Pharm: Anti-virals, fungals, etc. Flashcards
NRTIs (zidovudine, didanosine, zalcitabine, lamivudine, stavudine, emtricitabine, abacavir, tenofovir, adefovir)
Mechanism: inhibit reverse transcriptase, compete with nucleoside triphosphates to be added to viral DNA
Use: HIV; zidovudine (AZT) is used in pregnant mothers to reduce viral transmission
SE: neutropenia, megaloblastic anemia (zidovudine), pancreatitis (didanosine), peripheral neuropathy (zalcitabine, stavudine), lactic acidosis (abacavir), rash, GI upset
NNRTIs (nevirapine, efavirenz, delavirdine)
Mechanism: bind to and block reverse transcriptase
SE: SJS, hepatitis, CYP450 induction (nevirapine); headache, fatigue, nausea, rash, elevated LFTs (delavirdine); CNS disturbances and rash (efavirenz)
Protease inhibitors (saquinavir, ritonavir, indinavir, and other -navirs)
Mechanism: inhibit HIV protease and therefore replication; protease cleaves precursor proteins in mature proteins and is involved in formation of the viral core
SE: altered distribution of body fat, insulin resistance, hyperlipidemia, GI discomfort, paresthesias; ritonavir inhibits CYP450
Acyclovir
Mechanism: phosphorylated by viral thymidine kinase into an analog of dGTP; incorporation into viral DNA causes chain termination
Use: HSV 1 and 2, VZV, EBV
SE: GI upset, neurotoxicity (tremor, delirium), nephrotoxicity
Ganciclovir
Mechanism: phosphorylated by viral kinase into dGTP analogue > inhibits CMV DNA polymerase
Use: CMV infections (especially retinitis)
SE: pancytopenia, nephrotoxicity, seizures, headache
Foscarnet
Mechanism: pyrophosphate analog that inhibits viral DNA polymerase; does not require activation by a viral kinase
Use: second-line treatment of CMV infections, acyclovir-resistant HSV and VZV
SE: nephrotoxicity
Amantidine
Mechanism: binds to M2 surface protein proton channel on influenza, blocking the uncoating of viral RNA within host cells; stimulates release of dopamine in stiatum
Use: reduces duration of influenza infection; influenza prophylaxis; Parkinson’s
SE: CNS symptoms (ataxia, slurred speech, dizziness), GI upset
Zanamivir
Mechanism: inhibits neuraminidase, the viral enzyme necessary for replication and release of virus from cells
Use: treatment and prophylaxis of influenza A and B
Ribavirin, entecavir
Mechanism: guanosine analogue that inhibits guanine nucleotide synthesis and therefore viral RNA polymerase
Use: RSV bronchiolitis, influenza A and B, hepatitis C (ribavirin); hepatitis B (entecavir)
SE: hemolytic anemia, teratogenic
Amphotericin B
Mechanism: binds to ergosterol in the fungal cell membrane, alters membrane permeability, leading to death
Use: broad-spectrum anti-fungal (does not cross BBB > given intrathecally for meningitis)
SE: nephrotoxicity, abnormal LFTs, fever, chills, spasms, headache
Nystatin
Mechanism: binds to ergosterol and alters fungal cell membrane
Use: topical treatment for oral and cutaneous candidiasis; not used orally due to high toxicity
Flucytosine
Mechanism: converted to nucleotide analogues within the fungal cell that inhibit thymidylate synthase and therefore fungal DNA and RNA synthesis
Use: used in combination with Amphotericin B to treat systemic infxn with cryptococcus and candida
SE: bone marrow suppression, hepatotoxicity
Caspofungin
Mechanism: inhibits beta(1,3)-D-glucan synthase > disrupts fungal cell wall
Use: systemic candidiasis and aspergillosis
Ketoconazole, miconazole
Mechanism: inhibits formation of ergosterol by inhibiting fungal CYP450; also inhibits mammalian CYP450, disrupting gonadal and adrenal steroid synthesis
Use: broad-spectrum anti-fungal, Cushing syndrome, prostate cancer; miconazole is only used topically because of its high toxicity
SE: GI upset, abnormal LFTs, anti-androgen effects (decreased libido, gynecomastia, menstrual irregularities)
Fluconazole, itraconazole, voriconazole
Mechanism: inhibits formation of ergosterol by inhibiting fungal CYP450; also inhibits mammalian CYP450, but has minimal adrenal/gonadal effects
Use: broad-spectrum anti-fungal
SE: GI upset, abnormal LFTs, fevers, chills
Griseofulvin
Mechanism: interferes with microtubule function > inhibits mitosis and replication; active in keratin-rich tissues (skin, nails, hair)
Use: topical dermatophytic infections (e.g., onychomycosis); taken orally
SE: headaches, confusion, GI upset, allergy, hepatitis
Terbinafine
Mechanism: inhibits squalene epoxidase, an enzyme in ergosterol synthesis
Use: topical dermatophytic infections
Chloroquine, mefloquine, quinine
Mechanism: concentrates in parasite food vacuoles and prevents heme metabolism > toxicity and cell death
Use: chemoprophylaxis and treatment of P falciprum malaria; babesia (quinine)
SE: GI upset, pruritis, visual disturbances, ECG changes (chloroquine); cinchonism, Coombs+ hemolytic anemia (quinine); mental status changes (mefloquine)
Primaquine
Mechanism: not fully understood
Use: hepatic forms of P vivax and P ovale malaria
SE: hemolytic anemia in G6PD pts, abdominal pain
Nifurtimox
Mechanism: breakdown generates oxygen radicals
Use: T cruzi (Chagas disease)
Sodium stibogluconate
Mechanism: unknown
Use: leishmaniasis
Mebendazole, albendazole
Mechanism: inhibits microtubule synthesis and function
Use: whipworm, hookworm, roundworm, pinworm; albendazole also used for strongyloides, neurocysticercosis, hyatid disease, cutaneous larva migrans
SE: GI upset, allergy
Praziquantel
Mechanism: increases cell Ca uptake > parasite contraction and paralysis
Use: schistosomiasis, neurocysticercosis, hyatid disease, Taenia infxns
SE: GI upset, elevated LFTs
Niclosamide
Mechanism: inhibits worm production of ATP
Use: tapeworm (Taenia and D latum)
SE: GI upset
