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37, The answer is c. (Hardman, p 1179. Katzung, pp 815-816.) Amphotericin B may alter kidney function by decreasing creatinine clearance; if this occurs, the dose must be reduced. It also commonly increases potassium (K+) clearance, leading to hypokalemia, and causes anemia and neurologic symptoms. A liposomal preparation may reduce the incidence of renal and neurologic toxicity Vancomycin is less likely to cause kidney damage; if it does, the damage is less severe.

38, The answer is c. (Hardman, p 1183. Katzung, p 819.) Fluconazole penetrates into cerebrospinal fluid. where it is active against Cryptococcus neoformans. When it is given orally blood levels are almost as high as when it is given parente rally Amphotericin is administered intravenously and does not appear to be highly effective in fungal meningitis even when administered intrathecally

39, The answer is b, (Hardmant p 1158J Isoniazid inhibits cell-wall synthesis in mycobacteria. Increasing vitamin B6 levels prevents complications associated with this inhibition, including peripheral neuritis, insomnia, restlessness, muscle twitching, urinary retention, convulsions, and psychosis, without affecting the anti mycobacterial activity of INH.

40, The answer is b, (Hardman, p 1065.) Ciprofloxacin is a fluorinated quinolone derivative highly effective against P aeruginosa. Other derivatives in this class have less activity toward this organism, although they are effective against other common G ram-negative organisms.

41, The answer is b, (Katzung, pp 806-807.) Rifampin induces cytochrome P450 enzymes, which causes a significant increase in elimination of drugs, such as oral contraceptives, anticoagulants, ketoconazole, cyclosporine, and chloramphenicol. It also promotes urinary excretion of methadone, which may precipitate withdrawal.

42, The answer is c. (Hardman, pp 1129-1131.) All tetracyclines can produce negative nitrogen balance and increased blood urea nitrogen

(BUN) levels. This is of clinical importance in patients with impaired renal function. With the exception of doxycycline, tetracyclines should not be used in patients that are anunc. Doxycycline is excreted by the GI tract under these conditions, and it will not accumulate in the serum of patients with renal insufficiency.

43, The answer is e, (Hardmant pp 1094-1095J Penicillins were used in the treatment of meningitis because of their ability to pass across an inflamed blood-brain barrier The third-generation cephalosporin, ceftriaxone, is preferred because it is effective against |3-lactamase producing strains of H. influenzae that may cause meningitis in children.

44, The answer is a. (Hardman, pp 1116—1117.) Neomycin, an aminoglycoside, is not significantly absorbed from the GI tract. After oral administration, the intestinal flora is suppressed or modified and the drug is excreted in the feces. This effect of neomycin is used in hepatic coma to decrease the coliform flora, thus decreasing the production of ammonia that causes the levels of free nitrogen to decrease in the bloodstream. Other antimicrobial agents (e.g., tetracycline, penicillin G, chloramphenicol, and cephalothin) do not have the potency of neomycin in causing this effect.

4 5, The ans we rise, (Hardman., pp 1074- J 076.) Penicillinase h yd r o ly z es the p-lactam ring of penicillin G to form inactive penicilloic acid. Consequently, the antibiotic is ineffective in the therapy of infections caused by penicillinase-producing microorganisms such as staphylococci, bacilli. E, coli, P aeruginosa, and M. tuberculosis.

46, The answer is d. (Hardman, pp 1097-1098.) The antibiotic clavu-lanic acid is a potent inhibitor of ¡^-lactamases. The mode of inhibition is irreversible Although clavulanic acid does not effectively inhibit the transpeptidase, it maybe used in conjunction with a |i-lactamase-sensitive penicillin to potentiate its activity

47, The answer is b. (Hardman, pp ¡077-1086.) Piperacillin is a broad-spectrum, semisynthetic penicillin for parenteral use. Its spectrum of activity includes various Gram-positive and Gram-negative organisms including Psmdomonas. The indications for piperacillin are similar to those for car-benicillin, ticarcillin, and mezlocillin, with the primary use being sus-

pected or proven infections caused by P. aeruginosa. Penicillin G, nafcillin, erythromycin, and tetracycline are ineffective against Pseudomonas,

48, The answer is c. (Hardman, pp 1161-1162j An important problem in the chemotherapy of TB is bacterial drug resistance. For this reason, concurrent administration of two or more drugs should be employed to delay the development of drug resistance. Isoniazid is often combined with ethambutol for this purpose. Streptomycin or rifampin may also be added to the regimen to delay even further the development of drug resistance.

49, The answer is a, (Hardman, pp 1105-1108.) The activity of streptomycin is bactericidal for the tubercle bacillus organism. Other aminoglycosides (e.g., gentamicin, tobramycin, neomycin, amikacin, and kanamycin) have activity against this organism but are seldom used clinically because of toxicity or development of resistance.

50, The answer is d, (Hardman, pp 1155-1159.) Only actively growing tubercle bacilli are susceptible to the bactericidal property of 1NH The major action of 1NH is on the cell wall of the bacillus, where it prevents the synthesis of my colic acid

51, The answer is cL (Hardman, pp 1183-J184.) Mucocutaneous infections, tnosl commonly Candida albicans, involve the moist skin and mucous membranes. Agents used topically include amphotericin B. nystatin, miconazole, and clotrimazole. Ketoconazole and fluconazole are administered orally in pill form for treatment of chronic infections

52, The answer is b, (Hardman, p 1 ¡59J Rifampin inhibits RNA synthesis in bacteria, mycobacteria, and chlamydiae by binding to the DNA-dependent RNA polymerase; it also inhibits assembly of poxvirus particles. Rifampin is used as a single prophylactic agent for contacts of people with meningococcal or H. influenzae type b infections. Otherwise, it is not used alone because 1 in 10 organisms in a population exposed to rifampin will become resistant, possibly because of mutation or a barrier against rifampin's entry into cells.

53, The answer is c. (Hardman, pp 1135-1141.) Erythromycin, a macro-lide antibiotic, was initially designed to be used in penicillin-sensitive patients with streptococcal or pneumococcal infections. Erythromycin has become the drug of choice for the treatment of pneumonia caused by Mycoplasma and Legionella.

54, The answer is h. (Hardman, p I.12Sj Tetracycline is one of the drugs of choice in the treatment of Jiicfcettsia, Mycoplasma, and Chlamydia infections. The antibiotics that act by inhibiting cell-wall, synthesis have no effect on Mycoplasma because the organism does not possess a cell wall: penicillin G. vancomycin, and bacitracin will be ineffective. Gentamicin has little or no antimicrobial activity with these organisms.

55, The answer is c. (Hardman, p 1022.) Pyrantel pamoate is an antihelminthic that acts primarily as a depolarizing neuromuscular blocker. In certain worms, a spastic neuromuscular paralysis occurs, resulting in the expulsion of the worms from the intestinal tract of the host. Pyrantel also exerts its effect against parasites via release of acetylcholine and inhibition of c hoi in esterase.

56, The answer is d. (Hardman, pp 1110-11J3.) Streptomycin and other aminoglycosides can elicit toxic reactions involving both the vestibular and auditory branches of the eighth cranial nerve. Patients receiving an aminoglycoside should be monitored frequently for any hearing impairment owing to the irreversible deafness that may result from its prolonged use. None of the other agents listed in the question adversely affect the function of the eighth cranial nerve.

57, The answer is d. (Katzung, p 840. Hardman, pp ¡209-1211.) Amantadine's mechanism of action involves inhibition of uncoating of the influenza A viral DNA. The primary target is the membrane M2 protein. The drug does not affect penetration and DNA-dependent RNA polymerase activity Amantadine both reduces the frequency of illness and diminishes the serologic response to influenza infection. The drug has no action, however, on influenza B. As a weak base, amantadine buffers the pH of endosomes, thus blocking the fusion of the viral envelope with the membrane of the endosome.

58, The answer is d. (Hardman, pp 1105-1108.) The bactericidal activity of streptomycin and other aminoglycosides involves a direct action on the 3OS ribosomal subunit, the site at which these agents both inhibit protein synthesis and diminish the accuracy of translation of the genetic code. Proteins containing improper sequences of amino acids (known as rttfn.sen.se proteins) are often nonfunctional.

59, The answer is d, (Katzung, pp 831-832.) Zidovudine competitively inhibits 11IV-1 nucleoside reverse transcriptase. It is also incorporated in the growing viral DNA chain to cause termination Each action requires activation via phosphorylation of cellular enzymes. Zidovudine decreases the rate of clinical disease progression and prolongs survival in HIV-infected patients.

60, The answer is a, (Hardmari, p 1146J The llred man" syndrome is associated with vancomycin, thought to be caused by histamine release. Prevention consists of a slower infusion rate and p retreat merit with antihistamines.

61, The answer is e, (Hardman, pp 1092-1094.) Cefoxitin and cefmeta-zole are suitable for treating intraabdominal infections. Such infections are caused by mixtures of aerobic and anaerobic Gram-negative bacteria like B. fragilis. Cefoxitin alone has been shown to be as effective as the traditional therapy of clindamycin plus gentamicin.

62, The answer is a, (Hardman, pp 1143-1144.) Polymyxin B is poorly absorbed by the oral route. It is primarily administered by the topical route for the treatment of infections of the skin, mucous membranes, eye, and ear. Penicillin G can be administered both orally and. parenterally. Dicloxacillin is only given by the oral route. Carbenicillin and streptomycin are administered only by the parenteral route.

63, The answer is c. (Hardman, pp 996-997.. 1145-1146. Katzung, p 845.) Metronidazole is often used to treat antibiotic-associated enterocolitis, especially when caused by C. difficile. Vancomycin is no longer preferred because it induces selection of resistant staphylococci. Clindamycin is also associated with C difficile colitis, but in another way: a higher percentage of patients taking this over other antibiotics develop antibiotic-associated enterocolitis.

64, The answer is b, (Hardman, p 1062.) Sulfonamides should not be used in pregnant women who are at term because of their ability to cross the placenta and enter the fetus in concentrations sufficient to produce toxic effects. Sulfonamides should also not be given to neonates, especially premature infants, because they compete with bilirubin for serum albumin binding, resulting in increased levels of free bilirubin, which cause kern icterus.

65, The answer is a, (Hardman, pp 977-978.) Primaquine is effective against the extraerythrocyiic forms of P vivax and P ovale and is thus of value in a radical cure of malarial infection. It also attacks the sexual forms of the parasite, rendering them incapable of maturation in the mosquito and making ii valuable in preventing the spread of malarial infection.

66, The answer is b. (Hardman, p 1077.) Unlike the other listed, drugs, oxacillin is resistant to penicillinase. The other four agents are broad-spectrum penicillins, while oxacillin is generally specific for Gram-positive microorganisms. Use of pemcillinase-resistant penicillins should be reserved for infections caused by penicillinase-producing staphylococci

67, The answer is e, (Hardman, p 1206. Katzung, p 833.) A major adverse effeci of zidovudine is bone marrow depression that appears to be dose-and duration-dependent. The severity of the disease and a low CD 4 count contribute to the bone marrow depression.

68, The answer is c. (Hardman, p 16880 Thiabendazole has been shown to be effective against StronQfloides, cutaneous larva migrans, and Trithuris. Adverse effects consist of nausea, vertigo, headache, and weakness. Treatment usually involves oral administration for several days. It has been found to be ineffective in Asains, N. americanus, E. vermicularis, and T. saginata.

69, The answer is b, (Hardman, p 1299. Katzung: p 609.) Nephrotoxicity may occur in almost three-quarters of patients treated with cyclosporine. Regular monitoring of blood levels can reduce the incidence of adverse effects.

70, The answer is c. (Hardmanpp 970-972.) Chloroquine is a 4-ami no qui no line derivative that selectively concentrates in parasitized red blood cells, lt is a weak base, and its alkalinizing effect on the acid vesicle of the parasite effectively destroys the viability of the parasite.

71, The answer is c. (liardman, pp J134-11.35.) Hematologic toxicity is by far the most important adverse effect of chloramphenicol The toxicity consists of two types: (1) bone marrow depression (common) and (2) aplastic anemia (rare). Chloramphenicol can produce a potentially fatal toxic reaction, the "gray baby11 syndrome, caused by diminished ability of neonates to conjugate chloramphenicol with resultant high serum concentrations. Tetracyclines produce staining of the teeth and phototoxicity

72, The answer is d, (liardman, p 989.) Both trimethoprim-sulfamethoxazole and pentamidine are effective in pneumonia caused by P. ccznmi. This protozoal disease usually occurs in immunodeficient patients, such as those with AIDS. Nifurtimox is effective in trypanosomiasis and metronidazole in amebiasis and leishmaniasis, as well as in anaerobic bacterial infections. Penicillins are not considered drugs of choice for this particular disease state.

73, The answer is d, (tlardman, pp 1065—1067. Kaizung, p 797.) Bacterial DNA gyrase is composed, of four subunits, and levofloxacin binds to the strand-cutting subunits, inhibiting their activity

74, The answer is c. (liardman7 pp 1058-1059. Katzung, pp 793-795.) Trimethoprim inhibits dihydrofolic acid reductase. Sulfamethoxazole inhibits p-aminobenzoic acid (PABA) from being incorporated into folic acid by competitive inhibition of dihydropteroate synthase. Either action inhibits the synthesis of tetrahydrofolic acid.

75, The answer is a, (Hardman, p 1157. Katzung, p 804.) lsoniazid inhibits mycobacterial cell-wall synthesis by inhibiting my colic acid syn thesis by a mechanism that is noi fully understood.

76, The answer is a, (Katzungr p 800.) Fluoroquinolones are not recommended in patients less than 18 years old. They have a tendency to damage growing cartilage and cause arthropathy The arthropathy is generally reversible. Tendinitis may occur, and in rare instances in adults, this finding may lead lo tendon ruptures.

77, The answer is f. (Katzung, p 837.) Efavirenz is a specific inhibitor of H1V-1 viral growth. Its mechanism of action involves inhibition of nonnu-cleoside reverse transcriptase.

78, The answer is d< (Kalzung, p 839.) indinavir is a specific inhibitor of HTV-1 proteases. Cross-resistance can. occur with other protease inhibitors.

79, The answer is a, (Hardmant pp ¡110-1111.) All the aminoglycosides are potentially toxic to both branches of the eighth cranial nerve. The evidence indicates that the sensory receptor portions of the inner ear are affected rather than the nerve itself. Nephrotoxicity may develop during or after the use of an aminoglycoside Lt is generally more common in the elderly when there is preexisting renal dysfunction. In most patients, renal function gradually improves after discontinuation of therapy Aminoglycosides rarely cause neuromuscular blockade that can lead to progressive flaccid paralysis and potential fatal respiratory arrest. I ly per sensitivity and dermatologic reactions occasionally occur following use of aminoglycosides.

80, The answer is d* (Uavdman, p 1200. Katzung: p 830.) Nephrotoxicity and symptomatic hypocalcemia are major toxicities associated with foscar-net. Underlying renal disease, concomitant use of nephrotoxic drugs, dehydration, and rapid infusion of high doses increase the risk.

81, The answer is c. (Katzung, p 835j Dideoxycytidine causes dose-dependent peripheral neuropathies and adverse effects in the G1 tract, including nausea, diarrhea, and gastric and esophageal ulcerations and pancreatitis.

82, The answer is lb. (liardman, p 1131.) Chloramphenicol inhibits protein synthesis in bacteria and, to a lesser extent, in eukaryotic cells. The drug binds reversibly to the ribosomal subunit and prevents attachment of armnoacyl-transfer RNA (tRNA) to its binding site. The amino acid substrate is unavailable for peptidyl transferase and peptide bond formation.

83, The answer is d, (Hardman, p 1019.) Niclosamide is a halogenated sal icy lam lid e derivative. It exerts its effect against cestodes by inhibition of mitochondrial oxidative phosphorylation in the parasites. The mechanism of action is also related to its inhibition of glucose and oxygen uptake in the parasite.

84, The answer is a. (Haniman, pp 1020-1022.) Praziquantel is a broad-spectrum antihelminthic agent. It appears to kill the adult schistosome by increasing the permeability of the cell membranes of the parasite to Ca and consequent influx of Ca ions. This causes increased muscle contraction followed by paralysis.

85, The answer is a, (Hardman, pp 1084-1085J Amoxicillin is classified as an aminopenicillin along with ampicillin. Because it is less affected than ampicillin by the presence of food, it has a superior absorption in the G1 tract. It is sensitive to penicillinase and has a narrow spectrum of. activity toward certain Gram-positive and Gram-negative organisms, but noi Pseudomonas, Because it ts in the penicillin family; hypersensitivity reactions are a possibility

86, The answer is a. (Hardman, p ¡180. Katzung, pp 81 7-819J Fluconazole indirectly inhibits ergosterol synthesis. It inhibits cytochrome P4C>0: which is a key enzyme system for cytochrome P450-dependent sterol 14-a-demethylase. This leads to accumulation of 14-a-sterols, resulting in impairment of the cytoplasmic membrane.

87, The answer is e. (Hardman, pp 1H3-1144J Bacitracin, cycloserine, cephalotbin, and vancomycin inhibit cell-wall synthesis and produce bacteria that are susceptible to environmental conditions. Polymyxins disrupt the structural integrity of the cytoplasmic membranes by acting as cat ionic detergents On contact with the drug, the permeability of the membrane changes. Polymyxin is often applied in a mixture with bacitracin and/or neomycin for synergistic effects.

88, The answer is e. (Hardman, p 1086J Ticarcillin resembles carbenicillin and has a high degree of potency against Pseudomonas and Proteus organisms but is broken down by penicillinase produced by various bacteria, including most staphylococci- Oxacillin, cloxacillin, nafcillin, and dicloxacillin are all resistant to penicillinase and are effective against staphylococci.

89, The answer is b. (Hardmanf p 1203.) Tri(luridine inhibits viral activity in I1SV types 1 and 2, CMY vaccinia, and perhaps adenovirus. It acts as a viral DNA synthesis inhibitor by irreversibly blocking thymidylate synthetase. Tri flu rid ine triphosphate is a competitive inhibitor of thymidine triphosphate accumulation into DNA. It is used in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis caused by IISV 1 and 2.

90, The answer is a, (Hardman, pp 1086-J 089.) Intolerance of alcohol (disulfirarn-like reaction) has been noted only with certain cephalosporins. Cephalosporins with the methyhhiotetrazole side chain have been associated with a disulfiram-like reaction because the methyhhiotetrazole group has a configuration similar to disulfiratn, which blocks the metabolism of alcohol at the acetaldehyde step. Accumulation of a cet aid eh)-de is associated with the symptoms. The methylthiotetrazole side chain also results in hypoprothrom-binemia by interfering with the synthesis of vitamin K—dependent clotting factors.

91, The answer is a. (Hardman, pp 1074—1077.) Cephalosporins and penicillins have similar structures (they have a p-lactam ring), penicillins having a penicillic acid and the cephalosporins a cephalosporins acid moiety. Both groups of antimicrobials inhibit the transpeptidase enzyme necessary for cross-linking of the peptidylglycan layer necessary for eel I-wall stabilization. It appears that the mechanism is not totally identical for every drug for every bacterial species. Cephalosporins have a greater overall activity against Gram-negative organisms than do the penicillin G-type compounds. The hypersensitivity reactions associated with the penicillins and the cephalosporins appear to be identical in signs and symptoms. There is a crossover sensitivity between the penicillins and cephalosporins that must be considered when a patient is sensitive to either of these antibiotics. It occurs in about 5% to 10% of cases.

92, The answer is b, iHardman, p 1077.) Oxacillin is classified as a penicillinase-resistant penicillin thai is relatively acid-stable and, therefore, is useful for oral administration. Major adverse reactions include penicillin hyper sensitivity and interstitial nephritis. With the exception of methi-cilltn, which is 35% bound to serum proteins, all penicillinase-resistant penicillins are highly bound to plasma proteins. Oxacillin has a very narrow spectrum and is used primarily as an antistaphylococcal agent.

93, The answer is e. (Hardman, pp 995-998.) Metronidazole is a low-molecular-weight compound that penetrates all tissues and fluids of the body. Metronidazole's spectrum of activity is limited largely to anaerobic bacteria—including B, fragilis—-and certain protozoa. It is considered to be the drug of choice for trichomoniasis in females and carrier states in males, as well as intestinal infections with Giardia lambha.

94, The answer is c, (Katzung, pp 778—780) Clarithromycin is a macrolide antibiotic. It can inhibit cytochrome P450. This could lead to an increase in concentration of drugs that are metabolized by cytochrome P45G and. are given simultaneously with clarithromycin. When given with terfenadine, an antihistamine agent, the interaction may lead to cardiac arrhythmias

95, The answer is e. (Katzung, p 7617) Piperacillin is effective against P aeruginosa The ease with which these organisms develop resistance with single-drug therapy has necessitated that combination with aminoglycosides be used in pseudomonal infections.

96, The answer is cl. (Hardman, pp I 080-1082. Katzung, pp 759-760.) Because of its long duration of action, benzathine penicillin G is given as a single injection of 1.2 million units intramuscularly every three or four weeks for the treatment of syphilis. This persistence of action reduces the need for repeated injections, costs, and local trauma. Benzathine penicillin G is also administered for group A, p-hemolytic streptococcal pharyngitis and pyoderma. For the later stages of syphilis, up to three weekly doses of the agent is administered.

97, The answer is a, (Hardmant p 1082. Katzung, pp 764-766.) The third-generation cephalosporin, ceftriaxone, and cefixime are considered lirst-line drugs in the treatment of gonorrhea because most strains of Neisseria gonococci are resistant to the penicillins Amikacin and other aminoglycosides are used in serious infections caused by E. coli7 Enterobactei; Klebsiella, and Serraiia species However, spectinomycin, which is related to the aminoglycosides, can be used as a backup drug for gonorrhea.

98, The answer is b. (Katzung, p J129.) Ampicillin decreases the entero-hepatic circulation of estrogen, thereby reducing its efficacy It is thought that this occurs because of an alteration in the gastrointestinal flora Other oral antibiotics may produce a similar effect.

99, The answer is a. (Katzung, p 1124.) Decreased gastrointestinal absorption of ciprofloxacin occurs with antacids because of their ability to adsorb the fluoroquinolone. Other preparations containing divalent ions, such as iron, will impede fluoroquinolone absorption.

100-101. The answers are 100-c, 101-g, (Katzung, pp 879, 917-918. Hardman, pp 1010, 1022.) Pyrantel is the drug of choice against A. lurnbri-coides.. Its actions are as a depolarizing neuromuscular blocking agent and choli nest erase inhibitor. These actions cause spastic paralysis of the worms. Although benzimidazoles are also effective in treating A. lumbricoides and one of them could be considered the drug of choice, they have tetragenic potential. Filariasis is effectively treated with diethylcarbarnazine, a piper-azine derivative, which both suppresses and, in most cases, cures the infection. The drug is inactive against W bancrofti in vitro. However, in vivo activity appears to be due to a sensitization of the microfilaria to phagocytosis by the fixed macrophages of the reticuloendothelial system.

102, The answer is e. (Katzung7 p 842.) Ribavirin most likely interferes with guanosine triphosphate synthesis, resulting in inhibition of capping of viral messenger RNA and viral RNA-dependent RNA polymerase. It is effective in moderating infections with respiratory syncytial virus.

103, The answer is c. (Katzung, pp 827-828.) Famciclovir is active against herpes simplex and varicella zoster viruses. It is activated by a viral kinase to a triphosphate. The triphosphate is a competitive substrate for DNA polymerase. The incorporation of the famciclovir triphosphate into viral DNA results in chain termination.

104, The answer is d. (Kdtzung, pp 779—780\) Erythromycin is safe to use in pregnancy and is effective against Chlamydia. Levofloxacin is con-traindicated in pregnancy because animal studies have identified that cartilage erosion can occur during growth. Chlamydia are not sensitive to gcntamycin. however, il probably should not be used in pregnancy because of potential nephro- and ototoxicity Tetracycline may cause tooth enamel dysplasia and problems with bone during fetal development. Sulfamethoxazole-trimethoprim has severe consequences, particularly in the newborn, because it displaces bilirubin from albumin, which is then deposited in the brain causing a condition referred to as fcermcterus.

105, The answer is c, (Katzung, p 807.) Retrobulbar neuritis can occur with the use of ethambutol. It is dose related and typically occurs with prolonged therapy. The drug is not recommended for young children whose symptoms may not be easily assessed.

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