Antiparasitic Rx

Question 1

Albendazole.

Answer 1

intestinal round worms: whipworm, pinworm, ascaris, hookworm, strongyloides, echniococcosis; effective against both larval and adult stages

MOA binds to B tubulin which inhibits microtubule polymerization

well distributed in tissues (treats echnococcosis and cysticercosis) but is contraindicated in pregnant women and hepatic cirrhosis

Question 2

Ivermectin.

Answer 2

filarial round worm infection: loa loa, Onchocera volvulus (river blindness), Wuchereria bancrofti; also active against strongyloidiasis

potentiation or direct activation of glutamate gated chloride channels causing tonic paralysis of the musculature

active against microfilarial worms

Question 3

Metronidazole.

Answer 3

non-malarial protozoal infections: Entamoeba histolytica, Giardia lambda, Cryptosporidium parvum, Trichomonas

undergoes enzymatic nitroreduction within aerobic parasite, forming reactive intermediates that cause free radical damage and covalently bind to parasite proteins and DNA

contraindicated in the first trimester, should not be used with alcohol, some resistance among T. vaginalis strains

Question 4

Quinnine

Answer 4

fast acting blood schizonticides, used for tx of chloroquine resistant P. falciparum (PfCRT gene)

MOA: block the polymerization of heme into hemozoin crystals which is important in detox iron (caps the polymer)
induces insulin release and can cause hypoglycemia and decreases response to ACh (decreased excitability)

toxicity: cinchonism (ringing of the ears, headaches, nausea, blurred vision), hypersensitivity, blackwater fever (massive hemolysis, hemoglo binemia, hemoglobinuria and renal failure)

Question 5

Eflorithine.

Answer 5

treatment of African trapanosoma brucei gambiense

is an inhibitor of ornithine decarboxylase, blocks cell division

can cause anemia, diarrhea, leukopenia, IV can cause transient seizure, contraindicated in pregnancy

Question 6

Primaquine.

Answer 6

latent tissue schizonticide, ineffective against erythrocytic stages (P. vivix and P. ovale)
MOA unknown, may involve generation of ROS

contraindicated in G6PDH deficiency can cause hemolysis

Question 7

Arstesunate/ Artemether.

Answer 7

first line therapy for tx of blood schistozonts; very fast and potent, active against chloroquine resistant strains (semi syntethic derivative artemether); should not be used as a mono therapy

MOA: endoperoxide bridge “warhead” essential for activity, complexing with ferous non-heme iron and generates free radical damage of macromolecules and membranes

Question 8

Praziquantel.

Answer 8

tapeworms and flukes: Tania sanginata and sodium, Diphyllobotherium datum, Echinococcus granulosus, Schistosome, liver, lung and large intestine

MOA: calcium dependent blabbing of the surface of parasites changing the worm integument

usually a 3d regimen for flukes or a single does for tape worms

Question 9

mefloquine

Answer 9

blood schizonticide (fast acting), DOC for prophylaxis in areas with chlororquine resistance (1/week) and high doses can be used to treat disease

MOA does not inhibit polymerization but it may form toxic heme mefloquine complexes

Question 10

Chloroguanide

Answer 10

primary and latent tissue schizonticide, blood schizonticide (fast and slow acting),

resistance via mutation in enzyme complex near dihydrofolate reductase binding site; metabolized by CYP2C and 20% of Asians and Kenyans are deficient in the enzyme and cannot achieve therapeutic levels

MOA: prodrug that acts as a folate antagonist that inhibits bifunctional dihydrofolate reductase-thymidylate synthetase, inhibiting DNA synthesis

Question 11

Describe the life cycle of malaria.

Answer 11

sexual reproduction of the parasite occurs within the mosquito vector
infection via mosquito bite releases infectious form into blood, which travels to the liver
organisms released from the liver infect RBC and gametocytes can taken up by another mosquito

Question 12

Describe the length of fever cycle in different species of malaria.

Answer 12

P. falciparum 48h (broad)
P. vivax 48hr
P. ovale 48hr
P malariae 72hr

Question 13

Which forms of malaria can cause latent liver infection?

Answer 13

P. vivax and P. ovale are characterized by relapse of latent tissue forms

Question 14

Cloroquine

Answer 14

blood schizonticide used for both prophylaxis and treatment, less toxic/more effective than quinine

widespread resistance due to energy-dependent efflux mechanism

toxicity: high doses can have CV effects including hypotension and ECG abnormalities; contraindicated in those with liver disease or G6-PDH deficiency

Question 15

What is ACT?

Answer 15

artemisinin combination therapy recommended for treatment of uncomplicated P. falciparum malaria; choice of partner drug based on local resistance

Question 16

What special recommendation exist for tx. of pregnant women or infants/young children infected with malaria?

Answer 16

pregnancy: 1st trimester- quinine plus clindamycin /7d; 2nd-3rd trimester ACT plus clindamycin /7d
children: ACT with accurate dosing
travelers: atovaquone-proguanil; quinine + doxycline/ clindamycin; artemether-lumefantrine