Anti Malaria Drug ish Flashcards
Chloroquine
Indication:DOC for treatment and prophylaxis of vivax and
ovale (non-falciparum & uncomplicated falciparum malaria)
Preferred chemoprophylaxis in areas w/o resistant falciparum
MOA:Concentrates within parasite food vacuoles, raising the internal pH →
inhibition of growth
Interferes with biocrystallization of Hb to hemozoin (non-toxic
polymer) → lysis of parasite and RBC
Resistance:P. falciparum has mutations in the putative transporter (PfCRT)
Contraindicated in pts with: Psoriasis or porphyria
Retinal or visual field issues
AE:Pruritus (esp. Africans) Nausea, vomiting, abd. Pain, HA, anorexia, malaise, blurry vision, urticaria
Hemolysis in ↓G6PD
ECG changes in toxic doses
Quinine
Indication:1st line for severe falciparum disease
May need to combine with doxycycline
Safe to use in pregnancy b/c benefits outweigh the risks
MOA:Derived for cinchona tree
↓O2 uptake and CHO
metabolism
Intercalates DNA →
↓replication and
↓transcription
Resistance:Discontinue if hemolysis, HSN or
cinchonism develops
Avoid in pts with visual or auditory disturbance or cardiac abnormality
AE: Cinchonism→ tinnitus, HA, nausea, dizziness, flushing and visual disturbance Hypersensitivity Hematologic disturbance Hypoglycemia (↑insulin release) Uterine contractions Severe hypotension: rapid IV QT prolongation Blackwater feverà hemolysis and hemoglobinuria
Quinidine
Indication:1st line for severe falciparum disease
May need to combine with doxycycline
Safe to use in pregnancy b/c benefits outweigh the risks
MOA:Derived for cinchona tree
↓O2 uptake and CHO
metabolism
Intercalates DNA →
↓replication and
↓transcription
Resistance:Discontinue if hemolysis, HSN or
cinchonism develops
Avoid in pts with visual or auditory disturbance or cardiac abnormality
AE: Cinchonism→ tinnitus, HA, nausea, dizziness, flushing and visual disturbance Hypersensitivity Hematologic disturbance Hypoglycemia (↑insulin release) Uterine contractions Severe hypotension: rapid IV QT prolongation Blackwater feverà hemolysis and hemoglobinuria
Mefloquine
Indication:Effective against mild to moderate chloroquine resistant strains of falciparum & vivax
Chemoprophylaxis for falciparum & vivax→
only one for pregnant prophylaxis against
chloroquine resistant strains
Combo w/ artesunateàuncomplicated malaria
in SE Asia
MOA:Destruction of asexual blood forms of malarial pathogens through
unknown mechanisms
Chemically related to
quinine (don’t combine
the
Resistance:Contraindicated in pts with epilepsy, psych problems, arrhythmia or sensitivity to related
drugs
AE: Higher dose: leukocytosis, thrombocytopenia, aminotransferase, arrhythmias, bradycardia
Neuropsychiatric toxicity
Primaquine
Indication:DOC for eradication of dormant liver form of
vivax and ovaleàonly agent that is active
against the dormant liver forms
All Strains
MOA:Metabolites may act as oxidants disrupting mitochondria and binding to DNA
Resistance:Contraindicated in pregnancy and G6PD deficiency (test prior to beginning treatment
AE: Leukopenia, agranulocytosis,
leukocytosis, arrhythmia
Hemolysis or methemoglobinemia
in ↓G6PD
Malarone
Indication:Atovaquone +
Proguanil
Used in the treatment and prophylaxis of uncomplicated falciparum
Active against tissue and erythrocytic schizonts
Chemoprophylaxis 1-2 days before travel &
stopped 1 week after exposure
MOA:Disrupts mitochondrial election transport chain
Resistance:Contraindicated in pregnancy
AE: GI upset, HA, rash
Pyrimethamine
Indication:Combo for chemoprophylaxis
Intermittent preventive therapy in high risk patients
Pyrimethamine + Proguanil→ slow action
against erythrocytic forms
Mild/moderate chloroquine resistant falciparum (Pyrimethamine-Sulfadoxine
MOA:Pyrimethamine + Proguanil→
inhibit DHF reductase
Safe to use in pregnancy
Resistance:Common for P. Falciparum
AE: GI issues, rashes, itching
Pyrimethamine-Sulfadoxine:
erythema multiforme, Steven Johnson syndrome, toxic necrolysis
Proguanil
Indication:Combo for chemoprophylaxis
Intermittent preventive therapy in high risk patients
Pyrimethamine + Proguanil→ slow action
against erythrocytic forms
Proguanil→ some hepatic forms
MOA:Pyrimethamine + Proguanil→
inhibit DHF reductase
Safe to use in pregnancy
Resistance:Common for P. Falciparum
AE: GI issues, rashes, itching
Proguanil- mouth ulcers, alopecia
Sulfadoxine
Indication:Combo for chemoprophylaxis
Intermittent preventive therapy in high risk patients
Mild/moderate chloroquine resistant falciparum (Pyrimethamine-Sulfadoxine
Sulfonamides→ erythrocytic schizont
Safe to use in pregnancy
MOA:Sulfonamides inhibit dihydropteroate synthase
Resistance:Common for P. Falciparum
AE: GI issues, rashes, itching
Pyrimethamine-Sulfadoxine:
erythema multiforme, Steven Johnson syndrome, toxic necrolysis
Sulfadoxine: hematologic, GI, CND.
Dermatologic and renal toxicity
Doxycycline
Indication:Active against erythrocytic schizonts of all species
Combo w/ quinine→ completes therapy for
severe falciparum after giving quinine,
quinidine or artesunate
Chemoprophylaxis against most forms if taken daily
MOA:
Resistance:Contraindicated in pregnancy and
children <
Clindamycin can be an alternative
AE: GI upset, Vaginal candidiasis Photosensitivity Discoloration & hypoplasia of teeth, stunting of growth Fatal hepatotoxicity in pregnancy
Artemisinin
Indication:Derived from the qinghaosu plant
Coartem= artemether + lumefantrine
Treatment of severe falciparum (given IV)
No effect on hepatic stages
MOA:Binds iron, breaking down
peroxide bridges→
generation of free radical that damage proteins within
the parasite
Resistance:Should not be used as a single
agent to protect against resistance
If given alone àadmin for 5-7 days to avoid recurrent parasitemia
AE: High doses: Neurotoxicity & QT
prolongation
Can be used more in 2nd & 3rd trimesters; 1st trimester can be used
for txt of severe malaria
Halofantrine
Indication:Effective against erythrocytic stage of all spp.
MOA:
Resistance:Use is limited; Teratogenic
AE: cardiac toxicity
Lumefantrine
Indication:Effective against erythrocytic stage of all spp.
MOA:Fixed dose combo w/ artemether
Resistance:
AE: Minor QT
(insignificant clinically)
