QUESTIONS1. A 43-year-old very overweight man complains of not sleepingwell and feeling tired during the day. He tells his physicianthat his wife is the cause of the problem because she wakeshim up several times during the night because of his loudsnores. This appears to be a breathing-related sleep disorder,so you should probably write a prescription for(A) Buspirone(B) Eszopiclone(C) Flurazepam(D) Secobarbital(E) None of the above2. Which statement concerning the barbiturates is accurate?(A) Abstinence syndromes are more severe during withdrawalfrom phenobarbital than from secobarbital(B) Alkalinization of the urine accelerates the elimination ofphenobarbital(C) Barbiturates may increase the half-lives of drugs metabolizedby the liver(D) Compared with barbiturates, the benzodiazepines exhibita steeper dose-response relationship(E) Respiratory depression caused by barbiturate overdosagecan be reversed by flumazenil3. A 24-year-old stockbroker has developed a “nervous disposition.”He is easily startled, worries about inconsequentialmatters, and sometimes complains of stomach cramps. Atnight he grinds his teeth in his sleep. There is no history ofdrug abuse. Diagnosed as suffering from generalized anxietydisorder, he is prescribed buspirone. His physician shouldinform the patient to anticipate(A) A need to continually increase drug dosage because oftolerance(B) A significant effect of the drug on memory(C) Additive CNS depression with alcoholic beverages(D) That the drug is likely to take a week or more to beginworking(E) That if he stops taking the drug abruptly, he will experiencewithdrawal signs4. Which of the following best describes the mechanism ofaction of benzodiazepines?(A) Activate GABAB receptors in the spinal cord(B) Block glutamate receptors in hierarchical neuronal pathwaysin the brain(C) Increase frequency of opening of chloride ion channelscoupled to GABAA receptors(D) Inhibit GABA transaminase to increase brain levels ofGABA(E) Stimulate release of GABA from nerve endings in thebrain5. An 82-year-old woman, otherwise healthy for her age, has difficultysleeping. Triazolam is prescribed for her at one half ofthe conventional adult dose. Which statement about the useof triazolam in this elderly patient is accurate?(A) Ambulatory dysfunction does not occur in elderlypatients taking one half of the conventional adult dose(B) Hypertension is a common adverse effect of benzodiazepinesin elderly patients(C) Over-the-counter cold medications may antagonize thehypnotic effects of the drug

(D) The patient may experience amnesia, especially if she alsoconsumes alcoholic beverages(E) Triazolam is distinctive in that it does not cause reboundinsomnia on abrupt discontinuance6. The most likely explanation for the increased sensitivity ofelderly patients after administration of a single dose of a benzodiazepineis(A) Changes in brain function accompanying aging(B) Changes in plasma protein binding(C) Decreased hepatic metabolism of lipid-soluble drugs(D) Decreases in renal function(E) Increased cerebral blood flow7. A 28-year-old woman has sporadic attacks of intense anxietywith marked physical symptoms, including hyperventilation,tachycardia, and sweating. If she is diagnosed as sufferingfrom a panic disorder, the most appropriate drug to use is(A) Clonazepam(B) Eszopiclone(C) Flurazepam(D) Propranolol(E) Ramelteon8. Which drug used in the maintenance treatment of patientswith tonic-clonic or partial seizure states increases the hepaticmetabolism of many drugs including both warfarin and phenytoin?(A) Buspirone(B) Chlordiazepoxide(C) Eszopiclone(D) Phenobarbital(E) Triazolam9. A patient with liver dysfunction is scheduled for a surgicalprocedure. Lorazepam or oxazepam can be used for preanestheticsedation in this patient without special concern regardingexcessive CNS depression because these drugs are(A) Actively secreted in the renal proximal tubule(B) Eliminated via the lungs(C) Metabolized via conjugation extrahepatically(D) Reversible by administration of naloxone(E) Selective anxiolytics like buspirone

10. This drug used in the management of insomnia facilitatesthe inhibitory actions of GABA, but it lacks anticonvulsantor muscle-relaxing properties and has minimal effect on sleeparchitecture. Its actions are antagonized by flumazenil.(A) Buspirone(B) Chlordiazepoxide(C) Eszopiclone(D) Ramelteon(E) PhenobarbitalANSWERS1. Benzodiazepines and barbiturates are contraindicated inbreathing-related sleep disorders because they further compromiseventilation. In obstructive sleep apnea (pickwickiansyndrome), obesity is a major risk factor. Buspirone is a selectiveanxiolytic not a hypnotic. The best prescription you cangive this patient is to lose weight. The answer is E.2. Withdrawal symptoms from use of the shorter-acting barbituratesecobarbital are more severe than with phenobarbital.The dose-response curve for benzodiazepines is flatter thanthat for barbiturates. Induction of liver drug-metabolizing

enzymes occurs with barbiturates and may lead to decreasesin half-life of other drugs. Flumazenil is an antagonist at BZreceptors and is used to reverse CNS depressant effects ofbenzodiazepines. As a weak acid (pKa, 7), phenobarbital willbe more ionized (nonprotonated) in the urine at alkaline pHand less reabsorbed in the renal tubule. The answer is B.3. Buspirone is a selective anxiolytic with pharmacologic characteristicsdifferent from those of sedative-hypnotics. Buspironehas minimal effects on cognition or memory; it is not anadditive with ethanol in terms of CNS depression; tolerance isminimal; and it has no dependence liability. Buspirone is noteffective in acute anxiety because it has a slow onset of action.The answer is D.4. Benzodiazepines exert most of their CNS effects by increasingthe inhibitory effects of GABA, interacting with componentsof the GABAA receptor-chloride ion channel macromolecularcomplex to increase the frequency of chloride ion channelopening. Benzodiazepines do not affect GABA metabolism orrelease, and they are not GABA receptor agonists because theydo not interact directly with the binding site for GABA. Theanswer is C.5. In elderly patients taking benzodiazepines, hypotension isfar more likely than an increase in blood pressure. Elderlypatients are more prone to the CNS depressant effects ofhypnotics; a dose reduction of 50% may still cause excessivesedation with possible ambulatory impairment. AdditiveCNS depression occurs commonly with drugs used in overthe-counter cold medications, and rebound insomnia canoccur with abrupt discontinuance of benzodiazepines used assleeping pills. Alcohol enhances psychomotor depression andthe amnestic effects of the benzodiazepines. The answer is D.6. Decreased blood flow to vital organs, including the liver andkidney, occurs during the aging process. These changes maycontribute to cumulative effects of sedative-hypnotic drugs.However, this does not explain the enhanced sensitivity ofthe elderly patient to a single dose of a central depressant,which appears to be due to changes in brain function thataccompany aging. The answer is A.7. Alprazolam (not listed) and clonazepam are the most effectiveof the benzodiazepines for the treatment of panic disorders.Eszopiclone and flumazenil are hypnotics. Propranolol iscommonly used to attenuate excessive sympathomimeticactivity in persons who suffer from performance anxiety(“stage fright”). The answer is A.8. Chronic administration of phenobarbital increases the activityof hepatic drug-metabolizing enzymes, including severalcytochrome P450 isozymes. This can increase the rate ofmetabolism of drugs administered concomitantly, resultingin decreases in the intensity and duration of their effects. Theanswer is D.9. The elimination of most benzodiazepines involves theirmetabolism by liver enzymes, including cytochrome P450isozymes. In a patient with liver dysfunction, lorazepam andoxazepam, which are metabolized extrahepatically, are lesslikely to cause excessive CNS depression. Benzodiazepines arenot eliminated via the kidneys or lungs. Flumazenil is used toreverse excessive CNS depression caused by benzodiazepines.The answer is C.10. Only two of the drugs listed are used for insomnia, eszopicloneand ramelteon. Eszopiclone, zaleplon, and zolpidem are

related hypnotics that, though structurally different from benzodiazepines,appear to have a similar mechanism of action.However, these drugs are not effective in seizures or in musclespasticity states. Compared with benzodiazepines, the newerhypnotics are less likely to alter sleep patterns. Ramelteonactivates melatonin receptors in the suprachiasmatic nuclei.Buspirone is not a hypnotic! The answer is C.