Antiparasitic Chemotherapy II

Question 1

Discuss Ornithine analogues

Answer 1

Example: Eflornithine

It acts by inhibiting ornithine decarboxylase, the enzyme that catalyzes polyamine synthesis in trypanosomes. The polyamines are necessary for cell division.

• Eflornithine is used in the treatment of early and late stages of trypanosomiasis.
• It can cross the BBB, making it useful for cerebral trypanosomiasis
• Eflornithine has greater activity against T.b. gambiense than against T.b. rhodensiense

Question 2

Discuss Acetanilides

Answer 2

Example: Diloxanide
- It is effective in the treatment of intra-luminal amoebiasis, especially for conditions that don’t respond to nitroimidazoles.

• It is given orally as ester form, diloxanide furoate.
• It is also effective in eradicating the intra-colonic residual forms of E. histolytica

Question 3

Discuss Sulphated naphthylamines

Answer 3

Example: Suramin
Available as sodium salt i.e suramin sodium

Suramin acts by inhibiting essential enzymes in the trypanosomes such as glycerol phosphate oxidase, required for the generation of metabolic energy.

It is not absorbed from the GIT, hence it is given by IV route.

• It is used in the treatment of trypanosomiasis
• It acts only against blood and lymph forms of the trypanosomes
• It does not cross the BBB , and so it is not useful in cerebral trypanosomiasis
• Used to treat river blindness caused by filarial worm and onchocerca volvulus

Question 4

Discuss Folate Antagonists

Answer 4

Example: Proguanil, Trimethoprim, Pyrimethamin, Sulphonamides, Dapsone

• Proguanil, Trimethoprim and Pytrimethamin Inhibit folic acid metabolism by inhibiting dihydrofolate reductase (DHFR), which converts dihydrofolic acid (DHFA) to tetrahydrofolic acid (THFA)
• Sulphonamides and Dapsone inhibit dihyrofolic acid synthesase

Question 4

To achieve synergistic anti-plasmodial action, pyrimethamine is combined with ____.

Answer 4

A sulphonamide

Question 4

Examples of sulphonamides used in anti-malarial chemotherapy include:

Answer 4

• Sulphadoxine
• Sulphamethopyrazine

Question 4

Dapsone is more often used in the treatment of ____ and acts on the same site as ____, which is ____

Answer 4

Leprosy
Sulphonamide
The enzyme, dihydropteridoic acid synthetase

Question 5

Discuss Inhibitors of protein synthesis.

Answer 5

Some of the antibiotics that inhibit protein synthesis in bacteria also possess anti-protozoal activity.

Examples: tetracycline, doxycycline, minocycline, clindamycin, spiramycin

• TCN in combination with quinine may be used to treat chloroquine-resistant malaria.
• Tetracycline is also used to treat babesiosis, a disease similar to malaria but caused Babesia divergens and B. microti

Not common in Africa but can be seen in immunocompromised patients.

It is transmitted by the bites of ticks of Ixodes spp.

• Clindamycin is also active against the Babesia spp as well as amoebae.
• Spiramycin is active against Toxoplasma gondii and it is used as an alternative to antifolate in the treatment of toxoplasmosis.

Question 6

Discuss oxidants

Answer 6

Example: Artemisinin and its derivatives, artesunate, arteether and artemether.

• Artemisinin is a sesquiterpene lactone isolated from the herb, Artemisia annua

They are used to treat acute uncomplicated malaria

They do not affect the hepatic stages of plasmodium, hence they don’t produce radical cure of malaria.

The lactone structure of artemisinin-based compounds contains a peroxide moiety which is essential for their activity.

The peroxide group reacts with iron in heme, thus producing oxidative free radicals

The highly reactive free radicals interrupt DNA functions in plasmodium leading to death of the parasite.