Malaria

Question 1

Artemether-lumefantrine, Artesunate-amodiquine, Dihydroartemisinin-piperaquine, and Artesunate-mefloquine

Answer 1

Malaria
Artemisinin Derivatives
Therapeutic Use:
• *Uncomplicated/complicated (severe) falciparum malaria
• Used in combination (monotherapy discouraged)
• Standard therapy in endemic areas for falciparum malaria
MOA
• Production of free radicals due to iron cleavage of artemisinin endoperoxide bridge
o Free radicals leads to death of parasite
ADE
• *Nausea, *vomiting, *diarrhea, and dizziness

Question 2

Chloroquine, Amodiaquine

Answer 2

Malaria
4-Aminoqunioline
Therapeutic Use:
• Drug of choice treatment/prophylaxis (blood schizont)
   o *Uncomplicated nonfalciparum and sensitive falciparum malaria
MOA
• Prevent detoxification of heme into hemozoin (non-toxic) in the parasite food vacuole. Therefore have build-up of toxic heme that leads to death of parasite
ADE
• *High fever common
• GI complaints uncommon
CI
• *Psoriasis or porphyria

Question 3

Chloroquine resistance

Answer 3

Malaria
• Major hurdle to usage of drug in areas of high transmission of malaria
• Therefore, Artesunate has been used to tx falciparum instead of Chloroquine
- Various models, most relate to mutation in plasmodium falcipurum Chloroquine related transporter
• 1) *energy-coupled drug efflux: energy comes to transporter à helps efflux Chloroquine out of digestive vacuole and parasite
• 2) *leak of charged drug: chloroquine goes into food vacuole à gets de-protonated. Facilitated diffusion of chloroquine down gradient that’s maintained by proton pump
• 3) *pH-dependent changes: leads to less accumulation of Chloroquine in digestive vacuole à don’t have development of toxic heme that leads to death of parasite

Question 4

Quinine, Quinidine

Answer 4

Malaria
Therapeutic Use:
• *Severe/uncomplicated falciparum malaria
• Babesiosis
ADE
• *Cinchonism – *tinnitus, *headache, *nausea, dizziness, flushing, and *visual disturbances
• Hypersensitivity: rash and bronchospasm
• *Hemolysis, *leucopenia, thrombocytopenia
• *Hypoglycemia
CI
• *Underlying visual and auditory problems

Question 5

Primaquine

Answer 5

Malaria
Therapeutic Use:
• *Radical cure of acute vivax and ovale malaria (in addition to Chloroquine)
• *Terminal prophylaxis of vivax and ovale mal.
• *Chemoprophylaxis of malaria (but not drug of choice bc of side effects)
• Gametocidal Action
MOA
• *Drug of Choice: kills liver dormant forms of malaria (liver hypnozoites)
ADE
• *GI: nausea, epigastric pain, abdominal cramps
• Rare: leukopenia, leukocytosis, Cardiac Arrythmias
CI
• Patient history of myelosuppression
• Tested for *G6PD deficiency

Question 6

Atovaquone/Proguanil (Malarone)

Answer 6

Malaria
Therapeutic Use:
• *Chemoprophylaxis and treatment of falciparum malaria
Atovaquone MOA
• *Disrupts electron transport chain
• *Active against liver and erythrocytic schizonts
Proguanil MOA
• *Interferes with folate metabolism by inhibiting dihydrofolate reductase
ADE 
• *Nausea, *Vomiting, *Diarrhea
• Headache and *insomnia
Precautions
• *Pregnancy