Antiparasytic Drugs Flashcards
what are the targets for parasitic drugs?
- Enzymes found only in parasites
- enzymes found in both host and parasite but indispensible only in parasites
- common biochemical functions in parasite and host but have different pharm properties
Metronidazole
Tx for Giardia, Entabmoeba Histolytica, Trichomonas - all lumen dwelling protozoans
all these organisms have enzyme ferredoxin oxidoreductase (PFOR)
We dont have PFOR
MOA: ? its a prodrug, becomes radicalized
well absorbed, little toxicity, Dry mouth, metallic taste,
“Disulfiram-like” effect- avoid alcohol w/
Amebiasis: kills the trophozoite forms only.
- follow with iodoquinol to kill cyst forms
- also good for treating liver/brain cysts
Resistance is rare - change in PFOR activity
What are the drugs of choice for protozoal infections commonly encountered in US?
Metronidazole
Iodoquinol
Paromomycin
Nitazoxanide
Inhibitors of Folate synthesis
- Sulfonamides (sulfadiazine, sulfamethoxazole)
- Diaminopyrimidines (Pyrimethamine, Trimethoprim)
What are the drugs of choice for OPPORTUNISTIC PARASITIC infections commonly occuring in AIDS patients?
Cryptosporidium Parvum:
- Nitazoxanide
What are the drugs used for Prophylaxis and treatment of Malaria?
Chloriquine Quinine Mefloquine Primaquine Malarone Doxycycline Artemisinin Derivatives
What are the drugs of choice for helminthic infections commonly encountered in the US?
Benzimidazoles - Albendazole - Mebendazole - Thiabendazole Ivermectin Pyrantel Pamoate Praziquantel
MOA
Iodoquinol
Use for amebiais after metronidazole to get rid of cyst form
poorly absorbed - 20 days
MOA
Paromomycin
Dont know, prot synthesis?
only kills trophs in lumen
use following metronidazole for amebiasis for amebiasis
MO Resistance
Nitazoxanide
None
MOA
Nitazoxanide
Inhibits activity of PFOR
for C. PARVUM tx
mostly in AIDS pnts
MOA
TMP-SMX
(trimethoprim-sulfamethoxazole)
Treats: PNEUMOCYSTIC JIROVECII
Inhibit Folate synthesis
- Trimethoprim (diaminopyrimidine): inhibits DHFR - no tetrahydrofolate
- Sulfamethoxazole (sulfonamide): PABA analog - inhib dihydropteroate synthase - no folate, RASH
MO Resistance
TMP-SMX
has to do with PT MUTATIONS in either DHFR or dihydropteroate synthase
MOA
Pyrimethamine-Sulfadiazine
Treats: TOXOPLASMOSIS GONDII
Inhibits Folate synthesis
- Pyrimethamine (diaminopyrimidine): Inhibit of enzyme DHFR - prev form of tetrahydrofolate
- Sulfadiazine (sulfonamide): PABA analog, inhib dihydropteroate synthase, prev folate synth, RASH
MO Resistance
Pyrimethamine-Sulfadiazine
has to do with PT MUTATIONS in either DHFR or dihydropteroate synthase
MOA Chloroquine
Unclear, target HEMOGLOBIN degradation
worked well, dizzy, confusion
MO Resistance
Chloroquine
TONS of resistance
acquisition of some EXPORT PUMP in the parsite
MOA Quinine
Unclear, targets HEMOGLOBIN degradation
POOREST therapeutic:toxic ratio of all antimalarial drugs.
NOT used for prophylaxis, used for tx
MO Resistance
Quinine
Not much, growing in asia
MOA Mefloquine
Targets degradation of HEMOGLOBIN
PROPHYLAXIS drug
half life 14 days
Some report severe neuropsychiatric rxns receiving this for treatment.
works well against all species of plasmodium
MOA Primiquine
Only drug to get rid of LIVER FORMS of plasmodium.
activated by host metabolism, maybe interferes with mitochondrial function?
Can cause Hemolysis in G6PD deficiency
MOA
Malarone
Combo of ATOVAQUONE and PROGUANIL Good for tx of P. FALCIPARUM malaria as well as prophylaxis NO RESISTANCE yet atovaquone is lipophilic Proguanil inhibits DHFR enzyme
MOA
Doxycycline
antimalarial - for prophylaxis and tx Inhibit PLASMODIUM PROTEIN SYNTHESIS Primarily prophylaxis In combo for tx Photosensitivity, dermatitis, staining teeth
Artemisinin Derivatives
Extracted from chinese wormwood
treat FEVERS, TREATS MALARIA
not for prophylaxis
MOA Antihelminthics
unclear, INHIBIT MITOSIS in parasite, cause muscle paralysis of parasite
Benzimidazoles
- albendazole
- mebendazole
- thiabendazole
Poorly soluble, little absorbed
THIABENDAZOLE is better absorbed and also more toxic
admin on EMPTY STOMACH to keep absorption low
eat FATTY MEAL with tissue dwelling helminths for better absorption
Resistance in animals
Thiabendazole: GI, CNS tox
all are CONTRAINDICATED in preg and infants
For ASCARIS, PINWORM, HOOKWORM, WHIPWORM
- Thiabendazole good for STRONGYLOIDIASIS (intestinal and tissue infection), also for CUTANEOUS LARVAL MIGRANS (from animal poop on foot)
MOA
Ivermectin
cause HYPERPOLARIZATION OF MUSCLE CELLS, paralysis of worm, WELL ABSORBED/distribution
Tx: STRONGYLOIDIASIS, a bunch of other round worms that migrate through tissue
MOA
Pyrantel Pamoate
PARALYSIS of worm, via activation of CHOLINERGIC neurons.
Poorly absorbed from gut, good for tx INTESTINAL NEMATODES
Good for PINWORM! drug of choice
Treatment of entire household is recommended
MOA
Praziquantel
Tx Cestodes and Trematodes Increases the Ca permeability of the worms protective TEGUMENT COVERING, susceptible to immune system Easily absorbed, and tolerated works well with LIMITED # OF DOSES Flukes: 3 doses in 1 day Tapeworms: single dose Cysticercosis: 2 wks tx
