Home Books Katzung & Trevor's Pharmacology: Examination & Board Review, 11e

Examination 1

Phase 3 clinical trials typically involve

(A) Collection of data regarding late-appearing toxicities from patients previously studied in phase 1 trials

(B) Double-blind, closely monitored evaluation of the new drug in hundreds of patients with the target disease by specialists in academic centers

(C) Evaluation of the new drug under conditions of actual use in 1000–5000 patients with the target disease

(D) Measurement of the pharmacokinetics of the new drug in normal volunteers

(E) Postmarketing surveillance of drug toxicities

C (1) Phase 3 trials are carried out under the conditions of proposed use in (usually) several thousand patients.

A patient is admitted to the emergency department for treatment of a drug overdose. The identity of the drug is unknown, but it is observed that when the urine pH is alkaline, the renal clearance of the drug is much greater than when the urine pH is acidic. The drug is probably a

(A) Strong acid

(B) Weak acid

(C) Nonelectrolyte

(D) Weak base

(E) Strong base

B (1) According to the Henderson-Hasselbalch principle (Chapter 1), weak acids are less protonated (and more charged) in alkaline media, and weak bases are more protonated (and more charged) in acidic media. Strong acids and bases are fully ionized at any pH. Since the clearance of the unknown drug is greater in alkaline urine, the drug must be a weak acid.

A 66-year-old woman is in the coronary care unit after an acute myocardial infarction. She has developed signs of pulmonary edema of rapidly increasing severity and several drugs have been suggested. Furosemide, dobutamine, and digoxin can each

(A) Decrease conduction velocity in the atrioventricular node

(B) Decrease venous return

(C) Reduce pulmonary edema

(D) Increase peripheral vascular resistance

(E) Increase the amount of cAMP in cardiac muscle cells

C (9, 13, 15) Digoxin decreases atrioventricular conduction. Furosemide does not increase vascular resistance. Of the agents listed, only dobutamine increases cAMP. All 3 drugs reduce pulmonary edema, albeit probably by different mechanisms.

A 45-year-old man presents with pulmonary hypertension. Which of the following cause–treatment pairs is most relevant to this patient?

(A) Angiotensin II–minoxidil

(B) Atrial natriuretic peptide–losartan

(C) Bradykinin–furosemide

(D) Endothelin–ambrisentan

(E) Substance P–capsaicin

D (17) Endothelin is the peptide most closely associated with pulmonary hypertension, and ambrisentan is an orally active ET_A receptor antagonist.

A 45-year-old man with a duodenal ulcer and laboratory evidence of Helicobacter pylori infection was treated with omeprazole, clarithromycin, and amoxicillin. Which of the following is the most accurate description of the mechanism of omeprazole’s therapeutic action?

(A) Activation of prostaglandin E receptors

(B) Formation of protective coating over the ulcer bed

(C) Inhibition of bacterial protein synthesis

(D) Inhibition of H₂ histamine receptors

(E) Irreversible inactivation of H⁺/K⁺ ATPase

E (16, 59) Omeprazole, a proton pump inhibitor, very effectively reduces gastric acid secretion by being converted to an active metabolite that irreversibly inhibits the parietal cell H⁺/K⁺ ATPase that is responsible for acid secretion. Misoprostol activates prostaglandin E receptors. Sucralfate forms a protective coating over an ulcer bed, and cimetidine inhibits H₂ histamine receptors.

A patient discharged from the hospital after a myocardial infarction had been receiving small doses of procainamide to suppress a ventricular tachycardia. One month later, his local physician prescribed high-dose hydrochlorothiazide therapy for ankle edema, which was ascribed to congestive heart failure. Three weeks after beginning thiazide therapy, the patient was readmitted to the hospital with a rapid multifocal ventricular tachycardia. The most probable cause of this arrhythmia is

(A) Procainamide toxicity caused by inhibition of procainamide metabolism by the thiazide

(B) Direct effects of hydrochlorothiazide on pacemaker cells of the heart

(C) Direct effects of procainamide on pacemaker cells of the heart

(D) Block of calcium current by the combination of procainamide plus thiazide

(E) Reduction of serum potassium caused by the diuretic action of hydrochlorothiazide

E (14, 15) Cardiac automaticity is enhanced by hypokalemia. Thiazides, loop diuretics, and even carbonic anhydrase inhibitors can reduce serum potassium levels because they present more sodium to the cortical collecting tubules, which attempt to compensate by wasting potassium in exchange for sodium.

A 37-year-old female presented with epigastric pain for the last 3 days and two episodes of bilious vomiting. Four years earlier, she presented with similar complaints and was diagnosed as having acute pancreatitis with type 2 diabetes, hypertension, and combined dyslipidemia (elevated LDL and VLDL). Treatment was started with insulin, telmisartan, atorvastatin, and a low-fat diet. Which of the following additional drugs is required to fully treat her dyslipidemia?

(A) Cholestyramine

(B) Ezetimibe

(C) Gemfibrozil

(D) Mipomersen

(E) Pravastatin

C (35) The treatment includes a statin to lower the patient’s LDL, but a second drug is needed to lower the patient’s triglycerides. Cholestyramine is a resin used to lower LDL. Ezetimibe inhibits intestinal cholesterol absorption. Mipomersen is an antisense oligo against apoB-100, used to lower LDL in FH patients. Pravastatin is another HMG-CoA reductase inhibitor lowering LDL-cholesterol. Gemfibrozil is the only VLDL-lowering drug in the list. It is a fibrate acting on PPAR-α; the changes in gene transcription result in enhanced fatty acid oxidation and reduced triglycerides (VLDL).

While on vacation, a 35-year-old man with a 10-year history of myasthenia gravis loses his supply of medications. He is now admitted to the emergency department complaining of diplopia, dysarthria, and difficulty swallowing. The most appropriate drug from the following list for reversing myasthenic crisis in this patient is

(A) Calcium

(B) Neostigmine

(C) Pralidoxime

(D) Succinylcholine

(E) Vecuronium

B (7) The appropriate treatment for myasthenic crisis is an indirect-acting cholinomimetic, the same medication used for chronic therapy of this condition. Neostigmine is the only cholinesterase inhibitor in the list of choices.

A 4-year-old child was brought to an emergency department after ingesting a product found in the home. Her signs and symptoms include an elevated temperature; hot, dry skin; moderate tachycardia; and mydriasis. The most likely cause of these symptoms is

(A) Acetaminophen overdose

(B) Amphetamine-containing diet pills

(C) Exposure to an organophosphate-containing insecticide

(D) Ingestion of a medication containing atropine

(E) Ingestion of phenylephrine-containing eye drops

D (8, 58) The patient has characteristic signs of antimuscarinic (also known as anticholinergic) toxicity, caused by drugs such as atropine. Children are especially susceptible to the hyperthermia caused by antimuscarinic drug overdose.

A patient is admitted to a hospital emergency department 2 h after taking an overdose of diazepam. The plasma level of the drug at time of admission is 40 mg/L, and the apparent volume of distribution, half-life, and clearance of diazepam are 80 L, 40 h, and 35 L/day, respectively. The ingested dose was approximately

(A) 1.3 g

(B) 2.4 g

(C) 3.2 g

(D) 4.8 g

(E) 6.4 g

C (3) Two hours after an overdose of a drug with a 40-hr half-life, the plasma concentration will approximate that immediately after a loading dose. Using the loading dose equation (dose = V_d × C_p), we obtain dose = 80 L × 40 mg/L, or 3200 mg, or 3.2 g.

A semiconscious patient in the intensive care unit is being artificially ventilated. Random spontaneous respiratory movements are rendering the mechanical ventilation ineffective. A useful drug to reduce the patient’s ineffective spontaneous respiratory activity is

(A) Baclofen

(B) Dantrolene

(C) Pancuronium

(D) Neostigmine

(E) Succinylcholine

C (27) A drug that antagonizes nicotinic receptors at skeletal neuromuscular junctions (pancuronium) is required to inhibit spontaneous respiratory movements. Succinylcholine is not appropriate partly because it may initially stimulate N-receptors and also because its duration of action is very short.

A child with strabismus (“wandering eye”) is to be treated pharmacologically for a prolonged period. Which of the following drugs is used by the topical route in ophthalmology and causes mydriasis and cycloplegia lasting more than 24 h?

(A) Atropine

(B) Echothiophate

(C) Edrophonium

(D) Pilocarpine

(E) Timolol

A (8) Atropine has a very long duration of action in the eye (>72 hr). By interfering with accommodation in the dominant eye, atropine can sometimes prevent amblyopia. Timolol has no significant effect on accommodation, whereas the other drugs listed cause miosis and cyclospasm.

A 55-year-old surgeon has developed symmetric early morning stiffness in her hands. She wishes to take a nonsteroidal anti-inflammatory drug to relieve these symptoms. Which drug is an NSAID that is appropriate for chronic therapy of her arthritis?

(A) Colchicine

(B) Hydroxychloroquine

(C) Indomethacin

(D) Naproxen

(E) Sulfasalazine

D (36) Naproxen and indomethacin are the only NSAIDS listed here. Indomethacin is more potent and has more adverse effects compared with naproxen and is not the first NSAID of choice for milder symptoms. Colchicine exerts its anti-inflammatory effects by prevention of tubulin polymerization, and it is used predominantly in acute gout attacks. Hydroxychloroquine is an antimalarial with anti-inflammatory effects, and sulfasalazine inhibits the release of inflammatory cytokines (IL-1, IL-6, IL-12, and TNF-α).

A 36-year-old man presents with tingling and neuropathic pain in his feet. Blood test reveals macrocytic anemia. Which of the following drugs will probably be required in this case?

(A) Erythropoietin

(B) Filgrastim

(C) Folic acid

(D) Iron dextran

(E) Vitamin B₁₂

E (33) The most common cause of macrocytic anemia is deficiency of folic acid or vitamin B₁₂. The additional finding of neurologic abnormality suggests vitamin B₁₂ deficiency, which is treated with vitamin B₁₂ replacement.

A 72-year-old man with atrial fibrillation required oral anticoagulation to reduce his risk of ischemic stroke. He was started on rivaroxaban. What is the molecular target of rivaroxaban?

(A) Antithrombin III

(B) Factor X

(C) Factors IX, X, VII, and II

(D) Plasmin

(E) Thrombin

B (33, 34) Rivaroxaban is a direct factor X inhibitor. Antithrombin III is the target of heparin; warfarin inhibits vitamin K-dependent gamma-carboxylation of the clotting factors X, IX, VII, and II (mnemonic “1972”); plasmin is the active enzyme derived from plasminogen, and thrombin is the target of direct thrombin inhibitors (eg, dabigatran).

A 55-year-old man with a strong family history of cardiovascular disease has moderate hypertension and angina pectoris. Blood pressure is 160/109 mm Hg, and the ECG shows left ventricular hypertrophy. The rest of his physical examination and laboratory results are normal. His angina is precipitated by exercise. You have been asked to recommend a drug regimen for both conditions. The antihypertensive drug most likely to aggravate angina pectoris is

(A) Captopril

(B) Clonidine

(C) Hydralazine

(D) Methyldopa

(E) Propranolol

C (11, 12) Angina pectoris can be precipitated by tachycardia; vasodilators such as hydralazine typically cause increased heart rate.

A 55-year-old woman underwent chemotherapy for breast cancer. The chemotherapy reduced her neutrophils to near zero. Which of the following will accelerate the recovery of her neutrophils?

(A) Eltrombopag

(B) G-CSF

(C) Oprelvekin

(D) Romiplostim

(E) Vitamin B₁₂

B (33) G-CSF stimulates neutrophil growth. Eltrombopag, oprelvekin, and romiplostim stimulate platelets (thrombocytes). Vitamin B₁₂ is used to treat megaloblastic anemia.

A 46-year-old man consults you regarding his sexual performance issues. A drug that is used in the treatment of male erectile dysfunction and inhibits a phosphodiesterase is

(A) Finasteride

(B) Fluoxetine

(C) Mifepristone

(D) Sildenafil

(E) Timolol

D (12, 19) Inhibitors of phosphodiesterase, isoform 5, are useful in enhancing erection. Note: Because the mechanism involves increased cGMP in vascular smooth muscle, these drugs also potentiate the hypotensive action of nitrates.

A physician was considering erythromycin for treatment of a 47-year-old man with an upper respiratory tract infection. However, the physician noted that the patient was taking simvastatin for treatment of hypercholesterolemia and realized that erythromycin, an inhibitor of cytochrome enzymes, would inhibit the metabolism of simvastatin. The physician opted for a different class of antibiotic to avoid exposing the patient to higher concentrations of simvastatin and a risk of dose-dependent toxicity. Which of the following is the primary dose-dependent toxicity of simvastatin?

(A) Abdominal pain secondary to gallstone formation

(B) Blurred vision secondary to optic neuritis

(C) Elevated serum creatinine, possibly progressing to renal failure

(D) Increased serum uric acid concentration and increased risk of gout

(E) Muscle pain and weakness, possibly progressing to rhabdomyolysis

E (35) Rhabdomyolysis is a serious side effect that can occur with statins. Gallstones are a side effect of the fibrates; uric acid elevation is a side effect of niacin.

Although it does not act at any histamine receptor and has no effect on histamine’s metabolism, epinephrine reverses many effects of histamine. Epinephrine is a

(A) Chemical antagonist of histamine

(B) Competitive inhibitor of histamine

(C) Metabolic inhibitor of histamine

(D) Noncompetitive antagonist of histamine

(E) Physiologic antagonist of histamine

E (2) A physiologic antagonist opposes the action of other drugs by acting at a different receptor; histamine acts at H₁ and H₂ in the periphery, while epinephrine opposes histamine by acting at α₁ and β₂ adrenoceptors. Epinephrine also acts at α₂ and β₁ adrenoceptors.

Most drug receptors are

(A) Small molecules with a molecular weight between 100 and 1000

(B) Lipids arranged in a bilayer configuration

(C) Proteins located on cell membranes or in the cytosol

(D) DNA molecules

(E) RNA molecules

C (1) As described in Chapter 1, receptors are usually regulatory molecules or enzymes; proteins constitute the vast majority of regulatory and enzyme molecules.

The graph below shows the serum insulin level that results from a 2-injection regimen given to a child with type 1 diabetes. Assume that both injections (indicated by arrows along the time line) contain the same medication(s). The drug or drug combination that is most likely to generate the levels of insulin depicted in the figure is

(A) 100% Regular insulin

(B) 100% Lispro insulin

(C) 70% NPH insulin plus 30% regular insulin

(D) 100% NPH insulin

(E) 100% Insulin glargine

C (41) In order to replicate the physiological situation with a baseline and mealtime peaks, one needs to combine insulin preparations with different durations of action. Review duration of action of different insulin formulations in Figure 41–1.

In a laboratory demonstration of the interactions of drugs, an anesthetized dog is given several agents intravenously. Intravenous administration of norepinephrine in a subject already receiving an effective dose of atropine often

(A) Decreases blood sugar

(B) Decreases total peripheral resistance

(C) Increases heart rate

(D) Increases skin temperature

(E) Reduces pupil size

C (6, 8, 9) Atropine blocks vagal and other parasympathetic pathways. Norepinephrine causes vasoconstriction and increased blood pressure. The increase in blood pressure usually evokes a reflex bradycardia that is mediated by the vagus nerve. When vagal slowing is blocked, the beta-agonist action of norepinephrine is unmasked, resulting in tachycardia.

A 26-year-old woman comes to the outpatient clinic with a complaint of rapid heart rate and easy fatigability. Laboratory workup reveals low hemoglobin and microcytic red cell size. Which of the following is the most suitable therapy?

(A) Ferrous sulfate

(B) Folic acid

(C) Iron dextran

(D) Pyridoxine

(E) Vitamin B₁₂

A (33) The most common cause of microcytic anemia is iron deficiency, which can be treated in most patients with an oral iron supplement such as ferrous sulfate.

The graph below shows a quantal dose-response graph of the results of a study of a new drug in patients with hypertension. The label on the Y-axis (vertical axis) should be

(A) Cumulative maximal efficacy of the experimental drug in the patients

(B) Cumulative dose of the experimental drug in the patients

(C) Cumulative percentage of patients with a specified response to the drug

(D) Percentage of receptors bound to the drug

(E) Percentage of the maximal response to the drug that occurs at each dosage level

C (2) Quantal dose-response curves plot the percentage of the subjects that show a specified response (Y-axis) at each increment of dosage (X-axis); see Chapter 2.

Mr. Q has been given an intravenous dose of isoproterenol and is now manifesting an undesirably strong heart rate response. Which of the following most effectively blocks the heart rate response to a moderate dose of isoproterenol in conscious patients?

(A) Atropine

(B) Metaproterenol

(C) Phenoxybenzamine

(D) Pancuronium

(E) Propranolol

E (6, 8, 10) Isoproterenol causes tachycardia and facilitates arrhythmias through its β action. A β antagonist such as propranolol can prevent this action. Note that choice B, metaproterenol, is a β agonist; metoprolol is a β antagonist.

An accepted clinical use of antimuscarinic drugs is for treatment of

(A) Alzheimer’s disease

(B) Chronic obstructive pulmonary disease

(C) Glaucoma

(D) Hypertension

(E) Prostatic hyperplasia

B (8, 20) Antimuscarinic drugs are contraindicated in Alzheimer’s disease, glaucoma, and prostatic hyperplasia. They have no useful effect in hypertension. They can produce useful bronchodilation in COPD and appear to cause less cardiac toxicity than sympathomimetics.

Which of the following is an anticlotting prodrug that binds to and inhibits the platelet ADP receptor?

(A) Aspirin

(B) Clopidogrel

(C) Enoxaparin

(D) Fondaparinux

(E) Tirofiban

B (34) Clopidogrel is a prodrug, activated by CYP2C9 and CYP2C19. The active metabolite irreversibly binds ADP receptors. Aspirin exerts its antiplatelet effect through irreversible inhibition of COX-1 and COX-2. Enoxaparin is LMW heparin and acts through antithrombin III. Fondaparinux is a small portion of LMW heparin with similar actions. Tirofiban is a IIb/IIIa protein ligand.

A 70-year-old man has severe urinary hesitancy associated with benign prostatic hyperplasia. He has tried α blockers with little relief. His physician recommends a drug that blocks 5α-reductase in the prostate. Which of the following drugs did the physician most likely prescribe?

(A) Finasteride

(B) Flutamide

(C) Ketoconazole

(D) Leuprolide

(E) Oxandrolone

A (40) Finasteride is a 5α-reductase inhibitor. Flutamide is an androgen receptor antagonist. Ketoconazole is a cytochrome P450 inhibitor (also used as an antifungal agent). Leuprolide is a GnRH agonist used in depot form for prostate carcinoma. Oxandrolone is an anabolic androgenic steroid.

A 54-year-old contractor complains of anginal pain that occurs at rest. On examination, his blood pressure is 145/90 and his heart rate is 90. A treatment of angina that often decreases the heart rate and can prevent vasospastic angina attacks is

(A) Diltiazem

(B) Nifedipine

(C) Nitroglycerin

(D) Propranolol

(E) Timolol

A (12) Beta blockers usually decrease heart rate but are of no value in vasospastic angina. Nitrates usually increase heart rate. Calcium channel blockers such as diltiazem and verapamil decrease heart rate and are valuable in vasospastic angina, but nifedipine can increase heart rate.

Which of the following drugs is a partial agonist and can cause vasoconstriction in the absence of other drugs?

(A) Atropine

(B) Ergotamine

(C) Neostigmine

(D) Phentolamine

(E) Verapamil

B (16) Ergotamine is a potent vasoconstrictor but is a partial agonist at α adrenoceptors; as such, it can cause epinephrine reversal.

In a study of new diuretics, an investigational drug was given daily for 8 d and urine output was analyzed. The following data were obtained.

Which mechanism best explains the effects shown on the graph?

(A) Carbonic anhydrase inhibition

(B) Blockade of a Na⁺/K⁺/2Cl^– transporter in the ascending limb of the loop of Henle

(C) Blockade of a NaCl transporter in the distal convoluted tubule

(D) Osmotic diuresis

(E) Block of aldosterone in the cortical collecting tubule

C (15) The graph shows a moderate diuresis, some potassium wasting, and metabolic alkalosis. This is most consistent with a thiazide diuretic such as hydrochlorothiazide.

A 65-year-old man with cardiomyopathy has recurrent congestive heart failure. Addition of digitalis to his regimen is being considered.

In a patient receiving digoxin for congestive heart failure, conditions that may facilitate the appearance of toxicity include

(A) Hyperkalemia

(B) Hypernatremia

(C) Hypocalcemia

(D) Hypomagnesemia

(E) Hypophosphatemia

D (13) Digitalis toxicity is associated with hypokalemia and hypomagnesemia (and hypercalcemia). Hyperkalemia (choice A) is a trap for careless readers.

A 65-year-old man with cardiomyopathy has recurrent congestive heart failure. Addition of digitalis to his regimen is being considered.

The cellular cause of digitalis toxicity is

(A) Intracellular calcium overload

(B) Intracellular potassium overload

(C) Increased parasympathetic activity

(D) Increased adrenocorticosteroid levels

(E) Impaired sympathetic activity

A (13) Cardiac glycosides act primarily by inhibiting Na⁺/K⁺-ATPase and thus increase intracellular Na⁺. This in turn reduces Ca²⁺ expulsion by the Na⁺-Ca²⁺ exchanger. Excess digitalis results in an excess of intracellular Ca²⁺.

Which of the following effects are characteristic of methylxanthine drugs such as theophylline?

(A) Activation of adenosine receptors

(B) Blockade of the enzyme phosphodiesterase

(C) Decrease in the amount of cAMP in mast cells

(D) Inhibition of cardiac β receptors

(E) Sedation

B (20) The methylxanthines block phosphodiesterase and increase the concentration of cAMP. They may also block adenosine receptors.

Which of the following drugs often causes tachycardia and tremor when used in asthma?

(A) Albuterol

(B) Cromolyn sodium

(C) Ipratropium

(D) Montelukast

(E) Prednisone

A (20) Skeletal muscle tremor is a common adverse effect of beta-adrenoceptor agonists such as albuterol when used in asthma. Even when administered via inhalation, this side effect (as well as tachycardia) can occur. While an antimuscarinic can cause tachycardia, it will not cause tremor, and ipratropium is not usually absorbed in sufficient quantities to cause systemic antimuscarinic effects.

Angioneurotic edema precipitated by exposure to an allergen can cause life-threatening laryngeal edema. One of the probable mediators of such reactions is

(A) Angiotensin II

(B) Epinephrine

(C) Histamine

(D) Norepinephrine

(E) Serotonin

C (16) Several autacoids may be involved in the edema of angioneurotic allergic reactions. Histamine and bradykinin are probable contributors.

A 30-year-old patient in the intensive care unit is to receive a β-antagonist drug. Typical responses to β-receptor blockade include

(A) Bradycardia

(B) Increased renin secretion

(C) Increased skeletal muscle tremor

(D) Glycogen synthesis

(E) Lipolysis

A (10) Beta antagonists typically slow heart rate and increase PR interval. Renin secretion and tremor are decreased. Beta agonists increase lipolysis.

A patient has been taking aspirin for rheumatoid arthritis for 8 yr. Exacerbations are becoming worse, and she asks the physician about drugs that might stop the progression of the disease. Which of the following is a disease-modifying antirheumatic drug (DMARD)?

(A) Colchicine

(B) Epoprostenol

(C) Ketorolac

(D) Methotrexate

(E) Zafirlukast

D (36) Colchicine is used predominantly in acute gout attacks. Methotrexate reduces the number of inflammatory immune cells. Epoprostenol is a prostacyclin (PGI₂), and it is used in the treatment of pulmonary hypertension. Ketorolac is an NSAID with a strong analgesic effect and zafirlukast is a LT₄ receptor antagonist used in the treatment of asthma.

A neuronal cell body located in the substantia nigra has axonal projections to the striatum. The neurotransmitter that it releases, which exerts only inhibitory actions, is most likely to be

(A) Acetylcholine

(B) Dopamine

(C) Glutamic acid

(D) Norepinephrine

(E) Serotonin

B (21) Dopamine exerts slow inhibitory actions at synapses in specific neural systems including the nigrostriatal projections via G protein-coupled activation of postsynaptic potassium channels or by inhibition of presynaptic calcium channels.

A 40-year-old man had been consuming alcoholic beverages at lunch and in the evenings all his adult life. During the last 2 yr, his alcohol consumption had steadily increased, continuing throughout the day. In response to family pressures, he abruptly stopped drinking alcohol, and within a few hours he became increasingly anxious and agitated and showed symptoms of autonomic hyperexcitability. At this point, he was brought to the hospital.

In the emergency department, the symptoms increased in severity, with hyperreflexia progressing to seizures. He was given an intravenous injection of a drug that controlled the seizure activity and was then admitted to the ICU. During the recovery period, the same agent was used in oral form with gradual dose tapering. The drug he received as an injection and then as an oral pill was which of the following?

(A) Acamprosate

(B) Amitriptyline

(C) Diazepam

(D) Ramelteon

(E) Thiamine

C (22, 23, 58) The patient appears to be suffering from the alcohol withdrawal syndrome, which is treated with a long-acting sedative-hypnotic such as diazepam. Diazepam is available in parenteral and oral formulations.

In the first week of this patient’s recovery, he is at risk of a syndrome that is characterized by which of the following?

(A) Ascites, mental confusion, and elevated serum transaminases

(B) Headache, hypotension, and widespread petechiae

(C) Hyperglycemia, acidosis, and stupor

(D) Respiratory depression, miosis, and mental confusion

(E) Tremor, delusions, and visual hallucinations

E (23) This patient is at risk for delirium tremens, which is characterized by tremors, delusions, and hallucinations.

The pharmacokinetic characteristics of several hydantoin derivatives, each with anticonvulsant activity equivalent to that of phenytoin, were examined in phase 1 clinical trials. The rationale was to identify a drug with more desirable kinetic properties than those of phenytoin.

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Drug

Oral Bioavailability (%)

Plasma Protein Binding (%)

Elimination Kinetics

Cytochrome P450 Induction

ABC

First order

DEF

First order

GHI

Zero order

None

JKL

First order

None

MNO

First order

Based on the data shown in the table above, which drug has the optimum pharmacokinetic properties for oral use in the management of patients with seizure disorders?

(A) ABC

(B) DEF

(C) GHI

(D) JKL

(E) MNO

D (24) Compared with phenytoin, favorable characteristics of a new anticonvulsant would include good oral bioavailability, minimal plasma protein binding, first-order elimination kinetics, and no induction (or inhibition) of cytochromes P450.

The speed of induction of anesthesia with halogenated hydrocarbons (eg, halothane, isoflurane) is not affected by

(A) Arteriovenous concentration gradient

(B) Inspired gas partial pressure

(C) Minimal alveolar anesthetic concentration

(D) Pulmonary blood flow

(E) Ventilation rate

C (25) All of the factors listed influence the rate of induction of the anesthetic state except the minimal alveolar anesthetic concentration. MAC reflects potency and is defined as the minimum alveolar anesthetic concentration that eliminates response to a standard painful stimulus in 50% of patients.

A patient is to undergo surgery, and a short-acting anesthetic with a fast onset will be used. Recovery, unhampered by postoperative nausea, will be rapid because the clearance of the drug is greater than hepatic blood flow. The drug to be used is

(A) Enflurane

(B) Halothane

(C) Midazolam

(D) Phenobarbital

(E) Propofol

E (25) The onset of anesthesia with propofol is more rapid than intravenous barbiturates. Its clearance is greater than hepatic blood flow, which suggests extrahepatic elimination. The drug has antiemetic actions, and recovery is not delayed after prolonged infusion.

A patient with an incurable cancer is suffering from pain that is gradually increasing in intensity and levorphanol (a strong μ-receptor agonist) is prescribed. With chronic use of the drug, tolerance is not likely to develop to constipation or to

(A) Euphoria

(B) Nausea and vomiting

(C) Pupillary constriction

(D) Sedation

(E) Urinary retention

C (31) Although miosis is characteristic of all opioids except meperidine, which has a muscarinic blocking action, little or no tolerance occurs. Pupillary constriction due to opioids can be blocked by atropine and by naloxone.

Drugs activate or block a wide range of receptor types and their downstream receptor signaling pathways. Which of the following drugs mediates its effects by binding to and activating an intracellular receptor that, when activated, acts as a transcription factor, ultimately leading to the desired therapeutic effect?

(A) Albuterol

(B) Captopril

(C) Erythropoietin

(D) Morphine

(E) Prednisone

E (2, 39) Prednisone is a steroid and acts via binding the cytoplasmic steroid receptors, followed by a translocation of the receptor-ligand complex into the nucleus, altering gene transcription. All other agents listed in this question bind to membrane-bound extracellular receptors.

The primary clinical application of the 5-HT₂ receptor antagonist trazodone is the treatment of

(A) Bipolar disorder

(B) Chronic pain

(C) Insomnia

(D) Major depressive disorder

(E) Premenstrual dysphoric disorder

C (30) Nefazodone and trazodone are 5-HT₂ receptor antagonists with both anxiolytic and antidepressant actions. In addition, at a relatively low dose, trazodone is a widely used and effective hypnotic with minimal dependence liability compared with most of the sedative-hypnotic drugs used in sleep disorders.

The following data concern the relative activities of hypothetical investigational drugs as blockers of the membrane transporters (reuptake systems) for 3 CNS neurotransmitters.

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Blocking Actions on CNS Transporters for

Drug

Dopamine

Serotonin

Norepinephrine

UCSF 1

+++

None

UCSF 2

+++

++++

UCSF 3

None

UCSF 4

None

+++

UCSF 5

None

Key: Number of + signs denotes intensity of blocking actions

Which drug is likely to be effective in the treatment of major depressive disorders but may also cause marked adverse effects, including thought disorders, delusions, hallucinations, and paranoia?

(A) UCSF 1

(B) UCSF 2

(C) UCSF 3

(D) UCSF 4

(E) UCSF 5

B (29, 30) Enhancement of the actions of norepinephrine and/or serotonin via inhibition of reuptake transporters is characteristic of many antidepressants including the tricyclics and the SSRIs. However, inhibition of the reuptake of dopamine leading to enhancement of its CNS effects has been equated with thought disorders, delusions, hallucinations, and paranoia.

Of the following drugs, which has established clinical uses that include attention deficit hyperkinetic disorder, enuresis, and the management of chronic pain?

(A) Bupropion

(B) Citalopram

(C) Imipramine

(D) Risperidone

(E) Sertraline

C (30) Enuresis is an established indication for tricyclic antidepressants including imipramine, and they are also used as backup drugs to methylphenidate in attention deficit disorder. Chronic pain states that may be unresponsive to conventional analgesics often respond to tricyclics.

The selective serotonin reuptake inhibitors fluoxetine and paroxetine are potent inhibitors of hepatic CYP2D6 drug-metabolizing enzymes. This action may lead to changes in the intensity of the effects of

(A) Benztropine

(B) Codeine

(C) Gentamicin

(D) Lithium

(E) Methotrexate

B (30, 31) Codeine, oxycodone, and hydrocodone are all metabolized by cytochrome CYP2D6, which can be inhibited by certain SSRIs including fluoxetine and paroxetine. This may lead to a decreased analgesic effects of codeine that is normally metabolized in part via CYP2D6 forming the more active compound morphine.

A 45-year-old woman was suspected of having Cushing’s syndrome. To confirm the diagnosis, the patient was given an oral medication late in the evening and had blood drawn the following morning for laboratory testing. The oral medication was which of the following?

(A) Dexamethasone

(B) Fludrocortisone

(C) Glucose

(D) Ketoconazole

(E) Propylthiouracil

A (39) Cushing’s syndrome is a consequence of too much steroid production and is most commonly due to an ACTH-secreting pituitary adenoma. Dexamethasone will suppress ACTH production and thus can be used diagnostically to separate pituitary Cushing’s from those with ectopic ACTH-producing tumors. Fludrocortisone acts on mineralocorticoid receptors only. Glucose is already elevated as a consequence of the disease, and adding more will not be diagnostic. Ketoconazole will inhibit male hormone synthesis but will not provide differential diagnostic information. PTU (propylthiouracil) inhibits thyroid hormone signaling.

The reason why clozapine causes less extrapyramidal dysfunction than haloperidol when used in schizophrenia is that in the CNS, clozapine

(A) Activates GABA receptors

(B) Blocks dopamine release

(C) Has greater antagonism at muscarinic receptors

(D) Has a low affinity for dopamine D₂ receptors

(E) Is an α-receptor agonist

D (29) Clozapine has greater muscarinic and alpha-blocking activity than haloperidol, but neither of these is the primary reason why the drug is less likely to cause extrapyramidal dysfunction. The main reason is that clozapine has very low affinity for the dopamine D₂ receptor in the striatum.

A patient taking medications for a psychiatric disorder develops a tremor, thyroid enlargement, edema, and acneiform eruptions on the face. The drug he is taking is most likely to be

(A) Carbamazepine

(B) Haloperidol

(C) Lamotrigine

(D) Lithium

(E) Sertraline

D (29) Edema and thyroid enlargement are common adverse effects of lithium, although the latter does not usually involve hypothyroidism. Neurologic side effects of lithium include tremor, ataxia, and aphasia.

The mechanism of action of the hypnotic drug zolpidem is

(A) Activation of GABA_B receptors

(B) Antagonism of glycine receptors in the spinal cord

(C) Blockade of the action of glutamic acid

(D) Increased GABA-mediated chloride ion conductance

(E) Inhibition of GABA aminotransferase

D (21, 22) Though not benzodiazepines, zolpidem, zaleplon, and eszopiclone exert their hypnotic effects via interaction with benzodiazepine receptors in the CNS, leading to an increase in GABA-mediated chloride ion conductance.

After a very large overdose of diazepam a 2-year-old child is admitted to the hospital. Along with general supportive care, the administration of which of the following is most likely to be used to reverse the action of the benzodiazepine?

(A) Acetylcysteine

(B) Atropine

(C) Flumazenil

(D) Fomepizole

(E) Naloxone

C (22, 58) Diazepam is a benzodiazepine sedative-hypnotic drug whose action can be competitively inhibited by flumazenil. Acetylcysteine is used for acetaminophen overdose. Atropine is used in organophosphate poisoning, fomepizole is used for methanol or ethylene glycol poisoning, and naloxone is used for opioid overdose.

If an aerobic gram-negative rod causing bacteremia proves to be resistant to aminoglycosides, the mechanism of resistance is most likely due to

(A) Changed pathway of bacterial folate synthesis

(B) Decreased intracellular accumulation of the drug

(C) Formation of drug-trapping thiol compounds

(D) Inactivation by bacterial group transferases

(E) Induced synthesis of beta-lactamases

D (45) In gram-negative bacteria, the primary mechanism of resistance to aminoglycosides involves the plasmid-mediated formation of inactivating enzymes that acetylate, adenylate, or phosphorylate the drug molecule. Such enzymes are called group transferases.

A 54-year-old woman with a recent history of deep vein thrombosis had been stable on warfarin therapy for the last 2 mo. However, her most recent prothrombin time (PT) test revealed a markedly reduced INR. When asked about changes in diet or medication during the last several weeks, the woman said that she had recently begun taking a dietary supplement recommended by a friend. Based on this information, the supplement is most likely to contain which of the following?

(A) Ginkgo

(B) Ginseng

(C) Kava

(D) Ma huang

(E) St. John’s wort

E (3, 34, 60, 61) Warfarin is metabolized by CYP3A4 (and CYP1A and CYP2C). The patient’s INR is reduced; her plasma level of warfarin is subtherapeutic. This means the metabolism of warfarin is induced. St. John’s wort is a potent inducer of CYP3A4. The other drugs do not appear to affect the P450 enzyme family.

Beta-lactamase production by strains of Haemophilus influenzae and N gonorrhoeae confers resistance against penicillin G. Which of the following drugs is most likely to be effective against resistant strains of these organisms?

(A) Amoxicillin

(B) Ceftriaxone

(C) Clindamycin

(D) Gentamicin

(E) Vancomycin

B (43) The third-generation cephalosporins ceftriaxone and cefotaxime (not listed) are currently the most active beta-lactam antibiotics against beta-lactamase-producing strains of H influenzae and Neisseria. However, some resistance has been reported recently.

A 24-year-old woman is to be treated with levofloxacin for a urinary tract infection. A contraindication to the use of the antibiotic in this patient is

(A) Deep vein thrombosis

(B) Glucose-6-phosphate dehydrogenase (G6PD) deficiency

(C) Gout

(D) Q-T prolongation

(E) Use at the present time of a combined hormonal contraceptive

D (46) Patients with a history of cardiac irregularities should avoid certain fluoroquinolones including levofloxacin and moxifloxacin since they are known to cause QT prolongation.

A 39-year-old woman with recurrent sinusitis has been treated with different antibiotics on several occasions. During the course of one such treatment, she developed a severe diarrhea and was hospitalized. Sigmoidoscopy revealed colitis, and pseudomembranes were confirmed histologically. Which of the following drugs, administered orally, is most likely to be effective in the treatment of colitis caused by Clostridium difficile?

(A) Ampicillin

(B) Cefazolin

(C) Metronidazole

(D) Tetracycline

(E) Trimethoprim-sulfamethoxazole

C (43, 50) The anaerobic bacterium Clostridium difficile is a cause of life-threatening pseudomembranous colitis. The primary drugs used in management of such infections are vancomycin (not listed) or metronidazole.

In the management of patients with AIDS, trimethoprim-sulfamethoxazole is commonly used to prevent infection resulting from

(A) Campylobacter jejuni

(B) Mycobacterium avium-intracellulare

(C) Neisseria gonorrhea

(D) Pneumocystis jiroveci

(E) Treponema pallidum

D (46, 52) One double-strength tablet of sulfamethoxazole-trimethoprim three times weekly is prophylactic against P jiroveci infection in AIDS patients but may cause rash, fever, and leukopenia.

In a cancer cell, decreased ability to phosphorylate pyrimidines could result in resistance to the anticancer action of which of the following?

(A) Cisplatin

(B) Etoposide

(C) Fluorouracil

(D) Mercaptopurine

(E) Methotrexate

C (54) The question asks about antimetabolites. The two options in this class are mercaptopurine and fluorouracil. Mercaptopurine is a purine affecting purine metabolism leaving 5-FU, which is a suicide substrate for thymidylate synthase.

A 65-year-old woman with endometrial cancer came to an outpatient cancer treatment center for her first cycle of platinum-based chemotherapy. To prevent chemotherapy-induced nausea and vomiting, this patient is likely to be given which of the following?

(A) Famotidine

(B) Linaclotide

(C) Mesalamine

(D) Ondansetron

(E) Sumatriptan

D (16, 59) Ondansetron, a serotonin 5-HT₃ receptor antagonist, is a highly effective antiemetic. Famotidine is a H₂ receptor antagonist used for acid-peptic disease. Linaclotide is a laxative that stimulates Cl⁻ secretion into gut lumen, used for irritable bowel syndrome with constipation. Mesalamine is a form of 5-aminosalicylic acid (5-ASA) used for inflammatory bowel disease, and sumatriptan is a serotonin 5-HT_1D/1B agonist used for migraine headache.

A 20-year-old foreign exchange student attending college in California is to be treated for pulmonary tuberculosis. Because drug resistance is anticipated, the proposed antibiotic regimen includes ethambutol, isoniazid (with supplementary vitamin B₆), pyrazinamide, and rifampin. Provided that his disease responds well to the drug regimen and that the microbiology laboratory results show sensitivity to the drugs, it would be appropriate after 2 mo to

(A) Change his drug regimen to prophylaxis with isoniazid

(B) Discontinue pyrazinamide

(C) Establish baseline ocular function

(D) Monitor amylase activity

(E) Stop the supplementary vitamin B₆

B (47) A 4-drug initial regimen would be appropriate in this case, and if the laboratory reports show sensitivity to the drugs, it would be appropriate to discontinue pyrazinamide, maintaining the 3-drug regimen that includes both isoniazid and rifampin. Pyrazinamide has a high incidence of adverse effects including polyarthralgia as well as hepatic dysfunction, porphyria, and photosensitivity reactions.

An antifungal drug that binds to ergosterol forming “pores” that disrupt fungal membrane integrity is

(A) Amphotericin B

(B) Caspofungin

(C) Fluconazole

(D) Flucytosine

(E) Terbinafine

A (48) The amphipathic character of amphotericin B following its interaction with ergosterol in fungal cell membranes leads to artificial pores that disrupt membrane integrity. Nystatin, another polyene, acts similarly but is too nephrotoxic for systemic use.

A 20-year-old college student is brought to the emergency department after taking an overdose of a nonprescription drug. The patient is comatose. He has been hyperventilating and is now dehydrated with an elevated temperature. Serum analyses demonstrate that the patient has an anion gap metabolic acidosis.

Toxic exposure to which of the following drugs is the most likely cause of these signs and symptoms?

(A) Aspirin

(B) Acetaminophen

(C) Dextromethorphan

(D) Diphenhydramine

(E) Ethanol

A (36, 58) An overdose of aspirin will cause anion gap metabolic acidosis, as described here. Ethanol can also cause anion gap acidosis as ethanol metabolism generates NADH, leading to conversion of pyruvate to lactate, but the condition is often mild even without treatment. Acetaminophen causes liver failure in overdose, whereas dextromethorphan, an opioid, will cause respiratory depression and not hyperventilation. Diphenhydramine, an antihistamine, causes sedation through its effect on central histamine receptors but does not generally cause acidosis.

In the management of this patient, it would be most appropriate to

(A) Administer acetylcysteine

(B) Administer fomepizole

(C) Administer glucagon

(D) Alkalinize the urine

(E) Induce vomiting with syrup of ipecac

D (1, 58) Aspirin is a weak acid with a pKa of 3.5. Urinary alkalinization to a pH of 7.5 or above by administration of sodium bicarbonate will enhance urinary excretion of aspirin and other salicylates. Urinary alkalinization traps the charged, polar form of the salicylates in the renal tubule fluid. Hemodialysis is also very effective at removing salicylates.

This drug is prophylactic in meningococcal and staphylococcal carrier states. Although the drug eliminates a majority of meningococci from carriers, highly resistant strains may be selected out during treatment.

(A) Ciprofloxacin

(B) Clofazimine

(C) Dapsone

(D) Rifampin

(E) Streptomycin

D (47) Resistance emerges rapidly when rifampin is used as a single agent in the treatment of bacterial infections. When used in the meningococcal carrier state, highly resistant strains may be selected out during treatment.

Chemoprophylaxis for travelers to geographic regions where chloroquine-resistant Plasmodium falciparum is endemic is effectively provided by

(A) Doxycycline

(B) Malarone (atovaquone-proguanil)

(C) Mefloquine

(D) None of the drugs listed above

(E) Any of the drugs listed above

E (52) Doxycycline, atovaquone-proguanil (Malarone), and mefloquine are all prophylactic against chloroquine-resistant strains of P falciparum.

A cardiac Purkinje fiber was isolated from an animal heart and placed in a recording chamber. One of the Purkinje cells was impaled with a microelectrode, and action potentials were recorded while the preparation was stimulated at 1 stimulus per second. A representative control action potential is shown in red in the graph. After equilibration, a drug was added to the perfusate while recording continued. A representative action potential obtained at the peak of drug action is shown as the superimposed action potential (blue). No beta or calcium channel block was observed. Identify the drug from the following list.

(A) Adenosine

(B) Amiodarone

(C) Diltiazem

(D) Flecainide

(E) Fluoxetine

(F) Lidocaine

(G) Nitroglycerin

(H) Procainamide

(I) Sotalol

(J) Verapamil

H (14) The action potential has a markedly slowed upstroke and prolonged duration. These effects, without beta or calcium block (characteristic of amiodarone) are characteristic of group 1A drugs, including procainamide.

A 24-year-old man with a 7-year history of Crohn’s disease was suffering from persistent diarrhea, abdominal pain, and signs of systemic inflammation that were poorly controlled by first-line agents. The patient’s physician proposed treatment with an immunoglobulin-based agent that inhibits tumor necrosis factor (TNF). Which of the following drugs fits this description?

(A) Aldesleukin

(B) Cyclosporine

(C) Filgrastim

(D) Infliximab

(E) Interferon-γ

D (55) Infliximab is a chimeric monoclonal antibody that binds to tumor necrosis factor-alpha (TNF-α). Anti-TNF-α antibody-based drugs (etanercept, adalimumab) are increasingly used to treat inflammatory disorders such as rheumatoid arthritis.

A 43-year-old woman was brought to a hospital emergency department by her brother. Visiting the halfway house in which she lived, he had found her to be lethargic, with slurred speech. The patient had a long history of treatment for depression, and the brother feared that she might have overdosed on 1 or more of her prescription drugs. Physical examination revealed hypotension, tachycardia, decreased bowel sounds, dilated pupils, and hyperthermia. If this patient had taken a drug overdose, the most likely causative agent was

(A) Amitriptyline

(B) Celecoxib

(C) Lithium

(D) Ramelteon

(E) Zaleplon

A (30) Adverse effects of the tricyclic antidepressant amitriptyline include sedation, hypotension, tachycardia, and symptoms of muscarinic blockade such as decreased bowel sounds and pupillary dilation. In severe overdose, watch for the “3 Cs”—coma, convulsions, and cardiotoxicity.

A 30-year-old hospitalized patient with AIDS has a CD4 cell count of 50/μL. He is being treated with a highly active antiretroviral therapy (HAART) regimen consisting of zidovudine (ZDV), lamivudine (3TC), and indinavir. Other drugs being administered to this patient include ganciclovir, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole.

The drug in this patient’s regimen that inhibits posttranslational modification of viral proteins is

(A) Acyclovir

(B) Indinavir

(C) Lamivudine

(D) Rifabutin

(E) Zidovudine

B (49) Protease inhibitors such as indinavir act at the posttranslational step of HIV at which the viral enzyme cleaves precursor molecules to form the final structural proteins of the mature virion core.

None of the drugs being administered to this patient are useful for prevention or treatment of opportunistic infections caused by

(A) Candida albicans

(B) Cytomegalovirus

(C) Mycobacterium avium-intracellulare

(D) Pneumocystis jiroveci

(E) Toxoplasma gondii

A (48, 49) Prophylactic drugs used in this AIDS patient provide coverage against most opportunistic infections, including cytomegalovirus (ganciclovir), but there is no coverage against fungal infections commonly due to Candida albicans.

A 62-year-old woman who presented with pain in her hips, knees, and several vertebrae was diagnosed with Paget’s disease. She had been mostly immobile lately due to bone pain and presented with lethargy, fatigue, muscle weakness, anorexia, and constipation. Her serum calcium concentration was found to be 14 mg/dL (normal 9–10 mg/dL). In addition to the bisphosphonates, another drug that has proved useful in reducing bone pain and lowering serum calcium in female patients with Paget’s disease is which of the following?

(A) Calcitonin

(B) Fluoride

(C) Hydrochlorothiazide

(D) Raloxifene

(E) Teriparatide (recombinant form of PTH)

A (42) Paget’s is a condition of too much bone resorption leading to elevated serum calcium. Both the bisphosphonates (“dronates”) and calcitonin will inhibit this. Calcitonin is the drug of choice for the acute lowering of serum calcium. Fluoride and raloxifene affect bone formation. PTH and HTZ increase serum calcium.

A 46-year-old man has hypertension of 155/95. His cardiac and kidney function is normal. Losartan has been suggested as therapy. This drug provides an antihypertensive effect by which of the following effects?

(A) Accelerating the rate of enzymatic inactivation of amine neurotransmitters in the CNS

(B) Activating α₂-adrenoceptors located in the presynaptic membranes of CNS neurons that regulate peripheral SANS activity

(C) Blocking the transport of amine neurotransmitters from the cytoplasm to the inside of synaptic transmitter storage vesicles

(D) Inhibiting the uptake of amine neurotransmitters from the extracellular fluid into the cytoplasm in the presynaptic nerve terminus

(E) Interfering with the combination of angiotensin II with its receptor

E (6, 11) Losartan is a member of the angiotensin receptor-blocking group. It is a competitive antagonist of angiotensin II at its receptor.

Which vasodilator acts on vascular smooth muscle to block calcium influx via L-type channels?

(A) Diazoxide

(B) Diltiazem

(C) Hydralazine

(D) Minoxidil

(E) Nitroprusside

B (11) Diltiazem, as well as nifedipine and verapamil, act as vasodilators by reducing calcium influx via L-type channels. Hydralazine and nitroprusside act through release of nitric oxide. Diazoxide and minoxidil facilitate potassium channel opening.

In anesthesia protocols that include succinylcholine, which of the following is a premonitory sign of malignant hyperthermia?

(A) Acidosis

(B) Bradycardia

(C) Hypotension

(D) Transient hypothermia

(E) Trismus

E (25) Trismus, or masseter hypertonia, that results from the use of succinylcholine during induction of anesthesia is a rare and dangerous phenomenon. It presents to the anesthesiologist the immediate problem of airway management but it also must be recognized by the physician as a harbinger of malignant hyperthermia.

Diners at a popular seafood restaurant became ill after consuming clams and mussels. Consultation with the local coastal authorities revealed that the area from which the seafood had been harvested had recently had a major “red tide.” The consumption of shellfish harvested during a red tide (resulting from a large population of a dinoflagellate species) is not recommended because of contamination with saxitoxin, a drug that resembles tetrodotoxin. These toxins cause which of the following effects?

(A) Clonic-tonic seizures

(B) Malignant hypertension

(C) Nerve transmission blockade

(D) Renal failure

(E) Ventricular torsades de pointes arrhythmias

C (6) Dinoflagellates secrete saxitoxin, a blocker of voltage-gated Na⁺ channels in nerves. Exposure to this toxin results in block of transmission initially in sensory nerves (causing numbness and tingling) but may extend to block of motor nerves with paralysis of voluntary muscle, including the diaphragm.

A 66-year-old patient is diagnosed with hypertension and angina. A drug with benefits in both conditions is suggested. Which of the following drugs has both nonselective β-blocking and α₁-selective blocking action?

(A) Atenolol

(B) Carvedilol

(C) Nadolol

(D) Pindolol

(E) Timolol

B (10) Carvedilol is the only β blocker in the list that also has α-blocking action.

A 35-year-old woman who has never been pregnant suffers each month from pain, discomfort, and mood depression at the time of menses. She may benefit from the use of this selective inhibitor of the reuptake of serotonin in a form that can be taken once weekly.

(A) Amoxapine

(B) Bupropion

(C) Fluoxetine

(D) Mirtazapine

(E) Tranylcypromine

C (30) Approximately 5% of women of child-bearing age experience symptoms during the late luteal phase of the menstrual cycle that are more serious than PMS. It is referred to as premenstrual dysphoric disorder (PMDD). SSRIs, including a long-acting form of fluoxetine given weekly, are approved for this indication.

Which one of the following drugs is considered a first-line treatment for post-traumatic stress disorder?

(A) Citalopram

(B) Diazepam

(C) Imipramine

(D) Nefazodone

(E) Selegiline

A (30) SSRIs are considered first-line treatment of PTSDs and can benefit a number of symptoms including anxious thoughts and hypervigilance. Psychotherapeutic interventions are usually required in addition to antidepressants.

Adverse effects of the opioid analgesics do not include

(A) Diarrhea

(B) Emesis

(C) Increased intracranial pressure

(D) Respiratory depression

(E) Urinary retention

A (31) With the exception of diphenoxylate and loperamide, which are used for the treatment of diarrhea, constipation is considered an adverse effect of the opioid analgesics.

Drugs that selectively inhibit D₂ dopamine receptors in the CNS have efficacy in the treatment of schizophrenia. Efficacy in the treatment of schizophrenia is also seen with drugs that block

(A) α-Adrenoceptors or D₁ dopamine receptors

(B) D₄ dopamine receptors or 5-HT_2A serotonin receptors

(C) GABA_A receptors or 5-HT₃ serotonin receptors

(D) H₁ histamine receptors or β-adrenoceptors

(E) β-Adrenoceptors or NMDA receptors

B (29) Although all effective antipsychotic drugs block D₂ receptors, some are more potent inhibitors of D₄ dopamine receptors (eg, clozapine) or 5-HT_2A serotonin receptors (eg, olanzapine).

A 44-year-old patient suffering from an alcohol-use disorder enters a residential treatment program that emphasizes group therapy and also uses pharmacologic agents adjunctively. The patient is given a drug that decreases the craving for alcohol. Because the drug will not cause adverse effects if the patient consumes alcoholic beverages, it can be identified as which of the following?

(A) Bupropion

(B) Disulfiram

(C) Olanzapine

(D) Naltrexone

(E) Sertraline

D (23, 31, 32) Naloxone, a nonselective opioid receptor antagonist, is used by individuals recovering from alcohol-use disorders.

A 22-year-old woman presents with left lower quadrant abdominal pain and a purulent vaginal discharge that revealed gram-negative rods. A diagnosis is made of pelvic inflammatory disease possibly involving both N gonorrhoeae and C trachomatis. A drug or drug combination that provides adequate empiric coverage of the organisms involved in this infection is

(A) Clarithromycin

(B) Ceftriaxone plus doxycycline

(C) Metronidazole

(D) Norfloxacin plus ampicillin

(E) Trimethoprim-sulfamethoxazole

B (43, 44) Ceftriaxone (or cefixime) is a drug of choice for treatment of gonococcal infections, and chlamydial infections usually respond to a tetracycline. Though not listed, azithromycin as a single agent is considered a co-drug of choice for chlamydial infections and an alternative drug for gonococcal infections.

A 34-year-old man was diagnosed with Hodgkin’s lymphoma, and chemotherapy with multiple anticancer drugs was initiated. Which of the following agents is an agonist of a hormone receptor and is used in the treatment of Hodgkin’s lymphoma?

(A) Dacarbazine

(B) Doxorubicin

(C) Prednisone

(D) Procarbazine

(E) Vinblastine

C (39, 54) Hodgkin’s lymphoma is a cancer of lymph tissue found in the lymph nodes, spleen, liver, bone marrow, and other sites. It responds well to combinations that include prednisone. Prednisone and other glucocorticoids are selectively lymphocytolytic. All other agents listed in this question are cytotoxic agents.

Which of the following is a tyrosine kinase enzyme inhibitor that is used to treat chronic myelogenous leukemia?

(A) Anastrozole

(B) Doxorubicin

(C) Imatinib

(D) Rituximab

(E) Vincristine

C (54) Note that kinase inhibitors have names ending in “nib.” Anastrozole is an aromatase inhibitor. Doxorubicin is an antitumor antibiotic. Imatinib targets bcr-abl kinase. Rituximab is a monoclonal antibody against CD20. Vincristine is an alkaloid affecting microtubules.

A 17-year-old high school student presents with headache, fever, and cough of 2 days’ duration. Sputum is scant and nonpurulent, and a Gram stain reveals many white cells but no organisms. Because this otherwise healthy patient appears to have a community-acquired pneumonia, you should initiate treatment with

(A) Azithromycin

(B) Clindamycin

(C) Tetracycline

(D) Metronidazole

(E) Quinupristin-dalfopristin

A (44, 46) With respect to microbial etiology, the most likely organisms in community-acquired pneumonia (CAP) are S pneumoniae, H influenzae, and M catarrhalis. Depending on resistance patterns in the community, it is possible to treat CAP with a single antibiotic, and azithromycin is one of the antibiotics commonly used.

Relative to ciprofloxacin, levofloxacin has improved activity against

(A) Bacteroides fragilis

(B) Escherichia coli

(C) Haemophilus influenzae

(D) Mycoplasma pneumoniae

(E) Streptococcus pneumoniae

E (46) In the case described in question 90, though not listed, levofloxacin is also used both as a single drug and in drug combinations in CAP, precisely because the drug has much greater activity than ciprofloxacin against likely organisms, especially the pneumococcus.

Which of the following is the drug of choice for the management of osteoporosis caused by high-dose use of glucocorticoids?

(A) Alendronate

(B) Anastrozole

(C) Ethinyl estradiol

(D) Omeprazole

(E) Oxandrolone

A (42) “Dronates” inhibit bone resorption. Anastrozole is an aromatase inhibitor used for treatment of breast cancer. Ethinyl estradiol is an estrogen stimulating bone resorption. Omeprazole is a proton pump inhibitor. Oxandrolone is an androgen used when its anabolic action is needed (wasting due to illness: cancer, HIV, etc.)

A 45-year-old man who received an allogenic liver transplant received an immunosuppressive regimen containing prednisone, azathioprine, and cyclosporine. Which of the following most accurately describes the mechanism of anti-inflammatory activity of cyclosporine?

(A) Activation of phospholipase A₂

(B) Block of interleukin-2 receptors

(C) Competitive inhibition of inosine monophosphate dehydrogenase

(D) Inhibition of enzymes involved in purine metabolism

(E) Inhibition of the cytoplasmic phosphatase calcineurin

E (55) Cyclosporine exerts its immunosuppressive effect by binding to the immunophilin cyclophilin and forming a complex with the cytosolic phosphatase calcineurin, which is necessary for activation of the T-cell nuclear factor of activated T-cell (NF-AT) transcription factor. As a result, cyclosporine inhibits the synthesis of interleukins such as IL-2 by activated T cells.

Which one of the following drugs is appropriate for treating a patient with moderate-to-severe rheumatoid arthritis but is not appropriate for treating a patient with moderate-to-severe osteoarthritis?

(A) Acetaminophen

(B) Etanercept

(C) Ibuprofen

(D) Interferon α

(E) Fentanyl

B (36) Etanercept is not appropriate for osteoarthritis because it binds to and inactivates TNF-α. Thus, it will only be of use in inflammatory disorders that are mediated through TNF-α such as rheumatoid arthritis, juvenile-onset arthritis psoriasis, psoriatic arthritis, and ankylosing spondylitis.

An anesthetized subject was given an intravenous bolus dose of a drug (Drug 1) while the systolic and diastolic blood pressures (blue) and the heart rate were recorded, as shown on the left side of the graph below. While the recorder was stopped, Drug 2 was given (center). Drug 1 was then administered again, as shown on the right side of the graph.

Identify Drug 1 from the following list

(A) Atropine

(B) Diphenhydramine

(C) Echothiophate

(D) Endothelin

(E) Epinephrine

(F) Histamine

(G) Isoproterenol

(H) Norepinephrine

(I) Phentolamine

(J) Phenylephrine

(K) Terbutaline

J (9) This question and the following one require a combined knowledge of agonist and antagonist actions. Note that systolic and diastolic blood pressures are increased, but heart rate is decreased by drug 1. This is compatible with a strong α-agonist drug such as norepinephrine (choice H) or phenylephrine (choice J). The final choice must be withheld until the actions of drug 2 are evaluated. Following drug 2, there is no change in heart rate, suggesting that the bradycardia seen previously was a reflex response to the pressor effect. Thus, drug 1 lacks β-agonist effect; it is a “pure” α agonist.

Identify Drug 2 from the following list

(A) Angiotensin II

(B) Atropine

(C) Bethanechol

(D) Diphenhydramine

(E) Endothelin

(F) Epinephrine

(G) Isoproterenol

(H) Norepinephrine

(I) Phentolamine

(J) Phenylephrine

(K) Terbutaline

I (10) As noted in the answer to the previous question, the agonist drug (drug 1) is probably a strong α-agonist sympathomimetic. Drug 2 markedly reduces the pressor action of drug 1 (compatible with α blockade) and also suppresses the change in heart rate. If drug 1 was norepinephrine, its β-agonist effect on heart rate would have been unmasked. Thus, drug 2 is a simple α blocker.

A 35-year-old man presented with lethargy, weight gain, and muscle weakness. Lab findings confirm the diagnosis of hypothyroidism. In the treatment of hypothyroidism, thyroxine is preferred over liothyronine because thyroxine

(A) Can be made more easily by recombinant DNA technology

(B) Has a longer half-life

(C) Has higher affinity for thyroid hormone receptors

(D) Is faster acting

(E) Is more likely to improve a patient’s mood

B (38) Thyroxine (T₄) is preferred over liothyronine (T₃) because it has a longer half-life. It is less expensive and has a slower onset of action. It is converted into T₃ in the tissues; thus, the affinity for the receptor or the effects on the patient’s mood will be the same.

A 29-year-old G1P1 (gravida-1, para-1) woman presents with infertility of 12 months’ duration. Questioning reveals that the patient has had only 4 menstrual periods in the last year and that she sometimes notices breast nipple discharge. She has not been taking any prescription medications during the last year. A serum prolactin measurement reveals a concentration of 90 ng/mL (normal for a nonpregnant woman is <25 ng/mL). Based on these findings, which of the following drugs is most likely to help make this woman’s ovulation more regular and restore her fertility?

(A) Bromocriptine

(B) Desmopressin

(C) Leuprolide

(D) Prochlorperazine

(E) Spironolactone

A (37) This patient has signs and symptoms of hyperprolactinemia, which is caused by prolactin-secreting pituitary adenomas. Dopamine D₂ receptor agonists such as bromocriptine can be used to suppress the excessive prolactin secretion.

A 34-year-old woman seeks advice because she has been trying to get pregnant for 2 yr. You diagnose anovulation. Which of the following can increase LH and FSH output to induce ovulation?

(A) Clomiphene

(B) Diethylstilbestrol plus raloxifene

(C) Flutamide

(D) Letrozole plus finasteride

(E) Levonorgestrel

A (40) Clomiphene is a nonsteroidal compound. By selectively blocking estrogen receptors in the pituitary, clomiphene reduces negative feedback and increases FSH and LH output. The increase in gonadotropins stimulates ovulation.

A 55-year-old woman with type 2 diabetes was going to be started on metformin. Before initiating therapy, it is important to confirm that the patient has normal renal function because patients with unrecognized renal insufficiency who take normal doses of metformin are at increased risk of which of the following?

(A) Hypoglycemia

(B) Interstitial nephritis

(C) Lactic acidosis

(D) Liver failure

(E) Torsades de pointes cardiac arrhythmia

C (41) Metformin carries a black box warning for lactic acidosis. Note that metformin is a “euglycemic agent” (ie, it does not cause hypoglycemia).

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Examination 1

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Examination 1

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