Antipsychotics Flashcards
positive symptoms of schizophrenia
“presence of what shouldn’t be”:
*hallucinations
*delusions
*thought disorders
negative symptoms of schizophrenia
“lack of what should be”:
*losing interest and motivation in life and activities (e.g. relationships, sex)
*social inattentiveness
*affective flattening
*poverty of speech/content of speech
*poor self care, loss of persistence in school/work
typical antipsychotics - overview
*first generation
*effective against positive symptoms only
*more EPS
*seldom used (except haloperidol)
*MOA: D2 blockade > 5-HT2A blockade
atypical antipsychotics - overview
*second generation
*effective against positive AND negative symptoms
*less EPS
*used frequently
*MOA: 5-HT2A > D2 blockade
general MOA of typical antipsychotics
D2 blockade > 5-HT2A (serotonin) blockade
general MOA of atypical antipsychotics
5-HT2A (serotonin) blockade > D2 blockade
phenothiazines
*a class of typical antipsychotics
*example = chlorpromazine (Thorazine) (low potency)
butyrophenones
*a class of typical antipsychotics
*example = haloperidol (Haldol) (high potency)
chlorpromazine - drug class
LP phenothiazine (typical/first generation antipsychotic)
important atypical antipsychotics
*Clozapine (Clorazil)
*Risperidone (Risperdal)
*Olanzapine (Zyprexa)
*Quetiapine (Seroquel)
*Ziprasidone (Geodon)
*Aripiprazole (Ablify)
*Paliperidone (Invega)
clozapine - drug class
atypical antipsychotic
risperidone - drug class
atypical antipsychotic
olanzapine - drug class
atypical antipsychotic
quetiapine - drug class
atypical antipsychotic
ziprasidone - drug class
atypical antipsychotic
aripiprazole - drug class
atypical antipsychotic
paliperidone - drug class
atypical antipsychotic
pharmacokinetics/dynamics of atypical antipsychotics
*absorbed orally, but some have first pass metabolism (IV dose might be < PO dose)
*most have large Vd (very lipid soluble)
*hepatically metabolized (CP450)
mechanism for adverse drug effects of antipsychotics: loss of accommodation, dry mouth, difficulty urinating, constipation
*mechanism = muscarinic cholinoceptor blockade (anticholinergic effects)
*system causing the symptoms = autonomic nervous system
mechanism for adverse drug effects of antipsychotics: orthostatic hypotension, impotence, failure to ejaculate
*mechanism = alpha-adrenoceptor blockade
*system causing the symptoms: autonomic nervous system
mechanism for adverse drug effects of antipsychotics: Parkinson’s syndrome, akathisia, dystonias
*mechanism = dopamine receptor blockade
*system causing the symptoms = central nervous system
mechanism for adverse drug effects of antipsychotics: tardive dyskinesia
*mechanism = supersensitivity of dopamine receptors
*system causing the symptoms = central nervous system
mechanism for adverse drug effects of antipsychotics: toxic-confusional state
*mechanism = muscarinic blockade (anticholinergic effects)
*system causing the symptoms = central nervous system
mechanism for adverse drug effects of antipsychotics: amenorrhea-galactorrhea, infertility, impotence
*mechanism = dopamine-receptor blockade resulting in hyperprolactinemia
*system causing the symptoms = endocrine system
mechanism for adverse drug effects of antipsychotics: weight gain
*mechanism = possibly combined H1 and 5-HT2A blockade
akithisia
*a subjective feeling of restlessness
*one of the extrapyramidal symptoms (EPS) associated with antipsychotics
acute dystonic reactions
*abrupt onset muscular spasms of the neck, eyes, trunk, extremities
*one of the extrapyramidal symptoms (EPS) associated with antipsychotics
parkinsonism
*stiffness, tremor, bradykinesia
*one of the extrapyramidal symptoms (EPS) associated with antipsychotics
extrapyramidal symptoms
*akithisia (restless/can’t sit still)
*acute dystonic reactions
*parkinsonism
cause of extrapyramidal symptoms (EPS)
*associated with use of antipsychotics
*highest incidence with high potency typical agents (haloperidol)
MOA of extrapyramidal symptoms (EPS)
*D2 blockade + imbalance with M1 (Ach)
treatment for extrapyramidal symptoms (EPS)
*treat with ANTICHOLINERGIC drug
-benztropine
-trihexyphenidyl
-diphenhydramine**
*do NOT give levodopa
tardive dyskinesia (TD)
*a horrible adverse drug effect associated with antipsychotics
*late-occurring abnormal movements:
-mouth and tongue movements (lip smacking, sucking and puckering, facial grimacing)
-irregular movements of the limbs (choreoathetoid-like movements of the fingers and toes; slow, writing movements of the trunk)
*relative cholinergic deficiency secondary to SUPERSENSITIVITY OF DOPAMINE RECEPTORS
MOA of tardive dyskinesia
*relative cholinergic deficiency secondary to supersensitivity of DA receptors
*occurs after long-term use with antipsychotics (esp typicals)
tardive dyskinesia - treatment
*discontinue the drug (switch to newer atypical agent)
*can try high dose benzos
*VMAT inhibitors (block the uptake of dopamine into synaptic vesicles)
neuroleptic malignant syndrome (NMS)
*ADE associated with antipsychotics
*fever, rigidity, mental status changes, and autonomic instability
*from DA blockade
*TX: bromocriptine (DA agonist); DANTROLENE (a muscle relaxant)
treatment for neuroleptic malignant syndrome (NMS)
*bromocriptine (DA agonist)
*dantrolene (a muscle relaxant)
other neurologic ADEs of antipsychotics
*seizures (decreases seizure threshold) - esp with clozapine
*sedation (from central histamine-1 blockade)
hyperprolactinemia
*ADE of antipsychotics
*s/s: sexual dysfunction (decreased libido, infertility, impotence), amenorrhea, gynecomastia / galactorrhea, hypoestrogenism / osteopenia
general drugs that cause hyperprolactinemia
*all typical antipsychotics
*risperidone
*paliperidone
cardiovascular effects associated with antipsychotics
*alpha-1 blockade: orthostatic hypotension (reflex tachycardia) & impaired ejaculation
*QTc prolongation (be careful adding to other QTc drugs)
metabolic effects associated with antipsychotics
*weight gain
*diabetes mellitus
*dyslipidemia
ADEs of clozapine
*agranulocytosis
*myocarditis
(note - minimal EPS)
clozapine - unique facts
*minimal EPS and high efficacy
*causes AGRANULOCYTOSIS & MYOCARDITIS
**REQUIRES A SPECIAL PROGRAM (REMS) dictating who can prescribe it and frequency of CBC monitoring
ADEs of aripiprazole - general
probably the LEAST ADEs of all of the antipsychotics (used alot)
ADEs of clozapine - general
probably the MOST ADEs of all of the atypical antipsychotics (worst tolerated)
ADEs of olanzipine
*metabolic ADEs - weight gain, glucose abnormalities, and hyperlipidemia
ADEs of ziprasidone
*QTc prolongation
prochlorperazine
*antiemetic (treat nausea and vomiting)
*MOA: DA-receptor blockade in the chemoreceptor trigger zone and in stomach
*has high-potency ADEs (especially extrapyramidal symptoms - EPS)
promethazine
*antiemetic (treats nausea and vomiting)
*MOA: DA-receptor blockade in the chemoreceptor trigger zone and in stomach
*ADE = sedation (potent histamine-1 blocking effects)
antipsychotic drug used for acute agitation
haloperidol
drugs used for nausea and vomiting
*prochlorperazine
*promethazine
