Lecture 23.1: Antivirals Flashcards
What is the Mechanism of Action for Acyclovir?
- Inhibition of Viral DNA Replication
- Prodrug –> Acyclovir Triphosphate
- Viral Kinases = 1 Phos & Human Kinases = 2 & 3 Phos
What is the spectrum of Activity for Acyclovir?
- Herpes Simplex Virus 1 & 2 [HSV 1 & 2]
- Varicella Zoster Virus [VZV]
- HSV-1 > HSV-2 > VZV > EBV»_space; CMV
What is the Pharmacokinetics of Acyclovir?
- Very BAD orally [10-20%]; food dont help; Dose Dependent
- Widely distributed in body; correlates with Body H20
- Eliminated Renally by Glom and Tub = Renal Adjustments
- Removed During Hemodialysis
What are some of the clinical indications for Acyclovir?
- HSV Primary, Recurrent, Chronic
- HSV Encephalitis 10mg/kg IV [IV gets to brain]
- Muscocutaneous Disease 5mg/kg IV
- Shingles
- Severe VZV 10mg/kg IV
Dose adjust in obese people
What are some of the Adverse Effects for Acyclovir?
- Nausea, Vomiting Diarrhea [Very Common]
- Nephrotoxicity [Crystals]
- Neurotoxicity [Reversible]
- Thrombophlebitis
What is the Mechanism of Action for Valacyclovir?
- L-Valyl ester PRODRUG of Acyclovir
- Inhibition of Viral DNA Replication
- Prodrug –> Acyclovir Triphosphate
- Viral Kinases = 1 Phos & Human Kinases = 2 & 3 Phos
What is the Spectrum of Activity for Valacycolvir?
- HSV-1 & 2
- VZV
- HSV-1 > HSV-2 > VZV > EBV»_space;CMV
What is the Pharmacokinetics for Valacyclovir?
- Rapidly absorbed and completely converted to Acyclovir by Intestinal and hepatic metabolism = orally
- Bioavailability GREATER
- Removed via hemodialysis
ALL BECAUSE OF THE L-VALYL ESTER
What are hte clinical indications for Valacyclovir?
- Core Sores
- VZV [preferred over acyclovir]
- HSV Primary, Recurrent, Chronic
Adjust for renal issues
What are the Adverse Effects for Valacyclovir?
- Nausea, Vomiting Diarrhea [Very Common]
- Nephrotoxicity [Crystals]
- Neurotoxicity [Reversible]
- Thrombophlebitis
same as acyclovir
What is the Mechanism of action for Famciclovir?
- PRODRUG of Penciclovir –> Oral Fam rapidly converts to Pen
- Pen get Phos by viral kinase to Pen Mono –> cellular kinase to Pen Tri = Inhibition of Viral Replication
What is the Spectrum of Activity for Famciclovir?
- HSV-1
- HSV-2
- VZV
same as Acyclovir
What is the Pharmacokinetics for Famciclovir?
- Well Absorbed Orally; Food slows absorption [no need for food]
- Half Life 2.5h
- ~90% unchagned in urine
- Dose reduction in renal issues
What are some of the Clinical indications for Famciclovir?
- Cold Sore 1.5g once
- HSV Primary 250mg PO TID, Recurrent 125mg PO BID, Suppression 250 PO BID
- VZV 500mg PO TID
- HIV 500mg PO BID
What are som eof the Adverse Effects for Famciclovir?
- Well Tolerated
- Headache, Nausea, Vomiting, Diarrhea
DI: Probenecid decreases renal clearence
What is the Mechanism of Action for Ganciclovir?
- HSV & VZV: Viral Thymidine Kinase phos it
- CMV: CMV-encoded protein kinase phos it once –> then cellular for 2 & 3 Phos
- Ganciclovir tri INHIBITS viral DNA poly = inhibits viral replication
CMV Protein = UL97 gene
Resistance = UL97 Gene mutations
What is the Spectrum of Activity for Ganciclovir?
- HSV-1 & HSV-2
- VZV
- CMV
- EBV
What is the Pharmacokinetics for Ganciclovir?
- Low Oral Bioavailability
- Able to get into the EYE
- > 90% unchanged renally = DOSE adjust
- 50% removed during hemo
What is the Clinical indications for Ganciclovir?
- CMV Retinitis
What are some of the adverse effects for Ganciclovir?/
- Bone Marrow Suppression [reversible]
- Neutropenia is ~40%; can treat that with G-CSF
What is the mechanism of action for Valganciclovir?
- L-Valyl Ester of Ganciclovir = rapidly converted to Gan by intestinal and hepatic esterases
- HSV & VZV: Viral Thymidine Kinase phos it
- CMV: CMV-encoded protein kinase phos it once –> then cellular for 2 & 3 Phos
- Ganciclovir tri INHIBITS viral DNA poly = inhibits viral replication
What is the Spectrum of Activity for Valganciclovir?
- HSV-1 & HSV-2
- VZV
- CMV
- EBV
What is the Pharmacokinetics for Valganciclovir?
- Increased bioavailability of GAN when given as Val-GAN
- Major route of elim = Renal; Adjust Dose
- Hemo decerases GAN conc.
What are the indications for Valganciclovir?
- CMV Retinitis
What are the adverse effects of Valganciclovir?
- Bone Marrow Suppression [reversible]
- Neutropenia is ~40%; can treat that with G-CSF
- Hemtologic Toxicity
What is the mechanism of action for Letermovir?
- Inhibits the pUL56 subunit of the viral terminase complex of CMV
- Inhibition of CMV replication and prevention of CMV infections
What is the spectrum og activity for Letermovir>
- CMV
What is the pharmacokinetics for Letermovir?
- Well absorption
- Half-life 12h
- IV has hydroxypropyl betadex
- NO dosage adjustment for CrCl > 10; if CrCl < 50 monitor
What are some of the indications for Leteomvir?
- Prophylaxis of CMV; 480 mg IV or PO daily [1/2 this with cyclosporine]
What are some of the adverse effects for Leteomvir?
- Nausea, Vomiting, Diarrhea, cough, edema, fatigue, Ab pain
What are som eof the Drug Interactions for Leteromvir?
- Its a 3A4 Inhibitor
- Contraindicated with Pita/Simvastatin when taken with Cyclosporine
- DO NOT use with Riampin
What is the MEchansim of action for Foscarnet?
- Directly inhibits viral DNA Polymerase
- Does NOT require phosphorylation by Thymidine kinase or other kinases
NOT a PRODRUG
What is the spectrum of activity for Foscarnet?
- HSV-1 & HSV-2 [even ACV resistant strains]
- VZV [even ACV resistant strains]
- CMV [even GAN resistant strains]
What is the pharmacokinetics ofr Foscarnet?
- ONLY IV
- Bone sequesters 10-20% of a dose [kicking out Phos or Ca]
- > 80% unchanged renally - Adjust dose
What are some of the clinicla indications for Forcasnet?
- CMV Retinitis
- HSV & VZV resistant
What are some of the sdbverse effects for Foscarnet?
- Nephrotoxicity - dose limiting [WILL need to to rehydrate]
- Metabolic
- Nausea, Vomiting, Headache, Tremor, Seizures…
Very Toxic = why its a last line
What is the Mechanism of action for Amantadine & Rimantadine?
- Inhibits ion channels of the M2 protein = inhibition of uncoating of viral RNA within the host cell
What is the Spectrum of Activity for Amantadine & Rimantadine?
- Flu A
- NOT recommended for treatment OR prophylaxis of Flu A because of the high resistance
What is the pharmacokinetics for Amantadine & Rimantadine?
- Well Absorbed
- Aman: Half life 12-18h; Unchanged in the Urine [Adjust dose in renal issues]
- Riman: Half life 24-26h; Reduce dose by 50%
What are some of the clincial indicaitons for Amantadine & Rimantadine?
- Flu A
What are the adverse effects for Amantadine & Rimantadine?
- CNS - more common with Aman
- GI
What are the Neuraminidase Inhibitors that are used?
- Zanamivir, Oseltamivir, Peramivir
What is the Mechanism of Action for the Neuraminidase Inhibitors?
- prevents the virus from leaving the cell = decreased spread
- Neuraminidase helps viruses break through the cell wall and increase replication = increase spread
What is the spectrum of activity for the Neuraminidase Inhibitors?>
- Flu A & B
What are the Pharmacokinetics for Oseltamivir?
- Rapidly absorbed
- Half Life 22h when CrCl < 30 = Dose adjust
- NO DOSE ADJUST for morbid obese people
What are the Pharmacokinetics for Zanamivir?
- Inhaled
- Half Life 2.8h
- NO real drug interactions
What are the clinical indications for Zanamivir?
- Treatment of Flu > 7yo
- Prophylaxis of Flu > 5yo
- DO NOT give live vaccine until 48h after stopping Zanamivir
- DO NOT give Zanamivir until 2w after live vaccine
- DO NOT GIVE in asthma or COPD
** Symptomatic< 2days**
What are the Clinical indications for Oseltamivir?
- Treatment of Flu > 2w old
- Prophylaxis of Flu > 1yo
- DO NOT give live vaccine within 2w before or 48h after starting Oseltamivir
- CAN give inactive vaccine tho
