Fun2-antiparasitic + antifungal

Question 1

Amphotericin B

Answer 1

Rx. broadest spectrum- endemic mycoses, only therapy for zygomycetes

Mech: bind ergosterol- polyhydryl end associate- create aqueous channel

spectra: aspergillosis, zygomycosis, candidasis, cryptococcal meningitis, endemic mycoses

PK: give as colloidal deoxycholate, IV; large Vd, long t1/2, ABLC/liposomes/ABCD (mixtures)

toxicity: cytokine storm, convulsions, dec. GFR, blood dyscracias

C/I cyclosporine, tacrolimus, aminoglycosides

Question 2

Ketoconazole

Answer 2

Rx. nonmeningeal coccidioidomycosis, candidiasis

spectra: candida, coccidioides

Mech: inhib 14a-demethylase = stops ergosterol synth. (accum lanosterol)

PK: PO, no CSF, P450 metab

toxicity: inhib P450 of host sterol = decrease in sex steroids –> dec. fertility, libido

DI: Rifampin induces faster metab of azoles; dec. metab of cyclosporin

Question 3

Fluconazole

Answer 3

Rx. cryptococcal meningitis, coccidioidal meningitis, candidiasis, prophylaxis in neutropenic pt

Spectra: cryptococcus, coccidioides, candida

PK: CNS PENETRATION, PO, P450

Mech: inhib 14a-demethylase = stops ergosterol synth. (accum lanosterol)

toxicity: inhib P450 of host sterol = decrease in sex steroids –> dec. fertility, libido

DI: Rifampin induces faster metab of azoles; dec. metab of cyclosporin

Question 4

Itraconazole

Answer 4

Rx. endemic mycoses, tinea versicolor, oral dermatophytes, oral/esophageal candidiasis

spectra: histoplasma, blastomyces, sporotrix, aspergillus, dermatophytes, candida, coccidioides

Mech: inhib 14a-demethylase = stops ergosterol synth. (accum lanosterol)

toxicity: inhib P450 of host sterol = decrease in sex steroids –> dec. fertility, libido

DI: Rifampin induces faster metab of azoles; dec. metab of cyclosporin

Question 5

Flucytosine

Answer 5

Rx. cryptococcal meningitis, candidiasis; use in combo with AmphoB for better entry

spectra: cryptococcus, candida

Mech: prodrug- metab to 5-FU –> 5-dUMP to inhib Thymidylate Synthase

PK: PO, CSF, Vd to all tissue, renal elim; dev resistance quickly

Toxicity: blood dyscracias, GI toxicity, Bone Marrow toxicity

Question 6

Capsofungin (Echinocandin)

Answer 6

Rx. Aspergillosis, candidemia, febrile neutropenia, prophylaxis for P. jiroveci

Spectra: aspergillis, candida, P. jiroveci

Mech: COMPETITIVE inhib of B-1,3-D-glucan synthase

PK: IV, renal elim;

Toxicity: embryotoxic, C/I preg, infusion related hypersensitivity+HA release, mild hepatotoxicity

Question 7

*Mebendazole

Answer 7

Rx. broad- 1st line for nematodes

Spectra: all nematodes except threadworms

Mech: inhib microtubule assembly, block glucose uptake

PK: PO, single dose

Question 8

*Albendazole

Answer 8

PK: better GI absorption than Mebendazole

Rx. broad- 1st line for nematodes

spectra: all nematodes except threadworms

Mech: inhib MT assembly

Question 9

*Ivermectin

Answer 9

Rx. Broad- 1st line for Threadworm + Onchoceriasis; Filariasis, nematodes, arthropods, heartworm

Spectra: O. Vulvulus, threadworm, filariasis, heartworm (doggy), ticks+mites+scabies+lice

Mech: agonist of glutamate gated Cl- channel

PK: PO, single dose

Toxicity: NOPE

Question 10

Praziquantel

Answer 10

Rx. Cestode, Trematode infections

Spectra: Cestode (T.solium, diphyllobothrium), Trematode (schistoma, F. hepatica)

Mech: muscular paralysis + vacuolization of parasite’s cells, maybe bc dec. Ca2+ permeability

PK: PO

Toxicity: NOPE

Question 11

*Chloroquine

Answer 11

Rx. Malaria, but widespread resistance

Spectra: P. falciparum, P. vivax, P. malariae

Mech: inhib polymerization of heme in food vacuole –> toxic

PK: PO, parenteral

Question 12

*Malerone (atovaquone + proguanil)

Answer 12

Rx. prophylaxis and treatment of resistant malaria, pneumocystis pneumonia

Spectra: Plasmodium (toxoplasma, pneumocystis)

Mech: inhib Cyt-B4 of ETC in malarial mito; DHFR inhib (proguanil part)

C/I: pregnancy

Question 13

*Artemisinin (Coartem)

Answer 13

Rx. Drug Resistant malaria (1st line)

Spectra: drug resistant Plasmodium (falciparum)

Mech: unknown

PK: PO, parenteral= Artemeter, rapid action, short t1/2

Resistance from polymorph of K13-propeller protein

Toxicity: if you give a buttload- neurotoxicity

Question 14

Quinine

Answer 14

Rx. complicated and severe malaria

Spectra: drug resistant Plasmodium

Mech: none (ask the chinese maybe)

PK: parenteral form = *Quinidine Gluconate

Toxicity: CNS/head stuff and abdominal stuff
(tinnitus, headache, tremors, nausea, abdominal pain)

Question 15

Mefloquine

Answer 15

Rx. drug resistant malaria- give to preggos

spectra: P. falciparum, P. vivax, P. malariae

Mech: unknown

PK: unknown

Toxicity: hallucinations, mania, delirium

Question 16

*Primaquine

Answer 16

Rx. relapsing malaria

Spectra: P. vivax, P. ovale

Mech: inhib ETC

PK: dunno

Toxicity: C/I for G6PDH deficiency- hemolytic anemia; C/I for pregnancy

Question 17

*Pryimethamine (+ sulfonamide)

Answer 17

Rx. Toxoplasmosis

Spectra: T. gondii

Question 18

*Metronidazole

Answer 18

Rx. Anaerobic bacteria, amebiasis, candidiasis, trichomoniasis

spectra: amoeba, candida, Trichomonas vaginalis

Mech: enz reduction in anoxic environment –> generate free radicals to degrade intracell. DNA + prot

PK: po, renal elim

Toxicity; CNS- headache, drowsiness, GI distress, nausea
C/I alcohol

Question 19

*Iodoquinol + paramycin

Answer 19

Rx. asymptomatic amebiasis

toxicity: high neurotoxicity

Question 20

*Nifurtimox + Benzidazole

Answer 20

Rx. Chaga’s disease, only for early stage

Spectra: trypanosoma cruzi

Mech: oxidative stress (??)

Question 21

(Drugs for African sleeping sickness) T. brunei

Answer 21

Pentamidine
Suramin
Melarsoprol
Eflornithine + nifurtimox

Question 22

(Drugs for Leishmaniasis)

Answer 22

Liposomal AmphoB
pentostam
glucantimine
pentamidine
miltefosine
paramomycin