E (7, 31) Neither opioids nor muscarinic agonists decrease salivation, decrease sweating, or raise blood pressure. Opioids decrease peristalsis; muscarinics increase it. Both drug groups can cause miosis.*
A (19) Nitric oxide (NO) is not stored; it is synthesized on demand in response to acetylcholine, histamine, and other drugs in several tissues, including brain and endothelium. NO is released from the nitroprusside molecule.
B (1) The graph shows first-order elimination of the drug in question (note ordinate is a log scale). Aspirin, ethanol, and phenytoin are eliminated mainly by zero-order kinetics. Diazepam is the only drug in the list that is eliminated by first-order kinetics.
C (2) Membrane-bound tyrosine kinase receptors are activated by peptides such as insulin and epidermal growth factor, see Table 2–1.
C (3) During a continuous IV infusion, the plasma concentration approaches steady state according to the algorithm: 50% at 1 half-life, 75% at 2, etc. Since the sample was taken at two half-lives, the steady state concentration will be in the range of four-thirds the measured concentration (2.4/0.75) or 3.2 mg/L.
E (1) Before clinical trials can be carried out with a new drug, reproductive toxicity data must be provided for at least 2 species.
A (56) Carbon monoxide is a byproduct of combustion and can accumulate when a stove is used in a closed room, particularly when used longer than overnight.
B (6) Questions about the baroreceptor reflex are common; Figure 6–4 is very high yield. The major responses to hypotension are sympathetic discharge (choice B) and activation of the renin-angiotensin-aldosterone system. The damp skin associated with sympathetic discharge is due to activation of sweat glands.
C (10, 18) Mannitol is sometimes used to rapidly reduce intraocular pressure in acute angle-closure glaucoma. Of the drugs listed, only latanoprost is used in chronic glaucoma.
C (9) The graph shows a marked decrease in diastolic blood pressure and marked increase in heart rate, with only a small, transient increase in systolic blood pressure. These effects are characteristic of isoproterenol and similar β1, β2 agonists.
D (4, 23, 36) Chronic alcohol use induces hepatic cytochrome P450 mixed oxidase isozymes enzymes. Elevated P450 activity converts more acetaminophen into a toxic intermediate, which requires inactivation by glutathione (GSH). This alcohol-induced increase in P450 increases the risk of reaching a level of toxic acetaminophen metabolite that can overwhelm the liver’s detoxification capacity and result in severe hepatotoxicity.
C (4) Acetylation, glucuronidation, methylation, and sulfation are phase II conjugation reactions.
C (12) Although nitrates may dilate large and medium coronary vessels, they have little effect on the arterioles in ischemic tissue, which are already dilated maximally by local ischemia. A major beneficial effect is venodilation, leading to reduction in cardiac size, which decreases diastolic fiber length and reduces myocardial oxygen demand.
E (12) Verapamil and diltiazem are useful for prophylaxis of both effort and vasospastic angina. Calcium blockers reduce cardiac work and oxygen demand. They also cause constipation and sometimes peripheral edema that is not associated with heart failure.
B (7) Symptomatic paroxysmal sinus tachycardia often occurs in young patients and can sometimes be converted to normal sinus rhythm with increased vagal discharge. Brief amplification (5–15 min) of the vagal effects on the heart can be accomplished with a short-acting cholinesterase inhibitor such as edrophonium. Pyridostigmine (E) would have a much longer action (4–6 hr).
B (59) Metoclopramide, a dopamine D2 receptor antagonist, is a prokinetic drug that can be used to increase gastric emptying and intestinal motility in patients with diabetes-associated gastric paresis. Famotidine is a histamine H2 receptor antagonist used for acid-peptic disease. Misoprostol is a prostaglandin E1 analog used for acid-peptic disease and for medical abortions. Omeprazole is a proton pump inhibitor used for acid-peptic disease, and ondansetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic.
D (10) Reflex tachycardia is a major disadvantage of nonselective α blockers in the treatment of hypertension because the tachycardia is exaggerated by the α2 blockade of nonselective agents. The α1-selective blockers are much less likely to exaggerate this reflex response.
D (11) ACE inhibitors, arteriolar dilators, and β blockers do not ordinarily cause orthostatic hypotension; venodilators do. Peripheral α1 antagonists block sympathetic effects on both arterioles and veins and thus may cause orthostatic hypotension, especially with the first few doses.
D (15) This patient is hyperkalemic and slightly acidotic. These changes are typical of a K+-sparing diuretic such as spironolactone or eplerenone.
B (11) Of the drugs listed, only clonidine, an α2 agonist, is associated with severe rebound hypertension if stopped suddenly. It is speculated that this effect is due to down-regulation of α2 receptors.
D (14) The action potential is prolonged without significant slowing of the upstroke, so the drug effect is mainly on potassium channels (group 3 action) and not on both sodium and potassium channels (group 1A action).
C (10, 11) Hydralazine reduces blood pressure by direct vasodilation. Propranolol has indirect effects on vascular tone but (at least initially) reduces pressure by reducing cardiac output. Later, it probably reduces renin secretion and angiotensin II. Hydralazine thus evokes reflex sympathetic discharge and increases cardiac force, output, and rate, whereas propranolol blocks β adrenoceptors and reduces force, output, and rate.
E (15, 42) Thiazides increase calcium absorption from the urine into blood, whereas loop diuretics increase calcium excretion from the blood into the urine. None of the other options listed here affects serum calcium. Opioids are indicated for acute management of severe pain due to kidney stones.
C (15) Furosemide acts on the ascending limb of the loop of Henle and inhibits the major transporter in this segment, a Na+/K+/2Cl− transporter.
C (17) Substance P is the endogenous peptide closely associated with peripheral pain transmission, and capsaicin (the “hot” component from hot peppers) is an antagonist.
E (18) The cyclooxygenase enzymes are responsible for cyclizing arachidonate to prostaglandin precursors.
A (20) Albuterol, metaproterenol, and terbutaline are rapid-onset, selective β2 agonists used as first-line therapy for acute asthma.
C (20) Salmeterol and formoterol are slow-onset, long-acting, selective β2 agonists usually used by inhalation with corticosteroids in asthma prophylaxis. Indacaterol is similar but approved only for COPD.
E (26) Intravenous lidocaine causes typical local anesthetic toxicity including central nervous system stimulation with possible seizures. Cardiovascular depression may occur, but it is usually minor.
B (25, 27) Malignant hyperthermia is a rare disorder characterized by massive calcium release within skeletal muscle triggered by use of succinylcholine in anesthesia protocols. Dantrolene is given to block calcium release.
C (34) Deep vein thromboses are less responsive to the antiplatelet agents (aspirin, clopidogrel). Warfarin is teratogenic and is contraindicated in pregnancy. Lepirudin is a thrombin inhibitor that can be used parenterally only. A low-molecular-weight (LMW) heparin is the drug of choice to treat and prevent deep vein thromboses and is safe to use during pregnancy.
E (48) Amphotericin B and caspofungin are active against many systemic fungal infections, but they interfere with fungal cell wall functions. Voriconazole, an azole antifungal like fluconazole and itraconazole, interferes with cell membrane permeability by inhibiting ergosterol synthesis.
C (49) Acyclovir is a guanosine analog activated by viral thymidine kinases of HSV and VZV to form acyclovir triphosphate, a competitive substrate for DNA polymerase; it results in chain termination when incorporated into viral DNA.
B (53) Mebendazole is the primary drug for treatment of pinworm, roundworm, and whipworm infections. The drug is contraindicated in pregnancy. Mebendazole and thiabendazole (a more toxic azole) are inhibitors of microtubule synthesis in nematodes.
D (52) These dose-related symptoms are characteristic adverse effects of the alkaloids (eg, quinine, quinidine) derived from the bark of the cinchona tree and are termed cinchonism.
B (41) Canagliflozin is an SGLT2 inhibitor. Acarbose inhibits polysaccharide breakdown. Glipizide is a secretagogue. Metformin acts in the liver. Rosiglitazone is a PPAR-γ activator, and sitagliptin is a DPP-IV inhibitor.
C (55) Mycophenolate mofetil is an immunosuppressant whose active metabolite inhibits de novo production of guanosine monophosphate (GMP). Lymphocytes are particularly sensitive to the antimetabolite effect of mycophenolate mofetil because they lack the alternative salvage pathway for GMP synthesis that is present in most cells.
E (47) Mutations in the katG gene result in the underproduction of mycobacterial catalase-peroxidase, an enzyme that bioactivates INH, facilitating its interaction with its “target” ketoacyl carrier protein sythetase. The result is high-level resistance to INH. Mutations in the inhA gene result in low-level resistance with cross-resistance to pyrazinamide.
B (57, 58) Deferoxamine, a chelator with high selectivity and affinity for iron, is used intravenously for acute iron poisoning. Activated charcoal does not bind iron. Acetylcysteine is used for acetaminophen poisoning. Pralidoxime is used for organophosphate poisoning. Intravenous EDTA is used for lead poisoning; oral EDTA does not significantly reduce iron absorption after an oral iron overdose.
D (9) Albuterol and metaproterenol are β2-selective bronchodilators used in asthma and may cause undesirable cardiac stimulation in COPD patients. Metoprolol is a β blocker and would precipitate bronchospasm. Verapamil blocks calcium channels but has little useful effect in bronchospasm. Tiotropium is a long-acting muscarinic antagonist administered by inhalation and has a useful bronchodilator effect with little systemic effect.
C (11, 15) Spironolactone inhibits potassium excretion in the kidney by blocking aldosterone. Captopril reduces angiotensin II levels and secondarily reduces aldosterone. The combination may increase serum potassium to dangerous levels.
D (21, 28) Antagonism at dopamine D2 receptors in the CNS is equated with parkinsonian symptoms (Drugs A and D). However, in the case of Drug A, this action would be offset by its ability to block muscarinic receptors. M blockers, like benztropine, improve tremor and rigidity in parkinsonism but have little effect on bradykinesia.
B (22, 29) Clonazepam, a benzodiazepine, is effective in the management of absence seizures and is also used in the treatment of bipolar disorder.
A (23) Fomepizole, an antidote for ethylene glycol and methanol poisoning, inhibits alcohol dehydrogenase, which converts ethylene glycol and methanol to toxic metabolites.
B (24) Simple partial seizures can have the characteristics of the “jacksonian march.” Many drugs are used in management including those listed, with the exception of ethosuximide, which is useful in absence seizures but not effective in partial seizures or generalized tonic-clonic seizure states.
E (24) Myoclonic seizure syndromes are usually treated with valproic acid. Neural tube defects (spina bifida) are associated with the use of valproic acid during pregnancy. Lamotrigine is approved for adjunctive use but is often used as a sole agent, and several backup drugs are available including topiramate and zonisamide.
E (26) Local anesthetics block voltage-dependent sodium channels in excitable tissues including nerves, decreasing action-potential conduction. Rapidly firing fibers are more sensitive than slowly firing nerve fibers. Cocaine has this action and also blocks the reuptake of norepinephrine at sympathetic neuroeffector junctions with effects on both the heart and the CNS.
E (32) The signs and symptoms are those of high-dose abuse of dextroamphetamine or methamphetamine. There is no specific antidote, and supportive measures are directed toward protection against cardiac arrhythmias and seizures and control of body temperature.
D (27) Baclofen activates GABAB receptors, dantrolene blocks the release of calcium from skeletal muscle sarcoplasmic reticulum, halothane enhances skeletal muscle relaxants, and tubocurarine causes histamine release. Acetylcholinesterase inhibitors do not reverse skeletal muscle relaxation caused by succinylcholine.
A (31) Fentanyl is much shorter acting than morphine. Both drugs are μ-receptor activators, equivalent in terms of analgesic activity and reversible by naloxone. Both drugs cause respiratory depression at high doses.
C (23) Mental retardation, microcephaly, and facial dysmorphia are characteristics of fetal alcohol syndrome, caused by excessive use of ethanol during pregnancy.
C (9, 30, 61) Phenelzine, a rarely used antidepressant, is a potent MAO-B inhibitor and increases the amount of catecholamine transmitter stored in sympathetic nerve endings. When an indirectly acting sympathomimetic such as tyramine (found in some foods) avoids first-pass metabolism (due to MAO inhibition) and reaches the nerve endings, it can release large amounts of norepinephrine and cause a hypertensive crisis.
D (27) In phase I block, the action of succinylcholine is not reversed by acetylcholinesterase inhibitors. The drug is metabolized by pseudocholinesterases. It may cause histamine release, and it can cause hyperkalemia.
C (7, 8, 27) The acetylcholinesterase inhibitor pyridostigmine can reverse skeletal muscle relaxation (caused by vecuronium) but may also cause bradycardia. The later effect can be prevented by use of glycopyrrolate, which has muscarinic receptor blocking action.
E (29) Significant weight gain and hyperglycemia due to a diabetogenic action occur with several atypical antipsychotics, especially clozapine (not listed) and olanzapine. Neurologic dysfunctions are less common with the atypical agents.
E (30, 31) Naloxone is an opioid μ-receptor antagonist and will oppose the actions of opioids at this class of receptors including analgesia, miosis, and symptoms of opioid overdose including respiratory depression. However, respiratory depression due to nefazodone is not exerted via the μ-opioid receptor.
C (28) Entacapone is a catechol-O-methyltransferase inhibitor that enhances the action of levodopa by preventing its metabolism in the blood and peripheral tissues. It does not cross the blood-brain barrier and if used alone will not ameliorate symptoms of Parkinson’s disease.
B (22) The hypnotic action of ramelteon is thought to be due to its activation of melatonin receptors in the suprachiasmatic nuclei of the CNS.
A (43, 46) The drugs of choice for treatment of gonorrhea currently are the cephalosporins ceftriaxone and cefixime. Azithromycin and spectinomycin are alternatives. Resistance to amoxicillin is common.
A (44) The only drug likely to be effective in nongonococcal urethritis in a single dose is azithromycin, which has an elimination half-life of several days. Other drugs used in nongonococcal urethritis include clindamycin, ofloxacin, and the tetracyclines.
B (45) The aminoglycoside antibiotics are bactericidal inhibitors of protein synthesis. Recall that their actions continue well beyond their short half-lives because they exert a postantibiotic action.
D (44) Tetracycline use during pregnancy is discouraged since fetal exposure to these antibiotics may ultimately lead to irregularities in bone growth and dentition. In addition, gastrointestinal effects and the potential for hepatic dysfunction are increased in the pregnant patient.
B (39) Long-term use of prednisone has several side effects such as growth inhibition, diabetes, muscle wasting, and osteoporosis. Regarding the other options: Excess steroid use results in baldness. Corticosteroids (such as prednisone) can be used to treat some hemolytic anemias. Choice D is incorrect because it describes congenital adrenal hyperplasia, a condition in which the adrenal gland fails to make the hormones cortisol and aldosterone. Treatment would be to provide these hormones to restore physiological levels.
B (42) The bisphosphonates can cause esophageal irritation, which is managed by drinking lots of fluids and staying upright after taking the drug. Blue skin is an adverse effect of amiodarone. Color vision can be affected by anti-TB treatment. Priapism can be caused by sildenafil in combination with nitrates, and tendinitis is a side effect for fluoroquinolones.
C (44, 47) Azithromycin (not listed) or clarithromycin with or without rifabutin is recommended for primary prophylaxis against Mycobacterium avium complex (MAC) in patients with AIDS.
E (49) Efavirenz is used in highly active antiretroviral therapy (HAART) regimens against HIV. The drug is an allosteric inhibitor of HIV reverse transcriptase and does not bind to the active site of the enzyme.
B (43, 44, 46) In a community-acquired pneumonia, the wider spectrum cephalosporin ceftriaxone would cover typical organisms, and erythromycin would be active against the atypical organisms.
E (43, 44, 46) Single antimicrobial drug therapy would be inadequate coverage in a hospital-acquired pneumonia that could include possible infection due to multidrug-resistant staphylococci as well as gram-negative bacilli such as Pseudomonas aeruginosa. Vancomycin should cover gram-positive organisms, and piperacillin plus the penicillinase inhibitor would be active against most strains of likely gram-negative pathogens.
B (49) Many resistant strains of HSV commonly lack thymidine kinase, the enzyme involved in the viral-specific activation of acyclovir.
C (48) Fluconazole is the only antifungal drug listed. It is the drug of choice for treatment and secondary prophylaxis against cryptococcal meningitis.
E (54) Bleomycin is one of the 4 drugs for which myelosuppression is not dose-limiting. The 3 others are cisplatin for nephrotoxicity, doxorubicin for cardiotoxicity, and vincristine for peripheral neuropathy.
C (54) The toxicity of doxorubicin (one of the 4 drugs with unique dose-limiting toxicity; see Question 71) can be mitigated by dexrazoxane.
D (37) The posterior pituitary hormone oxytocin contracts uterine smooth muscle. It is used to augment labor and, in this case, to treat postpartum uterine atony.
C (40) Progestin acts on the endometrium, where estrogen agonists can induce proliferation and endometrial cancer. Progestin has been shown to reduce this risk. Progestin toxicity includes increased blood pressure and a decrease in HDL. Long-term use of progestin can lead to a reduction in bone density.
D (16) Diphenhydramine is a first-generation anti-H1 blocker with significant anti-motion sickness and sedative actions. Loratadine is a second-generation antihistamine with neither of these effects. Neither drug is effective in asthma or GERD, and neither blocks drug-metabolizing enzymes.
A (13) While therapeutic strategies in chronic heart failure include use of several different drug classes including diuretics and positive inotropic agents, only 3 drugs or drug groups have been shown to provide benefits in terms of survival: ACE inhibitors, certain β blockers including carvedilol, and the aldosterone antagonists spironolactone and eplerenone.
D (38) Methimazole and propylthiouracil (PTU) are small sulfur-containing thioamides that inhibit thyroid hormone synthesis by blocking peroxidase catalyzed reactions, iodination of thyroglobulin, and coupling of DIT and MIT (see Figure 38–1). Dexamethasone is an orally active corticosteroid, lithium is a mood stabilizer, and propranolol is a β-blocker capable of inhibiting the peripheral conversion of T4 to T3.
E (31) Meperidine is a strong opioid agonist with analgesic efficacy equivalent to that of morphine. The drug has a muscarinic blocking action and does not cause miosis or contraction of biliary smooth muscle. With long-term use, its metabolite normeperidine accumulates and may cause seizures.
C (35) Fibrates are the main triglyceride-lowering drugs. Cholestyramine, ezetimibe, and lovastatin mainly lower LDL cholesterol, whereas pioglitazone is an antidiabetic drug that increases insulin sensitivity through PPAR-γ activation.
D (34) Heparin is negatively charged and will be effectively complexed with the positively charged protamine. There is no antidote for options A through C. If the effect of warfarin is too great, vitamin K1 supplements or parenteral phytonadione (vitamin K1) can be added in addition to dose reduction. For urgent reversal of anticoagulation by any drug, fresh frozen plasma may be used.
A (35) Resins increase triglycerides (TGs), particularly in patients who are genetically predisposed to high TGs. Ezetimibe has no effect on TGs, but fibrates and niacin both lower TGs and lovastatin mostly lowers LDL cholesterol.
D (40) Combination hormonal contraceptives have clinical uses and beneficial effects in treatment of acne, hirsutism, and dysmenorrhea. In addition, with long-term use, they have been shown to reduce the risk of ovarian and endometrial cancer.
E (34) Warfarin interferes with gamma carboxylation of clotting factors IX, X, VII, and II, and the anticlotting factors protein C and protein S. Dabigatran, an oral thrombin inhibitor, carries the risk of bleeding and not thrombosis. Aspirin can cause gastrointestinal ulcers and bleeding. Heparin is the only drug on this list that can also cause thrombosis, but in the case of heparin, it is mediated not through protein C but rather through an immunologic reaction against heparin-platelet complexes.
D (59) Mesalamine is a form of 5-aminosalicylic acid (5-ASA) used as first-line treatment for inflammatory bowel disease. Aluminum hydroxide is an antacid used for symptomatic relief of heartburn. Metoclopramide is a prokinetic agent. Misoprostol and ranitidine are used for acid-peptic disease.
D (24) A number of antiseizure drugs have caused serious toxicities including hepatotoxicity with both valproic acid and felbamate. In the case of lamotrigine, which has been commonly used in the myoclonic seizures, toxic epidermal necrolysis (Stevens-Johnson syndrome) has occurred.
B (30) The selective serotonin reuptake inhibitor (SSRI) class of antidepressants has been shown to have therapeutic value in a wide range of psychiatric dysfunctions ranging from bulimia to obsessive compulsive disorder. One of the adverse effects of the use of SSRIs is diminished sexual function and interest.
A (14) Adenosine is favored for the prompt conversion of atrioventricular nodal rhythms to normal sinus rhythm. Adenosine has a very short duration of action (seconds) and good efficacy.
D (28) Pramipexole is a non-ergot dopamine agonist with high affinity for the D3 receptor. It is used as monotherapy in mild parkinsonism and together with levodopa in more advanced disease. Mental disturbances such as confusion, delusions, and impulsivity are more common with pramipexole than with levodopa.
D (33, 58) In cyanide poisoning, the vitamin B12 analog hydroxocobalamin reacts with cyanide to form cyanocobalamin, another form of B12 that is stored in the liver.
A (54) Cyclophosphamide is converted into acrolein, which damages the kidney. Mesna can bind to and detoxify acrolein. Note that the dose-limiting toxicity of cyclophosphamide is bone marrow suppression.
A (54, 55) Allopurinol interferes with the metabolism of azathioprine, increasing plasma levels of 6-mercaptopurine, which may result in potentially fatal blood dyscrasias. Concomitant use requires the dose of azathioprine to be reduced by 75%.
B (36) Treatment of gout falls into 2 categories: 1) to treat the acute attack where the goal is to reduce pain and inflammation, and 2) to prevent attacks by reducing the uric acid pool through inhibition of uric acid buildup (allopurinol and febuxostat) or by enhanced elimination (probenecid). Indomethacin is an NSAID that can reduce pain and inflammation. Morphine will reduce only the pain but not the inflammation, and methotrexate is more effective for immuno-inflammatory disorders.
C (33) Deficiencies of folic acid or vitamin B12 are the most common causes of megaloblastic anemia. If a patient with this type of anemia has a normal serum vitamin B12 concentration, folate deficiency is the most likely cause of the anemia. Deficiency of folic acid during early pregnancy is associated with increased risk of a neural tube defect in the newborn. In the US, cereals and grains are supplemented with folic acid in an effort to decrease the incidence of folic acid deficiency.
B (37) This woman’s central diabetes insipidus is due to insufficient posterior pituitary production of vasopressin. Desmopressin, a selective vasopressin V2 receptor agonist, can be administered orally, nasally, or parenterally to treat central diabetes insipidus.
E (38) Iodide salts inhibit iodination of tyrosine and thyroid hormone release. The salts also decrease vascularity and size of the hyperplasic thyroid gland. Onset of effect is rapid since both release and synthesis of hormones are inhibited. The effects are transient as the gland “escapes” from the iodide block after several weeks of treatment. Choice D is incorrect; propylthiouracil is the preferred thioamide treatment in pregnancy because it is less likely to cross the placenta and into breast milk.
A (40, 54) Anastrozole prevents conversion of testosterone to estradiol. Ethinyl estradiol is an orally available form of estradiol. Finasteride is a 5-α-reductase inhibitor. Spironolactone is an androgen receptor antagonist (used mainly as a K-sparing diuretic), and tamoxifen is a selective estrogen receptor modulator.
C (41) Glipizide is the only agent in this list that can stimulate insulin secretion, potentially leading to hypoglycemia. Canagliflozin is an SGLT2 inhibitor reducing renal glucose reabsorption. Acarbose and miglitol inhibit polysaccharide breakdown. Metformin acts in the liver. Rosiglitazone is a PPAR-γ activator.
A (34) Deep vein thromboses tend to be fibrin-rich and platelet-poor, making them less responsive to the antiplatelet agents (eptifibatide, clopidogrel). Unfractionated heparin carries the risk of triggering more heparin-induced thrombocytopenia. Warfarin will take several days to achieve a therapeutic effect. Argatroban (direct thrombin inhibitor) is the drug of choice for fast anticoagulation in patients with heparin-induced thrombocytopenia.
G (9, 10) See answers to questions 95 and 96 in Examination 1 (Appendix II). Drug 1 evokes a strong pressor effect and a bradycardia that is probably a reflex compensatory response. Thus, both norepinephrine and phenylephrine are possible answers. However, the effect of Drug 2 unmasks a tachycardia produced by Drug 1, so this agonist must be norepinephrine; phenylephrine does not have β agonist action.
I (10) See answers to the preceding question and to questions 95 and 96 in Examination 1. Drug 2 is an α blocker without β-blocking action.