Antivirals Part I

Question 1

Differentiate between viruses and bacteria.

Answer 1

Bacteria primarily replicate extracellularly while viruses replicate intracellularly exclusively. Viruses need intracellular machinery to make protein.

Question 2

What are two types viruses relative to genetic material.

Answer 2

DNA dependent or RNA dependent

Question 3

What are three main problems with eradicating viruses?

Answer 3

1. Antivirals must get intracellular to be effective
2. Antivirals are ineffective against dormant viruses
3. Viruses have a high rate of mutation leading to an increased chance of resistance

Question 4

Acyclovir is effective against what viruses?

Answer 4

HSV-1, HSV-2, Varicella Zoster

Some efficacy against Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV)

Question 5

Differentiate HSV-1 from HSV-2.

Answer 5

HSV-1: cold sores, mostly in the oral mucosa

HSV-2: genital herpes

Question 6

What illness is caused by EBV?

Answer 6

Mononucleosis and chronic fatigue syndrome

Question 7

Describe the pathophysilogy of varicella zoster.

Answer 7

Varicella lies dormant in a dermatome. It becomes active in a time of immune supression causing a vesicular rash along said dermatome.

Question 8

What is the significant complication of varicella in an adult patient?

Answer 8

Varicella pneumonitis

Question 9

Describe the mechanism of action of acyclovir.

Answer 9

Varicella makes DNA to replicate by linking nucleosides in a chain. Acyclovir binds to the chain and terminates chain growth and the virus can no longer replicate.

Question 10

State the AEs of acyclovir and explain why they occur.

Answer 10

There are almost no AEs because acyclovir does not affect non-viral cells. Patient may have tremors or other CNS side effects, but they are rare.

Question 11

T/F: Resistance to acyclovir is common.

Answer 11

True: the virus figures out to not attach acyclovir

Question 12

In what routes of administration is acyclovir available?

Answer 12

IV, PO, and topical - topical for HSV-1 and HSV-2. Topical use is not common.

Question 13

Describe valacyclovir

Answer 13

Pro-drug formulation of acyclovir.

Question 14

Define pro-drug.

Answer 14

A drug that is activated post metabolism

Question 15

Describe the potency of valacyclovir relative to acyclovir.

Answer 15

PO valacyclovir = IV acyclovir levels

Question 16

Describe penciclovir and what it is used for.

Answer 16

Topical drug that is never used.

Question 17

Describe famciclovir and what it is used for.

Answer 17

Pro-drug of penciclovir that has good PO absorption.

Question 18

Describe the treatment of varicella in adults and kids.

Answer 18

Kids = no treatment, Adults = acyclovir or similar

Question 19

Describe the mechanism of ganciclovir.

Answer 19

Viral DNA chain termination similar to acyclovir.

Question 20

What infection is ganciclovir first line for?

Answer 20

CMV - especially in HIV and transplants

Question 21

State the routes of administration of ganciclovir and describe the use of each.

Answer 21

PO - for suppression or secondary prophylaxis

IV - for treatment of CMV

Question 22

Describe valganciclovir and and state when it is used.

Answer 22

Pro-drug of ganciclovir that, when given PO, gives IV levels of ganciclovir. Used in PO treatment of CMV

Question 23

What part of the body does CMV like to infect?

Answer 23

Retina –> causes CMV retinitis

Question 24

What is the primary AE of valganciclovir?

Answer 24

Neutropenia

Question 25

Describe the mechanism of action of foscarnet and state how this is clinically relevant compared to acyclovir.

Answer 25

It inhibits DNA polymerase which gives it a role in resistant viral infections. It is second line, particularly against CMV.

Question 26

What is the significant AE of foscarnet and what is the clinical significance?

Answer 26

It is highly intolerable s/p nephrotoxicity. It can only be used IV and fluids must be given before and after drug administration to limit contact time with the kidney.

Question 27

Describe the mechanism and use for cidofivir.

Answer 27

Similar mechanism to foscarnet which gives it a role in resistance. Used in resistant CMV, HSV, varicella, etc.

Question 28

What is the significant AE of cidifovir and how is this managed differently than foscarnet?

Answer 28

Nephrotoxicity managed with fluids AND PO doses of probenecid just prior to administration of cidofivir. Probenecid prevents tubule secretion of cidofivir.

Question 29

What other drug might probenecid be given with and why?

Answer 29

Given with PCN to increase the half life of PCN by reducing its secretion. You can give less PCN.