Chemotherapy (anti-fungal, anti-parasitic, anti-viral)

Question 1

What are the classes of anti-malarial drugs?

Answer 1

1. Treatment of acute attacks: These drugs target the erythrocytic stage of parasite life cycle, producing radical cures for P. falciparum and P. malariae but not P. vivax and P. ovale as these produce hypnozyites that lie dormant in hepatocytes.
2. Producing radical cure: These drugs target the hepatocyte dwelling hypnozoites of P.vivax and P. ovale.
3. Chemoprophylaxis: Blocks transition from exoerythrocytic stage to erythocytic stage.
4. Preventing transmission: Destroys gametocytes and so prevents transmission.

Question 2

What is the functional significance of haemozoin for malaria?

Answer 2

• During erythrocytic stage, the plasmodium digests haemoglobin to obtain nitrogen in food vacuoles within erythrocytes
• Excess haem is prevented from accumulating by polymerisation into haemozoin (build-up of haem causes production of ROSs that damage the plasmodium)

Question 3

Why is inhibition of folate synthesis effective in treating malaria?

Answer 3

Like bacteria, Plasmodium need to synthesis folate de-novo

Question 4

What are the types of antiviral drugs?

Answer 4

1. Virucidal: Drugs that directly kill in tact viruses. These are usually too toxic for clinical use.
2. Antiviral: Does not affect existing viruses, but prevents viral replication and so gives the immune system opportunity to clear infection. This is the most common type of antiviral chemotherapy.
3. Immunomodulation: Drugs that activate/support the host’s own immune system in attacking virus.

Question 5

What are the binding kinetics of amantidine?

Answer 5

• M2 channel contains both high and low affinity binding sites.
• Amantidine binds to low affinity site when the pH is high (channel is closed), inhibiting pH sensor and prevents opening.
• It binds high affinity site when the pH is low (channel is open), blocking channel.

Question 6

How is selectiviity in aciclovir achieved?

Answer 6

1. Requires viral thymidine kinase
2. Viral DNAP selectivity

Question 7

What chemical modifications allow bioavailability of AZT be increased?

Answer 7

Addition of Val as it allows AZT to be transported into cells via Val transporters