Antimalarial Drugs

Question 1

Chemical classification

Answer 1

1. 4-Amjnoquinolones - Chloroquine, amodiaquine
2. 8-Aminoquinolones- Primaquine, tafenoquine.
3. Quinoline methanol- Mefloquine
4. Alkaloids- quinine,quinidine
5. antifolates- pyrimethamine, suplhadoxine, dapsone
6. Hydroxynapthoquinone- Atovaquone
7. Artemisinins- artemisinin, artemether,artesunate
8. Artless alcohol- lumefantrine

Question 2

Clinical classification

Answer 2

1.Tissue schizonticidals (preerythrocytic) and (hypnozoites) - Primaquine, Atovaquone, proguanil

2. Blood schizontocidals (erythrocytic stage) (rapid acting)- Chloroquine, Artemisinin, quinine, mefloquine
   (Short acting) - proquanil, Pyrimethamine + sulphadioxine, clindamycin
3. Gametocidals - artemisinin + primaquine
   Chloroquine + quinine
4. a. Casual prophylaxis- proquanil
   b. Suppressive prophylaxis- chloroquine
   c. Clinical cure -blood schizonticidals
   d. To prevent relapse- primaquine
   e. To prevent transmission/gametocidal-primaquine

Question 3

Chloroquine

Answer 3

MOA- inhibits conversion of harem to hemozin. This drug-haeme complex is toxic to parasite and damages plasmodial membrane.

Uses:

1. Malaria : Acute attack, radical cure of P.ovale,p.vivax, chemoprophylactic agent.
2. Amoebiasis-hepatitis
3. Lepra reaction
4. Rheumatoid arthritis
5. Infectious mononucleosis
6. Autoimmune disorder

Question 4

Quinine & quinidine

Answer 4

Similar MOA as chloroquine
Pharmaceutical effects:
1. Antimalarial actions
2. a. GIT: increases gastric acid secretion
b. CVS: depresses myocardium
c. Skeletal muscles: depresses contraction
d. CNS: Mild analgesic, antipyretic

Question 5

Artemisinin and derivatives

Answer 5

MOA- in acid vacuole of parasite, haeme iron cleaves endoperoxide bridge of artemisinin and free radicals are generated. Which damages proteins and lipid peroxidation= death of parasite.

Therapeutic uses;

1. Uncomplicated chloroquine resistant malaria and severe malaria
2. Artemisinin based combination therapy:
   a. 3day= Artemisinin+mefloquine,lumefantrine,amodiaquine.
   b. 7day= Artemisinin+ doxycycline+tetracycline+clindamycin.

Question 6

Preference of artemisinin over quinine in severe malaria

Answer 6

1. Lower risk of death
2. Rapid parasite clearance
3. Safe and well tolerated
4. Doesn’t require cardiac monitoring
5. Doesn’t require controlled rate of infusion
6. Lower risk of hypoglycaemia
7. No cross resistance with other antimalarials

Question 7

Treatment regimen for uncomplicated malaria

ACT REGIMEN

Answer 7

Artesunate 100mg BD - 3 days

Day 1= Sulphadoxine and pyrimethamine 1500mg/75mg single dose

Day 2- mefloquine 750mg
Day 3- mefloquine 500mg

Artesunate 2mg/kg oral dose+ Tetracycline 4mg/kg or Doxycycline 3.5mg or clindamycin 10mg -7days

Question 8

Treatment regimen for severe/complicated malaria of P.falciparum

Answer 8

Parenteral antimalarials should be administrated for at least 24hrs

Then complete course with oral ACT once patient is stable.

Artesunate- 2.4mg/kg at zero hour, repeat at 12hours and 24 hours

If patient is able to take orally after 24hrs, switch to full course 3 day oral ACT.