Antivirals Pt. 1 Flashcards
Influenza drugs
oseltamivir, zanamivir, amantadine, rimantadine
Main drug classes for Hep B/C
interferon alpha, 5A inhibitors, protease inhibitors, nucleotide/nucleoside inhibitors
5A inhibitors
daclatasvir, elbasvir, ledipasvir, ombitasvir
Protease inhibitors
grazoprevir, paritaprevir, simeprevir
Nucleotide/nucleoside inhibitors
adefovir, entecavir, lamivudine, sofosbuvir, tenofovir
Herpesvirus drugs
acyclovir, famciclovir, valacyclovir, trifluridine, ganciclovir, cidofovir
What are characteristics of viruses?
obligate intracellular parasites, no cell wall, no cell membrane, do not carry out metabolic processes
T/F antivirals are selective enough to prevent injury to the host
false, not selective enough
What is the structure of a virus?
protein layer surrounds and protects the genetic material– viral genome, nucleocapsid, viral tegument, envelope, envelope protein
What are DNA viruses?
herpes (simplex, zoster, cytomegalovirus) have DNA as nucleic material and need DNA polymerase
What are RNA viruses?
influenza and hepatitis, has RNA as nucleic material and need RNA polymerase
What are retroviruses?
HIV, has RNA as nucleic material and need reverse transcriptase to incorporate DNA into host DNA
When do viral symptoms appear?
late in the disease, viral particles have already replicated so drugs blocking viral replication may have limited effectiveness
T/F many antivirals are used as prophylactic agents
true
What are the six steps in the virus life cycle?
attachment, penetration, uncoating, biosynthesis, assembly, release
What treatments are available for respiratory viruses and what is prefered?
treatments available for influenza A and B but immunization against influenza is preferred
When are antiviral agents used?
when patient is allergic to vaccine, outbreak is due to a variant of the virus, outbreaks among unvaccinated people in closed settings
What enzymes do viruses causes influenza contain?
neuraminidase
Which two drugs selectively inhibit neuraminidase which is essential to the virus life cycle?
oseltamivir and zanamivir , stops replication and prevents new virions
What can you give to someone for influenza even if they’ve had the vaccine and why?
neuraminidase inhibitors because they do not interfere with the immune response to the influenza vaccine
When do you have to administer a neuraminidase inhibitor for it to be effective?
24-48 hours after onset of infection
What are the pharmacokinetics of oseltamivir?
orally active, prodrug (needs liver metabolism)
How is zanamivir administered?
intranasally not orally
What are adverse effects of neuraminidase inhibitors?
GI disturbances for oseltamivir (take with food) and bronchospasm with zanamivir (contraindicated for asthma and COPD)
What are the two inhibitors of viral uncoating?
amantadine and rimantadine
What are inhibitors of viral uncoating active against?
influenza A, treatment and prevention
What is the MOA of inhibitors of viral uncoating?
block viral membrane matrix protein M2 preventing fusion of the viral membrane with the cell membrane
What is the absorption of viral uncoating inhibitors?
well absorbed orally
Which inhibitor of viral uncoating readily penetrates the CNS and may accumulate to toxic levels in patients with renal failure?
amantadine
Which inhibitor of viral uncoating is extensively metabolized by the liver?
rimantadine
What are the adverse effects of inhibitors of viral uncoating?
GI problems, caution in pregnancy, CNS side effects with amantadine (insomnia dizziness and ataxia aka movement disorder
Why are inhibitors of viral uncoating infrequently used?
resistance develops rapidly and there is cross resistance between the two
What are the hepatic viral infection types?
ABCDE
Which hepatitis forms are most common cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma
Hep B and C (C worse)
T/F Hep B and C and blood borne
true
What do treatment of hepatic viral infections aim to do?
interfere with essential viral enzyme function or replication
What do enzyme 5A inhibitors do?
interfere with enzyme responsible for viral RNA replication and virion assembly
What do protease inhibitors do?
prevent viral maturation by interfering with hepatitis protease enzyme responsible for formation of essential enzymes and proteins
What do nucleotide/nucleoside inhibitors do?
inhibit reverse transcriptase/RNA polymerase and insert them into RNA chain resulting in termination of replication
Which two nucleotide/side inhibitors treat hepatitis AND HIV?
lamivudine and tenofovir
What does interferon alpha do?
synthesized by recombinant DNA technology for multiple uses
What is the MOA interferon alpha?
incompletely understood, thought to induce host cell enzymes to inhibit viral RNA translation and degradation of viral RNA
How is interferon alpha?
not active orally, subcutaneous delivery or IV/intralesion
What are the adverse effects of interferon alpha?
flu like symptoms (fever chills etc), fatigue and mental depression, symptoms improve with subsequent administration, interferon RETINOPATHY
What does interferon retinopathy consist of?
cotton wool spots and retinal hemorrhages in the posterior pole, occurs 3-5 months after starting treatment or as early as 2 weeks – improves with cessation
How often do you have to monitor patients on interferon alpha for retinopathy?
every 6 months or sooner if retinopathy is present
What is harvoni?
combination of sofosbuvir and ledipasvir (5A) don’t need that memorized lol, very expensive with 95% cure rate for hepatic infections
What is ritonavir?
can be given as a pharmacological booster, CYP450 inhibitor that increases the plasma concentration of other drugs, not active against hepatitis but is active against HIV
What are examples of infections from herpes?
cold sores, viral encephalitis, genital infections, corneal infections
T/F herpesvirus drugs are administered during the latent phase
false, there is no effect during the latent phase
When are herpes drugs effective?
during the acute phase of the infection or prophylactically
What is acyclovir used for?
treatment of HSV encephalitis and genital herpes
What is given prophylactically to seropositive (exposed) patients?
acyclovir
What is the MOA of acyclovir?
guanosine analog, inhibits DNA polymerase and is incorporated into viral DNA once activated by thymidine kinase (viral enzyme)
T/F if a patient doesn’t have an active herpes infection, acyclovir will pass through the body without side effects
true, exception: patients with kidney problems
How is acyclovir administered?
oral, IV or topical
What are the pharmacokinetics of acyclovir?
passes into CSF, accumulates in patients with renal failure
What is notable about valacyclovir?
ester of acyclovir with greater oral availability
What are adverse effects of acyclovir?
local irritation, headaches and GI disturbances, renal dysfunction at high doses
What is resistant to acyclovir?
cytomegalovirus because it lacks specific viral thymidine kinase
T/F famciclovir and valacyclovir are clinically equivalent to acyclovir
true but actually have longer half life requiring smaller dose
Which herpes virus drug is safest in pregnancy?
famciclovir
What is cidofovir approved for?
treatment of CMV induced retinitis in AIDs patients
What is the MOA of cidofovir?
inhibits viral DNA synthesis as a nucleotide analog of cytosine
What is the administration of cidofovir?
IV, intravitreal, and topical
What is a contraindication for cidofovir?
renal impairment and nephrotoxic drugs (INCLUDING NSAIDs) produces significant toxicity to the kidney
What is CMV retinitis?
inflammation of nerve fiber layer that occurs during HIV
T/F ganciclovir must be activated by viral enzyme
true (like acyclovir)
How is ganciclovir administered?
IV only, penetrates CSF, 20x greater activity agains CMV
What is the MOA of ganciclovir?
inhibits viral DNA polymerase and can be incorporated into viral DNA
What is the ester of ganciclovir that has a high oral bioavailability?
valgancyclovir
What are the adverse effects of ganciclovir?
dose-dependent neutropenia, carcinogenic and embryotoxic
What is the ocular preparation of ganciclovir?
zirgan, only targets virally infected cells and is much less toxic than trifluridine
What is the MOA of trifluridine?
fluorinated pyrimidine nucleoside analog that inhibits DNA synthesis
What is too toxic for systemic use and why?
trifluridine, able to incorporate into cellular DNA of host
How is trifluridine administered?
topical applications in the eye, drug of choice for HSV keratoconjunctivitis and epithelial keratitis
What is a main issue with trifluridine administration?
short half life (12 mins) requires frequent dosing and causes lots of irritation
What is herpes zoster?
shingles, recurrent varicella zoster virus which is contagious to those who have NOT had chicken pox
What are signs and symptoms of herpes zoster?
headache, malaise, fever, chills, neuralgic pain, unilateral vesicular eruption and hot, hyperesthesia and edema on half of the face
What does herpes zoster ophthalmicus present as?
keratitis, corneal edema, anterior uveitis – need to dilate looking for vitritis and retinitis
What can reactivate herpetic keratitis?
fever, hormonal change, UV radiation, trauma, trigeminal injury – risk of recurrence increases as years pass
What are signs and symptoms of herpetic keratitis?
mild discomfort, watering eyes, blurred vision, corneal ulceration (dendritic pattern), and stomal edema, KPs, descemet scars in disciform disease
What is the treatment for herpetic keratitis?
oral acyclovir will be shed in tears and is effective or topical trifluridine will work 9x/day
