Week 11 forest to pharmacy

Question 1

Malaria

Answer 1

it is a mosquito-borne infectious disease. which is caused by protist parasites. primarily the P.falciparum

Question 2

Plasmodium life cycle

Answer 2

is complex and offers numerous opportunities for pharmaceutical intervention.
There is the Erythrocytic Cycle. Exo-ertrythrocytic and sporogonic cycle.

Question 3

The two currently most widely used antimalarial drugs are

Answer 3

Chloroquine
(known commercially as Chloroquine FNA or Resochin)
or a combination of sulfadoxine and pyrimethamine
(Fansidar)

Question 4

Erythrocytic cycle

Answer 4

Plasmodium resident in erythrocytes must degrade hemoglobin to obtain essential amino acids
This process releases heme, which is soluble.
Plasmodium biocrystallises heme to form hemozoin

Question 5

Forest (Artemisia annua)

Answer 5

known hisotrically as qinghao
by dicotyledonous plant
extracts used in chinese medicine.

Question 6

Biosynthesis of aremisinin

Answer 6

is a sesquiterpene (c15) and a lactone endoperoxide.
occurs in glandular trichomes. uses sugars generated by photosynthesis to produce acetyl-CoA
enters biosyntheis pathway to produce farnesyl diphospate intermediate.

Question 7

explain the biosynthesis of artemisia

Answer 7

conversion of FPP to amorphadiene by th terpene synthase enzyme amorphadiene synthase (ADS).
then it is hydroxylated to yield artemisinin alcohol
oxidized to form artmenisinic aldehyde.
catalysed by a P450 with CPR.

double bond reductase (DBR2) catalysed the reduction of the DII double bond of artemisinin aldehyde to form dihydroartemisinin aldehyde.
(ALDH I) that catalyzes the oxidation of dihydroartemisinic aldehyde. spontaneously in the presence of sunlight.

Question 8

Mode of action

Answer 8

artemisinin needs to be converted into a redical species to be effective against plasmodium. ferrous heme is the most efficient activator of artemisinin.
The activity of Artemis in diminishes in the presence of free radical scavengers and antioxidants.

Question 8

tradition cultivation of Artemisia annua

Answer 8

leaves in china were collected from wild stands of the plant. low water solbulity of artemeisinin made it only somewhat effective.

Question 9

what are Plasmodium Spp

Answer 9

Protist Parasites

Question 10

Erythrocytic cycle

Answer 10

Plasmodium resident in erythrocytes must degrade hemoglobin to obtain essential amino acids
This process releases heme, which is soluble.
Plasmodium biocrystallises heme to form hemozoin

Question 11

Chloroquine effect on cycle

Answer 11

Chloroquine diffuses into the digestive vacuole of Plasmodium and prevents the formation of hemozoin
Heme concentration increases and chloroquine binds to heme to form the FP-chloroquine complex; a highly toxic complex that disrupts parasite membrane function

Question 12

Mixture of Sulfadoxine and Pyrimethamine

Answer 12

Sulfadoxine is a competitive inhibitor of dihydropteroate synthase, a key enzyme in folate synthesis
Pyrimethamine inhibits dihydrofolate reductase (which synthesise tetrahydrofolate, the active form of folate)
The products of the folate pathway (reduced folate cofactors) are essential for DNA synthesis and the metabolism of certain amino acids
Synergy between the two drugs due to their inhibition of two different steps in the biosynthesis of tetrahydrofolate accounts for the efficacy of the combination