ID Exam 3: Dr. Harold Treat Parasitic Infections

Tinidazole

• similar to metroindazole

• produce ROS - O2, OH, H2O2 (do not use alcohol)

Nitazoxamide

• prodrug: converted to 2 metabolites via hydrolysis + reduction to hydroxylamine

• blocks pyruvate:ferroxin oxidorectase

• readily converts pyruvate to acetyl CoA

• caused by disruption of bioenergics

Paromomycin

• oral for local effects - GI local effects

• Aminoglycoside ATB

• freezes initiation complex

• produces “nonsense” proteins

• human host immune defenses do not recognize these pathogens

Albendazole

• benzimidazole

• inhibition of fumarate reductase invoved in electron transport chain

• prevents transfer of electrons for NADH Complex I

• decrease energy supply to parasites

• decrease mobilization

Mebendazole

• binds to tubulin + caps association ends

• prevents mitosis

Triclabendazole

• decrease motility

• disrupts surface membrane

• active metabolite by CYP1A2

Ivermectin

• decrease motility of microfalaria (early stages in life cycle)

• allows cytotoxic cells of host to adhere to parasite

• take w/ corticosteroids, antihistamine, and/or NSAID

Praziquantel

• used to treat worms

• depend on parasite

• cause muscle contractions + paralysis via Ca2+ influx damages worm tegument

• Drug interactions: substrate for CYP3A4

Permethrin

• topical for lice

• inhibit Na+ influx through nerve cell membrane channels in parasite resulting in delayed repolarization + paralysis

Abametapir

• topical for lice

• inhibition of metalloproteinase, decrease egg development + survival

• highly lipid soluble, can get absorbed

• inhibit CYP3A4, 2B6, 1A2 - avoid drug using these isozymes for 2 weeks

Quinolines

• used to treat malaria

• hemoglobin provides amino acid to plasmodium sp.

• heme portion is toxic + metabolized to polymer hemzoin

• class of drugs binds to porphyrin rings (via quinoline ring) of heme + prevents polymerization

• Drug interactions: CYP3A4 + CYP2D6

Atorvaquone

• used to treat malaria

• MUST be used in COMBO w/ Proguanil

• mimics coenzyme Q (ubquinone) - part of ET chain

• inhibits mitochondrial respiratory chain in susceptible parasites

• selectively inhibit plasmodium

• prevents ATP synthesis (decrease energy source for parasite)

Proguanil

• used to treat malaria

• MUST be used in COMBO w/ Atorvaquone

• prodrug converted cycloguanil

• requires CYP2C19

• inhibits dihydrofolate reductase

• inhibit DNA synthesis

• Drug Interaction: any strong or intermediate inhibitor of CYP2C19 - prevent active form of drug

Artesunate

• IV ONLY

• produce free radicals provide a cidal effect by interacting with Iron

• digestion of heme in digestive vacuole provides source of Iron

• Iron reacts w/ artesunate to produce lethal carbon radicals