Microbiology - Antimicrobials (2) Flashcards
1
Q
Antifungal therapy (189)
A
2
Q
Amphotericin B
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Binds ergosterol (unique to fungi)
- Forms membrane pores that allow leakage of electrolytes.
- Amphotericin “tears” holes in the fungal membrane by forming pores.
- Clinical use
- Serious, systemic mycoses.
- Cryptococcus (amphotericin B with/without flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor.
- Intrathecally for fungal meningitis.
- Supplement K+ and Mg2+ because of altered renal tubule permeability.
- Serious, systemic mycoses.
- Toxicity
- Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”).
- Hydration decreases nephrotoxicity.
- Liposomal amphotericin decreases toxicity.
3
Q
Nystatin
- Mechanism
- Clinical use
A
- Mechanism
- Same as amphotericin B.
- Binds ergosterol (unique to fungi)
- Forms membrane pores that allow leakage of electrolytes.
- Topical form because too toxic for systemic use.
- Same as amphotericin B.
- Clinical use
- “Swish and swallow” for oral candidiasis (thrush)
- Topical for diaper rash or vaginal candidiasis.
4
Q
Azoles
- Examples
- Mechanism
- Clinical use
- Toxicity
A
- Examples
- Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
- Mechanism
- Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol.
- Clinical use
- Local and less serious systemic mycoses.
- Fluconazole for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.
- Itraconazole for Blastomyces, Coccidioides, Histoplasma.
- Clotrimazole and miconazole for topical fungal infections.
- Toxicity
- Testosterone synthesis inhibition (gynecomastia, esp. with ketoconazole), liver dysfunction (inhibits cytochrome P-450).
5
Q
Flucytosine
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase.
- Clinical use
- Systemic fungal infections (esp. meningitis caused by Cryptococcus) in combination with amphotericin B.
- Toxicity
- Bone marrow suppression.
6
Q
Echinocandins
- Examples
- Mechanism
- Clinical use
- Toxicity
A
- Examples
- Caspofungin, micafungin, anidulafungin.
- Mechanism
- Inhibits cell wall synthesis by inhibiting synthesis of β-glucan.
- Clinical use
- Invasive aspergillosis, Candida.
- Toxicity
- GI upset, flushing (by histamine release).
7
Q
Terbinafine
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Inhibits the fungal enzyme squalene epoxidase.
- Clinical use
- Dermatophytoses (especially onychomycosis—fungal infection of finger or toe nails).
- Toxicity
- GI upset, headaches, hepatotoxicity, taste disturbance.
8
Q
Griseofulvin
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Interferes with microtubule function
- Disrupts mitosis.
- Deposits in keratin-containing tissues (e.g., nails).
- Clinical use
- Oral treatment of superficial infections
- Inhibits growth of dermatophytes (tinea, ringworm).
- Toxicity
- Teratogenic, carcinogenic, confusion, headaches, increases P-450 and warfarin metabolism.
9
Q
Antiprotozoan therapy
- Toxoplasmosis
- Trypanosoma brucei
- T. cruzi
- Leishmaniasis
A
- Toxoplasmosis
- Pyrimethamine
- Trypanosoma brucei
- Suramin and melarsoprol
- T. cruzi
- Nifurtimox
- Leishmaniasis
- Sodium stibogluconate
10
Q
Chloroquine
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Blocks detoxification of heme into hemozoin.
- Heme accumulates and is toxic to plasmodia.
- Clinical use
- Treatment of plasmodial species other than P. falciparum (frequency of resistance in P. falciparum is too high).
- Resistance due to membrane pump that decreases intracellular concentration of drug.
- Treat P. falciparum with artemether/lumefantrine or atovaquone/proguanil.
- For life-threatening malaria, use quinidine in U.S. (quinine elsewhere) or artesunate.
- Toxicity
- Retinopathy
- Pruritus (especially in dark-skinned individuals).
11
Q
Antihelminthic therapy
A
- Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel
- Immobilize helminths.
- Use praziquantel against flukes (trematodes) such as Schistosoma.
12
Q
Antiviral therapy (191)
A
13
Q
Zanamivir, oseltamivir
- Mechanism
- Clinical use
A
- Mechanism
- Inhibit influenza neuraminidase –> decrease the release of progeny virus.
- Clinical use
- Treatment and prevention of both influenza A and B.
14
Q
Ribavirin
- Mechanism
- Clinical use
- Toxicity
A
- Mechanism
- Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.
- Clinical use
- RSV, chronic hepatitis C.
- Toxicity
- Hemolytic anemia.
- Severe teratogen.
15
Q
Acyclovir, famciclovir, valacyclovir
- Mechanism
- Clinical use
- Toxicity
- Mechanism of resistance
A
- Mechanism
- Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells –> few adverse effects.
- Guanosine analog.
- Triphosphate formed by cellular enzymes.
- Preferentially inhibits viral DNA polymerase by chain termination.
- Clinical use
- HSV and VZV.
- Weak activity against EBV.
- No activity against CMV.
- Used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis.
- Prophylaxis in immunocompromised patients.
- No effect on latent forms of HSV and VZV.
- Valacyclovir, a prodrug of acyclovir, has better oral bioavailability.
- For herpes zoster, use a related agent, famciclovir.
- Toxicity
- Obstructive crystalline nephropathy and acute renal failure if not adequately hydrated.
- Mechanism of resistance
- Mutated viral thymidine kinase.
