AntiMalarials Flashcards
(29 cards)
What are symptoms of complicated malaria?
prostration (general weakness), impaired consciousness, convulsions, renal injury, hypoglycemia, jaundice, pulmonary stress
most dangerous, most severe (can cause anemia and cerebral malaria, even death); drug resistance
P. malariae: milder disease
p. falciparum
mild dormant relapse of maalaria
p. ovale and vivax
What is life cycle of malaria?
Sporozoites when in the blood. Once in the liver stage (exo erythrocytic or merozoite): targeted with tissue schizonticides to prevent disease.
Human blood stage (erythrocytic schizogony): targeted with blood schizonticides as well to terminate clinical attacks.
Gametocyte stage: targeted with gametocides to prevent transmission
Human liver dormant stages (Hypnozoites can form in P. ovale and P. vivax infections): targeted with primaquine or tafenoquine to prevent relapse
What’s mechanism of action of chloroquine?
human heme is toxic to the malaria parasites, so to protect itself it makes heme into hemozoin via polymerization. Chloroquine prevents this polymerization causing lysis parasite and RBC
How does parasite resist chloroquine?
mutation of drug transporter protein
What are indications of chloroquine?
given orally because has long t1/2, treats uncomplicated malaria, serves as chemoprophylaxis for travel and safe for pregnancy and children
What are ADRs of chloroquine?
Low dose: transient pruritus (common); GI irritation, headache, blurring of vision.
High doses: Severe skin reactions; neuropathies, psychosis, hemolysis, irreversible retinal and auditory damage, Myocardial depression
Im or iv can cause severe hypotension and respiratory/cardiac arrest, should be avoided
What is MOA and pharmacokinetics of Quinine?
unknown MOA, but good against blood schizonticide and P. Vivax/ovale. short t1/2
What are clinical indications of quinine?
Parenteral for severe falciparum malaria, but i.v. Artesunate is now preferred;
Oral for Chloroquine-resistant falciparum: combine with doxycycline or, in children, clindamycin to reduce duration and toxicity.
What are ADRs and contraindications of quinine?
1)Cinchonism: auditory probs, reversible; 2) Hematotoxic effects: hemolysis (especially with G6PD deficiency)
3) Severe hypotension and QT prolongation
4) Blackwater fever (intavascular hemolysis)
5) Hypersensitivity reactions and hypoglycemia
Quinine should not be given concurrently with mefloquine;
What’s PK and indications to use mefloquine?
long half life so oral. Is used as first line drug for prophylaxis. Indicated for uncomplicate falciparum
ADRs of mefloquine?
Contraindicated in patients with epilepsy, psychiatric disorders, arrhythmias, cardiac conduction defects;
Not coadminister with quinine or quinidine due to potential cardiac arrest;
What is mechanism of action of artemisinin?
accumulate in parasite food vacuoles to release toxic free radicals in blood schizoticides. Only effective against quinine resistant. Most rapid acting anti malarial
What are indications for artemisinin?
Not used as monotherapy; 1st line for chloroquine or quinine-resistant malaria for uncomplicated, multidrug-resistant falciparum malaria in all endemic areas; E.g. Coartem (artemether-lumefantrine);
Severe malaria: I.v. Artesunate or rectally Artesunate and artemether
What are ADRs of artemisinin?
GI discomfort is the most common;
rare: neutropenia, anemia, delayed hemolysis, elevated liver enzymes, allergic reactions
What’s mechanism of action of Primaquine/Tafenoquine?
may acts as cellular oxidants and interferes ETC;
active against hepatic, hypnozoites, and gametocytic of all human malaria parasites
true or false: tafenoquine has longer t1/2 than primaquine
true
What are clinical indications of primaquine/tafenoquine?
Clinical Indication: Drug withheld until confirming G6PD status
- Therapy of acute Vivax and Ovale Malaria with conjunction with a blood schizonticide, e.g., chloroquine first; then primaquine for 14 days or single dose of Tafenoquine
- prophylaxis of Vivax and Ovale Malaria
- Chemoprophylaxis of malaria
- Gametocidal action to decrease transmission
What are ADRs and contraindications of primaquine/tafenoquine?
Hemolytic anemia or methemoglobinemia (cyanosis) in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency
May cause GI discomfort, headache, and rare hematotoxic effects and cardiac arrhythmias
Avoided in patients with potential myelosuppression, G6PD deficiency, and pregnancy
What’s mechanism of action of atovaquone?
disrupt mitochondrial electron transport to reduce ATP and pyrimidine biosynthesis in plasmodia;
active against tissue and erythrocytic schizonts;
What is pharmacokinetic activity of atovaquone?
Only given orally; highly protein-bound; absorption is increased by fatty food; Half-life about 2-3 days
What are indications and ADRs of atovaquone?
Clinical Indications: Good for children >5Kg; not for pregnancy
Atovaquone–proguanil Combination (Malarone): highly effective/synergistic for treating and chemoprophylaxis of falciparum malaria ( but more expensive than mefloquine or doxycycline)
Adverse effects: well tolerated
GI discomfort, headache, insomnia, and rash with higher dosage.
What is mechanism of action of antifolates: pyrimethamine, proguanil,sulfadoxine?
inhibits dihydropteroate synthase (e.g., Sulfadoxine) or dihydrofolate reductases blood schizonticide; Proguanil also inhibits hepatic form
