Anti malarials Flashcards
major antimalarial drugs
• Chloroquine • Quinine and Quinidine • Mefloquine • Primaquine • Atovaquone • Sulfadoxine-pyrimethamine • Doxycycline • Artemisinins
Chloroquine DOC ?
Drug of choice for both treatment & prophylaxis of all P. vivax and P. ovale malaria infections since 1940’s (dormant in liver )
• Use severely compromised by drug resistance
-for uncomplicated falciparum malaria
Chloroquine clinical applications ?
• Drug of choice in the treatment of non-falciparum and sensitive uncomplicated falciparum malaria • Preferred chemoprophylactic agent in areas without resistant falciparum malaria
chloroquine MOA ? antimalarial action ?
Concentrates in parasite food vacuoles • Prevents biocrystallization of hemoglobin breakdown product heme to non-toxic hemozoi
Antimalarial Action • Highly effective against blood parasites • NOT active against liver stage parasites
chloroquine PK ?Resistance ?
Pharmacokinetics • Oral • t1/2 = 3-5 days (only need to take once weekly)
Resistance • P. falciparum: mutations in putative transporter, PfCRT are common
chloroquine AE ? contraindications ?
Generally well tolerated (at therapeutic doses) • Pruritus (common in Africans) • Nausea, vomiting, abdominal pain, headache, anorexia, malaise, blurring of vision, urticaria (uncommon) • Hemolysis (G6PD-deficient people) • Can cause electrocardiographic change
contraindication s–> G6PD deficient patient
psoriasis or porphyria (may precipitate attacks) • retinal or visual field abnormalities
SAFE IN PREGNANCY & YOUNG CHILDREN
Quinine and quinidine overview and clinical application ?
Derived from cinchona tree bark • First-line therapies for severe falciparum disease • Resistance is uncommon but increasing • Quinidine (stereoisomer of quinine
Parenteral treatment of severe falciparum malaria (Quinidine) • Oral treatment of falciparum malaria (alternative in chloroquine-resistant areas) (Quinine)
quinine and quinidine MOA and antimalrial action
Antimalarial Action • Rapidly-acting, highly effective against blood parasites • NOT active against liver stage parasites
MOA • Depresses O2 uptake and carbohydrate metabolism • Intercalates into DNA, disrupting parasite’s replication and transcription
quinine and quinidine PK ? resistance ?
Pharmacokinetics • Quinine: oral treatment of uncomplicated malaria • Quinidine: IV treatment for severe malaria
Resistance • Likely to be increasing problem • Already common in some areas of South-east Asi
quinidine and quinine AE ?
- Cinchonism: tinnitus, headache, nausea, dizziness, flushing & visual disturbances • Hypersensitivity: skin rashes, urticaria, angioedema, bronchospasm • Hematologic abnormalities: hemolysis (G6PD deficiency), leukopenia, agranulocytosis, thrombocytopenia • Hypoglycemia: stimulation of insulin release • Uterine contractions: still used in treatment of severe falciparum malaria in pregnancy
- Severe hypotension: too rapid IV infusion • ECG abnormalities: QT prolongation • Blackwater fever: hemolysis & hemoglobinuria (likely hypersensitivity reaction)
quinine and quinidine contraindications
- Discontinue if signs of: • severe cinchonism • hemolysis • hypersensitivity
- Avoid if possible in patients with: • visual or auditory problems
• Use with caution in patients with: • underlying cardiac abnormalities
also G6PD deficient ppl
• Do not use concurrently with mefloquine • Can raise plasma levels of warfarin & digoxin • Reduce dose in renal insufficiency
Pregnancy • FDA Category C (however benefits do often outweigh risks in complicated malaria)
mefloquine MOA?
• Effective against many chloroquine-resistant strains • Chemically related to quinine
MOA • Destruction of the asexual blood forms of malarial pathogens. Details unknown.
mefloquine clinical application
- Chemoprophylaxis: effective against most strains of P. falciparum and P.vivax • Currently only medication recommended for chemoprophylaxis in pregnant women in chloroquine-resistant areas
- Treatment : can be used to treat mild to moderate acute malaria caused by P.falciparum and P.vivax • Mefloquine + artesunate used in treatment of uncomplicated malaria in regions of Southeast Asia
mefloquine PK ? resistance ?
Pharmacokinetics • Oral only • Elimination t1/2 = 20 days (weekly prophylactic dosing)
Resistance • Uncommon but has been reported •Associated with resistance to quinine but not chloroquine
mefloquine ae
Serious neurological and psychiatric toxicities: Dizziness, loss of balance, ringing in the ears, anxiety, depression, hallucinations
Weekly dosing: Nausea, vomiting, diarrhea, dizziness, sleep & behavioral disturbances,rash
Higher treatment doses: Leukocytosis, thrombocytopenia, aminotransferase elevations, arrhythmias, bradycardia
