Chapter 7 anti infective - antiviral drugs for DNA and RNA viruses + hepatitis Flashcards
acyclovir (zovirax)
valacyclovir (valtrex)
dna / rna
- triphosphate analog (meds metabolized by thymidine kinase and others to this)
- it inhibits DNA polymerase and incorporates into viral DNA
- binds ot viral thymidine kinase more readily than mammalian thymidine kinase
use
* herpes simplex I and II
* varicella zoster virus
resistance
* produce abnormal thymidine kinase or DNA polymerase
effects
* skin burning
* crystalline nephroathy if infused rapidly
* nausea, headache
IV/PO
valacyclovir better oral absorption
penciclovir (Denavir)
dna/rna
- triphosphate analog (meds metabolized by thymidine kinase and others to this)
- it inhibits DNA polymerase and incorporates into viral DNA
- binds ot viral thymidine kinase more readily than mammalian thymidine kinase
clinical use
* topical HSV (coldsores)
famciclovir (Famvir)
dna/rna
phosphoyrlated by viral thymidine kinase to penciclovir “triphosphate”
* inhibits DNA polymerase in HSV (herpes simplex virus)
inidcation
* shortens duration of herpes zoster and genital herpes
effects
* minimal toxicity
* headache
decrease dose w/ renal dysfunction
PO
ganciclovir (cytovene)
valganciclovir (valcyte)
dna/rna
- triphosphate analog (meds metabolized by thymidine kinase and others to this)
- it inhibits DNA polymerase and incorporates into viral DNA
- inside CMV-infected mammalian cells
indication
* cytomegalovirus retinitis
* CMV infections in immunocompromised hosts
resistance
* some resistant strains lack thymidine kinase; drug cannot be activated then
effects
* granulocytopenia (reduced number of blood granulocytes, namely neutrophils, eosinophils, and basophils)
* anemia
* thrombocytopenia (platelets)
* renal dysfunction
IV/PO
Do not coadminister zidovudine [HIV antiviral] (granulocytopenia) or imipenem-cilastatin [antibiotic] (seizures)
foscarnet (foscavir)
dna/rna
- analog of pyrophosphate (normal chemical that everyone has in the body. It is important for the healthy function of connective tissues such as bones, cartilage, and joints)
- competes for pyrophosphate site in viral but not human
- disrupts DNA polymerase and rever transcriptase
indication
* cytomegalovirus retinitis (viral infection of the retina of the eye resulting in inflammation)
* Acyclovir resistant HSV infection
resistance
* does not require phosphorylation
* this durg active against thymidine kinase-deficient strains
effects
* renal toxicity (frequent)
* sz
* hypocalcemia
* fever
* anemia
* diarrhea
CSF penetration variable
Note
* Deposited in bone and teeth
* Hydrate pt during therapy to protect kidneys
amantadine (symmeterl)
dna/rna
- prevenet virsu from entering suceptible cells
indication
* tx/prophylaxis of influenza A in elderly and pt w/ cardiopulmonary dysfunction
effect
* depression
* CNS toxicity
* CHF
* orthostatic hyptoension
* urinary retention
Excreted unmetabolized
Rimantadine (flumandine)
dna/rna
analog of amatadine uncertain mech but appears to inhibit viral uncoating
indication:
* tx/prophylaxis of influenza A in elderly and pt w/ cardiopulmonary dysfunction
* approved for prophylaxis in children
effects
* fewer CNS side effects
* still risk of seizures
Prolonged elimination w/ renal or hepatic dysfunction
Ribavirin (viraozle)
dna/rna
- unknown mech
indication
* hospitalized children w/ RSV or respiratory syncytial virus who are at risk for cardopulmonary complications
Infants are most severely affected by RSV. Signs and symptoms of severe RSV infection in infants include:
Short, shallow and rapid breathing Struggling to breathe — chest muscles and skin pull inward with each breath Cough Poor feeding Unusual tiredness (lethargy) Irritability
effects
* decreased pulmonary fx
* teratogenic in animal studies (substances that cause congenital disorders in a developing embryo or fetus.)
aerosol administration — absorbed systemically
zanamivir (relenza)
dna/rna
- inihibts influenza virus neuraminidiase (breaks open infected cells!)
indication
* influenza virus infection
effect
* minimal toxicity
inhalation
oseltamivir (Tamiflu)
dna/rna
- analog of adenosine monophosphate (one of the components of RNA and also the organic component of the energy-carrying molecule ATP. In certain vital metabolic processes, AMP combines with inorganic phosphate to form ADP (adenosine diphosphate) and then ATP)
indication
* influenza
adefovir (hepsera)
telbivudine (tyzeka)
entecavir (baraclude)
tenofovir (Viread)
laivudine (epivir)
hepatitis b agents
- nucleoside to control (not cure) chronic hep b
- Hep b infection may be exacerbated when drug is discontinued
- HIV testing should be offered to all candidates prior to starting to avoid inducing HIV drug resistance in infected patients
effects
* renal dysfunction + drug induced nephrotoxicity
* lactic acidosis
* liver damage
peginterferon
alfa 2a (pegasys)
hepatitis b
induces immune acitivty against hepatitis b
sofosbuvir (Sovaldi)
dasabuvir
chronic hepatitis C - agents used in combination
nucleotide analog HCV NS5B polymerase inhibitor (central role in viral genome replication and transcription.)
simeprevir (olysio)
paritaprevir
grazoprevir
chronic hepatitis C - agents used in combination
- HCV NS3/4A protease (viral genome encodes a polyprotein with an embedded viral protease that cleaves the polyprotein at several specific sites to generate mature viral proteins) inhibiors
- often used in combination products
Ledipasvir
Ombitasvir
Eibasvir
Daclatasvir (daklinza)
HCV NS5A protease inhibitors
* (viral genome encodes a polyprotein with an embedded viral protease that cleaves the polyprotein at several specific sites to generate mature viral proteins)
* Ledipasvir, ombitasvir, and elbasvir approved in combination with other hepatitis c drugs and not approved as single agents
