Antipsychotic (Neuroleptic) Agents

Question 1

Pharmacokinetics of antipsychotics

Answer 1

Oral and paprenteral admin
Metabolism within gut and liver (1st pass)
Lipid soluble–>high volume distribution

Question 2

MOA of antipsychotics

Answer 2

DA receptor antagonists (D2>D1)
Typical agents: strong DA antagonists–>high potency
Atypical agents: DA, H1, and 5-HT–>low potency

Question 3

Pharmacodynamic effects of antipsychotics

Answer 3

Antispychotic effects: reduce positive symptoms more than negative
Extrapyramidal syndrome (EPS): Parkinson-like effects, rigidity, tremor, bradykinesia (seen more with typical agents than atypical)
Akathesia: motor restlessness, anxiety
Dystonia: muscle spasm, hypertonus
Tardive dyskinesia: slow developing, involuntary movements of tongue, face, mouth, head; receptor up regulation when dose lowered; irreversible
Antiemetic: ecept for thioridazine
Endocrine: DA normally inhibits prolactin release
DA antagonists–>hyperprolactinemia–>decreased testosterone, gynecomastia, galactorrhea, menstrual irregularities, change in libido
Weight gain: atypical agents–>diabetes
Anticholinergic: urinary, dry mouth, blurred vision, mental confusion, constipation
Antihistaminic: sedation
Antiadrenergic (alpha-1 block): postural hypotension (diminished baroreceptors), reflex tachycardia, erectile dysfunction and impaired ejaculation

Question 4

Adverse effects of antipsychotics

Answer 4

DA-mediated: EPS effects, hyperprolactinemia, anticholinergic effects, antiadrenergic, antihistaminic
Neuroleptic malignant syndrome: hypertension, hyperthermia (rare)

Hepatic dysfunction: ALT and AST elevated

Uticaria and photosensitivity: metabolites accumulate in skin

Ocular opacity: depostion and crystallization of metabolites in lens

Cardiac arrhythmias: inhibit K+–>prolonged QT time, ventricular arrhythmias

Blood dyscrasias: leukopenia (especially with clozapine) requires periodic monitoring of blood

Decreased seizure threshold, disruption in temp regulation, hypothyroidism, cataracts, metabolic syndrome

Question 5

Therapeutic indications of antipsychotics

Answer 5

Schizophrenia (reduce positive signs)
Psychotic agitated behavior
Antiemetic (prochlorpromazine, phenergan)
Hiccoughs
Chronic neuropathic (central) pain syndromes
Tourette’s syndrome

Question 6

chlorpromazine
thioridazine
prochlorperazine
fluphenazine

Answer 6

Typical antipsychotics

Phenothiazines

Question 7

thioxene

Answer 7

Typical antipsychotics

Thioxanthenes

Question 8

haloperidol

Answer 8

Typical antipsychotics

Butyrophenones

Question 9

clozapine
olanzapine
risperidone
aripiprazole
quetiapine
ziprasidone

Answer 9

Atypical antipsychotics