Anti Malaria

Question 0

Quinine & Quinidine

Answer 0

An aminoquinoline, a blood schizonticide
Mech of action is unknown
For chloroquine resistant falciparum malaria esp cerebral malaria
Often used w doxycycline or clindamycin or sulfadoxine-pyrimethamine
Quinidine used IV in US for severe falciparum malaria
Quinine also used for Babesiosis
Adverse Effects: cinchonism (GI distress, headache, vertigo, blurred vision, tinnitus), arrhythmia, hemolysis in G6PD deficient, Blackwater fever (intravascular hemolysis)
Contraindicated in pregnancy

Question 1

Chloroquine

Answer 1

An aminoquinoline, blood schizonticide
Inhibits conversion of free heme into hemozoin thus induces parasite toxicity due to build up of free heme. Drug is incorporated into DNA of plasmodium thus inhibits proliferation. Also increases cellular pH thus decreasing plasmodium protease activity.
For tto of sensitive P. falciparum & non-P. falciparum. Combined w Primaquine for radical cure of P. vivax & P.ovale. For chemoprophylaxis for areas wo resistant falciparum malaria. For amebic liver abscess.
Adverse Effects: pruritis, hemolysis in G6PD deficient, impaired hearing, confusion, psychosis, seizures, hypotension, ECG changes (typical of aminoquinolines), pregnancy category C

Question 2

Primaquine

Answer 2

An aminoquinoline, tissue schizonticide, gametocide
Metabolites act as ox-red mediators resulting in generation of reactive oxygen species which interfere w mitochondrial electron transport in plasmodium
For radical cure w chloroquine thus eradicates liver stages of P.vivax & P.ovale, prophylaxis for P.vivax & P.ovale
Adverse Effects: pruritis, headache, methemoglobinemia, hemolysis in G6PD deficient, pregnancy category C

Question 3

Mefloquine

Answer 3

An aminoquinoline
Mech is unknown
For prophylaxis in chloroquine resistant P.falciparum, alt drug to quinine in acute attacks
Adverse Effects: psychiatric disorders, GI distress, skin rash, headache, dizziness, at high doses cardiac conduction disturbance, seizures, neurological symptoms

Question 4

Artesunate & Artemether

Answer 4

Artemisinins, blood schizonticides
Forms free radical cpmds that alkylate heme producing artemisin-heme adducts toxic to plasmodia
For severe malaria due to P.falciparum in combo w mefloquine or sulfadoxine-pyrimethamine, multi drug resistant strains of Plasmodium, schistosomes

Question 5

Atovaquone

Answer 5

Mech is unclear
For malaria, PCP, Babesia
Adverse Effects: rash, cough, NVD, fever, abnormal liver function tests
Contraindicated in pts w hx of cardiac conduction defects, psychiatric disorders, or seizures
Resistance due to mutations in cytB

Question 6

Pyrimethamine & Proguanil

Answer 6

Inhibit plasmodial dihydrofolate reductase thus inhibiting production of purines thus synthesis of nucleic acids, inhibit only plasmodia in exoerythrocytic stage
Use as: Sulfadoxine-pyrimethamine (Fansidar),
Atovaquone-proguanil (Malarone)
For areas w chloroquine resistant P.falciparum

Question 7

Doxycycline

Answer 7

Inhibits plasmodium protein synthesis by preventing access of aminoacyl tRNA to the acceptor site of the ribosome
For multi drug resistant P.falciparum
Contraindicated in pregnant women

Question 8

Halofantrine

Answer 8

Mech of action is unknown
For tto of erythrocytic stages of all 4 human malaria species including chloroquine resistant falciparum
Adverse Effects: not used as chemoprophylaxis bc QT prolongation & embryo toxicity