Antivirals for non-HIV Flashcards
Biosynthesis of a toxin from a non-toxic precursor
Common in nucleoside analogues that must phosphorylated to incorporate into viral DNA
Lethal synthesis
MOA of acyclovir and valacyclovir
Inhibit viral DNA synthesis through lethal synthesis
Drugs are monophosphates; host enzymes convert them to inhibitive triphosphates that terminate viral DNA synthesis
Acyclovir and valacyclovir lethal synthesis requires these 2 types of enzymes
Viral nucleoside kinase expression to phosphorylate drug (monophosphate)
Host enzymes to convert monophosphate to triphosphate form
Valacyclovir is converted to this in a first pass hydrolysis reaction
Acyclovir
This is converted to acyclovir in a first pass hydrolysis reaction
Valacyclovir
2 indications for acyclovir and valacyclovir
Herpes infections
Cytomegalovirus infections
3 main adverse effects of acyclovir and valacyclovir
Reversible renal dysfunction (crystallization of drug in renal tubule and collecting duct)
Neurological and renal toxicity with high dose or IV infusion
Thrombocytopenia purpura-hemolytic uremic syndrome (potentially fatal; most frequent in immunocompromised patients)
Reversible renal dysfunction, neurological and renal toxicity with high dose or IV infusion, and thrombocytopenia purpura-hemolytic uremic syndrome are adverse effects of these drugs
Acyclovir and valacyclovir
Thrombocytopenic purpura-hemolytic uremic syndrome is a potentially fatal adverse effect of these drugs
Is most frequent in immunocompromised patients
Acyclovir and valacyclovir
MOA of cidofovir
Lethal synthesis to activated cidofovir diphosphate (requires only host enzymes)
Cidofovir diphosphate incorporated into DNA slows or stops DNA pol activity
Drug that given concurrently reduces cidofovir toxicity
Probenecid
Blocks anion transporter on renal tubular epithelial cells that mediates cidofovir uptake
Probenecid given concurrently reduces the toxicity of this drug
Cidofovir
Black box warning of Cidofovir
Nephrotoxicity
MOA of Foscarnet
Competitive inhibitor of viral DNA polymerase
NO lethal synthesis required
2 adverse effects (black box warnings) of Foscarnet
Renal toxicity
CNS disturbances (including seizures)
Drug with renal toxicity as an adverse effect; should avoid concurrent use with other nephrotoxic drugs
Electrolyte disturbances in acute overdosage
Foscarnet
With foscarnet, concurrent use with these should be avoided
Other nephrotoxic drugs
These can occur in acute overdosage of foscarnet
Electrolyte disturbances
3 adverse effects of Ganciclovir and Valganciclovir
Acyclovir-like adverse reactions (renal dysfunction, neurological toxicity, thrombocytopenic purpura-hemolytic uremic syndrome)
Bone marrow suppression
Teratogenic, mutagenic, and oncogenic potential
4 black box warnings of Ganciclovir and Valganciclovir
Hematological toxicities
Carcinogenic and teratogenic activity
Aspermatogenesis
Appropriate oral and IV use only (ganciclovir only)
Hematological toxicities, Carcinogenic and teratogenic activity, Aspermatogenesis, and Appropriate oral and IV use only are black box warnings for these
Ganciclovir and Valganciclovir
Bone marrow suppression and teratogenic, mutagenic, and oncogenic potential are characteristic adverse effects of these
Ganciclovir and Valganciclovir
Aspermatogenesis is one of the black box warnings for these drugs
Ganciclovir and Valganciclovir
Acyclovir, Cidofovir, Foscarnet, Ganciclovir, Penciclovir, Famciclovir, and Trifluridine are drugs used for these infections
Herpes and cytomegaloinfections (DNA viruses)
Zanamivir, Oseltamivir, Amantadine, Rimantadine and Ribavirin are drugs used for these infections
Respiratory viral infections (RNA viruses)
MOA of Zanamivir and Oseltamivir
Inhibit influenza A and B virus neuraminidase
What is the function of viral neuraminidase?
Allows the virus to break free from the host cell to infect other cells
Does this describe Zanamivir or Peramivir:
Administered by inhalation or by nasal spray
Adverse effects similar to the symptoms of influenza
For patients >7 years
Can be used for prophylaxis
Zanamivir
Does this describe Zanamivir or Peramivir:
Administered IV, single dose over 15-30 minutes
For patients >2 years
Data for influenza B is limited
Not for prophylaxis
Peramivir
Oseltamivir (Tamiflu) is a prodrug that is activated by these
Esterases in GI tract or liver
Oral prodrug for RNA viruses that is activated by esterases in GI tract of liver
Oseltamivir (Tamiflu)
Drug with low incidence of self-injury, hallucinations and delirium reports, especially in children
Is under consideration for black box warning by FDA
Oseltamivir (Tamiflu)
Oseltamivir (Tamiflu) is under consideration for black box warning by FDA for these side effects
Low incidence of self-injury, hallucinations and delirium reports, especially in children
MOA of Ribavirin
Converted to monophosphate, diphosphate, and triphosphate forms
Monophosphate form inhibits guanosine triphosphate synthesis to block viral mRNA processing and influenza virus RNA pol
2 routes of administration of Ribavirin
Oral or IV
Drug for RNA viruses whose monophosphate form inhibits guanosine triphosphate synthesis to block viral mRNA processing and influenza virus RNA pol
Ribavirin
Hemolytic anemia risk in Ribavirin is increased when used with this
Interferon alfa
Ribavirin is contraindicated in these two groups
In pregnant women and male partners of pregnant women (due to mutagenic, teratogenic, and embryotoxic)
In patients with sickle cell anemia (high risk of anemia)
Dose dependent hemolytic anemia and mutagenic, teratogenic, and embryotoxic describes this drug for RNA viruses
Ribavirin
3 black box warnings of Ribavirin
Not recommended for monotherapy
Hemolytic anemia
Teratogenic and embryocidal (contraindicated in pregnant women, women who might be pregnant, and their male partners; two forms of birth control recommended for up to 6 months following treatment)
Hemolytic anemia is a characteristic adverse effect of this drug
Ribavirin
Interferon alfa + Ribavirin is used for these infections
Hep C viral infections
3 drugs that make the combo drug Vosevi
Sofosbuvir
Velpatasvir
Voxilaprevir
Component of the combo drug Vosevi that Prevents Hep C viral replication by inhibiting NS5B RNA polymerase
Sofosbuvir
Sofosbuvir prevents Hep C viral replication by doing this
Inhibiting NS5B RNA polymerase
Component of the combo drug Vosevi that Prevents Hep C viral replication by inhibiting NS5A protein essential for viral function
Velpatasvir
Component of the combo drug Vosevi that Prevents Hep C viral replication by blocking proteolytic activity of NS3/4A protease, needed for posttranslational processing of viral component proteins
Voxilaprevir
Velpatasvir prevents Hep C viral replication by doing this
Inhibiting NS5A protein essential for viral function
Voxilaprevir prevents Hep C viral replication by doing this
Blocking proteolytic activity of NS3/4A protease, needed for posttranslational processing of viral component proteins
Common adverse effects of Hep C drugs
Headache, fatigue, nausea, and diarrhea
Drug where hypertension is a typical sign of emerging nephrotoxicity and should be carefully monitored
Foscarnet
