Flashcards in Antiviral Chemotherapy And Prophylaxis Deck (47):
Mention 4 antiherpes drugs.
2. Valacyclovir (prodrug)
4. Famciclovir (prodrug)
What is the mechanism of action of antiherpes drugs?
Activated by viral thymidine kinase (TK) to forms that inhibit viral DNA polymerase.
What are the clinical applications of antiherpes drugs?
Treatment and prophylaxis for HSV-1, HSV-2, and VZV.
None of these drugs is active against TK- strains.
What are the pharmacokinetics of the main antiherpes drugs?
Acyclovir - Topical, oral, and IV.
Penciclovir - Topical.
Famciclovir and valcyclovir - Oral.
What are the main toxicities of antiherpes drugs?
Oral forms cause:
IV acyclovir may cause renal toxicity and CNS toxicity.
Mention some drugs against CMV.
What is the mechanism of action of the drugs against CMV?
1. Viral activation of ganciclovir to form inhibiting DNA polymerase.
2. No viral bioactivation for cidofovir and foscarnet.
What are the clinical applications of drugs against CMV?
Treatment of CMV infections in immunosuppression (AIDS) and organ transplantation.
What are the pharmacokinetics of drugs against CMV?
Ganciclovir - Oral, IV, intraocular forms.
Valganciclovir - Oral.
Cidofovir and foscarnet - IV.
What is the toxicity of ganciclovir?
1. Bone marrow suppression
2. Hepatic and neurologic dysfunction
What is the toxicity of cidofovir and foscarnet?
What is the toxicity of foscarnet?
CNS effects and electrolyte imbalance.
Mention some antihepatitis drugs.
What is the mechanism of action of antihepatitis drugs?
IFN-a - degrades viral RNA via activation of host cell RNAase.
Inhibition of HBV polymerase (others).
Rivabirin has multiple antiviral actions.
What are the clinical applications of antihepatitis drugs?
1. Suppressive treatment of HBV (all drugs except rivabirin).
2. Treatment of HCV (rivabirin +/- IFN-a).
What are the pharmacokinetics of antihepatitis drugs?
IFN-a - parenteral.
Adefovir/ Entacavir/ Lamivudine/ Ribavirin - oral.
Ribavirin also inhalational.
What is the toxicity of IFN-a?
4. Flu-like syndrome
What is the toxicity of adefovir?
1. Lactic acidosis
2. Renal and hepatic toxicity
What is the toxicity of ribavirin?
Mention 4 antiinfluenza drugs.
What is the mechanism of action of anti-influenza drugs?
Amantadine and rimantidine: block of M2 proton channels.
Oseletamivir and zanamivir: Inhibit neuraminidase.
What are the clinical applications of anti-influenza drugs?
M2 blockers virtually obsolete.
Others prophylaxis vs current flu strains and shorten symptoms.
What are the pharmacokinetics of anti-influenza drugs?
Oral forms except zanamivir (inhalational).
What is the toxicity of oseltamivir?
What is the toxicity of zanamivir?
Bronchospasm in asthmatics.
Mention 8 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).
What is the mechanism of action of nucleoside/nucleotide reverse transcriptase inhibitors?
Inhibit HIV reverse transcriptase after phosphorylation by cellular enzymes.
Cross resistance is common, but incomplete.
Mention some toxicities of NRTIs.
Zidovudine --> Bone marrow suppression.
Abacavir --> Hypersensitivity.
Didanosine --> Pancreatitis.
Stavudine and zalcitabine --> Peripheral neuropathy.
What are the pharmacokinetics of NRTIs?
1. Duration of action is usually longer than half-life.
2. Most undergo renal elimination.
What NRTIs undergo renal elimination, especially?
What is the toxicity of NRTIs?
Most NRTIs are not extensively metabolized by hepatic enzymes such as the CYP450 isoforms, so they have few interactions that concern their pharmacokinetic characteristics.
Mention 4 Non nucleoside reverse transcriptase inhibitors (NNRTIs).
What is the mechanism of action of NNRTIs?
1. Inhibit HIV reverse transcriptase after phosphorylation by cellular enzymes.
2. Cross resistance common, but incomplete.
What currently metabolizes all NNRTIs?
What are the pharmacokinetics of etravirine?
May induce formation of CYP3A4, but inhibits other CYP450s.
What may delavirdine and nevirapine cause?
Rash and increased liver enzymes.
What may efavirenz cause?
Mention 8 protease inhibitors.
What is the mechanism of action of protease inhibitors?
Inhibit viral protein processing.
Cross resistance between PIs is common.
What PIs may cause GI distress and diarrhea?
What PI may cause peripheral neuropathy?
What PI may cause rash?
What PI may cause hyperbilirubinemia and nephrolithiasis?
Mention 2 entry inhibitors.
What is the mechanism of action of entry inhibitors?
Block fusion between viral and cellular membranes (enfuvirtide).
CCR5 receptor blocker (maraviroc).
What are the pharmacokinetics of maraviroc and enfuvirtide?
1. Extrahepatic hydrolysis of enfuvirtide (subcutaneous injection).
2. P450 metabolism (maraviroc).
3. Inducers and inhibitors of CYP450 alter elimination of maraviroc - no effects on enfuvirtide.