Antiviral and Antiparasitic Drugs

Question 1

Why are viruses difficult to target with drugs?

Answer 1

Replicate inside host cells
Use host enzymes to make viral components
Advanced stage before detection.

Question 2

What kind of treatment does a vaccine provide?

Answer 2

Prophylactic treatment as they are there to prevent viral diseases.

Question 3

How are neuraminidase inhibitors used to treat viral infections?

Answer 3

Virus released from cell remains attached via sialic acid residues,
Neuraminidase produced by virus breaks bonds
Drug prevents virus infecting other cells

Question 4

Give some examples of neuraminidase inhibitors and what viruses are they used against.

Answer 4

Oseltamivir, Tamiflu

Used against Influenza A and B

Question 5

What drugs will inhibit genetic replication and integration of viral infections?

Answer 5

DNA polymerase inhibitors

Reverse Transcriptase (RT) inhibitors.

Question 6

What are DNA polymerase inhibitors used to treat?

Answer 6

Prevents DNA replication and therefore is used against DNA viruses such as herpes

Question 7

What are RT inhibitors used to treat?

Answer 7

Prevents RNA –> DNA copies and therefore is used against RNA retroviruses (HIV)

Question 8

Give an example of a DNA polymerase inhibitor?

Answer 8

Aciclovir:

used against herpes

Question 9

How does Aciclovir work?

Answer 9

Pro-drug,
Nucleoside analogue of guanine with an altered ribose.

Phosphorylated by viral thymidine kinase (TK) (viral more effective than host TK)
Used to make acyclo GMP
Triphosphate (acyclo GTP) inhibits viral DNA polymerase preventing viral chain extension.

Question 10

What are the RT inhibitors used to treat?

Answer 10

AIDS

Question 11

Give some examples of RT inhibitors?

Answer 11

Nucleoside analogue - Lamivudine

Non-nucleoside - Efavirenz

Question 12

How does an RT nucleoside analogue work (lamivudine)

Answer 12

Analogue of cytosine
Phosphorylated into a triphosphate
Inhibits RT (competition) not DNA polymerase.
Terminates Viral DNA chain.

Question 13

How do RT non-nucleoside drugs work against AIDS?

Answer 13

Efavirenz:

Active in the form that it is given

Denatures active site of RT enzyme

Question 14

What kind of drug is used to treat HIV?

Answer 14

Integrase inhibitors

eg. Raltegravir

Question 15

How does a integrase inhibitor work?

Answer 15

Viral DNA incorporated into chromosomal DNA using viral integrase enzyme
Inhibitor prevents this.
Therefore used in combination with nucleoside RT inhibitors

Question 16

What are the side effects of Raltegravir?

Answer 16

GI upset.

Hepatitis

Question 17

How do protease inhibitors work?

Answer 17

Used against AIDS:

HIV mRNA translated into 2 polyproteins - inert.
Cleaved into functional proteins by viral protease.
Therefore inhibitors prevent them becoming active and leave them inert.

Question 18

What is the main treatment regime for a patient with AIDS?

Answer 18

Highly active antiretroviral Therapy (HAART):

2 Nucleoside RT inhibitors + one of;
Non-nucleoside RT inhibitor, booster protease inhibitor, integrase inhibitor.

Question 19

What is malaria?

Answer 19

Disease caused by a protozoal bacterial which is a parasite.

Question 20

What are the 2 ways of infection from the malaria parasite in the liver?

Answer 20

Pre erythrocytic

Exo erythrocytic

Question 21

Why does the malaria parasite target RBCs?

Answer 21

Uses Hb as a source of energy and amino acids.

Causes blood vessels to rupture (haemolysis) and leads to fever.

The parasite produces proteins on the surface of the RBCs which bind to endothelium and causes blood vessels to clog.

Question 22

What are some various parasite species of malaria?

Answer 22

Plasmodium falciparum (malignant malaria)

P. vivax, P. Ovale (benign malaria)

Question 23

What are the sites of action of antimalarial drugs?

Answer 23

Haem polymerase inhibitors:
Enzyme present in lysosome of parasite.
Converts toxic haem to haemozoin
These drugs inhibit this so haem is toxic to parasite.

No effect on exoerythrocytic phase

Question 24

What are some examples of antimalarial drugs?

Answer 24

Chloroquine

Quinine

Mefloquine

Question 25

What is Artemisinin?

Answer 25

Synthetic antimalarial drug used to treat acute phase of infection.

Important in treating Pl. falciparum

Question 26

How does Artemisinin work to treat malaria?

Answer 26

Drug is activated by haem causing free radicals.

The free radicals bind to and modify proteins causing damage to membranes within the parasite.

Question 27

What points doe primaquine work at?

Answer 27

treatment in the liver

Prevention of transmission