Psychopharmacology Flashcards

Question

``` Which of the following is not a symptom of benzodiazepine withdrawal? A. Hallucinations B. Tremor C. Depression D. Tinnitus E. Depersonalization ```

Answer 1

A. Hallucinations Answer: A. Tremor, depression, tinnitus, depersonalization, insomnia, fatigue, sweating, concentration difficulties, increased sensory perception, and a sensation of movement or abnormal sway are features of benzodiazepine withdrawal. Psychotic symptoms are not classically seen.

Answer 2

B. Cimetidine Answer: B. Cimetidine inhibits hepatic enzymes and hence raises the level of many drugs, including benzodiazepines. The other drugs listed are enzyme inducers and hence increase metabolism.

Answer 3

D. Absent arms and legs Answer: D. Absent arms and legs is a teratogenic effect of thalidomide. Cleft lip and palate, respiratory depression, and withdrawal symptoms have been reported in children born to mothers taking benzodiazepines, but in general, their use in pregnancy is relatively safe if clinical issues outweigh the risks.

Answer 4

C. REM sleep rebound Answer: C. Benzodiazepines suppress REM sleep and stage 4 sleep. With chronic use, tolerance develops to this effect and after 2 weeks of continuous use, the total amount of REM sleep returns to normal. On withdrawal, the normal physiologic drive to induce REM sleep is unmasked and thus a rebound REM occurs.

Answer 5

B. 2-3 weeks Answer: B. Tolerance is defined as the need to use larger doses to achieve the same effects with repeated administration. Tolerance to the sedative effects may begin within days and is usually pronounced by 2 to 3 weeks. Tolerance to the anticonvulsant effects also occurs rapidly, and hence benzodiazepines cannot be used in seizure prophylaxis.

Answer 6

D. Alcohol Answer: D. Cross-tolerance occurs with other benzodiazepines, barbiturates, and alcohol, probably because of the proximity of their sites of action at the GABA benzodiazepine complex.

Answer 7

C. It is more likely in patients with passive and dependent personality traits. Answer: C. People with passive and dependent personality traits are more likely to develop withdrawal symptoms. Withdrawal symptoms are more prominent with longer duration of treatment and with the use of substances with a short half-life. Symptoms emerge within a few days of discontinuation of medication and may last for as long as 1 to 2 weeks.

Answer 8

A. Ebstein's anomaly Answer: A. Lithium administration during pregnancy is associated with Ebstein's anomaly. Anticonvulsants cause fetal craniofacial and neural tube defects.

Answer 9

B. Carbamazepine Answer: B. Carbamazepine can produce ataxia at therapeutic doses. Imipramine, pimozide, chlorpromazine, and fluoxetine do not typically produce ataxia.

Answer 10

D. Poor sleep with excess worry Answer: D. Poor sleep and excess worry can be features of benzodiazepine withdrawal but are more likely to be symptoms of anxiety. Hyperawareness of senses, abnormal body sensations, dysphoria, and metallic taste in the mouth are all symptoms of benzodiazepine withdrawal

Answer 11

E. They affect the reticular activating system. Answer: E. Wakefulness and sleep are mediated by the reticular activating system and other midbrain structures, particularly the locus caeruleus. Benzodiazepines act by modulating these parts of the brain. They do not block the reuptake of amines, nor do they inhibit monoamine oxidase. They have minimal effects on the cardiovascular system.

Answer 12

C. Acute dystonia Answer: C. Acute dystonia is a side effect of conventional antipsychotic agents. Benzodiazepines do not cause dystonia and may occasionally be useful to relieve it. Ataxia, drowsiness, and paradoxical aggression may be seen with the use of benzodiazepines. On occasion, a confusional state may be seen, especially in the elderly.

Answer 13

E. Their effects are antagonized by naloxone. Answer: E. The effects of benzodiazepines are antagonized by flumazenil, which is a benzodiazepine receptor antagonist. Benzodiazepines act on the GABA-A receptor. They produce hangover effects depending on the dose and half-life of the drug. They increase the flow of chloride ions into the neurons, which results in hyperpolarization of the cells. They are used to abort seizures; however, they cannot be used as prophylaxis for seizures because tolerance develops rapidly.

Answer 14

B. Diazepam Answer: B. All of the products listed except diazepam can cause tremors. Diazepam is used to treat tremors.

Answer 15

D. They potentiate the pressor effect of norepinephrine. Answer: D. Tricyclic antidepressants potentiate the pressor effects of norepinephrine. It has been suggested that tricyclic antidepressants given to patients who, following a myocardial infarction, may increase the risk of sudden death. They should be avoided in patients with glaucoma not cataract. Concurrent administration of antipsychotic drugs actually increases the effect of the tricyclic antidepressants and antipsychotics.

Answer 16

E. Diarrhea Answer: E. Tricyclic antidepressants have anticholinergic side effects, including dry mouth, urinary hesitancy, delirium, and constipation not diarrhea. Paralytic ileus may occasionally occur. Desipramine and nortryptiline have lower incidence of anticholinergic side effects.

Answer 17

D. Xerostomia Answer: D. Xerostomia or dry mouth is an anticholinergic side effect of tricyclic antidepressants. They can worsen glaucoma, cause hypotension, and result in the healing of gastric ulcers because of their anticholinergic effects. They do not have effects on the thyroid.

Answer 18

B. Nortryptiline Answer: B. Nortryptiline is the only tricyclic antidepressant that has consistently been shown to have an effective therapeutic window. The levels of some other tricyclics can be measured, but their usefulness is doubtful.

Answer 19

B. Antiarrhythmia drugs should be used routinely. Answer: B. Antiarrhythmia drugs are not used routinely following an overdose. Cardiotoxicity is the most common cause of death. Seizures and CNS depression can occur. The greatest number of deaths has occurred with amitriptyline, but the highest fatality rate is for desipramine.

Answer 20

C. Previous myocardial infarction 2 years ago Answer: C. A previous myocardial infarction 2 years ago does not automatically constitute a contraindication to the use of tricyclics. Glaucoma, heart block, prostatic hypertrophy, and cardiac arrhythmias can all be worsened by tricyclic antidepressants, which are therefore contraindicated.

Answer 21

B. Desipramine Answer: B. Desipramine, nortryptiline, and protryptiline are secondary amines. Amitriptyline, clomipramine, doxepine, imipramine, and trimipramine are tertiary amines. Amoxapine and maprotiline are tetracyclics.

Answer 22

C. Down-regulation of beta-adrenergic receptors Answer: C. One of the primary efforts of tricyclic antidepressants is the down-regulation of beta-adrenergic receptors with continued use. There is a decrease in 5-HT2 activity and cyclic AMP activity. There is blockade of histamine H1 receptors not H2 receptors.

Answer 23

D. Depression in inpatients with melancholic depression Answer: D. The strongest correlation between blood concentration monitoring and response to tricyclic antidepressants is seen in patients with severe depression with melancholic features.

Answer 24

B. Amitriptyline Answer: B. Amitriptyline has the most anticholinergic effects; desipramine has the least effect. Nortryptiline has the least effect on orthostatic hypotension.

Answer 25

D. Amitriptyline Answer: D. Amitriptyline is the most effective antidepressant to treat chronic pain.

Answer 26

C. Nortryptiline Answer: C. Nortryptiline has the least effect on orthostatic hypotension. It is most likely in patients who have preexisting orthostatic hypotension, and the elderly are particularly vulnerable.

Answer 27

E. Desipramine Answer: E. Desipramine is the most lethal tricyclic in overdose; however, most tricyclic overdose deaths occur with amitryptiline.

Answer 28

C. 50-150 ng per ml Answer: C. Therapeutic window is an optimal range of plasma concentration for a drug. The utility of this is most established for nortryptiline and is between 50-150 ng per ml.

Answer 29

B. Phenelzine Answer: B. The patient here presents with features of atypical depression. This has been shown to respond best to MAOIs.

Answer 30

E. Inhibition of MAO-B Answer: E. Changes in several presynaptic and postsynaptic receptors follow the increase in concentration of the amines and neurotransmitters caused by MAOIs. Down regulation of beta, alpha-adrenergic, 5-HT2, and tryptamine receptors occurs after long-term administration of MAOIs. Monoamine oxidase has two isoenzyme forms, MAO-A and MAO-B. They metabolize different neurotransmitters. Serotonin and norepinephrine are preferred substrates for the A form, dopamine is a substrate for both A and B, and phenylethylamine is metabolized by the B isoenzyme. MAOIs primary inhibit MAO-A.

Answer 31

C. Tyramine Answer: C. Tyramine, as substrate of MAO is present in certain fermented foodstuffs like red wine, cheese, yeast extracts, pickled fish, etc. Patients being treated with MAO inhibitors are unable to deaminate tyramine, normally broken down by MAO-A in the gut. This results in the displacement of intracellular stores of norepinephrine and can cause a pressor response resulting in hypertensive crisis or “cheese reaction.”

Answer 32

B. Banana Answer: B. Banana does not cause a hypertensive crisis with MAOIs, although the skin of a banana can.

Answer 33

E. Serotonin syndrome Answer: E. The symptoms described are typical of serotonin syndrome. The drug that the patient started taking recently for her migraines is sumatriptan. The combination of phenelzine and sumatriptan can cause serotonin syndrome. This syndrome can also occur if phenelzine is combined with SSRIs. Hence, when switching from MAOIs to SSRIs and tricyclics or vice versa, a minimum of 2 weeks “washout” period is required for drug clearance.

Answer 34

D. Fluoxetine Answer: D. When switching from SSRI to MAOI, a washout period of 5 weeks is recommended for fluoxetine because of its long half-life.

Answer 35

E. Alopecia Answer: E. Alopecia is not a side effect of MAOIs. MAOIs can precipitate manic episodes in patients with a history of bipolar disorder. They can cause blurred vision. They also lower the seizure threshold. A peripheral neuropathy resulting from pyridoxine deficiency can occur with phenelzine. A discontinuation syndrome may be seen on sudden cessation of MAOIs.

Answer 36

B. NSAIDs Answer: B. MAOIs do not interact with NSAIDs. Cough medicines, nasal decongestants, bronchodilators, appetite suppressants, and levodopa (L-dopa) can lead to a sympathomimetic crisis in conjunction with MAOIs. Clomipramine can cause serotonin syndrome. MAOIs potentiate the pharmacologic action of opiates. Their coadministration can lead to a severe toxic syndrome characterized by excitement, muscular rigidity, hyperpyrexia, flushing, hypotension, respiratory depression, and coma.

Answer 37

C. Pheochromocytoma Answer: C. A pheochromocytoma that secretes catecholamines would augment a sympathomimetic crisis. Concurrent use of tricyclic antidepressants is safe if it is monitored closely. MAOIs can be used in cardiac failure. They can also be used in asthma. Some of the hypertensive reactions may be treated with nifedipine, but they must be monitored because hypotension is a known side effect of MAOIs.

Answer 38

B. It blocks alpha-2 auto receptors. Answer: B. Mirtazapine acts by blocking presynaptic alpha-2 adrenergic autoreceptors, leading to an increase in the release of norepinephrine. Mirtazapine is also a potent antagonist of H1 receptors, which explains its somnolence-inducing effects. Mirtazapine reduces REM sleep, increases REM sleep latency, and improves deep sleep. It also causes increased appetite and weight gain. There are also reports of agranulocytosis with mirtazapine.

Answer 39

D. Priapism Answer: D. Priapism is not associated with nefazodone. It is associated with trazodone. All of the other mentioned effects can be caused by nefazodone.

Answer 40

C. Animal phobia Answer: C. Animal phobias typically respond to behavioral therapies.

Answer 41

D. Acetaminophen Answer: D. Of the drugs listed in the answer choices, only acetaminophen has no reaction when used in combination with MAOIs.

Answer 42

C. Fluvoxamine Answer: C. The half-life of fluvoxamine is about 15 hours. Fluoxetine has a half-life of about 4 to 6 days. Paroxetine about 21 hours, sertraline about 26 hours, and citalopram has a half-life of 35 hours.

Answer 43

C. 7 days Answer: C. Citalopram takes about 7 days to achieve steady state. Fluoxetine takes about 28 days, fluvoxamine about 5 to 7 days, paroxetine about 5 to 10 days, and sertraline about 7 days.

Answer 44

B. Long-term use results in reduced 5-HT function. Answer: B. Long-term use of SSRIs results in reduced 5-HT2 functions. The time to peak plasma levels varies from 4 hours for citalopram to 6 to 8 hours for fluoxetine. SSRIs are safe in patients with a history of cardiac disease.

Answer 45

D. Cardiac arrhythmias Answer: D. SSRIs are the safest antidepressants in patients with cardiac disease. They do not cause arrhythmias. They can cause diarrhea or constipation. They also have variable effects on the appetite. They can cause tremors.

Answer 46

B. Anorgasmia Answer: B. Anorgasmia, delayed ejaculation, and impotence have been reported with SSRIs. In fact some SSRIs may be used in the treatment of premature ejaculation. SSRIs do not have significant effects on blood pressure. They can cause clinically insignificant slowing of the heart rate. They do not cause alopecia or dry mouth.

Answer 47

E. Premature ejaculation Answer: E. SSRIs do not cause premature ejaculation. They cause delayed ejaculation. They are, however, responsible for nausea, convulsions, agitation, akathisia, dystonia, orolingual dyskinesia, and worsening of neuroleptic-induced parkinsonism.

Answer 48

D. There is very little data on SSRIs and breastfeeding. Answer: D. Sertraline is the most lethal SSRI in overdose. A washout period of 2 weeks should be observed for all SSRIs when switching to MAOIs except for fluoxetine, for which a 4-week washout period should be observed.

Answer 49

C. Paroxetine Answer: C. Paroxetine is most frequently associated with discontinuation on abrupt cessation. It is hence recommended that it be gradually tapered and withdrawn.

Answer 50

E. Inhibition of hepatic cytochrome P-450 isoenzyme Answer: E. The main difference that would be important in choosing among the different SSRIs would be their action on the P-450 isoenzyme. The other considerations would be less important because the clinical implications would be lower. Citalopram is the most selective inhibitor of 5-HT reuptake and paroxetine the most potent. In contrast to the tricyclic antidepressants, they have very little affinity for different types of adrenoceptor, muscarinic, and dopamine receptors.

Answer 51

B. Nausea Answer: B. The most common adverse effects reported with SSRIs are gastrointestinal in nature, with nausea being the most common.

Answer 52

C. Paroxetine Answer: C. All SSRIs can cause delayed ejaculations, and fluoxetine, paroxetine, and sertraline have been studied as a treatment for premature ejaculation. However paroxetine is most likely to cause delayed ejaculation.

Answer 53

A. Fluoxetine Answer: A. Abrupt discontinuation of fluoxetine is least likely to cause a discontinuation syndrome by virtue of its long half-life.

Answer 54

C. Alpha-adrenergic receptors Answer: C. Trazodone has antagonistic actions at peripheral alphaadrenergic receptors. This blockade accounts for adverse effects like orthostatic hypertension, dry mouth, and priapism. Trazodone also has significant antagonistic activity at 5-HT2A receptors. Chronic administration of trazodone down regulates 5-HT2 receptors causing a decrease in the number of receptor binding sites in the central nervous system. Trazodone has very little affinity for muscarinic, histamine, dopamine, and norepinephrine receptors.

Answer 55

D. Seizures Answer: D. Trazodone is not known to lower the seizure threshold.

Answer 56

C. Its use results in reduction of criminal activity. Answer: C. Methadone has been shown to reduce illicit drug use and criminality and increase employment in a number of studies. Methadone is typically given once a day. It blocks the euphoriant effects of heroin and acts as pure agonists at the mu-receptors.

Answer 57

D. Respiratory depression Answer: D. Methadone can cause respiratory depression. It causes hypotension, constipation, bradycardia, miosis, and hypothermia.

Answer 58

B. Chronic persistent hepatitis Answer: B. Risk of overdose is greatest during induction into maintenance treatment, prior to the development of tolerance. Death typically occurs 2 to 6 days after initiation of treatment. Chronic persistent hepatitis is often found in post-mortem examination suggesting that decreased methadone elimination may contribute to overdose in causing death.

Answer 59

D. Prolonged QT interval Answer: D. LAAM is associated with prolonged QT interval.

Answer 60

E. Erythromycin Answer: E. Erythromycin inhibits hepatic enzymes. All of the other mentioned drugs are hepatic enzyme inducers. The rate of metabolism increases, which would necessitate an increase in the dose.

Answer 61

B. Kidneys Answer: B. Lithium is not bound to plasma protein, is not metabolized, and is excreted unchanged solely by the kidney. It passes freely through the glomerular membrane. This is independent of serum concentration. Renal lithium clearance is relatively constant for each individual, but is proportional to glomerular filtration as measured by creatinine clearance. If creatinine clearance decreases lithium excretion will be reduced and serum lithium levels will rise. Sodium is required for renal lithium excretion. When sodium is depleted, lithium renal clearance is reduced, risking toxic serum levels of lithium.

Answer 62

C. Lithium Answer: C. Lithium is the only drug that has been shown to decrease mortality in patients with bipolar disorder. Clozapine has been shown to reduce mortality in patients with schizophrenia.

Answer 63

D. Episode pattern of mania, depression, euthymia Answer: D. An episode pattern of mania-depression-euthymia is associated with good response to treatment. Rapid cycling and mixed states respond better to carbamazepine and valproate. Comorbid substance use and atypical bipolar illness do not respond well to lithium. Other good prognostic factors are a good previous response to lithium, pure bipolar illness, and a family history of bipolar disorders. Poor prognostic factors include paranoid features and poor social support.

Answer 64

D. Obsessive-compulsive disorder Answer: D. Lithium is not used in the treatment of obsessive-compulsive disorder. It can be used in bipolar disorder, depression, schizoaffective disorder, and aggression and mood swings in patients with mental retardation.

Answer 65

B. Aphasia Answer: B. Lithium can cause dysarthria, especially in toxic doses. It does not, however, cause aphasia. Lithium causes a fine tremor. It may be alleviated by beta-blockers like propranolol. It can cause T-wave flattening and inversion on the ECG in about 30% of patients. This is benign and reversible. Lithium can also cause peripheral neuropathy.

Answer 66

E. Coarse tremor Answer: E. The presence of coarse tremors is highly suggestive of lithium toxicity. Other signs of toxicity are vomiting, diarrhea, dysarthria, ataxia, lassitude, restlessness, agitation, and seizures. Hemodialysis is the most effective treatment for lithium toxicity. Hypothyroidism, weight gain, polyuria, and exacerbation of psoriasis are side effects seen at therapeutic doses.

Answer 67

C. Hemodialysis Answer: C. Treatment of lithium toxicity involves supportive measures. Frequent determinations of lithium levels are useful to monitor progress. If renal function is unimpaired, it is normally only necessary to increase fluid intake. Increasing lithium renal excretion by saline infusion or osmotic diuresis can also be helpful. In severe intoxication, the most effective treatment is hemodialysis.

Answer 68

D. Hypertension Answer: D. Lithium does not cause hypertension. It causes all the other cardiac changes mentioned.

Answer 69

E. High-salt diet Answer: E. Lithium intoxication can be precipitated by dehydration, reduced renal clearance, or by drug interactions, such as with thiazide diuretics. Renal lithium elimination will be impaired by medical illness associated with pyrexia, vomiting, or diarrhea and reduced sodium intake. Adequate sodium levels are necessary for sodium excretion. In severe sodium deficiency states, lithium begins to be reabsorbed from the distal portions of the tubules. This elevates serum lithium levels, which in turn inhibit sodium reabsorption by inhibiting aldosterone.

Answer 70

D. Neutropenia Answer: D. Lithium can cause leukocytosis, which has no clinical relevance. Lithium can cause hypothyroidism and hyperthyroidism although hypothyroidism is more common. It can result in raised serum parathormone levels. The resulting elevation in serum calcium and parathyroid hormone is usually transient. It can cause erectile dysfunction.

Answer 71

C. Aspirin Answer: C. Aspirin, acetaminophen, and sulindac are safe with lithium. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis, which may reduce renal clearance of lithium and thus elevate plasma levels of lithium. This effect has been reported for indomethacin, ibuprofen, phenylbutazone, diclofenac, and piroxicam. Careful monitoring is needed for patients on lithium when they are started on NSAIDs, especially those who rely on prostaglandins to maintain optimal renal function, like the elderly and those in cardiac failure.

Answer 72

A. Alpha-1 Answer: A. Orthostatic hypertension is caused by blockade of alpha-1 adrenergic receptors. The elderly are at particular risk for development of orthostatic hypotension. Treatment includes drinking at least 2 liters of fluid per day, adding salt to food, reassessing the dosages of any antihypertensive medication, and wearing support hose.

Answer 73

C. NaC1 should be avoided. Answer: C. Sodium chloride may be needed in lithium toxicity if it is due to sodium depletion.

Answer 74

D. Rapid-cycling mania D. Carbamazepine is indicated for mixed mania and rapid-cycling bipolar disorder. Good response to lithium, family history of bipolar affective disorder, and bipolar I disorder are predictors of good response to lithium.

Answer 75

B. Marked cognitive decline Answer: B. Carbamazepine causes dizziness, diplopia, ataxia, sedation, confusion, dry mouth, hyponatraemia, abnormal liver function tests, rashes, leucopenia, thrombocytopenia, agranulocytosis, and aplastic anemia. It does not cause marked cognitive decline.

Answer 76

B. Hypernatremia Answer: B. Carbamazepine is associated with hyponatremia and sometimes causes water intoxication. The retention of water and dilutional hyponatremia is opposite to the effect of lithium and is an alternative to lithium for patients with severe diabetes insipidus. Patients on high doses of carbamazepine and the elderly are more prone to hyponatremia. Thrombocytopenia and leucopenia are recognized side effects of carbamazepine. If these symptoms appear, the drug needs to be discontinued. Carbamazepine can increase total cholesterol, but this is largely by increasing HDL and hence is unlikely to have deleterious consequences on the cardiovascular system.

Answer 77

A. Concurrent therapy with SSRIs Answer: A. Carbamazepine is contraindicated in patients with a history of bone marrow suppression, narrow-angle glaucoma, or hypersensitivity to tricyclic compounds. It should also be avoided in patients on MAOIs. A 2-week lag period should be observed between stopping an MAOI and starting carbamazepine.

Answer 78

D. Phenytoin Answer: D. Administration of phenytoin, phenobarbital, theophyllines, or valproate concurrently with carbamazepine can cause decreased carbamazepine plasma concentrations. All the other drugs mentioned increase carbamazepine plasma concentration.

Answer 79

D. GABA Answer: D. Valproate inhibits the catabolism of GABA, decreases GABA turnover, increases GABA type B receptor density, and increases the release of GABA. It hence acts primarily by potentiation of central nervous system GABA function.

Answer 80

B. Pure mania Answer: B. Pure mania is a predictor of good response to lithium. All the other conditions have been shown to be predictors of good response to valproate.

Answer 81

E. A 36-year-old man with bipolar I and good response to lithium Answer: E. In a healthy young male with bipolar disorder and good response to lithium, it is best to continue with lithium. Patients with partial response to lithium might respond well to valproate, likewise for rapidcycling mania. Comorbid head trauma and seizure disorder would also predict a good response to valproate.

Answer 82

C. Thrombocytosis Answer: C. Valproate causes thrombocytopenia not thrombocytosis. This is usually reversible. It also causes platelet dysfunction, coagulation disturbances, and agranulocytosis, though these are rare.

Answer 83

B. Phenytoin Answer: B. The serum concentration of phenytoin is decreased by valproate. Amitriptyline and fluoxetine may increase valproate concentrations. Valproate increases the serum concentration of phenobarbital and causes increased sedation. Serum concentration of diazepam is increased by valproate. These effects are mainly due to competition at protein binding sites.

Answer 84

D. Renal failure Answer: D. Valproate does not typically cause renal failure. It does however cause acute pancreatitis and weight gain. Valproate associated hepatotoxicity is an idiosyncratic reaction and is not related to the dosage. The risk factors for hepatotoxicity are young age, use of multiple antiepileptic drugs, and the presence of developmental delay or a metabolic disorder.

Answer 85

C. Bupropion Answer: C. Sexual dysfunction with SSRIs is one of the most commonly seen side effects with this class of drugs. The management may involve switching from the SSRI to nefazodone or bupropion, either of which is much less likely to cause sexual dysfunction.

Answer 86

E. Carbamazepine Answer: E. Carbamazepine can cause ataxia at therapeutic doses. The other drugs can cause ataxia, but only at high or toxic doses.

Answer 87

B. It is excreted through the kidneys Answer: B. Lithium can be detected in the saliva and is excreted through the kidneys. It is found in the ionized form, is absorbed from the gastrointestinal tract, is not bound to protein, and is not lipid-soluble.

Answer 88

B. Benzodiazepines Answer: B. Benzodiazepines do not cause weight gain. All the other classes of drugs mentioned have the propensity to cause weight gain.

Answer 89

E. Weight gain Answer: E. Lamotrigine is weight neutral. It can cause all of the other mentioned effects.

Answer 90

D. Weight gain Answer: D. Topiramate is unique among most anticonvulsants as it causes weight loss. Because of this side effect, it could, in theory, be combined with other anticonvulsants to counteract weight gain. Its side effects include psychomotor slowing, difficulty with concentration, speech and language problems, somnolence, fatigue, memory problems, irritability, and depression.

Answer 91

D. It can be given safely with MAOIs. Answer: D. Concurrent therapy with MAOIs is contraindicated when venlafaxine is being administered, and a washout period of 2 weeks should be maintained between the two agents. Venlafaxine is a selective serotonin and noradrenergic reuptake inhibitor. It has no affinity for cholinergic, histaminergic, and opioid receptors. It can lower the seizure threshold. Treatment with venlafaxine is associated with sustained hypertension, especially in patients treated with more than 300 mg per day.

Answer 92

B. Akathisia Some SSRIs, especially fluoxetine, are associated with an increase in psychomotor activation including akathisia, especially in the first 2 to 3 weeks of use. Most SSRIs have a very low propensity to cause sedation. They do not cause acute dystonia or tardive dyskinesia.

Answer 93

C. Olanzapine-benzisoxazole Answer: C. Risperidone is a benzisoxazole. Olanzapine is a thienobenzodiazepine. All the other associations are correct.

Answer 94

D. Impotence Answer: D. Typical antipsychotics can cause erectile dysfunction. They do not cause psoriasis, but they can cause discoloration of the skin in body parts exposed to sunlight. They cause postural hypertension, constipation, and dry mouth.

Answer 95

B. Leukocytosis Answer: B. Many older antipsychotic drugs can cause leucopenia, thrombocytopenia, and pancytopenia, although patients' blood counts usually return to normal. On the EEG, the drugs cause prorogation of the QT and PR intervals, blunting of T waves, and depression of the ST segment. They also can cause torsades de pointes. High doses of thioridazine can cause retinal pigmentation. Patients on long-term treatment with chlorpromazine can develop granular deposits in the anterior lens and posterior cornea. Many of the antipsychotics are associated with significant weight gain.

Answer 96

D. Hypothyroidism Answer: D. The main endocrine effect of chlorpromazine is elevation of prolactin levels, which can result in galactorrhea. They cause erectile dysfunction, retrograde ejaculation, and loss of libido. They also cause postural hypotension. Cardiac arrhythmias are especially associated with thioridazine.

Answer 97

E. Akathisia Answer: E. Haloperidol does not cause hypertension in combination with MAOIs. High potency antipsychotics such as haloperidol have minimal effects on the cardiovascular system. Haloperidol can, however, cause akathisia, cholestatic jaundice, and tardive dyskinesia and is particularly implicated in the causation of acute dystonia.

Answer 98

D. Spastic paraplegia Answer: D. By itself, trifluoperazine does not cause paraplegia. Like most typical antipsychotics, it can cause dystonia, myoclonus, oculogyric crisis, and restlessness.

Answer 99

B. High mortality if untreated Answer: B. Neuroleptic malignant syndrome is a potentially fatal complication caused by antipsychotic drugs. Its features include hyperthermia, muscle rigidity, autonomic instability, fluctuating consciousness, leucocytosis, myoglobinuria, and acute renal failure. It may have a mortality rate of 20-30% if untreated. It is twice as common in male patients than in female patients and is more likely to occur in younger patients.

Answer 100

B. MAOIs Answer: B. MAOIs do not induce hepatic enzymes. All the other drugs mentioned can.

Answer 101

D. Hypothermia Answer: D. Chlorpromazine can cause hypothermia. Thioridazine causes retinal pigmentation. Chlorpromazine can cause granular deposits in the anterior lens and posterior cornea. They do not cause hemolytic anemia although rarely they can cause leucopenia and thrombocytopenia. There is very little evidence to suggest any association between prenatal exposure to an antipsychotic and increased incidence of congenital malformations. Chlorpromazine causes postural hypotension not hypertension.

Answer 102

C. Phenobarbitone Answer: C. Phenobarbitone is excreted in alkaline urine.

Answer 103

D. Haloperidol is less likely to cause urinary retention. Answer: D. Because haloperidol is a high-potency antipsychotic with low anticholinergic potency, it is less likely than chlorpromazine to cause urinary retention. It does have some anticholinergic effects as well as antiemetic effects. Chlorpromazine is more likely than haloperidol to cause postural hypotension. It also can cause ejaculatory failure.

Answer 104

B. Thioridazine Answer: B. Thioridazine and other low-potency antipsychotics can worsen glaucoma and hence should be used with caution. The other drugs listed either have no effects or are used in the treatment of glaucoma.

Answer 105

D. Hyperthermia Answer: D. Hyperthermia is a feature of neurotic malignant syndrome. The onset is usually sudden and it results in hypertonicity of muscles.

Answer 106

C. It is worse on stopping antipsychotics. Answer: C. Tardive dyskinesia is a movement disorder that develops following long-term treatment with antipsychotics. It consists of involuntary movements of the mouth and tongue and choreoathetoid movements of fingers, toes, and trunk. When dosages of antipsychotics are decreased or discontinued, abnormal movements may worsen. Antiparkinsonian medications may worsen the movements. The movements are not painful and in many cases they are not distressing to the patient and are more often noticed by others. They disappear during sleep.

Answer 107

E. Male sex Answer: E. Tardive dyskinesia is more common in female patients. The prevalence increases with age and is higher in patients with a strong affective component to their illness and in those with brain injury. Longer duration of treatment and the dosage of antipsychotics are other risk factors.

Answer 108

E. It does not cause neuroleptic malignant syndrome. Answer: E. Risperidone-induced cases of neuroleptic malignant syndrome have been reported in the literature. Risperidone does have a high affinity for 5-HT2A receptors in addition to D2 antagonism. It also has high affinity for alpha-1 and alpha-2 receptors but low affinity for beta and muscarinic receptors. It can raise plasma prolactin levels, particularly at higher doses. Another dose-related effect is the development of extrapyramidal side effects. It is also associated with weight gain, although not as much as is olanzapine.

Answer 109

C. It can cause marked sedation. Answer: C. Olanzapine has antagonistic effects at 5-HT2A, D1, D2, M1, H1, 5-HT2C, 5-HT3, 5-HT6, and alpha-1 receptors. It is a stronger antagonist of 5-HT than dopamine. Its has higher M and H receptor antagonism than risperidone and ziprasidone. Its side effect profile includes weight gain, somnolence, orthostatic hypotension, rare extrapyramidal side effects, and development of diabetes mellitus. No hematologic changes have been reported. It is an effective antimanic agent, and its use in the maintenance therapy of bipolar disorder is being evaluated.

Answer 110

D. It has a high affinity for muscarinic receptors. Answer: D. Quetiapine has a high affinity for 5-HT2, H1, alpha-1, and alpha-2 receptors, moderate affinity for D2 receptors, and low affinity for D1 receptors. It has very low affinity for M1 and D4 receptors. It has a much lower receptor blockade profile than other antipsychotics, including clozapine. It has no extrapyramidal adverse effects and causes only transient elevations in serum prolactin levels. Other side effects include constipation, dry mouth, somnolence, and postural hypotension.

Answer 111

C. It has a high affinity for D4 receptors. Answer: C. Clozapine has a tenfold higher affinity for D4 receptors than other antipsychotics. It has a relatively low affinity for D2 receptors and a high affinity for 5-HT2 receptors. It causes a strong alpha-1 and alpha-2 receptor blockade. Clozapine has selective preference for the mesolimbic dopamine system as opposed to the striatal dopamine blockade by conventional antipsychotics.

Answer 112

A. Bradycardia Answer: A. The most common cardiovascular side effect of clozapine is tachycardia and hypotension not bradycardia; tachycardia is a direct effect of the vagolytic properties of clozapine. Rarely, clozapine can cause hypertension. Clozapine has marked effects on weight, which may be because of strong affinity of the 5-HT1 and H1 receptors for the drug. Hypersalivation is another distressing side effect of clozapine seen in one-third to one-half of persons being treated with clozapine. It also lowers the seizure threshold and can precipitate seizures. Valproate is the preferred drug to treat clozapine-induced seizures. Agranulocytosis is seen in 1-2% of patients on clozapine and is the most well-known and potentially fatal side effect of clozapine.

Answer 113

C. Clozapine Answer: C. Clozapine has the greatest propensity to precipitate seizures. The risk of seizures increases with dosages of more than 500 mg per day. A preexisting seizure disorder or head trauma is a risk factor. The risks can be lowered by monitoring clozapine concentration, ordering an EEG before raising the dosage to more than 600 mg per day, and lowering the dosage after a seizure has occurred.

Answer 114

E. The risk of agranulocytosis increases with age. Answer: E. Agranulocytosis develops in 1-2% of patients on clozapine, and the risk increases with age. The risk is highest in the first 3 months of treatment. Risk is higher in females. White blood cell monitoring should be done weekly for the first 6 months and then every other week. Any fever or sign of infection is an indication for a white blood cell count. If the patient has a WBC count below 2,000 or a granulocyte count below 1,000, clozapine should be discontinued. Other hematologic changes with clozapine are eosinophilia, leucopenia, neutropenia, and thrombocytopenia.

Answer 115

C. Decreased frontal fast activity on EEG Answer: C. Chronic barbiturate intoxication causes increased frontal fast activity on EEG. It can cause dysarthria, nightmares, delirium, and brisk tendon reflexes.

Answer 116

E. They can be used exclusively in the luteal phase. Answer: E. SSRIs can be used exclusively in the luteal phase in the treatment of premenstrual syndrome. They can be combined with other hormonal treatments. They are well tolerated. They do not inhibit ovulation, and the side effect profile is the same irrespective of the condition for which they are used.

Answer 117

C. Diazepam Answer: C. Benzodiazepines are not known to reduce libido. The other drugs, including antipsychotics and antidepressants, can suppress the libido.

Answer 118

B. Urinary retention Answer: B. Drugs with anticholinergic properties cause mydriasis, cycloplegia, urinary retention, and increased urinary tract infections and constipation.

Answer 119

D. All of the above Answer: D. Aripiprazole, which was approved by FDA in 2002, is a novel antipsychotic. It is a partial agonist at the dopamine receptors. So it acts as a dopamine agonist at the hypodopaminergic areas and as a dopamine antagonist at the hyperdopaminergic areas. Partial agonist activity at the 5-HT1A receptor also contributes to the overall efficacy of aripiprazole as an antipsychotic.

Answer 120

D. 50-150 Answer: D. It has been estimated that around 8.5% of all the psychiatric patients require mechanical restraints for agitation. Because the use of mechanical restraints has been associated with around 50 to 150 deaths per year, it is advisable to try other types of interventions such as verbal, behavioral, or environmental interventions and pharmacologic interventions before resorting to mechanical restraints.

Answer 121

E. All of the above Answer: E. The haloperidol and lorazepam injection can be administered using the same syringe. The combination helps to calm agitated patients more quickly. Therefore the patients require far fewer injections. There is a reduced incidence of extrapyramidal side effects with the combination, and there is less need for concomitant treatment with cholinergic drugs.

Answer 122

B. Profound sedation Answer: B. An ideal parenteral antipsychotic should achieve the clinical effect without sedating the patient. The following are considered as features of an ideal parenteral antipsychotic: quick onset of therapeutic effect, calming without sedation, low risk of EPS, low risk of hypotension, and low risk of cognitive impairment.

Answer 123

E. All of the above Answer: E. Around 85% of the patients with schizophrenia exhibit cognitive impairment to a certain extent. Cognitive functions show a rapid decline during the prodromal period. Patients treated with conventional antipsychotic medications show a further decline in cognitive functions. Impaired cognitive function is considered a poor prognostic indicator.

Answer 124

E. All of the above Answer: E. According to the definition of metabolic syndrome, the patients should have three of the following five features for a diagnosis to be made: abdominal obesity obesity (men >40 inches; women >35 inches), elevated triglycerides (>150 mg/dl), low HDL (men 130/85 mm Hg ), and elevated fasting blood glucose (>110 mg/dl).

Answer 125

C. The ratio of the median toxic dose to the median effective dose Answer: C. Median effective dose is the dose at which 50% of the patients have a specified therapeutic effect. The median toxic dose is the dose at which half of the patients have the specified therapeutic effect. Therapeutic index is the ratio of median toxic dose to median effective dose.

Answer 126

E. All of the above Answer: E. Taking neostigmine 30 mg orally before sexual intercourse helps patients with ejaculatory dysfunction. Bethanechol and yohimbine can be used for impaired erectile dysfunction, as can Viagra, Cialis, and Levitra. Cyproheptadine can be given to females with orgasmic dysfunction.

Answer 127

A. Carbamazepine Answer: A. Carbamazepine is an inducer of CYP 2D6 isoenzyme, whereas fluoxetine and paroxetine are inhibitors.

Answer 128

E. All of the above Answer: E. All of the following drugs can inhibit CYP 3A4 isoenzyme: fluoxetine, fluvoxamine, paroxetine, and sertraline. This effect leads to cardiotoxic effects when these medicines are combined with nonsedating antihistamines like terfenadine and astemizole. But they can be used with later developed antihistamines like cetrizine and loratidine. Fluvoxamine also leads to inhibition of CYP 1A2 isoenzyme.

Answer 129

A. Acetazolamide Answer: A. Acetazolamide when coadministered with lithium leads to a decrease in lithium concentration, whereas the thiazides, indomethacin, and furosemide lead to an increase in lithium levels. Acetazolamide, a carbonic anhydrase inhibitor, leads to decreased lithium concentrations because it increases clearance of lithium. Theophylline also leads to a decreased lithium concentration when coadministered. Most NSAIDs, when coadministered with lithium, lead to decreased clearance of lithium and lead to increased concentrations.

Answer 130

E. All of the above Answer: E. All of the following drugs can lead to an increase in tricyclic drug levels when coadministered: SSRIs, cimetidine, quinidine, disulfiram, methylphenidate, and methadone. When tricyclic antidepressants are coadministered with SSRIs and cimetidine, the dosage of the tricyclics should be lowered.

Answer 131

E. All of the above Answer: E. All the SSRIs when combined with MAOIs can lead to serotonin syndrome. The other medications that can lead to serotonin syndrome when combined with MAOIs include L-tryptophan, St. John's wort, and buspirone.

Answer 132

E. Phenytoin Answer: E. Phenytoin and valproate lead to a decrease in the level of carbamazepine when coadministered with carbamazepine. Erythromycin, allopurinol, cimetidine, fluoxetine, fluvoxamine, and lamotrigine lead to an increase in carbamazepine concentration when coadministered.

Answer 133

C. Nicotine D. All of the above Answer: C. Nicotine leads to a decrease in the haloperidol concentration. Carbamazepine, phenobarbital, and rifampin lead to decreased concentration of haloperidol when coadministered.

Answer 134

D. All of the above Answer: D. Perphenazine (Trilafon) is a phenothiazine. In addition to the known antipsychotics, metoclopramide (Reglan) and prochlorperazine (Compazine) can lead to extrapyramidal side effects because of their D2-receptor-blocking properties.

Answer 135

E. More than 80% Answer: E. According to the studies conducted by Farde et al., occupancy of more than 80% of the D2 receptors in the nigrostriatal tract leads to increased incidence of EPS. Occupancy of around 60-70% of the D2 receptors in the mesolimbic and mesocortical tract is necessary for therapeutic efficacy.

Answer 136

E. After 2 weeks Answer: E. Patients who develop NMS can be rechallenged with the same antipsychotic medication or a different antipsychotic around 2 weeks after the resolution of NMS. The antipsychotic drug should be restarted at a low dosage and then slowly increased with monitoring.

Answer 137

D. Leucopenia is a feature of NMS. Answer: D. It is not leucopenia but leukocytosis that is a feature of NMS. Atypical antipsychotics, including clozapine, can lead to the development of NMS. One of the first steps in the treatment of NMS is to stop the antipsychotics. Since this is not possible with depot preparations, they have a higher mortality rate.

Answer 138

E. More than 90% Answer: E. Around 95% of the people who develop acute dystonia develop it within 3 days of being started on antipsychotics.

Answer 139

B. CYP 3A4 Answer: B. The main pathway involved in the metabolism of carbamazepine to its metabolite, carbamazepine 10,11-epoxide, is CYP 3A4 isoenzyme. So any substance that inhibits CYP 3A4 when coadministered with carbamazepine leads to an increase in carbamazepine levels. Oxcarbamazepine, a ketoderivative of carbamazepine, is minimally metabolized by CYP 3A4 isoenzyme.

Answer 140

B. Hirsutism Answer: B. Valproate can lead to hair loss not hirsutism. The other side effects associated with valproate are sedation, tremor, weight gain, dysarthria, elevation of hepatic transaminase levels, and fatal hepatotoxicity in pediatric patients, thrombocytopenia, agranulocytosis, hemorrhagic pancreatitis, and encephalopathy.

Answer 141

D. All of the above Answer: D. Low-potency antipsychotics lead to hypotension because of their alpha-blocking properties and can also lead to a worsening of cognitive functions because of their anticholinergic properties. Low-dosage, highpotency antipsychotics are preferred for elderly patients with dementia when they are agitated.

Answer 142

D. St. John's wort Answer: D. St. John's wort induces enzymes that increase the metabolism of oral contraceptive pills. Therefore, when treating sexually active women in the reproductive age group, it is necessary to discuss drug interaction with over-the-counter antidepressants like St. John's wort.

Answer 143

B. ALT Answer: B. Tacrine is associated with liver toxicity. Therefore, a patient taking tacrine should be followed up with liver function tests. Serum gluatamic pyruvic transaminase (SGPT), otherwise known as alanine amino transferase (ALT), is most specific for hepatic toxicity due to tacrine and its usage must be monitored for the first 16 weeks of treatment.

Answer 144

B. Starting the patient on same dose of clozapine Answer: B. When the patient has been off clozapine for more than 36 hours, treatment needs to resume at the starting dosage and the dose slowly increased. Starting the patient on the same dosage as before the interruption can lead to development of orthostatic hypotension, which can result in a fall and injury to the patient.

Answer 145

D. Alcohol infusion Answer: D. Panic attacks can be provoked in patients with panic disorder by various methods like infusion of substances like lactate, flumazenil, and isoproterenol. Panic attacks can also be provoked by carbon dioxide inhalation. About 70% of the patients with panic disorder provoked by lactate develop panic attacks.

Answer 146

B. Amphetamine acts by inhibiting the uptake of dopamine. Answer: B. Amphetamines act by releasing dopamine from presynaptic terminals. Methyphenidate acts in the CNS mainly by inhibiting the reuptake of dopamine. Cocaine acts by leading to the release of dopamine in the CNS. Amphetamine intoxication leads to pupillary dilation.

Answer 147

B. Less than 1% Answer: B. Delta 9 tetrahydrocannabinol (THC) is the metabolite responsible for most of the psychoactive effects of cannabis. Less than 1% of the THC inhaled penetrates the blood-brain barrier.

Answer 148

C. Anomaly of tricuspid valve Answer: C. Ingestion of lithium during the first trimester of pregnancy can lead to Ebstein's anomaly, which is characterized by a congenital anomaly of the tricuspid valve in which the septal and posterior leaflets are displaced into the right ventricle.

Answer 149

B. Moniz Answer: B. Cerletti and Bini were the two Italian physicians who did pioneering work with convulsive treatment. Delay and Deniker introduced chlorpromazine in the 1950s. Vaughn and Leff expounded the theory of “expressed emotions among highly critical relatives of schizophrenia with poor prognosis.” Egaz Moniz, a Portuguese neurologist, along with his colleague Almeida Lima, introduced prefrontal leucotomy. Moniz was awarded the Nobel Prize in 1949.

Answer 150

C. Thioridazine Answer: C. Thioridazine when used in excess of 1,000 mg/day can lead to retinal pigmentation, known as retinitis pigmentosa, which can lead to visual impairment. Hence thioridazine should not be prescribed in dosages greater than 800 mg/day. The visual impairment associated with thioridazine is permanent and does not remit with stopping the medication.

Answer 151

D. Retinal pigmentation with long-term use Answer: D. Patients receiving chlorpromazine develop photosensitivity reactions leading to sunburns or rash when they are exposed to sunlight. This can be prevented by the use of sunscreen or by avoiding direct sunlight. People using chlorpromazine for a long time develop lenticular and corneal deposits leading to visual impairment. Some patients also develop slate gray discoloration of the skin when exposed to sunlight. Retinal pigmentation is a side effect of thioridazine.