Lange: Antivirals, Antifungals, etc.

Question 1

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)—“vudines” mostly

Answer 1

Activated by IC phosphorylation–>inhibit HIV reverse transcriptase–>messed up DNA synthesis–>defective viral particle Use = HIV tx Lamivudine–also used for Hepatitis B SE: neutropenia AZT–>megaloblastic anemia/BM suppression (Think of AZT as the biggest name) Didanosine–>pancreatitis

Question 2

Nucleotide Reverse Transcriptase Inhibitors (-fovirs):

Answer 2

Don’t need phosphorylated Also inhibit reverse transcriptase Uses = HIV and Hepatitis B infections

Question 3

Non-Nucleoside Reverse Transcriptase Inhibitors (-vir-):

Answer 3

Bind specifically to reverse transcriptase–>decreased DNA synthesis Use = HIV tx SE: *Nevirapine–>Stevens-Johnson syndrome; fulminant hepatitis* *Efavirenz–>delusion and nightmares (CNS disturbances)*

Question 4

Protease inhibitors (-navirs):

Answer 4

Inhibit HIV protease–>virus is unable to replicate d/t no mature proteins for core particle made Uses = HIV SE = altered body fat distribution (“Fat PiG”)/hyperlipidemia

Question 5

*Acyclovir

Answer 5

Viral thymidine kinase–>phosphorylates (activates) acyclovir–>dGTP analogue–>incorporates–>inhibits viral DNA synthesis Uses = HSV1, HSV2, VZV, EBV (oral hairy leukoplakia)–Herpes mostly! *SE = nephrotoxicity (via crystallization); neurotoxicity (delirium, tremor)*

Question 6

Ganciclovir

Answer 6

Viral kinase–>phosphorylates (activates) ganciclovir–>guanosine analogue–>inhibits CMV DNA polymerase–>decreased CMV DNA synthesis Uses = CMV infections, especially CMV retinitis SE = pancytopenia

Question 7

Foscarnet

Answer 7

Pyrophosphate analogue–>inhibits viral DNA polymerase But does not require kinase activation! Use = 2DOC for CMV infections and acyclovir-resistant HSV/VZV infections SE = nephrotoxicity (–>hypoCa and hypoMg–>szs)

Question 8

Amantadine

Answer 8

Binds M2–>blocks uncoating of viral RNA Use = reduce length of influenza A symptoms Also stimulates DA release from SN (Can help tx Parkinson’s) SE = CNS sx

Question 9

Oseltamivir (-ivirs)

Answer 9

Inhibits Neuraminidase–>decreased viral replication/release Use = tx and prophylaxis of both influenza A and B

Question 10

‘R’ibavirin

Answer 10

Guanosine analogue–>inhibits viral ‘R’NA polymerase–>inhibits viral ‘r’eplication Uses = ‘R’SV bronchiolitis

Question 11

Amphotocerin B

Answer 11

Binds ergosterol–>pores (altered cell membrane permeability)–>cell death Uses = systemic mycotic infections SE = nephrotoxic (–>hypoK and hypoMg) Can–>arrhythmias Can’t cross BBB, so give intrathecally for fungal meningitis

Question 12

Nystatin

Answer 12

Similar MOA to Amphotocerin B More toxic so only used topically for oral and cutaneous Candida

Question 13

Flucytosine

Answer 13

“FlU = 5FU” Converted into 5-FU (nucleotide analogue) inside fungal cell–>inhibits thymidylate synthase–>inhibits fungal DNA and RNA synth Use = added to amphotocerin B to combat fungal meningitis and systemic fungal infections

Question 14

Caspofungin

Answer 14

*Inhibits glucan synthase*–>disrupts polysaccharide fungal cell wall Tx of systemic fungal infections

Question 15

Ketoconazole

Answer 15

Inhibits fungal P450–>inhibits ergosterol synthesis Also inhibits our P450–>disrupted gonadal and adrenal steroid synth–>gynecomastia, decreased libido, etc Uses = broad-spectrum antifungal Can be given as an antifungal vaginal suppository (for vaginal candidiasis) Also used to tx Cushing syndrome

Question 16

Fluconazole

Answer 16

Same as ketoconazole (inhibits P450) But doesn’t affect mammal steroid synth as much! Means no gynecomastia Uses = systemic fungal infections Especially cryptococcal meningitis (Lifelong prophylaxis) and Candidal sepsis

Question 17

Griseofulvin

Answer 17

Interferes with microtubule function in keratin-rich tissues–>inhibits mitosis–>inhibits fungal cell replication Uses = oral antifungal for dermatophytic fungal infections (like tinea corporis)

Question 18

Terbinafine

Answer 18

Also for dermatophytic fungal infections Inhibits squalene epoxidase–>decreased ergosterol synthesis

Question 19

Chloroquine (-quines–exception is primaquine):

Answer 19

Tx of Plasmodium falciparum and blood form of the others Quinine and mefloquine tx Plasmodium falciparum if it is drug resistant Quinine SE = Cinchonism (tinnitus, H/A, dizziness)

Question 20

Pyri”meth”amine

Answer 20

Inhibits DHFR–>decreased DNA synthesis (Like Tri”meth”oprime) Uses = tx and prophylaxis of Plasmodium falciparum and tx of *Toxoplasma gondii*

Question 21

Primaquine

Answer 21

Uses = tx hepatic forms of P. vivax and P. ovale Don’t give in pregnancy (–>fetal hemolytic anemia)

Question 22

Pentamidine

Answer 22

Prophylaxis for PCP (like Dapsone)

Question 23

Nifurtimox

Answer 23

Tx of Trypanosoma cruzi (Chagas)

Question 24

Suramin

Answer 24

Tx of early Trypanosoma brucei infections (=African sleeping sickness with recurring fever and LAD…tsetse fly)

Question 25

Melarsoprol

Answer 25

Tx of late Trypanosoma brucei infections (It “sure” is nice to go to sleep. And melatonin helps with sleep.)

Question 26

*Sodium stibogluconate

Answer 26

Tx of Leishmaniasis (=spiking fevers, HSM…sandfly)