For our beloved student

1. Anti Malarial drugs
What is malaria?. Malaria is an infectious disease caused by
protozoa; plasmodium.
Five species of plasmodium causing malaria in humans
 P. falciparum
 P. vivax,
 P. malariae,
 P. ovale.
 Plasmodium. knowlesi,
Note. P knowlesi is a pathogen of monkeys, but has recently been
recognized to cause illness, including severe disease, in humans
in Asia

4. Quinine
According to a legend, an Indian with a high fever
was lost in an Andean jungle(Peru). Thirsty, he
drank from a pool of stagnant water and found
that it tasted bitter. Realizing that the water had
been contaminated by the surrounding quina-
quina trees he thought he was poisoned.
Surprisingly, his fever soon abated, and he shared
this accidental discovery with fellow villagers,
who thereafter used extracts from the quina-
quina bark to treat fever.

5. Common anti malarial drugs
1. Quinine
2. Chloroquine
3. Amodiaquine
4. Pyrimethamine
5. Proguanil
6. Primaquine
7. Artemisinin

6. Chloroquine/quinine
 Antimalarial Action and Resistance: Chloroquine is a highly effective blood
schizonticide. It is also moderately effective against gametocytes of P vivax, P
ovale, and P malariae but not against those of P falciparum. Chloroquine is
not active against liver stage parasites.
Mechanism of action: The parasite digests the host cell’s hemoglobin to obtain
essential amino acids from globin protein. The process releases large amounts
of heme, which is toxic to the parasite. To protect itself the parasite has the
ability to polymerizes the heme to nontoxic hemozoin. Cholroquine/quinine
prevent the polymerization to hemozoin by binding with heme. The
accumulation of heme results in lysis of both the parasite and the RBC.
Chloroquine resistant parasites have acquired an efflux system that expels the
drug from the food vacuole.

7.  Chloroquine’s mode of action is associated with heme
detoxification. During intraerythrocytic
development, P. falciparum degrades hemoglobin
down to amino acids (AA) in its acidic food vacuole.
Heme released from hemoglobin (Hb) is toxic and
destroys cellular membranes unless it is converted to
an inert biomineral, termed hemozoin or malaria
pigment. Chloroquine (CQ) binds to heme, thereby
preventing biomineralization of heme. The build-up
of membrane-lytic heme/chloroquine complexes kill
the parasite.

8. What is heme?
 Heme is a cofactor consisting of an Fe²⁺ ion
contained in the centre of a large heterocyclic
organic ring called a porphyrin.

11. Adverse effects (chloroquine)
Nausea, vomiting, abdominal pain, headache,
anorexia, malaise, blurring of vision, . Rare
reactions include hemolysis in glucose-6-
phosphate dehydrogenase (G6PD)-deficient
persons, impaired hearing, confusion,
psychosis, seizures.
Safe in pregnancy.

12. Self study topics
 Side effects of quinine
 Chloroquine dosing
 Artemether/lumefantrine dose

13. Side effects of quinine
 mild headache,
 flushing,
 unusual sweating,
 nausea,
 upset stomach,
 muscle weakness,
 ringing in the ears,
 decreased hearing,
 dizziness,
 spinning sensation,
 blurred vision, and
 temporary changes in color vision.

14. THANK YOU