Virus - Antiviral agents

Question 1

Acyclovir and valacyclovir

The mechanism of action (MOA)

Answer 1

MOA: guanosine analog; activated by herpes thymidine kinase → inhibits viral DNA polymerase

Question 2

Acyclovir and valacyclovir

Indication(s) (IND)

Answer 2

IND: HSV (treatment and prophylaxis for oral, genital, and ocular herpes), VZV (chickenpox and shingles)

Question 3

Acyclovir and valacyclovir

. Significant side effects and uniquetoxicity (TOX)

Answer 3

TOX: neurotoxic (delirium and tremors) and nephrotoxic

Question 4

Ganciclovir

The mechanism of action (MOA)

Answer 4

MOA: guanosine analog; activated by human thymidine kinase → inhibits CMV DNA polymerase

Question 5

Ganciclovir

Indication(s) (IND)

Answer 5

IND: CMV (retinitis, pneumonia, colitis), especially in immunocompromised people

Question 6

Ganciclovir

Significant side effects and uniquetoxicity (TOX)

Answer 6

TOX: bone marrow suppression, nephrotoxic, and ↓ spermatogenesis (toxicity → acyclovir because activated by human enzyme)

Question 7

Foscarnet

The mechanism of action (MOA)

Answer 7

MOA: pyrophosphate analog; inhibits viral DNA polymerase (no activation required)

Question 8

Foscarnet

Indication(s) (IND)

Answer 8

IND: CMV, HSV (refractory infections)

Question 9

Foscarnet

Significant side effects and uniquetoxicity (TOX)

Answer 9

TOX: reversible nephrotoxicity and anemia

Question 10

Nucleoside RT inhibitors (zidovudine—azidothymidine [AZT], didanosine—ddl, zalcitabine—ddC, lamivudine-3TC, and stavudine—d4T)
The mechanism of action (MOA)

Answer 10

MOA: nucleoside analogs; activated by phosphorylation → inhibits RT → prevents incorporation of viral genome into host DNA

Question 11

Nucleoside RT inhibitors (zidovudine—azidothymidine [AZT], didanosine—ddl, zalcitabine—ddC, lamivudine-3TC, and stavudine—d4T)
Indication(s) (IND)

Answer 11

IND: part of combination therapy for HIV

Question 12

Nucleoside RT inhibitors (zidovudine—azidothymidine [AZT], didanosine—ddl, zalcitabine—ddC, lamivudine-3TC, and stavudine—d4T)
Significant side effects and uniquetoxicity (TOX)

Answer 12

TOX: bone marrow suppression, peripheral neuropathy, pancreatitis (especially ddl), lactic acidosis, and macrocytic anemia (AZT)

Question 13

Nonnucleoside RT inhibitors (nevirapine, delavirdine, and efavirenz)
The mechanism of action (MOA)

Answer 13

MOA: binds directly to and inhibits HIV RT → prevents incorporation of viral genome into host DNA

Question 14

Nonnucleoside RT inhibitors (nevirapine, delavirdine, and efavirenz)
Indication(s) (IND)

Answer 14

IND: part of combination therapy for HIV

Question 15

Nonnucleoside RT inhibitors (nevirapine, delavirdine, and efavirenz)
Significant side effects and uniquetoxicity (TOX)

Answer 15

TOX: rash (including Steven-Johnson), ↑ liver enzymes, inhibits P-450, vivid dreams/CNS changes (with ef avirenz)

Question 16

Protease inhibitors (saquinavir, ritonavir, indinavir, nelf inavir, and amprenavir) 
 The mechanism of action (MOA)

Answer 16

MOA: blocks protease enzyme → inhibits assembly of viral core and new viruses

Question 17

Protease inhibitors (saquinavir, ritonavir, indinavir, nelf inavir, and amprenavir) 
 Indication(s) (IND)

Answer 17

IND: part of combination therapy for HIV

Question 18

Protease inhibitors (saquinavir, ritonavir, indinavir, nelf inavir, and amprenavir) 
Significant side effects and uniquetoxicity (TOX)

Answer 18

TOX: GI upset, insulin resistance, ↑ lipids, fat redistribution syndromes, interstitial nephritis, and thrombocytopenia (indinavir)

Question 19

Amantadine and rimantadine

The mechanism of action (MOA)

Answer 19

MOA: inhibits viral penetration and uncoating; releases dopamine (DA) from intact nerve terminals

Question 20

Amantadine and rimantadine

Indication(s) (IND)

Answer 20

IND: influenza A treatment/prophylaxis, Parkinson disease

Question 21

Amantadine and rimantadine

Significant side effects and uniquetoxicity (TOX)

Answer 21

TOX: CNS effects: confusion, ataxia, and slurred speech (less with rimantadine); teratogenesis

Question 22

Zanamivir and oseltamivir

The mechanism of action (MOA)

Answer 22

MOA: neuraminidase inhibitor → alters virion aggregation and release

Question 23

Zanamivir and oseltamivir

Indication(s) (IND)

Answer 23

IND: influenza A and B treatment and prophylaxis (oseltamivir)

Question 24

Zanamivir and oseltamivir

Significant side effects and uniquetoxicity (TOX)

Answer 24

TOX: bronchospasm in patients with asthma /COPD) (zanamivir)

Question 25

Ribavirin

The mechanism of action (MOA)

Answer 25

MOA: guanosine analog; activated by phosphorylation → inhibits inosine-5’-monophosphate (IMP) dehydrogenase

Question 26

Ribavirin

Indication(s) (IND)

Answer 26

IND: RSV, hantavirus, and chronic hepatitis C

Question 27

Ribavirin

Significant side effects and uniquetoxicity (TOX)

Answer 27

TOX: hemolysis (when given IV)

Question 28

Interferon-α

The mechanism of action (MOA)

Answer 28

MOA: human glycoproteins that interfere with ability of viruses to replicate (block protein synthesis and degrade mRNA)

Question 29

Interferon-α

Indication(s) (IND)

Answer 29

IND: chronic hepatitis B and C, genital warts, Kaposi sarcoma, and hairy cell leukemia

Question 30

Interferon-α

Significant side effects and uniquetoxicity (TOX)

Answer 30

TOX: bone marrow suppression

Question 31

What constitutes highly active antiretroviral therapy (HAART)?

Answer 31

Two nucleoside RT inhibitors and a protease inhibitor or nonnucleoside RT inhibitor. Note: no patient should ever be on monotherapy as resistance is invariable.

Question 32

When is HAART typically initiated?

Answer 32

CD4+ 500 cells/mL or very high viral load

Question 33

Which drug is used to prevent vertical transmission during pregnancy?

Answer 33

Zidovudine (AZT)