Antiparasytic Drugs

Question 1

what are the targets for parasitic drugs?

Answer 1

• 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

Question 2

Metronidazole

Answer 2

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

Question 3

What are the drugs of choice for protozoal infections commonly encountered in US?

Answer 3

Metronidazole
Iodoquinol
Paromomycin
Nitazoxanide
Inhibitors of Folate synthesis
- Sulfonamides (sulfadiazine, sulfamethoxazole)
- Diaminopyrimidines (Pyrimethamine, Trimethoprim)

Question 4

What are the drugs of choice for OPPORTUNISTIC PARASITIC infections commonly occuring in AIDS patients?

Answer 4

Cryptosporidium Parvum:

- Nitazoxanide

Question 5

What are the drugs used for Prophylaxis and treatment of Malaria?

Answer 5

Chloriquine
Quinine
Mefloquine
Primaquine
Malarone
Doxycycline
Artemisinin Derivatives

Question 6

What are the drugs of choice for helminthic infections commonly encountered in the US?

Answer 6

Benzimidazoles
 - Albendazole
 - Mebendazole
 - Thiabendazole
Ivermectin
Pyrantel Pamoate
Praziquantel

Question 7

MOA

Iodoquinol

Answer 7

Use for amebiais after metronidazole to get rid of cyst form

poorly absorbed - 20 days

Question 8

MOA

Paromomycin

Answer 8

Dont know, prot synthesis?
only kills trophs in lumen
use following metronidazole for amebiasis for amebiasis

Question 9

MO Resistance

Nitazoxanide

Answer 9

None

Question 10

MOA

Nitazoxanide

Answer 10

Inhibits activity of PFOR
for C. PARVUM tx
mostly in AIDS pnts

Question 11

MOA
TMP-SMX
(trimethoprim-sulfamethoxazole)

Answer 11

Treats: PNEUMOCYSTIC JIROVECII
Inhibit Folate synthesis
- Trimethoprim (diaminopyrimidine): inhibits DHFR - no tetrahydrofolate
- Sulfamethoxazole (sulfonamide): PABA analog - inhib dihydropteroate synthase - no folate, RASH

Question 12

MO Resistance

TMP-SMX

Answer 12

has to do with PT MUTATIONS in either DHFR or dihydropteroate synthase

Question 13

MOA

Pyrimethamine-Sulfadiazine

Answer 13

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

Question 14

MO Resistance

Pyrimethamine-Sulfadiazine

Answer 14

has to do with PT MUTATIONS in either DHFR or dihydropteroate synthase

Question 15

MOA Chloroquine

Answer 15

Unclear, target HEMOGLOBIN degradation

worked well, dizzy, confusion

Question 16

MO Resistance

Chloroquine

Answer 16

TONS of resistance

acquisition of some EXPORT PUMP in the parsite

Question 17

MOA Quinine

Answer 17

Unclear, targets HEMOGLOBIN degradation
POOREST therapeutic:toxic ratio of all antimalarial drugs.
NOT used for prophylaxis, used for tx

Question 18

MO Resistance

Quinine

Answer 18

Not much, growing in asia

Question 19

MOA Mefloquine

Answer 19

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

Question 20

MOA Primiquine

Answer 20

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

Question 21

MOA

Malarone

Answer 21

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

Question 22

MOA

Doxycycline

Answer 22

antimalarial - for prophylaxis and tx
Inhibit PLASMODIUM PROTEIN SYNTHESIS
Primarily prophylaxis 
In combo for tx
Photosensitivity, dermatitis, staining teeth

Question 23

Artemisinin Derivatives

Answer 23

Extracted from chinese wormwood
treat FEVERS, TREATS MALARIA
not for prophylaxis

Question 24

MOA Antihelminthics

Answer 24

unclear, INHIBIT MITOSIS in parasite, cause muscle paralysis of parasite

Question 25

Benzimidazoles

• albendazole
• mebendazole
• thiabendazole

Answer 25

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)

Question 26

MOA

Ivermectin

Answer 26

cause HYPERPOLARIZATION OF MUSCLE CELLS, paralysis of worm, WELL ABSORBED/distribution
Tx: STRONGYLOIDIASIS, a bunch of other round worms that migrate through tissue

Question 27

MOA

Pyrantel Pamoate

Answer 27

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

Question 28

MOA

Praziquantel

Answer 28

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