Anti malarial Flashcards
What is the primary cause of malaria?
Caused by protozoal parasite - Plasmodium genus
Four species: vivax, falciparum, ovale, and malariae. Plasmodium falciparum is the most dangerous.
What is the conventional therapy for malaria?
Quinine and quinine-based drugs
Increasing drug resistance is a significant problem.
What are the two main classifications of antimalarial drugs based on their mechanism of action?
a) Those affecting DNA synthesis
b) Those affecting the utilization of folic acid
What is the mechanism of action of aminoquinolines?
They affect DNA synthesis by complexing with DNA
They possess a flat ring system that interacts with DNA.
What adverse reactions can quinine cause?
Ringing in the ears and partial deafness
What drug largely replaced quinine as the antimalarial of choice?
Chloroquine
It has far fewer side effects.
What is the significance of the endoperoxide group in artemisinin?
It is the pharmacophore and essential for antimalarial activity
What is artemisinin derived from?
Natural product from Chinese plant (Artemisia annua)
What is the primary mechanism of action of artemisinin?
Acts as a ‘molecular trigger’ activated by ferrous ions
Produces radical species that lead to cell death.
Fill in the blank: The most recent addition to malaria drug therapy are _______.
artemisinins and its derivatives
What is the structural feature that is essential for the activity of artemisinin analogues?
Trioxane group
True or False: Artemisinin is activated in uninfected red blood cells.
False
Activation requires ferrous ions which are not available in uninfected cells.
What are the key metabolites generated by artemisinin’s action?
Radical mechanisms leading to cell death
Ferric hydroxide is generated as a result.
What is the role of iron in the mechanism of action of artemisinin?
Iron reacts with artemisinin and activates it
What are some examples of drugs that affect the utilization of folic acid?
- Biguanides
- Proguanil
- Cycloguanil
- Pyrimethamine
What is the primary structure-activity relationship for artemisinin?
Dihydroartemisinin, artemether, artether, and sodium artesunate are more active than artemisinin
What is the result of bonding aminoquinolines to DNA?
Prevents the required separation of complementary strands of the parent helical DNA
What is a notable characteristic of artemisinin’s analogues?
Analogues lacking the trioxane group have poor activity
What is the significance of the lactone carbonyl group in artemisinin?
It is not essential for activity
What is the role of the quinoline ring in quinine’s mechanism of action?
Forms a charge transfer complex with DNA
What are artemisinin derivatives often combined with to improve therapy?
Other antimalarial agents
To reduce resistance development and increase synergism.
What is the structural feature of artemisinin that contributes to its hydrophobic nature?
Multicyclic structure
Fill in the blank: The action of drugs that affect DNA synthesis is _______.
schizonticidal
