Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Section V λ Antimicrobial Agents

19.Which one of the following drugs is most likely to be associated with elevations of pancreatic enzymes, including amylase and lipase?

A.Erythromycin

B.Didanosine

C.Isoniazid

D.Zidovudine

E.Pyrazinamide

20.The major mechanism of HSV resistance to acyclovir is

A.a structural change in viral thymidine kinase

B.a mutation in the gene that encodes DNA polymerase

C.the loss of ability to produce viral thymidine kinase

D.changes in reverse transcriptase

E.mutations in the gene that codes for phosphotransferase

21.Despite its “age,” penicillin G remains the drug of choice in the treatment of infections caused by which of the following organisms?

A.B. fragilis

B.T. pallidum

C.H. influenzae

D.E. coli

E.S. aureus

22.Which one of the following drugs is most likely to be equally effective in the treatment of amebic dysentery and “backpacker’s diarrhea”?

A.Ciprofloxacin

B.Diloxanide

C.Metronidazole

D.Quinacrine

E.Trimethoprim-sulfamethoxazole

214

Chapter 5 λ Antimicrobial Drug List and Practice Questions

Answers

1.Answer: D.Life-threatening invasive aspergillosis, with necrotizing pneumonia, most commonly occurs in severely immunocompromised patients. The mortality rate approaches 50%, but high intravenous doses of amphotericin B may be lifesaving. Intravenous amphotericin B causes infusion-related hypotension (via histamine release), fever, and chills, which may be attenuated by the prior administration of NSAIDs and antihistamines. Adrenal steroids may provide supplementary stress support. Amphotericin B binds to ergosterol in fungal membranes, opening pores and disrupting membrane permeability.

2.Answer: E. For antitubercular activity, isoniazid (INH) must first be metabolically activated via a catalase present in mycobacteria. A decrease in expression of the cat G gene that encodes this enzyme is the mechanism of high-level resistance to INH.

3.Answer: A. Azithromycin is highly effective as an oral agent in the management of pharyngitis caused by gram-positive cocci and may necessitate only a short course of therapy. In patients who have marked hypersensitivity to penicillins, it is inappropriate to use a cephalosporin, even though cefaclor is active against common oropharyngeal pathogens. Doxycycline should not be used in children. One must assume that complete cross-allergenicity exists between different members of the penicillin class of antibiotics, and, in any case, penicillin G is not usually given orally because of its lability in gastric acid. Vancomycin would need parenteral administration, and this antibiotic should be reserved for more serious bacterial infections.

4.Answer: C. Organisms associated with sexually transmitted diseases include chlamydia, neisseria gonorrhea, treponema (syphilis), trichomonas, and gardnerella vaginalis. The latter two organisms are effectively treated with the drug metronidazole. Metronidazole has a chemical structure that results in a disulfiram-like effect on aldehyde dehydrogenase, causing reactions with ethanol. Patients should be cautioned not to consume alcoholic beverages while on this drug.

5.Answer: B. Ceftriaxone is eliminated largely via biliary excretion, and decreases in renal function do not usually require a dose reduction. All of the other antimicrobial drugs listed are eliminated by the kidney, at rates proportional to creatinine clearance, so major dose reductions would be needed in patients with renal dysfunction to avoid toxicity.

6.Answer: B. Mebendazole is the drug of choice for treatment of all nematode infections (hookworm, roundworm, pinworm, whipworm). Pyrantel is considered equally effective as mebendazole for nematodes. Praziquantel is used for tapeworms (cestodes) and flukes (trematodes).

215

Section V λ Antimicrobial Agents

7.Answer: A. Macrolides (azithromycin) are effective for common causes of pneumonias such as Strep pneumonia, Haemophilus influenza, Mycoplasma, Legionella, and Chlamydophila. The drugs work at the 50S ribosomal subunit to inhibit translocation of the peptidyl tRNA from the acceptor to the donor site.

8.Answer: B. The most common pathogens implicated in bacterial meningitis in a neonate (age <1 month) are group B streptococci, followed by E. coli. Meningococci and pneumococci become prevalent after 1 month of age, and H. influenzae is becoming rarer since the availability of a vaccine. A third-generation cephalosporin (e.g., cefotaxime) would be administered because it provides coverage for most of the organisms mentioned. However, ampicillin is also needed to cover for Listeria monocytogenes, which occurs with an incidence of 7 to 8% in neonatal meningitis.

9.Answer:A.Clindamycin has a mechanism of action similar to, if not identical with, erythromycin and related macrolides. They bind to rRNA bases on the 50S subunit to prevent translocation of peptidyl-mRNA from the acceptor to the donor site. Chloramphenicol also binds to the 50S subunit but interferes with the activity of peptidyltransferase. Gentamicin and tetracyclines bind to the 30S ribosomal subunit. Imipenem is a cell-wall synthesis inhibitor, acting similarly to beta-lactams.

10.Answer:A.Microbial resistance to fluoroquinolones is increasing, and some strains of Streptococcus pneumoniae are now resistant to ciprofloxacin. The mechanism can involve changes in the structure of topoisomerase IV, one of the “targets” of fluoroquinolones, which inhibit nucleic acid synthesis. Pneumococcal resistance to penicillins is also increasing via changes in penicillin-binding proteins (PBPs). The other mechanisms listed underlie microbial resistance to other antibiotics as follows: sulfonamides (choice B), macrolides (choice C), extended-spectrum penicillins (choice D), and betalactams (choice E).

11.Answer: B.Aminoglycosides like gentamicin work on aerobic gram negative rods. They require oxygen to enter bacteria, and, as such, do not treat any anaerobes including Bacteroides fragilis. They can be used with penicillins such as ampicllin against Listeria for a synergistic effect.

12.Answer: E.Drugs that cause oxidative stress may precipitate acute hemolysis in patients who lack G6PD because they have a limited ability to generate NADPH, which restricts the formation of glutathione. Drugs in this category include primaquine, quinine, nitrofurantoin, sulfonamides, and TMP-SMX.

13.Answer: E. Antistaph penicillins are inherently resistant to cleavage by bacterial beta-lactamases. Instead, resistance develops when the target for these drug, PBPs, are altered such that the drug doesn’t bind effectively.

216

Chapter 5 λ Antimicrobial Drug List and Practice Questions

14.Answer: E. HAART in the management of HIV infection is reported in many but not all patients to decrease viral load, increase CD4 cells, slow disease progression, and reduce opportunistic infections. However, in terms of the chemotherapy of AIDS, the word cure has little meaning. Discontinuance of HAART, after suppression of viral RNA copies below the sensitivity of the best current methods of analysis, is followed by the reemergence of detectable viral RNA in the blood within a few months.

15.Answer: D. Neuraminidase is an enzyme on the lipid envelope of influenza A and B virions that prevents their clumping together and also their binding to the surface of cells that have been already infected. Neuraminidase inhibitors interfere with this activity and reduce the availability of virions for entry into noninfected cells. Oseltamivir and zanamivir decrease the severity and duration of symptoms if given within a day or two of onset.

16.Answer: E. Vancomycin is usually considered to be a backup drug to metronidazole in colitis due to Clostridium difficile on the grounds that it is no more effective, is more costly, and should be reserved for treatment of resistant gram-positive coccal infections. None of the other drugs has activity in pseudomembranous colitis—indeed, they may cause it!

17.Answer: B. AIDS patients being treated with protease inhibitors (e.g., indinavir) have developed a syndrome involving derangement of lipid and CHO metabolism. Changes in lipid metabolism and distribution occur quite commonly, and type 2 diabetes has also been reported. Indinavir is also notable for its tendency to precipitate in the urinary tract, causing nephrolithiasis, unless the patient is maintained in a high state of hydration.

18.Answer: C. Fluconazole is distinctive in terms of its ability to penetrate into the cerebrospinal fluid, reaching levels similar to those in the blood. It is effective against C. neoformans and has become the most appropriate drug to use in both prophylaxis and suppression because of its oral efficacy and low toxicity compared with amphotericin B. Flucytosine is also active against C. neoformans but is not used alone because of rapid emergence of resistance. Nystatin is too toxic for systemic use.

19.Answer: B. Pancreatic dysfunction, heralded by large increases in serum amylase and lipase, is associated with the use of several reverse-transcrip- tase inhibitors (RTIs). Didanosine appears to be the worst offender, and pancreatitis is the most characteristic adverse effect of this particular NRTI. Conditions enhancing susceptibility to drug-induced pancreatic dysfunction include hypertriglyceridemia, hypercalcemia, and history of excessive ethanol use. Liver dysfunction including hepatitis may occur with the antitubercular drugs, isoniazid, and pyrazinamide. Cholestasis is associated with the estolate form of erythromycin.

20.Answer: C. To inhibit DNA polymerases in HSV, acyclovir must undergo

initial monophosphorylation by a viral specific thymidine kinase (TK). Most HSV strains resistant to acyclovir lack this enzyme and are thus TK− strains. A few strains of HSV are resistant to acyclovir by structural changes in TK that lower substrate affinity or by mutations in the gene that encode viral DNA polymerases.

217

Section V λ Antimicrobial Agents

21.Answer: B. Indications for the use of penicillin G are currently limited for a number of reasons. The drug has a narrow spectrum, is susceptible to beta-lactamases, and may cause hypersensitivity. Also, alternative antibiotics

are available. However, penicillin G remains the drug of choice in syphilis, usually given IM as benzathine penicillin G, but as the Na+ or K+ salt IV in neurosyphilis. What would you do for patients who are highly allergic to penicillins? (Consider tetracyclines, or possibly desensitization.)

22.Answer: C. In amebic dysentery caused by Entamoeba histolytica and gastrointestinal infections with diarrhea (“backpacker’s diarrhea”) due to Giardia lamblia, metronidazole is the drug of choice. Diloxanide is a backup drug for noninvasive intestinal amebiasis, but it has minimal activity in Giardia infections. Quinacrine has effectiveness in giardiasis but not amebiasis. TMPSMX has antiprotozoal effectiveness in Pneumocystis jiroveci, pneumonia. Ciprofloxacin is devoid of antiprotozoal activity.

218