Antipsychotic Agents Flashcards
What are the positive symptoms of Schizophrenia?
(1) hallucinations
(2) delusions
(3) aggressive behaviors
What are the negative symptoms of Schizophrenia?
(1) lack of speech or emotional expression
(2) social withdrawal
What are the cognitive symptoms of Schizophrenia?
(1) Difficulties with concentration and memory
(2) Executive decision making abilities
What is the prevalence of Schizophrenia? When does it present?
- 1% of population over 18 years old
- typically presents in early adulthood or late adolescence
T/F Schizophrenia has a weak genetic component.
FALSE; strong genetic component (identical twin 48% concurrence rate; fraternal 17%, parent 10%) with multiple genes involved
What is the cost to society for Schizophrenia?
Large, >$65 billion overall/year, 1/3 mental health beds used
What is the suicide risk for Schizophrenia? Amount homeless?
- High suicide risk, 25-50% of patients attempt suicide, and 5-10% succeed; mortality rate higher than the general population
- 1/3 homeless are Schizophrenic (200,000 people)
T/F Schizophrenia is one of the most challenging diseases in terms of drug compliance.
TRUE
What is the relapse rate with drug compliant patients? How many are non-compliant?
20-40% relapse rate; >80% non-compliant
T/F The shorter the first untreated period, the worse the outcome.
FALSE; the longer the first untreated period, the worse the outcome
What is the first antipsychotic drug? What is its mechanism of action?
Chlorpromazine; sedative
Does Chlorpromazine treat positive symptoms, negative symptoms, cognitive symptoms?
Preferentially treats psychotic symptoms (especially positive symptoms) while leaving patients relatively conscious (leaves alone the negative symptoms)
T/F Chlorpromazine is more sedating that newer atypical antipsychotic drugs.
TRUE
What are the classifications of TYPICAL antipsychotics?
(1) Phenotiazines: Chlorpromazine
(2) Butyrophenones: Haloperidol
What is the mechanism of action for TYPICAL antipsychotics?
(1) Blocking dopamine receptors (especially D2) in mesocortical and mesolimbic pathways
What is the dopamine hypothesis?
(1) Both amphetamine and cocaine blocks reuptake of dopamine and foster psychotic symptoms
(2) Antipsychotics block dopamine D2 receptors
T/F Clinical properties of antipsychotic drugs correlate well with affinities of D1 and D2 receptors. (typical antipsychotics)
FALSE; D2 and not D1
What is HAMS referring to regarding typical antipsychotics?
- Histamine, alpha-1 adrenergic, muscarinic-cholinergic, and serotonin
- Typical antipsychotics have affinities for these receptors as well (they have their own unique receptor binding profile)
What are common problems concerning TYPICAl antipsychotics? (3)
(1) Persistent symptoms in ~30% of patients (“treatment refractory”)
(2) Only modest improvement of negative cognitive symptoms
(3) Side effects include extrapyramidal symptoms (EPS) and Hyperprolaceinemia due to D2 blockade in tuberoinfundibular system
T/F Drugs such as Haloperidol produce EPS which causes a drug-induced Parkinsonism.
TRUE
How are ATYPICAL antipsychotics defined? How are they pharmacologically characteried?
- defined by reduced tendency to cause EPS (and hyperprolactinemia)
- Pharmacologically characteried by
~ relatively weak D2 receptor blocking activity
~ serotonin 2A (5-HT2A) receptor antagonism
What is a more common side effect of ATYPICAL antipsychotics?
Metabolic syndrome (weight gain, hyperlipidemia, hyperglycemia)
What are the atypical antipsychotic drugs? (5)
(1) Apripiprazole
(2) Ziprasidone
(3) Olanzapine
(4) Risperidone
(5) Clozapine
What is the selection of antipsychotics based upon?
Anticipated side effects rather than therapeutic expectancy (+ or - symptoms)
What is the time course for antipsychotics?
from 48 hours for some acute symptoms to several weeks for hospitalized patients
What are antipsychotics also indicated for?
(1) Schizoaffective disorder
(2) Manic phase in bipolar disorder
(3) Tourette’s syndrome
(4) Huntington’s disease
(5) autistic disorders
What are the 3 effects of EPS?
(1) Parkinsonism
(2) Tardive Dyskinesia
(3) Neuroleptic Malignant Syndrome
T/F Treatment for EPS Parkinsonism includes L-DOPA.
FALSE; never should L-DOPA be used; you will use anti-muscarinic drugs (benztropine)
T/F There is no adequate treatment for Tardive dyskinesia.
TRUE
What is Tardive dyskinesia?
- Stereotyped, repetitive involuntary, choreoathetoid movements of the face, eyelids, mouth, tongue, extremities, trunk
- can be irreversible in adults, most important problem with long term use (20-50%)
What is the treatment for Neuroleptic malignant syndrome? Is this life threatening?
- Immediate discontinuation of the drug
- dopamine receptor agonist (bromocriptine) and muscle relaxant (diazepam or dantrolene)
- Yes
- symptoms include fever, muscle rigidity, leukocytosis, autonomic instability
Why does Chlorpromazine have many side effects?
(especially autonomic)
- due to relatively high muscarinic and alpha-1 adrenergic receptor blocking activity
- highly sedative
Does Haloperidol have more or less autonomic side effects?
LESS; sever EPS and hyperprolactinemia
Which drug is the most efficacious among the antipsychotics? When is this drug used?
Clozapine; only used for patients resistant to typical antipsychotics
What are the side effects of Clozapine?
- 1-2% of patients develop agranulocytosis
- weight gain, sedation, hyperlipedemia, lowering seizure threshold
T/F Strict blood monitoring is necessary for Clozapine?
TRUE, because of the agranulocytosis
What drugs are widely regarded as the second most effective atypical antispsychotic drugs? What are their mechanism of action?
(1) Olanzapine- relatively strong histamine receptor antagonism (H1)
(2) Risperidone- most potent D2 receptor blocker; much less potent anti-muscarinic activity
T/F Apripirazole is associated with EPS and hyperprolactinemia at higher doses.
FALSE; Risperidone is because it is a D2 blocker
What drugs lower seizing threshold?
(1) Olanzapine
(2) Clozapine
Which drug is structurally similar to clozapine?
Quetiapine (strong H1 receptor antagonism)
- associated with weight gain, sedation
Which drug is minimally sedating? What is it’s mechanism of action?
Aripiprazole; partial D2 agonist (high affinity for D2 receptors but has ~30% of intrinsic activity of dopamine)
- 5-HT2A antagonist
What does Ziprasidone do? What does it have a low affinity to?
- prolonges QTc interaval (not indicated for patients with heart problems)
- low affinity for muscarinic, alpha-1 and H1 receptors (less sedation, less postural hypotension, less weight gain)
