SKELETAL 3 Flashcards
In bipolar affective disorder, although ___ has been the mainstay of treatment for many years, the use of newer antipsychotic agents and of several antiseizure drugs is increasing.
lithium
Receptor, found in the caudate putamen, nucleus accumbens, cerebral cortex, and hypothalamus, is negatively coupled to adenylyl cyclase.
D2 receptor
A drug with significant D4 and 5-HT2 receptor-blocking actions, has virtually no affinity for D2 receptors.
Clozapine
Is an antagonist at the D2, 5-HT2A, and 5-HT1D receptors and an agonist at the 5-HT1A receptor.
Ziprasidone
Is a partial agonist at D2 and 5-HT1A receptors but is a strong antagonist at 5-HT2A receptors.
aripiprazole
Is the major effect that correlates with therapeutic benefit for older antipsychotic drugs.
Dopamine receptor blockade
Dopaminergic tracts in the brain include:
➢mesocortical-mesolimbic pathways:
➢nigrostriatal tract:
➢tuberoinfundibular pathways:
➢chemoreceptor trigger zone:
➢mesocortical-mesolimbic pathways: regulates mentation and mood
➢nigrostriatal tract: extrapyramidal function
➢tuberoinfundibular pathways: control of prolactin release
➢chemoreceptor trigger zone: emesis
Presumably underlies antipsychotic effects
Mesocortical-mesolimbic dopamine receptor blockade
Adverse effects resulting from receptor blockade in the other dopaminergic tracts, a major problem with older antipsychotic drugs
- extrapyramidal dysfunction
- hyperprolactinemia
Antipsychotic drugs reduce some of the POSITIVE SYMPTOMS of schizophrenia, including:
➢Hyperactivity
➢Bizarre ideation
➢Hallucinations
➢Delusions
Is effective in some schizophrenic patients resistant to treatment with other antipsychotic drugs.
Clozapine
Newer atypical drugs are reported to improve some of the NEGATIVE SYMPTOMS of schizophrenia, including:
➢emotional blunting
➢social withdrawal
➢lack of motivation
The newer antipsychotic drugs are often used with lithium in the initial treatment of
mania
Several second-generation drugs are approved for treatment of acute mania; two of these are approved for maintenance treatment of bipolar disorder.
- aripiprazole and
- olanzapine
Is used mainly in Tourette’s syndrome; it is rarely used in schizophrenia.
Molindone
With the exception of ___, most phenothiazines have antiemetic actions; prochlorperazine is promoted solely for this indication.
thioridazine
most often present in short side-chain phenothiazines, provides the basis for their use as antipruritics and sedatives and contributes to their antiemetic effects.
H1-receptor blockade
This toxicity may be reversed by a decrease in dose and may be antagonized by concomitant use of muscarinic blocking agents.
ANTIPSYCHOTIC DRUGS
Extrapyramidal toxicity occurs most frequently with ___ and the more potent piperazine side-chain ___ (eg, fluphenazine, trifluoperazine).
- haloperidol
- phenothiazines
Choreoathetoid movements of the muscles of the lips and buccal cavity and may be irreversible
Tardive dyskinesias
Tend to develop after several years of antipsychotic drug therapy but have appeared as early as 6 mo.
Tardive dyskinesias
Antimuscarinic drugs that usually ameliorate other extrapyramidal effects generally ___ the severity of tardive dyskinesia symptoms
increase
- There is no effective drug treatment for this.
- Switching to clozapine does not exacerbate the condition.
- It may be attenuated temporarily by increasing neuroleptic dosage; this suggests that it may be caused by dopamine receptor sensitization.
Tardive dyskinesias
older antipsychotic agents, ___ has the strongest autonomic effects and the weakest.
- thioridazine
- haloperidol
and most of the atypical drugs have intermediate autonomic effects.
Clozapine
Regarding muscarinic receptor blockade, atropine-like effects (dry mouth, constipation, urinary retention, and visual problems) are often pronounced with the use of ___. These effects also occur with clozapine and most of the atypical drugs but not with ziprasidone or aripiprazole.
thioridazine and phenothiazines with aliphatic side chains (eg, chlorpromazine)
Regarding α-receptor blockade, postural hypotension caused by α blockade is a common manifestation of many of the older drugs, especially ____. Failure to ejaculate is common in men treated with this.
phenothiazines
The atypical drugs, especially clozapine and ziprasidone, also block α receptors and can cause ____.
orthostatic hypotension
Toxicities due to a diabetogenic action occur with several of the atypical agents, especially clozapine and olanzapine. These effects may be especially problematic in pregnancy.
Significant weight gain and hyperglycemia
Fluphenazine and haloperidol are the ___ sedating of the older drugs; ___ appears to be the least sedating of the newer agents.
- least
- aripiprazole
Visual impairment caused by retinal deposits has occurred with ____; at high doses, this drug may also cause severe conduction defects in the heart resulting in fatal ventricular arrhythmias.
thioridazine
Causes a small but important (1–2%) incidence of agranulocytosis and at high doses has caused seizures.
Clozapine
This drug (and possibly ziprasidone) overdose, because of cardiotoxicity, is more difficult to treat.
Thioridazine
Is effective in treatment of the manic phase of bipolar disorder and continues to be used for acute-phase illness and for prevention of recurrent manic and depressive episodes.
Lithium
Increase the renal clearance of lithium.
Caffeine and theophylline
Are both approved as monotherapy for acute mania.
- Olanzapine and
- quetiapine
Edema is a common adverse effect of___; acneiform skin eruptions occur; and leukocytosis is always present.
lithium therapy
The use of lithium during pregnancy is thought to increase the incidence of
congenital cardiac anomalies (Ebstein’s anomaly)
has antimanic effects equivalent to those of lithium and is now widely used in the Unites States for this indication, often as a first choice in acute illness.
Valproic acid
Concerning hypotheses for the pathophysiologic basis of schizophrenia, which statement is accurate?
(A) All clinically effective antipsychotic drugs have high affinity for dopamine D2 receptors
(B) Dopamine receptor-blocking drugs are used to alleviate psychotic symptoms in parkinsonism
(C) Drug-induced psychosis can occur without activation of brain dopamine receptors
(D) Serotonin receptors are present at lower than normal levels in the brains of untreated schizophrenics
(E) The clinical potency of clozap
Drug-induced psychosis can occur without activation of brain dopamine receptors
Which statement concerning the adverse effects of antipsychotic drugs is accurate?
(A) Acute dystonic reactions occur very infrequently with olanzapine
(B) Akathisias due to antipsychotic drugs are managed by increasing the drug dose
(C) Blurring of vision and urinary retention are common adverse effects of haloperidol
(D) Retinal pigmentation is a dose-dependent toxic effect of clozapine
(E) The late-occurring choreoathetoid movements caused by conventional antipsychotic drugs are alleviated by atropine
Acute dystonic reactions occur very infrequently with olanzapine
Haloperidol is not an appropriate drug for management of
The amenorrhea-galactorrhea syndrome
Which statement concerning the use of lithium in the treatment of bipolar affective disorder is accurate?
(A) Excessive intake of sodium chloride enhances the toxicity of lithium
(B) Lithium alleviates the manic phase of bipolar disorder within 12 h
(C) Lithium dosage may need to be decreased in patients taking thiazides
(D) Since lithium does not cross the placental barrier, it is quite safe in pregnancy
(E) The elimination rate of lithium is equivalent to that of creatinine
Lithium dosage may need to be decreased in patients taking
thiazides
