generally less severe
DRESS risk prolong QTc
what is Lurasidone (Latuda)
similar clinical features as risperidone and ziprasidone similar SE profile as ziprasidone less severe compared to R highly potent
What is aripiprazole (abilify)
high affinity for D2/D 3; also acts as a 5HT2A antagonist.acts as a D 2 partial agonist: drug action varies with the level of dopamine in different brain regions also acts as a partial agonist at 5HT1A receptors (useful fordepression)
low risk of EPS side-effects similar to ziprasidone: sedation (H1), orthostatic
hypotension (α1), low antimuscarinic activity low risk of weight gain, risk of diabetes
akathisia (restlessness)
How does aripiprazole effect DA response when dopamine levels are high?
when dopamine levels are high in the limbic system aripiprazole lowers the DA response but only to intermediate level
How does aripiprazole effect DA response when dopamine levels are low?
when dopamine levels are low (eg in the striatum or cortex of SZ patients) aripiprazole increases the DA response to the same intermediate level
effects of aripiprazole
by lowering D2 activity into the normal range in the limbic system it reduces + symptoms of SZ
by ensuring that D2 activity stays in the normal range in the striatum it reduces EPS risk
by increasing D2 activity into the normal range in the cortex it reduces negative symptoms of SZ
what is Pimavanserin (Nuplazid)
inverse agonist targeting 5HT2a used to reduce PD psychosis including hallucinations and delusions caused by dopamine treatments prolongs Qtc interval
what is cobenfy
combines two compounds: xanomeline and trospium chloride
xanomeline targets M1 and M 4 acetylcholine receptors as an
agonist, lowering dopamine levels
reduces positive and negative symptoms, improves cognitive
symptoms in some patients
trospium chloride prevents xanomeline from affecting peripheral
muscarinic receptors, lowering side-effects
first ever approved SZ drug that doesn’t target the D2 receptor
GI side effects (nausea, constipation)
Drugs that end with pine
clonazapine, olanzapine, quetiapine,asenapine
drugs that end with done
risperidone, ziprasidone and lurasidone
