Antiviral Drugs Flashcards
(18 cards)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Drug examples?
Mechanism of action?
Drug examples: Zidovudine, Tenofovir, Lamivudine, Abacavir, Emtricitabine, Didanosine, Stavudine
Mechanism: Inhibits HIV reverse transcriptase thereby blocking viral DNA synthesis.
Note, these agents (except Tenofovir) must be phosphorylated by tyrosine kinase to become active, then they compete with nucleotide triphosphates to be added to the newly synthesized DNA strand ultimately causing DNA chain termination as these drugs lack 3’OH
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Clinical uses?
Side effects?
Zidovudie and Didanosine specific side effects?
Clinical uses: HIV (Lamivudine also treats Hep B)
Side effects: Bone marrow suppression (can be reversed with G-CSF and EPO), lactic acidosis, megaloblastic anemia (from Zidovudine), and pancreatitis (from Didanosine)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Drug examples?
Mechanism of action?
Drug examples: Nevirapine, Efavirenz, Delaviridine
Mechanism: Bind directly to HIV reverse transcriptase, thereby blocking DNA synthesis (i.e. do not compete with nucleotides and do not require tyrosine kinase phosphorylation to be active)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Clinical uses?
Side effects?
Clinical uses: HIV
Side effects: Stevens-Johnson syndrome (rash), fulminant hepatitis, induction of CYP450s
Protease Inhibitors
Drug examples?
Mechanism of action?
Drug examples: Ritonavir, Lopinavir, Atazanavir, Darunavir, Fosamprenavir, Saquinavir, Indinavir
Mechanism: Inhibit the HIV protease enzyme which is responsible for cleaving precursor proteins into mature proteins that are involved in forming the core of the viral particle - if the protease enzyme is inhibited, the virus is unable to replicate
Protease Inhibitors
Clinical uses?
Side effects?
Clinical uses: HIV
Side effects: Altered distribution of body fat (buffalo hump or truncal obesity), insulin resistance, hyperglycemia, hyperlipidemia. Ritonavir inhibits CYP450 system causing increased serum levels of other drugs
Raltegravir
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: HIV Integrase inhibitor, thus blocking HIV genome integration into host cell chromosome
Clinical uses: HIV
Side effects: Hypercholesteroleemia
Maraviroc
Mechanism of action?
Clinical uses?
Mechanism: Fusion inhibitor that blocks HIV attachment to host cells. Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.
Clinical uses: HIV
Enfuvirtide
Mechanism of action?
Clinical uses?
Mechanism: Fusion inhibitor that blocks HIV penetration into host cells via binding/blocking gp41
Clinical uses: HIV
Acyclovir
Related drugs?
Mechanism of action?
Related drugs: Valacyclovir, penciclovir, famciclovir
Mechanism: Undergoes phosphorylation by viral Thymidine Kinaes into an analog of dGTP which is then incorporated into viral DNA causing chain termination
Acyclivor
Clinical uses?
Side effects?
Clinical uses: HSV1, HSV2, VZV, EBV. Used to treat gentinal herpes, herpes encephalitis. Famciclovir best agent for treating VZV.
Side effects: Not many systemic side effects since drug is not phosphorylated in unaffected cells
Oseltamivir
Related drug?
Mechanism of action?
Clinical uses?
Related drug: Zanamivir
Mechanism: Inhibit influenza neuraminidase to block release of progeny virus
Clinical uses: Treatment of both influenza A and B
Ribavirin
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Blocks guanine nucleotide synthesis via inhibition of inosine monophosphate dehydrogenease
Clinical uses: RSV, chronic hepatitis C
Side effects: Hemolytic anemia, very teratogenic
Ganciclovir
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Guanosine analog that inhibits CMV viral DNA polymerase - activated via 2 phorphorylation reactions. The first by CMV viral kinase to make the monophosphate form and the second by cellular kinases that produce the active triphosphate (GTP) form.
Clinical uses: CMV infections, especially in CMV retinitis (often seen in AIDS and other immunocompromised patients)
Side effects: Pancytopenia and renal toxicity
Foscarnet
Mechanism of action?
Clinical uses?
Sid effects?
Mechanism: Pyrophosphate analog that inhibits viral DNA polymerase (does not require activation by viral kinase)
Clinical uses: 2nd line treatment for CMV retinitis and other CMV infections. Also treats acyclovir-resistant HSV and VZV infections.
Side effects: Nephrotoxicity
Cidofovir
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Inhibits viral DNA polymerase (does not require activation by viral kinase)
Clinical uses: CMV retinitis in immunocompromised patients and acyclovir-resistant HSV.
Side effects: Nephrotoxicity (give with probenicid and IV saline to decrease toxicity)
Amantadine
Related drug?
Mechanism of action?
Clinical uses?
Related drug: Rimantadine
Mechanism: Binds M2 surface protein of influenza A to block viral uncoating in host cells
Clinical uses: No longer useful due to high levels or resistance. Was used to reduce the duration of Influenza A symptoms
Interferons
Mechanism of action?
Clinical uses of each - alpha, beta, gamma?
Side effects?
Mechanism: Glycoproteins synthesized by viral-infected host cells that “exhibit a wide range of antiviral and anti-tumor properties”
Clinical uses:
IFN alpha - chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, conduloma acuminatum, renal cell carcinoma, malignant melanoma
IFN beta - MS
IFN gamma - Chronic granulomatous disease
Side effects: Neutropenia and myopathy
