Antivirals (incomplete) Flashcards
what are the categories of antivirals
Respiratory virus infection therapy
anti-herpesviruses
Anti-hepatoviruses
nucleoside analogs
NS5A and plymerase inhibitors
what are respiratory virus infection therapy drugs
Oseltamivir
Amantadine
what are anti-herpesviruses medication
acyclovir
valacyclovir
famciclovir
foscarnet
what are antihepatoviruse medications
interferons
what are nucleoside analogs
ribavirin
lamivudine
tenofovir
entecavir
what are NS5A and Polymerase inhibitors
ledipasvir
sofosbuvir
what are strategies for controling viral infections
avoiding exposure
control of vectors
immunization
other ways to activate host resistance
what are respitoary virus infections
influena A and B
SARS-CoV02 antivirals - paxlovid
what are hepatic viral infections
hepatitis B and C virus
what are herpes and cytomegalovirus infections
HSV
VZV
CMV
- all cause latent infections
what is Paxlovid used for
SARS-CoV02 - aka COVID
What is oseltamivir
neuraminidase inhibitor used for treating the flu
MOA: inhibitor or neurominadase
AKA tamiflu
used for inflenza A an dB - administered within 24048 hours of symptoms, decreases viral load and used for prophylaxis
what is neurominadase
enzyme that is essential for cleaving the virus from the host cell and allowing spread of virus from cell to cell
how is oseltamivir hydrolyzed
by the liver in its active form - active orally as a prodrug
what are the pharmacokinetics and ADRs of Oseltamivir
PO - dose adjustment in renal impairment
GI side effects: m/c N/V - recommend taking with food
What are influenza treatment recommendations
CDC recommends treating patients who are at higher risk for influenza complications:
< 2yo or > 65 yo, comorbidities or immunosuppressed, pregnant or post-partum, morbidly obese and nursing homes/other chronic-care facilities
what drug is currently ineffective in treating influenza because of rate of resistance
amantadine
What is Acyclovir
antiviral against herpres virus
MOA: guanosine analogs, inhition of transcription- activated by viral thymidine kinase (TK) - activated in infected cells so few adverse effects
acycloGTP inhibits viral DNA polymerase by chain termination
What is the spectrum of activity for acyclovir
HSV1 and 2 - not effective against latent virus
VZV - cause of chickenpox, zoster
NO activity against CMV
Where is acyclovir metabolised
renal metabolism; requires dose adjustment for renal impairment
what are the AE of acyclovir
generally well tolerated. more SE associated with IV admin.
mild GI symptoms (N/V)
Nephrotoxicity - IV acyclovir can crystallize the renal tubules causing renal dysfunction, minimize risk by hydration and adjusting dose based on GFR
Neurotoxicity - lethargy, confusion, delirium - IV.
what is obstructive crystaliline nephropathy
crystalization in the renal tubules causing renal dysfunction - SE of IV acyclovir
what was created to overcome poor bioavailability of acyclovir
valavylovir (prodrug)
what is valacylovir
aka valtrex
hydrolyzed by first pass enzymes in intestine and liver - 99% converstion rate to acyclovir
5x more expensive
same spectrum of activity and ADRS - HA more common
What is Famciclovir
used for herpes virus
overcomes poor bioavailability of penvivlovir
metabolized to penciclovir which requires phosphyrlation by viral thymidine kinase in infected cells to become active
it selectively inhbitis viral DNA polymerase by chain termination
same spectrum and ADRs of acyclovir
what causes acyclovir resistance
mutation or loss of viral thymidine kinase (TK-) which is the first step in phosphylation of acyclovir
What is foscarnet
used for herpesviruses
inorganic pyrophosphate analog
directly inhibits DNA. plymerase (does NOT require activation of viral kinase)
what is foscarnet used for
treatement of immunocompromised patients with cytomegalovirus (CMV) retinitis and mucocutaneous acyclovir-resistant HSV and VZV infections
IV only
what are the foscarnet toxicities
renal dose adjustment
GI effects: N/V/D
may cause ELECTROLYTE ABNORMALITIES: hypokalemia, hypocalcemia, hypomagnesemia, hypophosphatemia
Nephrotoxicity (reversible)
what is Haptatis B
can be found in all body fluids and is transmitted by percutaneous or mucosal contact with infectious body fluids.
what are high risk transmission sources for HBV
sex with infected parner
IVDU - sharing needles
birth to an infected mother
contact with blood or open sores of an infected person
needle stick or sharp instrument exposure
sharing items such as razors, toothbrush with infected person
what are the three types of chronic HBV
latent
chronic liver disease
cirrhosis
what is the serologic responses to acute HBV infection
+HBsAg and IgM anti-HBc
what is the serologic responses to chronic HBV infection
+HBsAg and IgG anti-HBc
What are interferons
HBV and HCV treatment
MOA: IFN alpha2b and alpha2a: host cytokines (proteins) with complex viral, immuno-modulatory and antiproliferative activites
thoughts to induce gene transcription of host cell enzymes that inhibit viral RNA; increases phargocytic activity of macrophages; increase cytotoxicity of lymphocytes for target cells
what are the AE of interferons
flu-like symptoms shortly after admin (IV/SQ)
mood disorders, depression, somnolence, confusion, profound fatigue, weight loss, seizure, myelosuppression, rash, cough, myalgia, alopecia, tinnitus, reversible hearing loss, retinopathy, pneumonitis, cardiotoxicity, autoimmune reaction
discontinued in US
What are the goals of HBV antiviral therapy
suppression of HBV DNA levels
seroconversion of HBeAg- positive to HBeAg-negative
loss of HBsAg detection
decrease risk of liver damage
What is Lamivudine
antiviral against chronic hep B
cytosine analog works to inhibit viral DNA synthesis by inhibiting HBV DNA polymerase (also works against HIV reverse transcriptase)
HIV testing prior to treatment initiation
growing resistance
what are the pharmacokinetics of Lamivudine
good Po absoprtion
dose-adjustment in renal impairement (if CrCl <50)
what are the AE of Lamivudine
generally well tolerated
HA and dizziness may occur
may cause pancreatitis
-rare: lactic acidosis and severe hepatomegaoly
what is entecavir
phosphorylated to guanosine triphosphate and competes as substrate for HBV DNA polymerase thereby inhbiting the enzyme
not preferreed to lamivudine -resistant strains (tenofovir preferred)
weakly active against HIV
what is the pharmacokinetics and ADR to entecavir
dose- adjustment in renal impairment (if CrCl<50)
AE: may vause increase ALT levels, mild GI upset, mild hyperglycemia, HA
RARE: lactic acidosis and severe hepatomegaly
What is the MOA of tenofovir
inhibit replication of HBV by inhibiting HBV DNA plymerase (also works against HIV reverse transcriptase)
HIV testing prior to treatment initiation
may be used in patients who had prior treatment of developed drug resistance - preferred if lamivudine- resistance
what is the medication of choice for lamivudine resistance
tanofovir
what are pharmacokinetics for tenofovir
2 formulations available: tenofovir disoproxil fumarate and tenofovir alafenamide (associated with less renal and bone toxicity)
dose adjustment in renal impairment (if CrCl<50)
what are the AE of tenofovir
Gi effects
rash
hypercholesterolemia
decreased bone mineral density
what is the box warning for HBV infection medcations
post-treatment exacerbation of hepatitis
