Antiprotozoal (including Malaria)

Question 1

Adverse effects of Chloroquine.

Answer 1

CHLOROQuine

C- Convulsioms
H- Hemolysis in G6PD deficiency
L- Lowers BP
O- Ocular toxicity- Corneal deposits, loss of vision, Bull’s eye retinopathy (maculopathy)
R- Rashes
O- Ototoxicity (hearing loss)
Quine- QRS complex and T wave abnormalities on ECG

Question 2

MOA of Primaquine. Its uses.

Answer 2

MOA: Produces metabolites which act as oxidants and cause hemolysis or the infected RBCs.

Uses:
Should be taken with food.
G6PD status should be checked before giving this drug.

1) Vivax malaria: Given for 14 days along with clinical curative (eg Chloroquine) to achieve radical cure
Dose= 15 mg OD for 14 days

2) Falciparum malaria: For gametocidal action, single dose given after achieving clinical cure
Dose = 45 mg OD

Question 3

Drug regimen of Uncomplicated and Complicated malaria

Answer 3

Uncomplicated malaria:
1. P Vivax/ovale- CQ 600mg 1 day > 300mg 2 days + PQ 15mgx14 days

2. Falciparum
   - ACT (3 examples) + PQ
   - Or, Quinine 600x4 + Doxy 100mg/ Clinda 600mgx2 —7 days

Complicated or severe malaria:
1) Artesunate iv. 2.4 mg/kg repeated after 12 & 24 hours, continue next 7 days (switch to 3 day oral ACT asap)

2) Quinine diHCL iv. 20 mg/kg L.D -> 10mg/kg M.D. for 7 days (switch to oral Quinine when possible for 7 days)

Question 4

Give examples with dosage of Artemisinin Combination Therapy (ACT).

Answer 4

1. Artesunate (100mg) 3 days + Sulfadoxine (1500mg) and Pyrimethamine (75mg) single dose
2. Artemether (80mg) + Lumefantrine (480mg) both BD x 3 days
3. Arterolane (150mg) + Piperaquine (750mg) x 3 days

Question 5

MOA of Artemisinins.

Answer 5

Artemisinin molecules have an endoperoxide bridge. It interacts with iron of Heme.
This leads to breaking of the bridge, releasing a highly reactive Free radicals which damage the membranes and ER of the parasite, leading to lysis.

Question 6

What is the dose of Primaquine in Falciparum malaria and why is it given?

Answer 6

45mg single dose of Primaquine is given after clinical cure of falciparum malaria.
This is done to kill the gametes of the parasite.

Question 7

Why is Primaquine given in Vivax/ovale malaria? What is the dose?

Answer 7

It is given along with eythrocytic schizontocide drugs (clinical cure) to kill the hypnozoites present in the liver. This results in radical cure of malaria.

Dose: 15mg/day for 14 days

Question 8

MOA of Atovaquone-Proguanil?

Answer 8

Atovaquone causes collapse of mitochondrial membranes of the parasite, this prevents ATP synthesis.

Proguanil potentiates the action of Atovaquone by producing mitochondrial toxicity. It also inhibits plasmodial DHFRase enzyme, preventing folate synthesis.

Question 9

MOA of Chloroquine.

Answer 9

It gets accumulated in the acidic vaculoes of parasite and raises its pH.
Interferes with Hemoglobin degradation and thus interferes with nutrition of the parasite.

It inhibits polymerisation of heme (which is toxic to the parasite) to Hemozoin.
It also forms a complex with heme and causes damage to parasite membrane.