Antipsychotics Flashcards
Schizophrenia
schizo- divided phrenos- mind Impaired perception of reality social and/or occupational dysfuntion Disorganized thinking Delusions and sometimes hallucinations
Schizophrenia Symptoms
Positive: Delusions- false personal beliefs that are not subject to reason, Hallucinations- perceptions that occur without connection to appropriate source, Disorganized speech, grossly disorganized or catatonic behavior, Thought disorder- disruptions of the norml flow of thoughts throughout the day, disorganized thinking
Negative: Emotional Flatness, lack of expression, inability to start and follow through with an activity, brief speech phrases that lack content
Antipsychotics- Indication
Acute and maintenance treatment of schizophrenia
Psychosis associated with acute mania and depression
Adjunctive treatment for agitation due to psychiatric conditions, delirium, tremors and dementia
Psychosis from any number of medical causes
Typical Antipsychotic
Primarily Dopamine2 receptor antagonist
Atypical Antipsychotic
Block both dopamine and serotonin receptors
Atypical (3rd gen) Antipsychotic
Partial agonist for Dopamine d2 and 5-HT1a, antagonist at 5-HT2a
Abilify
Partial agonist may actually modulate dopamine activity in areas where it might be high or low, superior to simply blocking
Antipsychotic Pharmacology
Central blockade of dopamine receptors
limbic areas–> antipsychotic effects
basal ganglia –> extrapyramidal side effects
brainstem chemoreceptors –> antinausea and antiemetic effects
hypothalamus–> block dopamine inhibition of anterior pituitary prolactin release –> increased prolacting
Pharmacology Typicals (General)
Peak levels in 1-4 hours, half lives for 8-36 hours
Metabolized by liver
Most have active metabolites
Have limited oral bioavailability but IM injection can result in 2-3 times higher blood levels
Both low and high potency drug exist
Low- require relatively larger doses, more likely to produce sedation, hypotension, and anticholinergic effects
Typicals Delay
Delay in clinical efficacy that could lead to non-compliance and relapse
D2 blockade not sufficient
Initial response, presynaptic blockade that leads to increase in dopamine
Tolerance to presynaptic effects allows postsynaptic blockage to be more effective
Typicals
Decades of new experience with these agents
- New and serious side effects are being discovered with the 2nd generation atypical drug
Availability of long acting decanoate preparations of haloperidol and fluphenazine
Much less expensive and well tolerated
Typicals Side effects
Anticholinergic- Dry mouth, blurred vision, Constipation, Memory and concentration difficulties
Alpha-adrenergic blockade- Hypothension
Antihistaminergic Side effects- Sedation, drowsiness, weight gain
Akathisa- Subjective or observable restlessness, persists until dose is lowered
Tardive dyskinesia- Syndrome of abnormal involuntary movements
Atypicals
Fewer extrapyramidal side effects, increased compliance, fewer relapses
Can be more effective for first break patients
Recommended to elderly patients- more at risk for hypotension and tachycardia
Treat both positive and negative symptoms
Risperidone- Atypical 2nd
Injectable
extended release microspheres
Provides long acting coverage, deep intramuscular injection every 2 weeks
Negative Symptoms Typicals vs Atypicals
negative symptoms due to dopamine hypofunction in the cortex
Typicals not effective for negative symptoms
Atypicals have great affinity for blocking serotonin receptors than for dopamine
This indirectly increases DA levels in cortex, blocks psychotic effects of excess DA in limbic system
Mechanism of Action Atypicals
Antagonism of 5-HT receptors also increases glutamate levels in cortex
Blockade of NMDA glutamate can produce hallucinations- glutamate- NMDA hypofunction model of schizophrenia
NMDA hypofunction leads to excess release of glutamate in frontal cortex, damaging cortical neurons leading to schizophrenia
Hyperdomamine activity lead to positive symptoms and glutamate leads to negative symptoms
