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Katzung Pharm-Antimicrobials Pt. 2

Terms in this set (20)

Which statement about the mechanisms of action of antiviral drugs is accurate?
(A) Acyclovir has no requirement for activation by phosphorylation
(B) Ganciclovir inhibits viral DNA polymerase but does not cause chain termination
(C) Increased activity of host cell ribonucleases that degrade viral mRNA is one of the actions of interferon-α
(D) The initial step in activation of foscarnet in HSV- infected cells is its phosphorylation by thymidine kinase
(E) The reverse transcriptase of HIV is 30-50 times more sensitive to inhibition by fosamprenavir than host cell
DNA polymerases
(C) Increased activity of host cell ribonucleases that degrade viral mRNA is one of the actions of interferon-α
Acyclovir is activated by host cell kinases. Like acyclovir, ganciclovir inhibits viral DNA polymerase and causes chain termination. However, foscarnet inhibits viral DNA polymerase without requiring bioactivation. Fosamprenavir is the prodrug of amprenavir, an inhibitor of HIV protease; it has no significant effect on reverse transcriptase.
A 30-year-old male patient who is HIV- positive and symptomatic has a CD4 count of 250/μL and a viral RNA load of 15,000 copies/mL. His treatment involves a 3-drug antiviral regimen consisting of zidovudine, didanosine, and ritonavir. The patient is taking acyclovir for a herpes infection and ketoconazole for oral candidiasis. He now complains of anorexia, nausea and vomiting, and abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal an amylase activity of 220 U/L, and a preliminary diagnosis is made of acute pancreatitis.
If this patient has acute pancreatitis, the drug most likely to be responsible is
(A) Acyclovir
(B) Didanosine
(C) Ketoconazole
(D) Ritonavir
(E) Zidovudine
(B) Didanosine
Gastrointestinal problems occur with most antiviral drugs used in HIV-positive patients, and acute pancreatitis has been reported for several reverse transcriptase inhibitors. However, didanosine's most characteristic adverse effect is a dose-limiting acute pancreatitis. Other risk factors that are relative contraindications to didanosine are advanced AIDS, hypertriglyceridemia, and alcoholism.
A 30-year-old male patient who is HIV- positive and symptomatic has a CD4 count of 250/μL and a viral RNA load of 15,000 copies/mL. His treatment involves a 3-drug antiviral regimen consisting of zidovudine, didanosine, and ritonavir. The patient is taking acyclovir for a herpes infection and ketoconazole for oral candidiasis. He now complains of anorexia, nausea and vomiting, and abdominal pain. His abdomen is tender in the epigastric area. Laboratory results reveal an amylase activity of 220 U/L, and a preliminary diagnosis is made of acute pancreatitis.
In the further treatment of this patient, the drug causing the pancreatitis should be withdrawn and replaced by
(A) Atazanavir
(B) Cidofovir
(C) Foscarnet
(D) Lamivudine
(E) Ribavirin
(D) Lamivudine
Symptomatic AIDS patients should be treated with a HAART regimen regardless of a relatively high CD4 count or a relatively low HIV RNA load. Because didanosine must be discontinued, lamivudine would be a good NRTI replacement. Use of a second protease inhibitor (eg, atazanavir) with a single reverse transcriptase inhibitor could be as effective as regimens that include 2 reverse transcriptase inhibitors, although there may be an increased possibility of drug interactions. Atazanavir use is associated with electrocardiograhic PR-interval prolongation, which may be exacerbated by other causative agents such as the calcium channel blocker verapamil which an older patient might be taking for angina.
In an accidental needlestick, an unknown quantity of blood from an AIDS patient is injected into a resident physician. The most recent laboratory report on the AIDS patient shows a CD4 count of 20/μL and a viral RNA load of greater than 107 copies/mL. The most appropriate course of action regarding treatment of the resident is to
(A) Determine whether HIV transmission has occurred by monitoring the patient's blood
(B) Treat with a single high dose of zidovudine
(C) Treat with full doses of zidovudine for 4 wk
(D) Treat with single doses of zidovudine and indinavir
(E) Treat with zidovudine plus lamivudine plus ritonavir for 4 weeks
(E) Treat with zidovudine plus lamivudine plus ritonavir for 4 weeks
The viral RNA titer in the blood from the AIDS patient in this case is very high, and this needlestick must be considered as a high-risk situation. Although full doses of zidovudine for 4 wk has been shown to have prophylactic value, in high- risk situations combination regimens are favored. Optimal prophylaxis in this case might best be provided by the combination of zidovudine with lamivudine (basic regimen), plus the addition of protease inhibitors (expanded regimen).
A patient with AIDS has a CD4 count of 45/μL. He is being maintained on a 3-drug regimen of indinavir, didanosine, and zidovudine. For prophylaxis against opportunistic infections, he is also receiving cidofovir, fluconazole, rifabutin, and trimethoprim-sulfamethoxazole.
The drug most likely to suppress herpetic infections and provide prophylaxis against CMV retinitis in this patient is
(A) Fluconazole
(B) Cidofovir
(C) Indinavir
(D) Rifabutin
(E) Trimethoprim-sulfamethoxazole
(B) Cidofovir
Ganciclovir (not listed) has been the most commonly used drug for prevention and treatment of CMV infections in the immunocompromised patient. However, cidofovir is also very effective in CMV retinitis and has good activity against many strains of HSV, including those resistant to acyclovir.
A patient with AIDS has a CD4 count of 45/μL. He is being maintained on a 3-drug regimen of indinavir, didanosine, and zidovudine. For prophylaxis against opportunistic infections, he is also receiving cidofovir, fluconazole, rifabutin, and trimethoprim-sulfamethoxazole.
The dose of indinavir in this patient may need to be increased above normal. This is because
(A) Fluconazole slows gastric emptying
(B) Ganciclovir increases the renal clearance of indinavir
(C) Gastric absorption is inhibited by fluconazole
(D) Rifabutin increases hepatic drug metabolism
(E) Sulfamethoxazole increases indinavir plasma protein binding
(D) Rifabutin increases hepatic drug metabolism
Drug interactions can be severe in the immunocompromised patient because many of the drugs administered can influence the pharmacokinetic properties of other drugs. Rifabutin, like rifampin, acts as an inducer of several isoforms of hepatic cytochrome P450. This action can result in an increased clearance of other drugs, including indinavir.
A 27-year-old nursing mother is diagnosed as suffering from genital herpes. She has a history of this viral infection. Previously, she responded to a drug used topically. Apart from her current problem, she is in good health. Which drug to be used orally is most likely to be prescribed at this time?
(A) Amantadine
(B) Foscarnet
(C) Ritonavir
(D) Trifluridine
(E) Valacyclovir
(E) Valacyclovir
Three of the drugs listed (foscarnet, trifluridine, valacyclovir) are active against strains of herpes simplex virus. Foscarnet is not used in genital infections (HSV-2) because clinical efficacy has not been established, it has poor oral bioavailability and the drug causes many toxic effects. Trifluridine is used topically but only for herpes keratoconjunctivitis (HSV-1). Valacyclovir is converted to acyclovir by first-pass metabolism in the intestine and liver.
Oral formulations of this drug should not be used in a pregnant AIDS patient because they contain propylene glycol. One of the characteristic adverse effects of the drug is hyper- pigmentation on the palms of the hands and soles of the feet, especially in African-American patients.
(A) Amprenavir
(B) Emtricitabine
(C) Efavirenz
(D) Fosamprenavir
(E) Zalcitabine
(B) Emtricitabine
Three of the drugs listed should be avoided, or used with extreme caution, in the pregnant patient. Oral forms of amprenavir and emtricitabine both contain propylene glycol, a potentially toxic compound. Efavirenz has caused fetal abnormalities in pregnant monkeys. However, one of the distinctive adverse effects of emtricitabine is hyperpigmentation.
Which of the following statements about interferon-α is false?
(A) At the start of treatment, most patients experience flu-like symptoms
(B) Indications include treatment of genital warts
(C) It is used in the management of hepatitis B and C
(D) Lamivudine interferes with its activity against hepatitis B
(E) Toxicity includes bone marrow suppression
(D) Lamivudine interferes with its activity against hepatitis B
Lamivudine is used in monotherapy of HBV infections and does not oppose the beneficial effects of interferon-α when both agents are used together in the treatment of hepatitis B.
More than 90% of this drug is excreted in the urine in intact form. Because its urinary solubility is low, patients should be well hydrated to prevent nephrotoxicity. Which drug is described?
(A) Acyclovir
(B) Efavirenz
(C) Indinavir
(D) Trifluridine
(E) Zidovudine
(A) Acyclovir
Acyclovir is eliminated in the urine by glomerular filtration and by active tubular secretion, which is inhibited by probenecid. Nephrotoxic effects, including hematuria and crystalluria, are enhanced in patients who are dehydrated or who have preexisting renal dysfunction. Adequate hydration is equally important in the case of indinavir because it causes nephrolithiasis. However, more than 80% of a dose of indinavir is eliminated via hepatic metabolism. Trifluridine is used topically to treat herpes keratoconjunctivitis.
Interactions between this drug and cell membrane components can result in the formation of pores lined by hydrophilic groups present in the drug molecule.
(A) Caspofungin
(B) Flucytosine
(C) Griseofulvin
(D) Nystatin
(E) Terbinafine
(D) Nystatin
The polyene antifungal drugs amphotericin B and nystatin are amphipathic molecules that can interact with ergosterol in fungal cell membranes to form artificial pores. In these structures, the lipophilic groups on the drug molecule are arranged on the outside of the pore, and the hydrophilic regions are located on the inside. The fungicidal action of the polyenes derives from this interaction, which results in leak- age of intracellular constituents.
Which statement about fluconazole is accurate?
(A) Does not penetrate the blood-brain barrier
(B) Drug of choice in treatment of aspergillosis
(C) Induces hepatic drug-metabolizing enzymes
(D) Has the least effect of all azoles on drug metabolism
(E) Oral bioavailability is less than that of ketoconazole
(D) Has the least effect of all azoles on drug metabolism
The azoles with activity against Aspergillus are itraconazole and voriconazole. Fluconazole is the best absorbed member of the azole group by the oral route and the only one that readily penetrates into cerebrospinal fluid. Although fluconazole may inhibit the metabolism of some drugs, it has the least effect of all azoles on hepatic microsomal drug-metabolizing enzymes.
A 37-year-old woman with leukemia was undergoing chemotherapy with intravenous antineoplastic drugs. During treatment, she developed a systemic infection from an opportunistic pathogen. There was no erythema or edema at the catheter insertion site. A white vaginal discharge was observed. After appropriate specimens were obtained for culture, empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin intravenously. This regimen was maintained for 72 h, during which time the patient's condition did not improve significantly. Her throat was sore, and white plaques had appeared in her pharynx. On day 4, none of the cultures had shown any bacterial growth, but both the blood and urine cultures grew out Candida albicans.
At this point, the best course of action is to
(A) Continue current antibiotics and start griseofulvin
(B) Continue current antibiotics and start amphotericin B
(C) Stop current antibiotics and start itraconazole
(D) Stop current antibiotics and start amphotericin B
(E) Stop current antibiotics and start terbinafine
(D) Stop current antibiotics and start amphotericin B
The antibiotic regimen should be stopped immediately, since the condition of the patient did not improve after 3 d of such treatment, the cultures were negative for bacteria, and the clinical picture suggested that the patient had a fungal infection. This was subsequently confirmed by blood culture.
A 37-year-old woman with leukemia was undergoing chemotherapy with intravenous antineoplastic drugs. During treatment, she developed a systemic infection from an opportunistic pathogen. There was no erythema or edema at the catheter insertion site. A white vaginal discharge was observed. After appropriate specimens were obtained for culture, empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin intravenously. This regimen was maintained for 72 h, during which time the patient's condition did not improve significantly. Her throat was sore, and white plaques had appeared in her pharynx. On day 4, none of the cultures had shown any bacterial growth, but both the blood and urine cultures grew out Candida albicans.
If amphotericin B is administered, the patient should be pre-medicated with
(A) Diphenhydramine
(B) Ibuprofen
(C) Prednisone
(D) Any or all of the above
(E) None of the above
(D) Any or all of the above
Infusion-related adverse effects of amphotericin B include chills and fevers (the "shake and bake" syndrome), muscle spasms, nausea, headache, and hypotension. Analgesic- antipyretics, antihistamines, and glucocorticoids all have been shown to be helpful. The administration of a 1-mg test dose of amphotericin B is sometimes useful in predicting the severity of infusion-related toxicity.
A 37-year-old woman with leukemia was undergoing chemotherapy with intravenous antineoplastic drugs. During treatment, she developed a systemic infection from an opportunistic pathogen. There was no erythema or edema at the catheter insertion site. A white vaginal discharge was observed. After appropriate specimens were obtained for culture, empiric antibiotic therapy was started with gentamicin, nafcillin, and ticarcillin intravenously. This regimen was maintained for 72 h, during which time the patient's condition did not improve significantly. Her throat was sore, and white plaques had appeared in her pharynx. On day 4, none of the cultures had shown any bacterial growth, but both the blood and urine cultures grew out Candida albicans.
Candida is a major cause of nosocomial bloodstream infection. The opportunistic fungal infection in this patient could have been prevented by administration of
(A) Caspofungin
(B) Flucytosine
(C) Nystatin
(D) Voriconazole
(E) None of the above
(E) None of the above
In the case of opportunistic candidal infections in the immunocompromised patient, no prophylactic drugs have been shown to be clinically effective. Prophylaxis against other fungi may be effective in some instances, including suppression of cryptococcal meningitis in AIDS patients with fluconazole. However, prophylactic use of azoles may contribute to the development of fungal resistance.
A 28-year-old man living on the East Coast was transferred by his employer to California for several months. On his return, he complains of having influenza-like symptoms with fever and a cough. He also has red, tender nodules on his shins. His physician suspects that these symptoms are due to coccidioidomycosis contracted during his stay in California.
This patient should be treated immediately with
(A) Amphotericin B
(B) Caspofungin
(C) Ketoconazole
(D) Terbinafine
(E) None of these drugs
(E) None of these drugs
A travel history can be important in the diagnosis of fungal disease. If this patient has a fungal infection of the lungs, it is probably due to C immitis, which is endemic in dry regions of the western United States. Pulmonary symptoms of coccidioidomycosis are usually self-limiting, and drug therapy is not commonly required in an otherwise healthy patient. Tender red nodules on extensor surfaces constitute a good prognostic sign. Erythema nodosum is a delayed hypersensitivity response to fungal antigens. No organisms are present in the lesions, and it is not a sign of disseminated disease.
A 28-year-old man living on the East Coast was transferred by his employer to California for several months. On his return, he complains of having influenza-like symptoms with fever and a cough. He also has red, tender nodules on his shins. His physician suspects that these symptoms are due to coccidioidomycosis contracted during his stay in California.
Which is the drug of choice if this patient is suffering from persistent lung lesions or disseminated disease caused by Coccidioides immitis?
(A) Amphotericin B
(B) Flucytosine
(C) Itraconazole
(D) Micofungin
(E) Terbinafine
(C) Itraconazole
In progressive or disseminated forms of coccidioidomycosis, systemic antifungal drug treatment is needed. Until recently, amphotericin B was the recommended therapy, but fluconazole or itraconazole are now generally preferred. Note that the risk of dissemination is much greater in African Americans (10% incidence) and in pregnant women during the third trimester.
Which drug is least likely to be effective in the treatment of esophageal candidiasis if it is used by the oral route?
(A) Clotrimazole
(B) Griseofulvin
(C) Ketoconazole
(D) Itraconazole
(E) Nystatin
(B) Griseofulvin
Griseofulvin has no activity against Calbicans and is not effective in the treatment of systemic or superficial infections caused by such organisms. "Swish and swallow" formulations of clotrimazole and nystatin have been used commonly. Most of the azoles are effective in esophageal candidiasis.
Serious cardiac effects have occurred when this drug was taken by patients using the antihistamines astemizole or terfenadine
(A) Amphotericin B
(B) Griseofulvin
(C) Ketoconazole
(D) Terbinafine
(E) Voriconazole
(C) Ketoconazole
Ketoconazole was the first oralazole introduced into clinical use, but it has a greater propensity to inhibit human cytochrome P450 enzymes than other azoles and is no longer widely used in the United States. Cardiotoxicity may occur when ketoconazole is used by patients taking astemizole or terfenadine as a result of the ability of ketoconazole to inhibit their metabolism via hepatic cytochromes P450.
Regarding the clinical use of liposomal formulations of amphotericin B, which statement is accurate?
(A) Amphotericin B affinity for these lipids is greater than affinity for ergosterol
(B) Less expensive to use than conventional amphotericin B
(C) More effective in fungal infections because they increase tissue uptake of amphotericin B
(D) They decrease the nephrotoxicity of amphotericin B
(E) They have a wider spectrum of antifungal activity than conventional formulations of amphotericin B
(D) They decrease the nephrotoxicity of amphotericin B
Liposomal formulations of amphotericin B result in decreased accumulation of the drug in tissues, including the kidney. As a result, nephrotoxicity is decreased. With some lipid formulations, infusion-related toxicity may also be reduced. Lipid formulations do not have a wider antifungal spectrum; their daily cost ranges from 10 to 40 times more than the conventional formulation of amphotericin B.
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