Antivirals

Front 1

1) Blocks uncoating by interfering with viral M2 protein (ion channel)

2) Influenza A prophylaxis
Reduces symptoms (must be given w/in first 2 days)"

3)Renal dz: reduce dose

4) CNS effects

Back 1

Amantidine

1) Mech
2) Use
3) Metabolism
4) Toxicity

Front 2

1) Blocks release from cell and penetration into respiratory epithelium by competitively inhibiting neuraminidases

2) Influenza A, B tx (w/in 48 hours), Influenza prophylaxis (<1 yr)

Only used in high risk pts

4) NVD, Bronchiitis

Back 2

Oseltamivir

1) Mechanism
2) Use
3) Toxicity

Front 3

1) Thymidine analog that interferes with DNA synthesis

2) Ophthalmic dz d/t Herpes simplex virus 1, 2

3) Ophthalmic use only

Back 3

Trifluridine

1) Mechanism
2) Use
3) Administration

Front 4

1) Comp dGTP inhibitor and chain terminator, incorprates into DNA but lacks free 3'OH.

10-30x selective for herpes vs. host DNA polymerase, 40-100x faster when phosphorylated by herpes

2) IV: Systemic herpes virus, severe initial genital herpes
Oral: Primary genital herpes, primary herpetic gingivostomatosis
Topical: Early to primary genital herpes

3) Selective for herpes as activated herpes thymidine kinase

4) Well tolerated, rash, itching, NV, headache, fatigue

Back 4

Acyclovir

1) Mechanism
2) Use: IV, Oral, Topical
3) Metabolism
4) Toxicity

Front 5

1) Converted to penciclovir, phosphorylated by herpes and host kinases, inhibits viral DNA polymerase

2) Herpes zoster <3 days, Recurrent genital herpes

3) Better absorption, less dosing than acyclovir

4) Well tolerated, rash, itching, NV, headache, fatigue

Back 5

Famciclovir

1) Mechanism
2) Use
3) Administraton
4) Toxicity

Front 6

1) Comp dGTP inhibitor and chain terminator (similar to acyclovir)

2) Recurrent herpes of lips and face

3) Poor bioavailability, only used topically

4) Skin irritation, rash at site of application

Back 6

Penciclovir

1) Mechanism
2) Use
3) Metabolism
4) Toxicity

Front 7

1) Comp DGTP inhibitor and chain terminator (similar to acyclovir, except first phosphorylation cat by CMV protein kinase)

2) CMV retinitis, prophylaxis (CMV affects AIDs and org transplant patients)

3) BM suppression (WBCs first, then RBCs, platelets), reduced with zidovudine

Back 7

Ganciclovir

1) Mechanism
2) Use
3) Toxicity

Front 8

1) Binds to pyrophosphate binding site and inhibits CMV DNA polymerase, does not require activation or conversion by kinases

2) CMV retinitis, acyclovir-resistant herpes simplex

3) Renal damage (reversible), leads to electrolyte imbalances, seizures

Back 8

Foscarnet

1) Mechanism
2) Use
3) Toxicity

Front 9

1) Cytidine nucleoside analog that inhibits reverse transcriptase domain of hep B DNA polymerase, requires phosphorylation to be active

2) Hepatitis B

3) ND

Back 9

Lamivudine (3TC)

1) Mechanism
2) Use
3) Toxicity

Front 10

1) dAMP analog that inhibits reverse transcriptase domain of hepatits B DNA polymerase, requires phosphorylation to be active

2) Hepatitis B, HIV

3) GI upset

Back 10

Tenofovir

1) Mechanism
2) Use
3) Toxicity

Front 11

1) Inteferes with viral mRNA synthesis by 1) inhibiting GTP synthesis (monophos), 2) inhibiting GTP-dep mRNA capping (triphos)

2) Hepatitis C (w/ interferon), Severe RSV (aerosol, in children)

3) Aerosol: Drug can get clogged in resp equip, pulmonary fx depression, rash

IV/oral: BM suppression, anemia

Back 11

Ribavarin

1) Mechanism
2) Use
3) Toxicity

Front 12

1) Produced by host cells when infected, spread to adjacent cells, induce production of proteins that block translation of viral mRNA

2) Condyloma acuminata (genital warts)
Hep B (w/ lamivudine, tenofovir)
Hep C (w/ ribavarin)

3) Flu-like syndromes, BM suppression, neurotoxicity, myalgia, makes pt feel lousy

Back 12

Interferon

1) Mechanism
2) Use
3) Toxicity

Front 13

1) Reversibly inhibits Hep C NS3 protease to block formation of infectious viral particles

2) Hepatitis G genotype I (w/ ribavarin, interferon)

3) Anemia, neutropenia
CI - Other CYP3A inducers or substrates

Back 13

Boceprevir

1) Mechanism
2) Use
3) Toxicity

Front 14

1) Thymidine nucleoside analog that is phosphorylated by host (not viral) kinases, inhibits reverse transcriptase and acts as DNA chain terminator to inhibit DNA synthesis

2) HIV in adults/ children

3) BM suppression, myopathy

Toxicity if given with other drugs metabolized by glucoronyl transferase (compete with AZT, more shunted to CYP450s, produces toxic metabolite that causes BM suppression)

Back 14

Zidovudine (AZT)

1) Mechanism
2) Use
3) Toxicity

Front 15

1) dCMP nucleoside analog that inhibits reverse transcriptase, must be phosphorylated

2) HIV in adults, children, hepatitis B

Synergistic with AZT (if virus develops resistance to AZT, becomes more sensitive to 3TC vice versa, given in conjunction for powerful tx)

3) ND, rash

Back 15

Lamuvidine (3TC) **HIV**

1) Mechanism
2) Use
3) Toxicity

Front 16

1) Prodrug hydrolyzed to tenofovir phosphonate, competes with dATP for incorporation, inhibits reverse transcriptase and causes chain termination

2) HIV combination tx

Back 16

Tenofovir **HIV**

1) Mechanism
2) Use

Front 17

1) 3TC analog that competes with dCTP for incorporation, inhibits reverse transcriptase and causes chain termination

2) HIV combination tx

Back 17

Emtricitabine

1) Mechanism
2) Use

Front 18

1) Competes with dGTP for incorporation, inhibits reverse transcriptase and causes chain termination

2) HIV combination tx

3) Hypersensitivity rxn in pts with genetic mutation, do genetic test before tx

Back 18

Abacavir

1) Mechanism
2) Use
3) Toxicity

Front 19

1) Non-nucleoside reverse transcriptase inhibitor, doesn't require phosphorylation for activity

2) HIV combination tx

3) Rash, CNS/psychiatric symptoms, nightmares

Back 19

Efavirenz

1) Mechanism
2) Use
3) Toxicity

Front 20

1) Competitively inhibits viral protease from cleaving inert Gag-pol polypeptide into separate functional proteins that can infect cells

2) HIV-1,2 (with reverse transcriptase inhibitors), significantly decreases viral blood load

3) Diabetes, alterations in lipid metabolism, fat redistribution (buffalo hump, gut), CYP3A inhibition (alters metabolism of other drugs)

Back 20

Lopinavir

1) Mechanism
2) Use
3) Toxicity

Front 21

1) Potent inhibitor of CYP 3A4

2) Protease inhibitor, small amount with lopinavir prevents its metabolism, increases effect, can reduce dose of lopinavir

Back 21

Ritonavir

1) Mechanism
2) Use

Front 22

1) Binds to gp41 subunit of HIV glycoprotein, blocking conformational change and thereby preventing fusion of viral and CD4+ membranes

2) HIV-1 only, last ditch effort

3) SubQ injection

4) Local injection site rxns, DN, fatigue

Back 22

Enfuvirtide

1) Mechanism
2) Use
3) Administration
4) Toxicity

Front 23

1) Noncompetitive, allosteric inhibitor of CCR5 chemokine co-recetpor, blocks entry of HIV into cells

Only drug to target human protein, used early

2) CCR5-tropic HIV-1

3) Hepatotoxicity, CV events

Back 23

Maraviroc

1) Mechanism
2) Use
3) Toxicity

Front 24

1) Inhibits HIV-1 integrase activity, preventing integration of HIV-1 DNA into genome

2) HIV-1, drug resistant HIV

Back 24

Raltegravir

1) Mechanism
2) Use