Pharm: Anti-virals, fungals, etc.

Question 1

NRTIs (zidovudine, didanosine, zalcitabine, lamivudine, stavudine, emtricitabine, abacavir, tenofovir, adefovir)

Answer 1

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

Question 2

NNRTIs (nevirapine, efavirenz, delavirdine)

Answer 2

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)

Question 3

Protease inhibitors (saquinavir, ritonavir, indinavir, and other -navirs)

Answer 3

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

Question 4

Acyclovir

Answer 4

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

Question 5

Ganciclovir

Answer 5

Mechanism: phosphorylated by viral kinase into dGTP analogue > inhibits CMV DNA polymerase
Use: CMV infections (especially retinitis)
SE: pancytopenia, nephrotoxicity, seizures, headache

Question 6

Foscarnet

Answer 6

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

Question 7

Amantidine

Answer 7

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

Question 8

Zanamivir

Answer 8

Mechanism: inhibits neuraminidase, the viral enzyme necessary for replication and release of virus from cells
Use: treatment and prophylaxis of influenza A and B

Question 9

Ribavirin, entecavir

Answer 9

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

Question 10

Amphotericin B

Answer 10

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

Question 11

Nystatin

Answer 11

Mechanism: binds to ergosterol and alters fungal cell membrane
Use: topical treatment for oral and cutaneous candidiasis; not used orally due to high toxicity

Question 12

Flucytosine

Answer 12

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

Question 13

Caspofungin

Answer 13

Mechanism: inhibits beta(1,3)-D-glucan synthase > disrupts fungal cell wall
Use: systemic candidiasis and aspergillosis

Question 14

Ketoconazole, miconazole

Answer 14

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)

Question 15

Fluconazole, itraconazole, voriconazole

Answer 15

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

Question 16

Griseofulvin

Answer 16

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

Question 17

Terbinafine

Answer 17

Mechanism: inhibits squalene epoxidase, an enzyme in ergosterol synthesis
Use: topical dermatophytic infections

Question 18

Chloroquine, mefloquine, quinine

Answer 18

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)

Question 19

Primaquine

Answer 19

Mechanism: not fully understood
Use: hepatic forms of P vivax and P ovale malaria
SE: hemolytic anemia in G6PD pts, abdominal pain

Question 20

Nifurtimox

Answer 20

Mechanism: breakdown generates oxygen radicals
Use: T cruzi (Chagas disease)

Question 21

Sodium stibogluconate

Answer 21

Mechanism: unknown
Use: leishmaniasis

Question 22

Mebendazole, albendazole

Answer 22

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

Question 23

Praziquantel

Answer 23

Mechanism: increases cell Ca uptake > parasite contraction and paralysis
Use: schistosomiasis, neurocysticercosis, hyatid disease, Taenia infxns
SE: GI upset, elevated LFTs

Question 24

Niclosamide

Answer 24

Mechanism: inhibits worm production of ATP
Use: tapeworm (Taenia and D latum)
SE: GI upset