EXAM #4: ANTIVIRAL DRUGS Flashcards
What type of genome do the Herpesviruses contain?
dsDNA
What is being targeted in some way by all the drugs that treat Herpesviruses?
viral DNA polymerase
What stage of disease caused by the Herpesviruses is targeted by antiviral drugs?
Lytic stage i.e. productive phase of infection ONLY
What type of drug is Acyclovir?
Nucleoside analog
What is the MOA of Acyclovir?
1) Competitive inhibitor of viral DNA polymerase
2) Causes chain termination via incorportation into the viral genome
What is required for the activation of Acyclovir?
Phosphorylation by viral thymidine kinase
How causes resistance with Acyclovir?
Mutation of thymidine kinase
What are the clinical indications for ORAL Acyclovir?
1) Genital herpes (HSV-2)
2) Varicella zoster (VZV)
What are the clinical indications for IV Acyclovir?
1) Severe/ disseminated disease
2) Neonate infections
3) HSV encephalitis
4) VZV in immunocompromised patients
What major toxicity is associated with Acyclovir?
Nephrotoxicity
This is combated partly by proper hydration prior to administration
What is Valacyclovir?
Acyclovir prodrug with a Valine moiety
What is the utility of Valacyclovir?
Increased oral bioavilibility compared to Acyclovir
What are the clinical indications for Valacyclovir?
1) Genital herpes (HSV-2)
2) Varicella
3) Oral herpes (HSV-1)
What is unique about Foscarnet compared to Acyclovir?
Does NOT require phosphorylation by Thymidine Kinase
What are the indications for Foscarnet?
1) HSV and VZV infections that are RESISTANT to Acyclovir
2) CMV Retinitis
3) CMV Colitis
4) CMV Esophagitis
*Note that it is ONLY given IV
What is the major toxicity associated with Foscarnet?
1) Renal impairment/ nephrotoxicity
2) Changes in blood chemistry
What type of drug is Ganciclovir?
Acyclic guanosine analog
What is the MOA of Ganciclovir?
1) Phosphorylation by CMV viral kinase
2) Competitive inhibition of viral DNA polymerase
3) Chain termination upon incorportion
How does Ganciclovir compare to Acyclovir?
B/c it is phosphorylated by a CMV enzyme, it is much more effective in treating CMV infections
What is the mechanism of Ganciclovir resistance?
Mutation of the CMV viral kinase (UL97)
What are the clinical indications for Ganciclovir?
1) CMV-anything
2) Prevention of CMV disease in transplant recipients
How is Ganciclovir administered for CMV retinitis?
Intraocular
What are the major adverse effects associated with Ganciclovir?
1) Myelosuppression
2) CNS toxicity
3) Injection site reaction to IV
What is Valganciclovir?
Prodrug of Ganciclovir
*Higher oral bioavalibility
What are the clinical indications for Valganciclovir?
1) CMV Retinitis
2) Prophylaxis in transplant recipients
What type of drug is Trifluridine?
Fluorinated pyrimidine nucleoside
What is the MOA of Trifluridine?
1) Phosphorylation by cellular enzymes
2) Competitive inhibition of thymidine incorporation into DNA
What are the clinical indications for Trifluridine?
HSV-1 and HSV-2 induced:
- Keratoconjunctitivitis
- Keratitis
What type of virus is the Influenza virus?
Segmented ssRNA
What family does the Influenza virus belong to?
Orthomyxovirus
What is the most common complication of the seasonal flu?
Pneumonia
What type of drug is Oseltamivir?
Sialic acid analog
*Prodrug that is metabolized to active form by liver
What is the MOA of Oseltamivir?
Neurominidase inhibitor
*Note that it is taken ORALLY
What causes resistance to Oseltamivir?
Point mutations in hemagglutinin or neurominidase genes
What are the clinical indications for Oseltamivir?
1) Influenza A or B
- Within 48 hours of symptom onset
- Kids 1+ years
2) Prophylaxis for influenza
What is the major advese effect associated with Oseltamivir?
Neuropsychiatric symptoms
What type of drug is Zanamivir?
Sialic acid analog
What is the MOA of Zanamivir?
Neurominidase inhibitor i.e. same as Oseltamivir
*Note that it is INHALED
How is Zanamivir administered?
Inhalation
What are the clinical indications for Zanamivir?
Influenza A or B infection EXCEPT 7+ years old
What is the major adverse effect associated with Zanamivir?
Bronchospasm and decreased pulmonary function
When is Zanamivir contraindicated?
Patients with pre-existing pulmonary disease
What class of drug is Peramivir?
Neuroaminidase inhibitor
*Note that it is given IV
How is Peramivir administered?
IV
What are the clinical indications for Peramivir?
Acute uncomplicated influenza that onset in less than 48 hours
What are the major toxicities associated with Peramivir?
1) Steven Johnson’s Syndrome
2) Neuropsychiatric syndromes
What is the MOA of Amantidine and Rimantadine?
Inhibition of the Influenza A M2 protein, an ion channel protein required for nucleocapsid release
What is the mechanism of resistance to Amantidine and Rimantadine?
Mutations in Influenza A M2 protein
What are the clinical indications for Amantadine and Rimantadine?
Influenza A (48 hour stipulation)
What type of virus is RSV?
Eneveloped ssRNA virus
What viral family does RSV fall in?
Paramyxovirus
What is the difference between the disease caused by RSV in different age groups?
Under 1 y/o= bronchiolitis and pneumonia
Kids/adults= cold
Elderly= severe respiratory infection
What type of drug is Ribavirin?
Guanosine analog
What is the MOA of Ribavirin?
1) Phosphorylation by adenosine kinase
2) Interferes with GTP/ mRNA capping
How is Ribavirin administered?
Aerosol for RSV
What are the clinical indications for Ribavirin?
1) RSV
2) Hepatitis C (+ pegylated INF-a)
What are the major adverse effect associated with Ribavirin?
Hemolytic anemia
What are the contraindications for Ribavirin?
1) Pregnancy
2) Anemia
3) Ischemic vascular disease
4) Severe renal disease
What are the major MOAs of the direct acting antivirals used to treat Hepatitis C?
1) Protease inhibitors (prevent cleavage of immature virions into mature)
2) RNA Polymerase Inhibitors (genome replication)
3) HCV NS5A inhibitors (virion assembly)
What are the two DAA Protease Inhibitors?
1) Partaprevir
2) Simeprevir
What is the result of protease inhibition in HCV infection?
Inhibits the enzyme necessary for cleavage of immature viral polypeptides into mature proteins needed for infection
What drugs are the HCV RNA polymerase inhibitors?
1) Sofosbuvir
2) Desabuvir
What drugs are the HCV NS5A inhibitors?
1) Ledipasvir
2) Ombitasvir
How is Partaprevir commonly administered?
Orally, in combination with ombitasvir and ritonavir
What leads to Partaprevir resistance?
NS3 mutations i.e. protease mutations
How is Simeprevir commonly administered?
Orally in conjunction with Sofosbuvir or ribavirin + peylated INF-a
What causes Simeprevir resistance?
Genetic polymorphism in NS3 that hast to be screened for prior to use of the drug
How is Ledipasvir commonly given?
Orally with Sofosbuvir
How is Ombitasvir commonly given?
Orally with Paritaprevir and ritonavir
What is the MOA of Sofosbuvir?
Nucleotide analog prodrug
What is the MOA of Desaburive?
Non-nucleoside analog that inhibits HCV RNA-RNA polymerase
What should you avoid giving Sofosbuvir with?
Potent inducers of p-glycoprotein e.g. Rifampin
How is Desaburive commonly administered?
Orally with Ombitasvir, Partiaprevir, and Ritonavir
