L8 Antimalarial Agents

Question 1

________________(the most deadly type of malaria infection) can lead to cerebral malaria

Answer 1

Plasmodium falciparum (the most deadly type of malaria infection) can lead to cerebral malaria

Question 2

___________ (most common type of malaria) causes relapse if treatment was not completed (Hides in liver)

Answer 2

P. Vivax (the most common type of malaria) causes relapse if treatment was not completed Hides in liver

Question 3

Life Cycle of Malaria?

Answer 3

Consists of sexual (within mosquito) and asexual (within human host) cycles

Pre/Exoerythrocytic stage of development and multiplication in the liver
Parasitized liver cells rupture => merozoites released =>
Enter red blood cells and form motile intracellular parasites, trophozoites (development and multiplication), erythrocytic stage

Erythrocytic Stage
During maturation within red blood cell, the parasite remodels the host cells

Parasitic proteins and phospholipids are inserted into the cell membrane

Host hemoglobin is digested and provides a source of amino acids

The parasite undergoes rapid growth and division (schizogony) producing new merozoites for re-infection of RBCs

Mosquito Stage and Reinfection
Upon entry into RBCs, some merozoites differentiate into male and female forms (termed gametocytes)

Fertilization occurs in the mosquito –formation of zygote

Development into oocyst (sporocyst)

Further stage of division and multiplication, leading to rupture of sporocyst and release of sporozoites

Migration of sporozoites to salivary gland of mosquito and re-infection into human host via bite

Question 4

What casues periodic episodes of fever in Malaria?

Answer 4

Periodic episodes of fever due to synchronised rupture of RBCs (release of merozoites and debris)

Question 5

In certain forms of malaria(___________), resting forms (_________) of the parasite are found in the liver: can last for months/years and may contribute to relapse, post-therapy

Answer 5

In certain forms of malaria (P. Vivax) resting forms (Hypnozoites) of the parasite are found in the liver: -can last for months/years and may contribute to relapse, post-therap

Question 6

Diagnosis of malaria?

Answer 6

Dipstick test: not as effective when parasite levels are below 100parasites/mL of blood

Blood examination: Thick and thin blood film

PCR: determine the species of plasmodium

Question 7

Presentations of Malaria

In Different Plasmodium?

Answer 7

Presentations of Malaria
Children can present with hypoglycemia, fever, febrile seizure

Mild anemia common

Fever is usually continuous or irregular. Classic periodicity may be established after some days.

P Falciparum (Cerebral Malaria, NO splenic/hepatic involvement)

P Vivax/Malariae (Rupture of the spleen, Hepatic dysfunction, Thrombocytopenia)

Question 8

Anti Malarial Agent Classes?

Answer 8

Class A: Drugs used to treat the acute attack (erythrocytic stage)

Class B: Drugs affecting the exoerythrocytic hypnozoites

Class C: Drugs blocking exoerythrocytic–erythrocytic stage conversion

Class D: Drugs that prevent transmission –gametocyte production

Question 9

Class A Antimalialr Agents/MOA

Answer 9

Blood schizonticide agents

Chloroquine/Quinine (Quinoline)
Effective against erythrocytic forms of all four Plasmodium species (if sensitive)

MOA: Inhibits haem polymerase (haem => haemozoin) preventing digestion of hemoglobin by parasite => Decreased amino acids for parasite viability

Quinine used for multi-drug resistant Plasmodia strains

Folate Antagonists
Block DNA synthesis (Dihydrofolate reductase/dihydropteroate synthetase)

Pyrimethamine and proguanil inhibit dihydrofolate reductase => Decreased tetrahydrofolate (blood schizonticide agent)

Dapsone (sulphone) & Sulphadoxine (sulphonamide) compete with PABA for dihydropteroate synthetase

Question 10

Class B Antimalarial Agents/MOA/Side Effects

Answer 10

Tissue schizonticidal agents act on the schizonts in the liver

Primaquine
Effective against exoerythrocytic forms (hypnozoites)

Destroys sexual forms of all Plasmodia species

S/E:GI disturbances, hemolytic anemia

Question 11

Class C Antimalarial Agents/MOA

Answer 11

Block link between exoerythrocytic and erythrocytic stages

Chloroquine, mefloquine, proguanil, pyrimethamine, dapsone, and doxycycline

Administer for 1 week prior to travel to endemic areas until one month after return

Question 12

Class D Antimlarial MOA

Answer 12

Destroy the gametocytes thus preventing transmission by the mosquito

Rarely used for this action alone –affect other stages of life cycle

Question 13

Artemisinin (Class _____)
_______________

Fast-acting ______ schizonticidal agent

Effective against ______________ and _________ malaria

______________ is the Only US FDA approved ACT

Artemisinin are the most potent ___________drugs: They destroy ______________ but has no effect on ___________

Answer 13

Artemisinin (Class A)
FIRST LINE: “Artesunate is the treatment of choice for adults with severe malaria”

Fast-acting blood schizonticidal agent

Effective against chloroquine-resistant and cerebral malaria

Artemether–Lumefantrine is the Only US FDA approved ACT

Artemisinin are the most potent gametocidal drugs: They destroy immature gametocytes but has no effect on mature gametocytes

Question 14

Primaquine (Class ___)
Only effective drug against ___________. Thus to be used for radical cure of _________ malaria

Check for ________________ as it may cause hemolysis in deficient people.

Only drug that kills ___________ and also accelerates ____________

Answer 14

Primaquine (Class B):
Only effective drug against hypnozoites. Thus to be used for radical cure of vivax malaria

Check for G6PD deficiency as it may cause hemolysis in deficient people.

Only drug that kills mature gametocytes and also accelerates gametocyte clearance

Question 15

Act on (erythrocytic) stage of the parasite thereby terminating clinical illness?

Answer 15

Blood Schizonticidal Drugs

Quinine, artemisinins, chloroquine

Question 16

Act on primary tissue forms of plasmodia which initiate the erythrocytic stage. They block further development of the
infection?

Answer 16

Tissue Schizonticidal Drugs

Primaquine, pyrimethamine

Question 17

Destroy sexual forms of the parasite thereby preventing the transmission of

Answer 17

Gametocytocidal drugs

Primaquine, artemisinins, quinineb

Question 18

Act on persistent liver stages of P.ovale and P.vivax which cause recurrent illness

Answer 18

Hypnozoitocidal drugs

Primaquine

Question 19

These act by affecting further development of gametocytes into oocytes within the mosquito thus abating transmission

Answer 19

Sporozontocidal drugs

Primaquine, proguanil

Question 20

Prescribing for uncomplicated P. falciparum? MOA?

Answer 20

Artemisinin Combination are the best

MOA:
Production of free radicals that kill the parasite.
Active against All human malaria parasites.
Does Not affect the hepatic stage.

Question 21

Prescribing for Severe Malaria?

Answer 21

Artesunate

Fluid therapy for rehydration.

Blood transfusion: usually used in children, because anemia is severe (Hb < 5 g/dl)

Question 22

Prescribing for P. Vivax, P. Ovale, P. Malaria? MOA/Contraindications?

Answer 22

Chloroquine

For radical cure of P.vivax and P.ovale:Primaquine(( 15 mg daily for 14 days.

It destroys the Hypnozoite phase in the liver.

It may cause hemolysis with G6PD deficient patients.

Question 23

Malaria and Pregnancy

________, ___________, ___________ & ______________ can be used safely in any trimester.

Artesunate, artemether and Mefloquine can be use in IInd and IIIrd trimesters.

Clindamycin can be used in pregnancy but __________ and ___________ are contraindicated.

Answer 23

Malaria and Pregnancy

Quinine, Chloroquine, Sulphadoxine & Pyrimethamine can be used safely in any trimester.

Artesunate, artemether and Mefloquine can be use in IInd and IIIrd trimesters.

Clindamycin can be used in pregnancy but Doxycycline and Primaquine are contraindicated.