From Jen: Antivirals/fungals/TB

Question 1

Protease inhibitors

Answer 1

Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir

MOA: Inhibit maturation of new virus by blocking protease in progeny virions

Toxicity: GI intolerance, hyperglycemia, lipodystrophy, thrombocytopenia (indinavir)

Question 2

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Answer 2

zidovudine (AZT)
didanosine (ddI)
zalcitabine (ddC)
stavudine (d4T)
lamivudine (3TC)
abacavir

Question 3

NRTI/NNRTI

Answer 3

MOA: preferentially inhibit reverse transcriptase of HIV; prevent incorporation of DNA copy of viral genome into host DNA

Toxicity: Bone marrow suppression, peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), megaloblastic anemia (AZT)

Use: HAART uses reverse transcriptase inhibitors and protease inhibitors
Initiated when CD4<500 or high viral load

AZT for general prophylaxis in pregnancy

Question 4

Non-nucleoside reverse transcriptase Inhibitors (NNRTIs)

Answer 4

Nevirapine
Efavirenz
Delavirdine

Question 5

Fusion Inhibitors

Answer 5

Enfuvirtide

MOA: bind viral gp41 subunit; inhibit conformational change required for fusion with CD4 cells. Block entry and subsequent replication

Toxicity: Hypersensitivity rxn, rxn at subQ injection site, increased risk of bacterial pneumonia

Use: pts with persistent viral replication despite antiretroviral therapy in combination with other drugs

Question 6

Isoniazid (INH)

Answer 6

MOA: synthesis of mycolic acid

Use: only agent used solo prophylaxis against TB

Toxicity: hepatotoxic, neurotoxic (co-administer B6)

**metabolized by acetylation in liver- fast acetylators increase risk of hepatotoxicity

Question 7

Rifampin

Answer 7

MOA: inhibits DNA-dependent RNA polymerase

Use: TB, delays resistance to dapsone when used against leprosy, prophylaxis against meningococcus and chemoprophylaxis against Hib

Toxicity: hepatotoxic, induce P450, orange body fluids

Question 8

Amphotericin B

Answer 8

MOA: Binds ergosterol; forms membrane pores that allow leakage of electrolytes.

Use: cryptococcus, blastomyces, coccidioides, aspergillus, histoplasma, Candida, Mucor
Intrathecal use for fungal meningitis; does not cross BBB

Toxicity: fever/chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis, nephrotoxic.

**liposomal amphotericin reduces toxicity

Question 9

Nystatin

Answer 9

MOA: binds ergosterol disrupting fungal membranes. **Too toxic for systemic use!!!

Use: Swish and swallow for oral candida, topical for diaper rash or vaginal candidiasis

Question 10

Azoles

Answer 10

MOA: Inhibit fungal sterol (ergosterol) synthesis

Use: systemic mycoses
Fluconazole: cryptococcus in AIDS pts (cross BBB), all candida infections

Ketoconazole: blastomyces, coccidioides, histoplasma, candida

Clotrimazole/miconazole topical

Toxicity: hormone synthesis inhibition (keto-gynecomastia), liver dysfunction (inhibits P450), fever, chills

Question 11

Azole drugs

Answer 11

Fluconazole
Ketoconazole
Clotrimazole
Miconazole
Itraconazole
Voriconazole

Question 12

Flucytosine

Answer 12

MOA: Inhibits DNA synthesis by conversion to 5-fluorouracil

Use: systemic fungal infections in combination with amphotericin B

Toxicity: N/V/D, bone marrow suppression

Question 13

Capsofungin

Answer 13

MOA: Inhibits cell wall synthesis by inhibiting synthesis of beta-glucan

Use: invasive aspergillosis

Toxicity: GI upset, flushing

Question 14

Terbinafine

Answer 14

MOA: Inhibits the fungal enzyme squalene epoxidase

Use: Used to treat dermatophytoses (especially onychomycosis)

Question 15

Griseofulvin

Answer 15

MOA: Interferes with microtubule function, disrupts mitosis, deposits in keratin-containing tissues.

Use Oral tx of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)

Toxicity: Teratogenic, carcinogenic, confusion, headache, induces P450s, and warfarin metabolism

Question 16

Tenofovir

Answer 16

Nucleotide analog