Clinical Use Of Antiviral Drugs

Question 1

Why is t difficult to develop a safe anti viral agent?

Answer 1

Virus use cellular receptors to get inside cells so we need to obliterate intracellular parasites. However a virus must replicate inside cells and take over host cell biochemistry. They have high mutation rate and latency is common amongst them. When genetic integration is achieved its hard to treat them.

Question 2

What are the targets of virus specific enzymes?

Answer 2

1. Thymine kinase of herpes virus
2. Protease enzyme of HIV
3. Reverse transcriptase of HIV
4. DNA polymerase of HBV

Question 3

What are our two choice of treatment for viral infections?

Answer 3

It can either be virus specific or family specific.

However some agents have broad activity

Question 4

Why is it hard to tell whether a treatment is working or not?

Answer 4

We can’t grow it on a culture and see if a drug works or not.

Question 5

Examples of anti viral drugs to treat acute infections

Answer 5

Oseltamivir is used for influenza

Aciclovir is used to treat chicken pox.

Question 6

What are example of drugs that treat chronic viral infections?

Answer 6

PEP can be given post exposure prophylaxis to prevent infection of HiV.

PREP is given pre exposure prophylaxis l.

Aciclovir can be given post exposure prophylaxis but still allows infection of VZV.

People with CMV can be given ganiclovir and foscarnet as prophylaxis for deactivated infection such as in transplants.

Question 7

Why do you have to start anti viral treatments early after diagnosis?

Answer 7

Because antiviral agents are incapable of eradicating latent infections.

Question 8

When may resistance develop when using anti viral agents?

Answer 8

If single agent is used during acute infection, it may also develop if used for long term prophylaxis.

Question 9

How do you treat herpes?

Answer 9

Use aciclovir or valaciclovir and those can be give IV oral and tropical

Ganiclovir and valganiclovir can only be given IV or oral

Foscarnet is IV or tropical

Cidofovir is only IV

Question 10

How does aciclovir enters cells and work?

Answer 10

Aciclovir is not the active form but it can easily be taken into cells, after which it gets phosphorylated to ACV triphosphate. Herpes simplex thymidine kinase have 100 times for affinity for ACV compare to cellular phosphokinase so herpes simplex virus are more likely to take in ACV

It acts as a DNA chain terminator, it blocks addition of GTP so replication stops and cell death occurs

Question 11

What is aciclovir used to treat?

Answer 11

It is used to treat herpes simplex virus for encephalitis, genital infection and suppressive therapy for recurrent genital herpes

It can also be used to treat varicella zoster virus for treatment of chicken pox, shingles as well as prophylaxis for chicken pox

It can be used as prophylaxis for cytokegalovirus

Question 12

What is ganiclovir used for?

Answer 12

Primarily given to cytomegalovirus for treatment of reactive infection in organ transplant recipients

It is also given to treat congenital infection in infants

Given as prophylaxis in case of mismatch in transplant patients

Question 13

What are valaciclovir and valganiclovir

Answer 13

Both of these are pro drug. It have better bio availability

Valaciclovir is used to treat VZV in the immunocompromised and anti CMV onto phyletic in transplant patients

Valganiclovir is another drug used in prophylaxis for cytomegalo virus

Question 14

What foscarnet used for?

Answer 14

Foscarnet is used to treat cytomegalo virus infection in the immunocompromised. It may also be used against ganiclovir resistance

It have renal toxicity so not used for renal transplant patients

Question 15

What’s a drug for CMV but very nephrotoxic?

Answer 15

Cidofovir

Question 16

How can virus be resistant to viral drugs?

Answer 16

There are two main mechanisms:

 - thymidine kinase mutants 
 - DNA polymerase mutants 

If the mutation I curse in thymidine kinase then drugs that does not require phosphorylation are still effective

If the mutation occurs in DNA polymerase then all drugs are rendered less effective

Question 17

Zanamir and oseltamir are two drugs used to treat influenza how do they work?

Answer 17

Both zanamivir and oseltamivir inhibit virus release from infected cells via inhibition of neuraminidase

Zanamivir is given IV or inhaled

Oseltamivir is given oral

Question 18

Effectiveness of antiviral drugs:neuraminidase inhibitors

Answer 18

They produce 1 day reduction in symptom reduction and treatment must be done early and should be used to those in risk groups.

Could be helpful in post exposure prophylaxis

Question 19

What is the treatment of hep B

Answer 19

The treatment is to reduce immune response to control it. We can't cure it because it t corporates it's self into the host DNA. We give antiviral such as:
Lamivudine
Tenofovir 
Entecavir 
Adefovir 

Those drugs can be given singly or in combination