Antipsychotics Flashcards
What are the positive symptoms of schizophrenia (3)?
hallucinations, delusions, aggressive behaviors
What are the negative symptoms of schizophrenia (2)?
lack of speech or emotion expression, social withdrawal
What are the cognitive symptoms of schizophrenia (2)?
difficulties with concentration and memory, executive decision making abilities
what are some bad things about schizophrenia?
high suicide risk, homeless, non-compliance, expensive treatment
What are the two classifications of typical antipsychotics?
phenothiazines, butyrophenones
What is the phenothiazine?
Chlorpromazine
What is the butyrophenones?
Haloperidol
Which was the first antipsychotic?
Chlorpromazine
What are two characteristics of Chlorpromazine?
it preferentially treats psychotic sxs (esp. positive symptoms) while leaving pts relatively conscioius, it’s more sedating than newer atypical antipsychotic drugs
What is the mechanism of action of typical antipsychotics?
block dopamine receptors, especially D2
What is the dopamine hypothesis?
1) both amphetamine and cocain block reuptake of DA and foster psychotic symptoms
2) antipsychotics block DA D2 receptors
Which DA receptors do typical antipsychotics antagonize?
D2!
What other receptors do typical antipsychotic drugs have affinities for?
HAMS: Histamine, a1 Adrenergic, Muscarinic, Serotonin (5HT). each drug has a iunique binding profile
What are two problems with typical antipsychotics?
1) persistent sxs in ~30% patients (treatment refractory)
2) only modest improvement of negative and cognitive sxs
What are the side effects of typical antipsychotics?
extrapyramidal symptoms (EPS - parkinsonism) due to D2 receptor blockade in the nigrostriatal pathway, hyperprolactemia due to D2 blockade in the tuberoinfundibular system
What defines the atypical antipsychotics?
reduced tendency to cause EPS and hyperprolactinemia
What are the two characteristics of the atypical antipsychs?
relatively weak D2 dopamine receptor blocking acitvity, Serotonin 2A (h-HT2A) receptor antagonism
does 5-HT@A antagonism affect antipsychotic effects?
no because inhibition of DA release by serotonin is not as prominent in mesocoritcal/mesolimbic pathways
which dopamine pathways do relief of psychosis happen?
mesolimbic (positive symptoms) and mesocortical (negative symptoms?)
true or false: each atypical agent has a unique receptor blocking profile
true
what syndrome is more common with atypical antipsychotics?
metabolic syndrome
What are the atypical antipsychotics?
clozapine, olanzapine, quetiapine, resperidone, ziprasidone, aripiprazole
What is selection of antipsychotics based on?
less on therapeutic expectancy, e.g. positive or negative symptoms, really based on anticipated side effects
What do the different side effects of antipsychotics depend on?
their potencies at other non-dopamine receptors
What else are antipsychs indicated for (5)?
schizoaffective disorder, manic pahse of bipolar disorder, Tourette’s syndrome, Huntington’s disease, autistic disorders
Which drugs cause weight gain as a side effect?
clozapine, olanzapine
which drug causes sedation?
chlorpromazine
What are the three extrapyramidal symptoms (EPS)?
Parkinsonism, tardive dyskinesia, neuroleptic malignant syndrome
3 points about Parkinsonism?
1) identical sxs as parkinson’s disease
2) treated with ant-muscarinic drugs (benztropine)
3) L-DOPA should never be used!
What is tardive dyskinesia?
sterotyped, repetitive involuntary movements of face, eyelids, mouth, tongue, extremities, trunk
what is often the most important problem associated with long term antipsychotic use and can be irreversible in adults?
tardive dyskinesia
is there treatment for tardice dyskinesia?
no
what is neuroleptic malignant syndrome?
life-threatening marked muscle rigidity, fever, autonomic instability, leukocystosis believed to result from excessively rapid blockade of postsynaptic dopamine receptors
what is the treatment for neuroleptic malignant syndrome?
immediate discontinuation of antipsychotics, Dopamine receptor agonist )bromocriptine) and muscle relaxant (diazepam)
What is Chlorpromazine?
prototype neuoleptic, inexpensive. many side effects, especially autonomic, because of relatively high muscarinic and a1 adrenergic receptor blocking activity. highly sedative. a1=5HT@A>D2>D1
What is haloperidol?
inexpensive, potent, relatively clean drug with fewer autonomic effects. severe EPS and hyperprolactinemia. D2>a1>D4>5HT2A>Da>H1
What is Clozapine?
less likely to cause EPS. most efficacious. agranulocytosis (dec. WBC): life threatening. other side effects: weight gain, sedation, hyperlipidemia, lowering seizure threshold. only used for patients resistant to typical antipsychotics. strict blood monitoring is mandatory.
What is Olanzapine?
olanzapine and risperidone are widely regarded as the second most effective atypical antipsych drugs next to clozapine. relatively strong histamine receptor H1 antagonism. side effects: sedation, metabolic syndrome, lowering seizure threshold.
What is Quetiapine?
structurally similar to clozapine. strong histamine H1 receptor antagonism (sedation, weight gain)
What is Risperidone?
most potent D2 receptor blocker among atypical antipsychs (associated with EPS and hyperprolactinemia at higher dose). much less potent anti-muscarinic activity
What is Ziprasidone?
low affinity for muscarinic, a1 and H1 receptors (less sedation, less postural hypotension, less weight gain). prolongs QTc interval (not indicated for patients with heart problems)
What is Aripiprazole?
partial agonist for D2: high affinity for D2 receptors but only has 3-% of intrinsic activity of DA. 5-HT2A receptor antagonist. minimally sedating.
What is the 1st antipsychotic, sedative?
chlorpromazine
What is the d2 receptor antagonist?
haloperidol
what is the d2 receptor partial agonist?
aripiprazole
what causes prolongation of QTc interval?
ziprasidone
what causes agranulocytosis?
cloazapine
what is potent d2 blocking atypical?
risperidone
what drug is most widely used; metabolic syndrome?
olanzapine
