Antimalarials Flashcards
Life Cycle of P. falciparum and P. malariae
1 cycle of liver invasion; only erythrocytic parasites have to be eliminated
Life Cycle of P. vivax and P. ovale
dormant (hypnozoite) hepatic stage; erythrocytic and hepatic parasites have to be eliminated
What is malarial paroxysm?
Fever, anemia, hepatosplenomegaly, jaundice; occurs every 2-3 days in established infections
Which plasmodium species is cerebral malaria associated with?
P. falciparum; includes irritability, seizures, and coma
Most severe malaria due to microvascular effects
P. falciparum
How should uncomplicated malaria be treated?
Oral antimalarials
How should complicated malaria be treated?
Aggressively with parenteral antimalarials
MOA of Chloroquine
Concentrates in parasite food vacuoles and prevents biocrystallization of heme to non-toxic hemozoin ==> lysis of RBC and parasite
Antimalarial Action of Chloroquine
Only effective against blood parasites; NO ACTIVITY AGAINST LIVER PARASITES
Resistance to Chloroquine
P. falciparum has mutations in putative transporter (PfCRT)
PK of Chloroquine
Oral; take once a week due to long half-life
AE of Chloroquine
Well tolerated; pruritus in Africans, Hemolysis in G6PD deficiency, GI effects, headache, blurred vision, ECG changes
Contraindications of Chloroquine
Patients with Psoriasis, Porphyria, retinal or visual field abnormalities
True or False: Chloroquine is safe in pregnancy and young children
True
First line therapies derived from Cinchona tree and used for severe falciparum disease
Quinine and Quinidine
Oral treatment of falciparum malaria that is alternative to in Chloroquine-resistant areas
Quinine
Parenteral treatment of severe falciparum malaria
Quinidine
Antimalarial action of Quinine and Quinidine
Active against blood parasites but NO ACTIVITY AGAINST LIVER STAGE PARASITES
MOA of Quinine and Quinidine
Decreases oxygen uptake and carbohydrate metabolism; intercalates into parasite’s DNA, disrupting replication and transcription
PK of Quinine
Oral treatment for uncomplicated malaria
PK of Quinidine
IV treatment of severe malaria
Resistance to Quinine and Quinidine
Increasing; common in Southeast Asia
AE of Quinine and Quinidine
Cinchonism (tinnitus, flushing, headache, visual disturbance), Black water fever, QT prolongation, hypoglycemia (stimulates insulin release), uterine contractions (still used in severe falciparum treatment), hemolysis in G6PD deficiency
ALSO:
hypersensitivity (angioedema, urticaria, bronchospasm), other hematologic abnormalities
Contraindications of Quinine and Quinidine
Concurrent use with Mefloquine, Warfarin, and Digoxin; pregnancy (Cat. C), patients with auditory or visual problems, underlying cardiac problems, G6PD deficiency
PK of Quinine and Quinidine
Reduce dose in renal insufficiency
MOA of Mefloquine
Chemically related to Quinine; destroys asexual blood forms of malarial pathogens
Activity of Mefloquine
Effective against many Chloroquine-resistant strains
Only medication recommended for chemoprophylaxis in pregnant women in Chloroquine-resistant areas
Mefloquine
Treatment for uncomplicated malaria in Southeast Asia
Mefloquine + Artesunate
Chemoprophylactic effective against most strains of P. falciparum and P. vivax
Mefloquine
Can be used to treat mild moderate acute malaria caused by P. falciparum and P. vivax
Mefloquine
Resistance is uncommon but associated with resistance to Quinine but not Chloroquine
Mefloquine
PK of Mefloquine
Oral; weekly prophylactic dosing
Contraindications of Mefloquine
Coadministration with Quinine, Quinidine, or Halofantrine; patients with history of epilepsy, psychiatric disorders, arrythmias, drug sensitivities
True or False: Mefloquine is considered safe in young children and pregnancy.
True
AE of Mefloquine
Neuropsychiatric toxicities (hallucinations, tinnitus, loss of balance, etc.); weekly dosing causes N/V, dizziness, sleep and behavioral disturbances; high doses cause hematologic disorders, arrhythmias, bradycardia, elevations in aminotransferases
DOC for eradication of hypnozoites in P. vivax and P. ovale
Primaquine