Flashcards in Pharm antivirals Deck (59):
are antiretrovirals virustatic or virucidal?
what are the five major classes of antiretroviral medications?
1. nucleoside reverse transcriptase inhibitors (NRTI's) and nucleotide RTI's (tenofovir))
2. non-nucleoside reverse transcriptase inhibitors (NNRTI's)
3. protease inhibitors
4. entry inhibitors
5. integrase inhibitors
what are the NRTI's?
zidovudine, lemivudine, emtricitabine, abacavir, tenofovir
what is the mechanism of NRTI's?
viral DNA chain termination via inhibition of viral reverse transcriptase. Tenofovir is a nucleoTide, the others are nucleosides and need to be phosphorylated to be active
what does zidovudine mimic? lemivudine? emtricitabine? abacavir? tenofovir?
zidovudine = thymidine.
lemivudine = cytosine.
emtricitabine = cytosine.
abacavir = guanine.
tenofovir = adenosine.
which NRTIs can also be used for HBV?
lamivudine, emtricitabine, tenofovir
zidovudine side effects
granulocytopenia, anemia, nausea, vomiting
lamivudine and emtricitabine side effects
headache, nausea, vomiting, rash, neutropenia, pancreatitis (NOT SERIOUS)
abacavir side effects
hypersensitivity reaction - associated with HLA-B5701 mutation
tenofovir side effects
what are the NNRTI's?
efavirenz, nevirapine, rilpivirine, etravirine
inhibit reverse transcriptase through direct enzyme inhibition (do not require phosphorylation to be active) - NONCOMPETITIVE!
what are NNRTI's and NRTI's used to treat?
NNRTIs side effects
rash and hepatotoxicity - efavirenz also has vivid dreams and CNS symptoms (stop when ax wielding elves appear in dream!), teratogenic, P450 metabolism
what are the HIV protease inhibitors?
-navir (NA VIRUS! NO NEW VIRUS!)
ritonavir, fosamprenavir, atazanavir, darunavir, lopinavir
HIV protease inhibitors (-navir) mechanism
prevent cleavage of protein chain into functional subunits
which HIV protease inhibitor has "good" drug interactions? how?
ritonavir "boosts" other drug concentrations by inhibiting cytochrome P-450
HIV protease inhibitors (-navir) side effects
GI intolerance (n/v, diarrhea), metabolic toxicities!! (dyslipidemia, hyperglycemia, lipodystrophy)
what are the 3 steps of HIV attachment and fusion?
1. HIV gp120 binds CD4 molecule
2. conformational change occurs in gp120 and then binds the coreceptor CCR5 or CXCR4
3. further conformational changes in gp120 expose gp41 protein which mediates fusion of the viral and cell membranes
what are the HIV entry inhibitors?
enfuvitide and maraviroc
binds gp41, inhibiting viral entry
enfuvirtide side effects
skin reaction at injection sites
binds CCR-5 on surface of Tcells/monocytes, inhibiting interaction with gp120 - TARGET IS ON HOST CELL!
maraviroc side effects
hepatotoxicity (rare) - cough, fever, URI, rash, musculoskeletal symptoms, ab pain, dizziness
what are the integrase inhibitors?
-tegravir (GRAB the HIV before it integrates!)
raltegravir, elvitegravir, dolutegravir
integrase inhibitors mechanism
inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
integrase inhibitors (-tegravir) side effects
myopathy and rhabdo - headache, neausea, diarrhea, pyrexia
what are the common HAART regimen combinations?
3 active agents together; typically 2 NRTIs + integrase inhibitor, PI, or NNRTI
what is commonly prescribed as initial therapy in HIV? disadvantage of this class?
NNRTI based regimen because of advantage of lower pill burden (preserve PI for later use). disadvantage is only one single mutation is needed to confer resistance and cross resistance develops for entire class
what is the preferred NNRTI? exception?
efavirenz - exception pregnancy
hepatitis C virus virology
ssRNA virus belonging to Flavivirdae - most common serotypes 1a and 1b
what are the old drug classes used for treating HCV?
ribavirin (nucleoside analog - high risk of anemia) and interferon (indirect mechanism - side effects and poor efficacy)
what are the newer drug therapies used for HCV?
nucleoside/nucleotide NS5B polymerase inhibitors, NS5A inhibitors, NS3/4A protease inhibitors
what are the NS5B polymerase inhibitors?
sofosbuvir and partaprevir
what are the NS5B polymerase inhibitors (sofosbuvir and partaprevir) mechanism?
compete with viral nucleotide to cause chain termination - active across all HCV genotypes
NS5B polymerase inhibitors (sofosbuvir and partaprevir) side effects
relatively safe - fatigue, headache, GI, anemia
what are the NS5A inhibitors?
ledipasvir, daciatasvir, ombitasvir
NS5A inhibitors mechanism
inhibits HCB NS5A viral phophoprotein required for viral replication
NS5A side effects
relatively safe - fatigue, headache, GI
what are the NS3/4A protease inhibitors?
simeprevir, boceprevir, telaprevir
NS3/4A protease inhibitors mechanism
prevent viral maturation through the inhibition of protein synthesis
NS3/4A side effects
differ slightly depending upon the agent: anemia, rash, itching, GI, drug interactions
approach to HVC therapy
combination therapy! esp. simeprevir and sofosbuvir
herpes virus virology and life cycle
dsDNA virus - clinical disease appears a few days after initial establishment of infection - viral particles taken up by nerves and transported to nerve cell bodies in dorsal root ganglia of spinal cord where reactivation occurs
what drugs are used to treat HSV?
guanosine nucleoside antivirals:
acyclovir, penciclovir, valacyclorvir, famciclovir
guanosince nucleoside antivirals (for HSV) mechanism
valacyclovir prodrug fro acyclovir; famciclovir prodrug of penciclovir. after phosphorylation by cellular enzymes, interferes with viral DNA synthesis by competing with DNA analogues to cause viral DNA chain termination
acyclovir, penciclovir, valacyclovir, famciclovir side effects
CNS changes and renal dysfunction when used at higher doses
what is the DOC for CMV infection?
ganciclovir (purine analog guanine)
afterphosphorylation, causes viral DNA chain termination
ganciclovir side effects
neutropenia, thrombocytopenia (a GANG of cycle running over all the herpes and neutrophils)
foscarnet clinical use
CMV retinitis in immunocompromised when ganciclovir fails and acyclovir-resistant HSV
directly inhibits herpesvirus DNA polymerase or HIV reverse transcriptase - does not require any kinase activation so it is active against the purine analog guanine resistant
foscarnet side effects
nephrotoxicity (reversible but severe), electrolyte abnormalities leading to seizures (hypo/hyper calcemia, phosphatemia, hypomagnesmia, hypokalemia), myelosuppression
best strategy for influenza
what is used to treat influenza?
neuraminidase inhibitors (-mivir) = ME most likely to get flu;
oseltamivir, zanamivir, peramivir
neuraminidase inhibitors (-mivir for flu) mechanism
prevent viral release from host cells by inhibiting influenza neuraminidase
neuraminidase inhibitors side effects
GI, neuropsychiatric (agitation, anxiety, altered mental status)
which of the neuraminidase inhibitors for influenza is inhaled therapy? IV formulation only? oral?
zanamivir inhaled; peramivir IV; oseltamivir oral