Anti-Psychotics Flashcards
Almost all anti-psychotics have what kind of properties concerning DA?
DA D2 receptor antagonist properties
What are 6 common pharmacokinetic properties of anti-psychotics?
Significant first pass elimination of oral dose, highly lipid soluble, metabolized in liver by microsomal CYP450’s, duration of action greater in elderly patients, relatively safe (higher therapeutic indices than most classes of CNS agents), high degree of plasma protein binding 92-97% (significant drug interactions)
What are the 4 neurologic side effects of D2 receptor antagonists that occur by disturbing the DA/ACh balance in the basal ganglia?
Acute dystonia (hours-days), akinesia (days-weeks), akathisia “constant restlessness/Parkinsonian like symptoms” (weeks-months) and tardive dyskinesia (months-years)
How do you manage acute symptoms of D2 receptor antagonists?
MCR antagonists
Atypical anti-psychotic
What are 4 endocrinologic side effects of D2 receptor antagonists that are caused by a lesser impact on hypothalamic DA/5HT regulatory balance influencing pituitary hormone secretion?
Decreased HPA axis responsiveness to stress, decreased gonadotropins, decreased growth hormone, increased prolactin (women - galactorrhea/amenorrhea, osteoporosis: men - impotence decreased libido)
How can you lessen the endocrinologic side effects?
Atypical anti-psychotics
What are 2 examples of typical anti-psychotics?
Haloperidol, chlorpromazine
What are 4 examples of atypical anti-psychotics?
Clozapine, olanzepine, risperidone, aripiprazole
What are anti-psychotic induced side effects on MCR, a1, and H1 receptor antagonism in the CNS?
Sedation, cognitive impairments, decreased seizure threshold (clozapine 2-5%), increased appetite/weight gain
What are anti-psychotic induced side effects on MCR and a1 receptor antagonism in the ANS?
Hypotension, tachycardia, dry mouth, constipation, urinary retention, nasal stuffiness, sexual dysfunction
What are anti-psychotic induced metabolic side effects on a1 and H1 receptor antagonism?
Hyperlipidemia, impaired glucose tolerance (leads to diabetes), metabolic syndrome: increased risk of CAD, hypertension, stroke
What is described as late occurring stereotypical oral facial movements, risk factors are: age, gender, renal/CV disease, length of treatment (3% year on haloperidol), treatment: reduce dosage or switch to atypical antipsychotic (clozapine)?
Tardive dyskinesia
What is described as severe muscle rigidity, ANS-CV instability, sweating, hyperrexia, myoglobinurea, treatment: muscle relaxants (dantrolene/diazepam), D2 receptor agonists (bromocriptine), switch to atypicals
Neuroleptic malignant syndrome
What condition can be caused by clozapine, occurs in 1-2% of patients and requires weekly blood counts for 6 months and every third week there after?
Severe agranulocytosis
What are other uses of antipsychotics?
Acute management of manic symptoms, antiemetic, neuroleptic analgesia (haloperidol/fentanyl)
What agents enhance glutamate/ACh release?
Clozapine, olanzepine, risperidone
What antipsychotic is an Antiemetic, low potency antipsychotic – phenothiazines; blocks D2, alpha 1, 5HT 2A, muscarinic, and H1 receptors, used for Psychiatric: schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase), non-psychiatric: antiemetic, hiccups, pre-operative sedation, Atropine-like effects fairly common, contraindicated with excess alcohol consumption, may cause Extrapyramidal (dystonia, akinesia, akathisia, and tardive dyskinesia), anticholinergic (dry mouth, constipation), alpha receptor blockade (hypotension), histamine (sedation); toxicity results in neuroleptic malignant syndrome (rigidity, myoglobinuria, autonomic instability, and hyperpyrexia), H1 receptor blockade, CNS depression, decreased seizure threshold, QT prolongation
Chlorpromazine
What Antipsychotic – butyrophenone; blocks D2, 5HT 2A, and alpha receptors, used for Schizophrenia, psychosis, acute mania, and Tourette syndrome, Extrapyramidal side effects are more common; neuroleptic malignant syndrome is treated with dantrolene and dopamine agonists, may cause Extrapyramidal (dystonia, akinesia, akathisia, and tardive dyskinesia), endocrine (galactorrhea), anticholinergic (dry mouth, constipation), alpha blockade (hypotension), and histamine (sedation); prolonged QT syndrome; toxicity results in neuroleptic malignant syndrome (rigidity, myoglobinuria, autonomic instability, and hyperpyrexia), tardive dyskinesia
Haloperidol
What Atypical antipsychotic – blocks D2, D4, alpha 1, 5HT 2 and muscarinic receptors, is used for Schizophrenia, useful for positive and negative symptom, Second line agent used for refractory schizophrenia; weekly blood counts for patients on this agent due to agranulocytosis, may cause Agranulocytosis, extrapyramidal (occurs at a lower rate than typicals), anticholinergic (dry mouth, constipation), alpha blockade (hypotension), histamine (sedation); toxicity results in neuroleptic malignant syndrome (occurs at a lower rate than typicals), weight gain, hypercholesterolemia?
Clozapine
What is an Atypical antipsychotic – blocks D2, 5HT 2, alpha 1 and HT receptors, used for Schizophrenia, useful for positive and negative symptoms, Second line used for refractory schizophrenia may cause extrapyramidal (occurs at a lower rate than typicals), anticholinergic (occurs at a lower rate than other agents), alpha blockade (hypotension), and histamine (sedation); toxicity results in neuroleptic malignant syndrome (occurs at a lower rate than typicals), hyperprolactinemia
Risperidone
What is an Atypical antipsychotic – 5HT 2 receptor antagonist and a D2 partial agonist that is used for Major depression?
Aripiprazole
