EXAM 5 antiparasitic lacount

Question 1

Pediculosis (lice) treatments

Answer 1

OTC:
A-200, Pronto, R&C, Rid, Triple X

Prescription:
- Spinosad 0.9% topical suspension
- Benzyl alcohol lotion
- Ivermectin lotion
- Malathion lotion

Question 2

Pediculosis OTC treatment MOA

Answer 2

naturally occurring pyrethrins (chrysanthemum flower extract) or synthetic pyrethroids

Nerve membrane sodium channel toxins that do not affect sodium channels

Question 3

Spinosad MOA

Answer 3

Nicotinic acetylcholine receptor agonist

Rapid excitation of insect nervous system causes death

Question 4

Helminth infections (worms) - drug therapy

Answer 4

Benzimidazoles: mebendazole, thiabendazole, albendazole, triclabendazole

Pyrantel pamoate

Question 5

Benzimidazoles MOA

Answer 5

MOA: binds tubulin, inhibits formation of microtubules
* Microtubules grow from “plus” end, so benzimidazoles cap microtubules
* Are shortened from minus end
* Inhibits cell division, secretion parasite molecules, glucose uptake

Can bind to mammalian tubulin: higher affinity to helminth tubulin

Question 6

Albendazole - clinical

Answer 6

DOC for pinworms

Variable absorption

rapidly converted to albendazole sulfoxide (active metabolite with increased activity)

Question 7

Pyrantel pamoate MOA

Answer 7

Depolarizing neuromuscular blocking agent

Causes release of acetylcholine and inhibition of cholinesterase

Worms paralyzed and expelled

Question 8

Malaria vaccine

Answer 8

targets parasites that are injected by mosquitos

4 shot regimen beginning at 5 months

Question 9

Antimalarial drug targets

Answer 9

not a single drug active against all stages
* Tissue schizonticides: kill liver stage parasites
* Blood schizonticides: kill erythrocytic forms
* Gametocytocides: kill sexual stages and block transmission

Question 10

Antimalarial drugs

Answer 10

Artemisinin

4-aminoquinolines

8-aminoquinolone

Atovaquone

Antifolates

Antibiotics

Question 11

Artemisinin MOA

Answer 11

(produg) must be activated via heme-iron in food

Activated artemisinin may form free radicals:

• Akylates parasite protein/lipis/dna
• Triggers unfold protein response
• Inhibits translation, proteasome, mitochondria

May inhibit phosphatidylinositol-3-kinase

Rapid blood schizonticide

Question 12

Artemisinin Resistance

Answer 12

mutations in Kelch 13 gene delays progress through the life cycle
- Remains in ring stage longer
- ART has short half-life and dormant until ART decrease

Question 13

4-aminoquinolines drugs

Answer 13

quinine
chloroquine
mefloquine
aminoquinoline

Question 14

4-aminoquinolines MOA

Answer 14

interfere with heme polymerization
- Malaria parasites ingest hemoglobin from host cells
- Degrade hemoglobin to Aas and free heme in food vacuoles
- Free heme is toxic
- Parasites polymerize heme into hemozoin, which is nontoxic
- Chloroquine accumulates in food vacuole and inhibits heme polymerization

Question 15

Chloroquine resistance

Answer 15

mutations in PfCRT1
- Localized to food vacuole
- Over-expression of PfMDR1

Question 16

8-aminoquinolone: primaquine MOA

Answer 16

Step 1: hydroxylation by CYP2D6 (OH-PQm)
Step 2:
- Spontaneous oxidation to quinoneimines (produces H2O2)
- CYP NADPH: oxidoreductase reduces quinoneimeimines to create catalytic cycle of H2O2 production
- H2O2 kills plasmodium parasites

Question 17

8-aminoquinolone: primaquine metabolism

Answer 17

CYP2D6

High risk of hemolysis in patients with G6PD deficiency

Question 18

Antibiotics used antimalarial

Answer 18

Tetracycline, doxycycline, and clindamycin

Question 19

Antibiotics MOA

Answer 19

blood schizonitides

Target componenets of apicoplast: plant-like organelle that carries out many essential biochemical processes