Antiviral therapy

Question 1

Oseltamivir, zanamivir

Answer 1

Inhibit influenza neuraminidase -> decrease release of progeny virus
treat and prevent both Influenza A and B

Question 2

Acyclovir, famciclovir, valacyclovir

Answer 2

Guanosine analogs. Phosphorylated by HSV/VZV THYMIDINE kinase and not phosphorylated in uninfected cells
inhibits viral DNA polymerase

HSV and VZV. Weak against EBV and no activity against CMV
HSV - mucocutaneous and genital lesions and encephalitis
Prophylaxis in Immunocompetents. No effect on latent infections.
Valacyclovir - prodrug for acyclovir. better oral availability

Tox: crystalline nephropathy and acute renal failure
MOR: mutated viral thymidine kinase

Question 3

Ganciclovir

Answer 3

5-monophosphate by CMV viral kinase. Guanosine analog. Triphosphate by cellullar kinase.
inhibits viral DNA polymerase.

Use: CMV esp in immunocompromised.
Tox: Leukopenia, neutropenia, thrombocytopenia, renal toxicity
MOR: mutated viral kinase

Question 4

Foscarnet

Answer 4

Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhbitor. Does not need activation by viral kinase

Use: CMV retinitis in immunocompromised patients when gangciclovir fails; acyclovir resistant HSV

Tox: nephrotoxicity, electrolyte prob: hypo/hypercalcemia, phosphatemia, hypokalemia, hypomagnesemia); Seizures!

MOR: mutated DNA polymerase

Question 5

Cidofovir

Answer 5

inhibits viral DNA polymerase. No need phosphorylation by viral kinase
Use: CMV retinitis in compromised. Acycovir resistant HSV.

Tox: nephrotoxicity; give probenicid to decrease toxicity

Question 6

HIV therapy

Answer 6

HAART - at time of HIV diagnosis; strong indication: low CD4 cell counts

Question 7

NRTI

Answer 7

Abacavir, Didanosine, lamivudine, Stavudine, Tenofovir, Zidovudine ( for general prophylaxis and pregnancy to decrease fetal transmission)

Competitively inhibit nucelotide binding to reverse transcriptase and terminate DNA chain (lacks 3’ OH group)
Tenofovir is Nucleotide; the others are nucleosides, so need phosphorylation

Tox: Bone marrow suppression (reverse with G-CSF and eryhtropoietin), peripheral neuropathy, lactic acidosis, anemia (ZDV), pancreatitis (didanosine)

Question 8

NNRTI

Answer 8

Delavirdine, Efavirenz, Nevirapine

Bind reverse transcriptase at a different site than NRTI. Dont need phosphorylation to be active or compete with nucleotides

Toxicity: Rash and hepatotoxicty - all NNRTI
Vivid dreams and CNS symptoms - efavirenz
Delavirdine and efavirenz are containdicated in pregnancy

Question 9

Protease inhibitors

Answer 9

-Navirs: Ritonavir
Assembly of virions depend on HIV-1 protease (pol gne) - cleaves polypeptides of HIV mRNA. Protease inhibitors prevent maturation of new viruses

Ritonavir increase other drug concentration by inhibiting cyt P450.
Tox: Hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria.

Rifampin - CYP induces is CI with protease inhibitos b/c can decrease protease inhibitor concentration

Question 10

Integrase inhibitors

Answer 10

Raltegravir
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase

Increase creatine kinase - toxicity

Question 11

Fusion inhibitors

Answer 11

Enfuvirtide: binds gp41, inhibiting viral entry
maraviroc: Binds CCR5 on Tcell or monocyte surface and inhibits interaction with gp120

Tox: skinreaction at injection sites

Question 12

Interferons

Answer 12

Glycoprotein made by virus infected cells, antiviral and antitumor properties

IFN-alpha: Chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, RCC, malignant melanoma
IFN-Beta: Multiple sclerosis
IFN-gamma: CGD

Toxicity: Neutropenia, myopathy

Question 13

Hepatitis C therapy

Answer 13

Ribavirin, SImeprevir(protease inhibito, prevent viral replication), Sofosbuvir (inhibit HCV RNA dep-RNA polymerase - chain terminator)

Ribavirin: Inhibit guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
Use: Chronic HCV, also used in RSV (pavlizumab in children)
Sofosbuvir, Simeprevir - not monotherapy; used with Ribavirin
Toxicity: hemolytic anemia, severe teratogen

Question 14

Antibiotics to avoid in pregnancy

Answer 14

Sulfonamides - Kernicterus
Aminoglycosides - Ototoxicity
Fluoquinolones - Cartilage damage
Clarithromycin - Embryotoxic
Tetracycline - discolored teeth, inhibition of bone growth
Ribavirin (antiviral) - teratogenic
Griseofulvin - teratogenic
Chloramphenicol -Gray baby syndrome