Antimalarial Drugs Flashcards
PLASMODIUM SPECIES
- Plasmodium falciparum (majority of serious complications & deaths)
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium ovale
Symptoms and treatment of uncomplicated infection
Usual symptoms like fever, chills, diaphoresis, headaches, nausea and vomiting, body aches and general malaise
Treat with oral antimalarials
Symptoms and treatment of complicated infection
Symptoms: impaired consciousness /coma, severe normocytic anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, circulatory shock, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria, repeated generalized convulsions, and/or parasitemia of >5%
Treat with parenteral (IV) antimalarials
BLOOD SCHIZONTICIDES
CHLOROQUINE/ HYDROXYCHLOROQUINE QUININE/QUINIDINE MEFLOQUINE ARTEMISININ LUMEFANTRINE ATOVAQUONE-PROGUANIL SULFADOXINE-PYRIMETHAMINE DOXYCYCLINE CLINDAMYCIN
Which drug is the DOC for non-falciparum and sensitive uncomplicated falciparum malaria
• Preferred chemoprophylactic agent in areas without resistant falciparum malaria
CHLOROQUINE
Chloroquine is Highly effective against blood parasites but NOT active against _______
Highly effective against blood parasites But NOT active against liver stage parasites
Which drug
Prevents biocrystallization of hemoglobin breakdown product heme to non- toxic hemozoin, and thus causing parasite toxicity due to buildup of free heme
CHLOROQUINE
Pharmacokinetics and resistance of chloroquine
Pharmacokinetics
• Oral
• t1/2 = 3-5 days (only need to take once weekly)
Resistance
• P. falciparum: mutations in putative transporter, PfCRT* (P. falciparum Chloroquine Resistance Transporter)
This drug causes hemolysis in g6pd deficient patients and pruritus in Africans
Chloroquine
It is also contraindicated in people with :
• Psoriasis or porphyria (may precipitate attacks)
• Retinal or visual field abnormalities
SAFE IN PREGNANCY & YOUNG CHILDREN
Which drug is
Used as an alternative to chloroquine in chloroquine sensitive areas . Chemoprophylaxis and treatment of uncomplicated malaria
HYDROXYCHLOROQUINE
MOA: precise mechanism is unknown
• weak base and may exert its effect by concentrating in the acid
vesicles of the parasite inhibiting polymerization of heme
• can also inhibit certain enzymes by its interaction with DNA.
HYDROXYCHLOROQUINE
Adverse Effects
- GI upset, nausea, vomiting, headache (MOST COMMON)
- Itching
- hemolysis (in G6PD deficient patients)
- retinopathy , visual disturbances
HYDROXYCHLOROQUINE
Contraindications
• Psoriasis and known hypersensitivity to chloroquine
SAFE IN PREGNANCY & CHILDREN
Parenteral treatment of severe/complicated falciparum malaria
Quinidine
Oral treatment of falciparum malaria or uncomplicated malaria (alternative in chloroquine resistant areas)
Quinine
MOA OF QUININE & QUINIDINE
Intercalates into DNA, disrupting parasite’s replication and transcription
Quinine and quinidine adverse effects
CCHHHUB
- Cinchonism: tinnitus, headache, nausea, dizziness, flushing & visual disturbances
- Cardiotoxicity: QT prolongation Torsades de pointes
- Hypersensitivity: skin rashes, urticaria, angioedema, bronchospasm
- Hematologic abnormalities: hemolysis (G6PD deficiency), leukopenia, agranulocytosis, thrombocytopenia
- Hypoglycemia: due to stimulation of insulin release
- Uterine contractions: still used in treatment of severe falciparum malaria in pregnancy
- Blackwater fever: hemolysis & hemoglobinuria (likely hypersensitivity reaction)
WHEN TO DISCONTINUE QUININE & QUINIDINE?
- severe cinchonism
- hemolysis
- hypersensitivity
QUININE & QUINIDINE contraindications
AVOID IN PATIENTS WITH
• visual or auditory problems
USE WITH CAUTION IN PATIENTS WITH
• underlying cardiac abnormalities
QUININE & QUINIDINE Should not be used concurrently with ? • Can raise plasma levels of ? • Reduce dose in renal insufficiency FDA Category C- however, benefits do often outweigh risks in complicated malaria
QUININE & QUINIDINE
Should not be used concurrently with mefloquine
• Can raise plasma levels of warfarin & digoxin
• Reduce dose in renal insufficiency
FDA Category C- however, benefits do often outweigh risks in complicated malaria
This drug destroys asexual blood forms of malarial pathogens. It is effective against most strains of P. falciparum and P.vivax and the only medication recommended for chemoprophylaxis in pregnant women in chloroquine resistant areas
MEFLOQUINE
- Last resort drug
- Treatment of uncomplicated falciparum malaria (given with Artesunate)
Pharmacokinetics of mefloquine
- Oral only
* Elimination t1/2 = 20 days (weekly prophylactic dosing)
Adverse effects and contraindications of mefloquine
- Neuropsychiatric: Dizziness, loss of balance, ringing in the ears, anxiety, depression, hallucinations- MOST SERIOUS
- GI upset, rash- seen in LOW doses (weekly dosing)
- Leukocytosis, thrombocytopenia, elevated liver enzymes, arrhythmias- HIGH doses
Contraindications
• Patients with history of:
Epilepsy, psychiatric disorders, arrhythmias, cardiac conduction defects,sensitivity to related drugs
DO NOT co-administer with quinine or quinidine
SAFE in young children & pregnancy
Artemisinin subtypes
- Artesunate : oral, IV, IM, rectal
- Artemether: oral, IM, rectal
- Dihydroartemisinin: oral
Coartem = artemether + lumefantrine
ARTEMISININ: MOA and pharmacokinetics
Binds iron leading to generation of free radicals
NOT used alone for chemoprophylaxis. If used alone, artesunate must be administered 5-7 days (otherwise recurrent parasitemia results)
