Antipsychotics Flashcards
What are 8 prototype antipsychotics?
chlorpromazine
fluphenazine
haloperidol
clozapine
risperodone
olanzapine
aripiprazole
quetiapine
What are the different subtypes of dopamine receptors? How are they subdivided? What is the most common target of antipsychotics? Where are they distributed?
Currently, five unique genes encoding dopamine receptors have been identified
and their products characterized. These five receptor subtypes fall into three classes:
those that stimulate adenylate cyclase (the so-called D1 family comprising the D1 and D5
subtypes), those that attenuate stimulated adenylate cyclase and act on ion channels (the
D2 family comprised of the D2 and D4 receptors) and the D3 receptor, the signal
transduction pathway for which has not yet been convincingly determined. These
receptors each have a unique pharmacological profile and non-identical patterns of
expression within the brain. These facts may explain the varying therapeutic profiles of
the neuroleptics. Preclinical studies suggest that the D2 family is the target for
antipsychotic agents.
D1
/D5
in caudate/putamen, cortex and thalamus
have similar distribution in brain, being present
D2
is highest in basal ganglia, lower in limbic regions
D3
/D4
are higher in limbic regions than in basal ganglia
What are the positive symptoms of schizophrenia? Negative symptoms?
Positive symptoms psychotic thinking agitated turmoil hallucinations delusion
Negative symptoms
ῆflattened affect (apathy)
ῆamotivation
ῆemotional and social withdrawal
Describe 6 side effects of neuroleptics in order of shortest time of onset to longest.
Acute dystonia Spasm of muscles of tongue, face, neck, back; may mimic seizures; not hysteria
Akathisia Motor restlessness; not anxiety or ᾿ agitation῀
Parkinsonism Bradykinesia, rigidity,variable tremor, mask
facies, shuffling gait
Neuroleptic malignant syndrome Catatonia, stupor, fever,
unstable blood pressure, myoglobinemia; can be fatal
Perioral tremor (᾿ rabbit῀ syndrome) Perioral tremor (may be a late variant of parkinsonism)
Tardive dyskinesia Oral-facial dyskinesia; widespread
choreoathetosis or dystonia
What are some characteristics of typical antipsychotics? What are two categories?
“Anti-Psychotics
““Typical””
-block D2 receptors
-alleviate positive symptoms of psychosis
-little action on neg. symptoms
-high incidence of EPS and TD!
-2/3 of pts have persisten parkinsonism
-30-60% of pts partial/ no response to drugs
-50% rehospitalized within 1 yr
-increased dose stabilize response but quality of life goes down “
Phenylthiazines and other heterocyclic drugs
What are characteristics of phenylthiazines? What are two prototypes?
“Phenylthiazenes
- first synthesized from aniline dyes
- found to be antihistamine and sedative
- led to synthesis of chlorpromazine
- potentiate anesthetics leading to diminished arousal and motility, increased tendency for sleep”
Chlorpromazine, fluphenazine
Is chlorpromazine low/high potency? How are side effects mediated? What are they?
” -low potency (but not in clinical efficacy)
-side effects mediated via histamine, adrenergic and cholinergic receptors” “
- sedation
- weight gain
- cardiotoxicity
- lowering of seizure threshold
- skin photosensitivity”
How does fluphenazine compare to chlorpromazine? Low/High pot? What does this mean? How is it administered?
” -high potency, higher risk of EPS (extrapyr) , less sedation
-used in depot injections for compliance reasons”
What kind of drug is haloperidol? H/L pot? Side effects?
Other heterocyclic (typical)
-high potency “
-high incidence of EPS (50-90% of pts)
and tardive dyskinesia (20-50% of pts)
-lower sedation/autonomic side effects
-can cause leukopenia”
What are the side effects of malindone? How does it compare to phenylthiazines and other drugs?
can cause EPS, sedation, postural hypotension
not as much weight gain as other drugs
lower reduction in seizure threshold compared to
phenothiazines
What are some characteristics of atypical antipsychotics? What are some prototypes?
"Anti-Psychotics ""Atypical"" -act as antag at D2/D3/D4 and 5-HT receptors -lower rehospitalization rates -effective for some refractory pts -treat +/- symptoms -decreased EPS/ little no TD -little/no effect on prolactin levels
Clozapine Risperidone Aripiprazole Olanzapine Quetiapine
Is clozapine high/low potency? What side effects are noteworthy? For which patients is it especially good?
- low potency “
- agranulocytosis in 1% of pts -> weekly blood tests req.
- lowers seizure threshold
- can reduce violence and aggression”
For which patients is risperidone especially effective? Whta symptoms does it treat? What are the side effects like?
effective for refractory schizophrenia
treats negative symptoms
low doses causes little side effects
higher doses can see EPS, QT prolongation
What are the receptors/action of Aripiprazole? What makes it unique? What are the side effects?
” -partial agonist at D2/ 5-HT1A, antagonist at 5-HT2
- 5-HT reuptake inhibitor
- used for bipolar/ depressive disorders
- hepatic metabolism (CYP system) -> drug/drug interactions” -increased sedation
What patients does olanzapine treat? What are the side effects? What makes it unique?
- improves both positive and negative symptoms
- little in way of EPS at normal dosage” “
- increases appetite and alters lipid and glucose metabolism
- can lead to diabetes”
