Antivirals and Disinfectants Flashcards
NRTIs
abacavir (ABC) • didanosine (ddI) • emtricitabine (FTC) • lamivudine (3TC) • stavudine (d4T) • tenofovir (TDF) – nucleotide reverse transcriptase inhibitor • zidovudine (AZT)
NNRTIs
non nucleoside transcriptase inhibitors
delavirdine (DLV) • efavirenz (EFV) • etravirine (ETV) • nevirapine (NVP) • rilpivirine (RPV)
PIs
Protease Inhibitors
amprenavir (APV) • atazanavir (ATV) • fosamprenavir (f-APV) • indinavir (IDV) • lopinavir/ritonavir (LPV/r) • nelfinavir (NFV) • ritonavir (RTV or r) • saquinavir (hard gel capsule and tablet formulations) (SQV) • tipranavir (TPV) • darunavir (DRV)
Additional Agents for secondary treatment
Fusion inhibitor – enfuvirtide (T20) • CCR5 antagonist – maraviroc (MVC) • Integrase inhibitor – raltegravir – elvitegravir – dolutegravir
Tenofovir Disoproxil Fumarate (Viread)
• Take without regard to food
• Adverse effects
- renal insufficiency
• Special considerations
– renal dosing
– use with emtricitabine for pre-exposure prophylaxis (PrEP) and post- exposure prophylaxis (PEP)Emtricitabine (Emtriva)
• Take without regard to food
• Adverse effects
– Hyperpigmentation of the palms
– Skin discoloration
Well tolerated and does not usually have any adverse effects
*looks like secondary syphilis
Zidovudine (Retrovir)
• Taken without regard to food
• Adverse effects
– hyperpigmentation of nails and toes (next slide)
– bone marrow suppression
Used as an IV infusion peripartum in women who have viral loads > 400
** drug of choice for pregnant women
Lamivudine (Epivir)
• Taken without regard to food • Adverse effects – diarrhea – malaise, fatigue – headache • Special considerations – Epivir HBV! • Caution! – Renal dosing requirements **paired with Zidovudine and used for pregnant women
Combination Products
• emtricitabine + tenofovir (Truvada®) – 1 tablet PO daily
emtricitabine + tenofovir + efavirenz (Atripla®) – 1 tablet PO daily
emtricitabine + tenofovir + elvitegravir + cobicistat (Stribild®) – 1 tablet PO daily
Efaviranz (Sustiva)
• Avoid taking with high-fat foods – increases serum concentrations by 39-79% – take on empty stomach • Adverse effects – central nervous system (CNS) effects • 52% of patients in clinical trials • subside after 2-4 weeks – rash – elevated liver function tests (LFTs) – teratogenic – false-positive cannabinoid test! • Drug interactions – Mixed CYP450 3A4 inducer and inhibitor
- needs to be taken right before bed
- *cannot be used for pregnant women
Rilpivirine (Edurant)
non nucleoside • Not for use in high viral loads Drug interactions – CYP450 inducer – Avoid use with proton pump inhibitors
Nevirapine (Viramune)
• Take without regard to food
Adverse Effects:
– hepatitis, including fatal hepatic necrosis
– higher frequency in women with CD4 > 250, men with CD4 > 400
» avoid initiation in these populations
PIs Class Issues
– Drug interactions • Emphasize importance of using same pharmacy for all prescriptions – Metabolic syndrome • Insulin resistance/hyperglycemia • Increased cholesterol and triglycerides • Lipodystrophy/fat redistribution – Heptatotoxicity – GI intolerance – Osteopenia and osteoporosis
Ritonavir (Norvir)
pharmacokinetic booster with other protease inhibitors • 100-400mg/dayin1-2divided doses • Do NOT refrigerate oral solution • Adverse effects – GI upset – taste perversion – circumoral tingling
Atazanavir (Reyataz)
• Take with food
• Special considerations
– separate dosing from antacids and H2-blockers – proton pump inhibitors
• when to avoid
• Adverse effects
– indirect hyperbilirubinemia – prolonged PR interval on EKG – nephrolithiasis
– lack of effect on lipids!
Darunavir (Prezista)
• Take with food
• Special considerations
– Must take darunavir and ritonavir at the same time – Caution in sulfa-allergic patients
– New 600 mg tablet arrived in late spring 2008
• Adverse effects – Rash
Lopinavir/ritonavir (Kaletra)
• Take without regard to meals • Special considerations – Melt-extrusion technology • No refrigeration needed!! – Drug of choice in pregnancy • Adverse effects – asthenia – as with ritonavir
Integrase Inhibitor Raltegravir (Isentress)
• Take without regard to food • Special considerations – metabolized by glucuronidation • Adverse effects – headache – nausea – diarrhea – increased creatine kinase
Integrase Inhibitor Stribild®
• Take with food • Special considerations • “Quad Pill” – Drug interactions – Elevations in serum creatinine – Increased creatine kinase
Initial Treatment Considerations
– Results from resistance testing – Dosing convenience/adherence issues – Adverse effects – Drug interactions – Pregnancy potential/CD4 count – Comorbidities
Antivirals for HSV and VZV
• Treatments are virustatic
– Arrest DNA synthesis by inhibiting viral DNA polymerase
• Must be initiated within 48-72 hours of rash onset
Acyclovir (Zovirax)
Mechanism of action
– Phosphorylated into the active triphosphate form, where it becomes incorporated into the viral DNA
– Viral replication is inhibited
– Active against HSV-1 and HSV-2 as well as VZV
• Special considerations
– Role for topical therapy, role for IV therapy, patient expectations
Valacyclovir (Valtrex)
• Mechanism of action
– L-valyl ester prodrug of acyclovir
• Dosing
– Acute infection
– Suppression of recurrent episodes – Reduction of transmission
• Adverse effects
– Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
• In immunocompromised patients
• Special considerations
– Less frequent dosing than acyclovir
– Higher plasma concentrations than acyclovir
Famciclovir (Famvir)
Mechanism of action
– Rapidly phosphorylated by viral thymidine kinase to penciclovir monophosphate
• Competitively inhibits viral DNA polymerase and prevents viral replication through inhibition of herpes virus DNA synthesis
• Adverse effects
– Fatigue, GI upset, headache
• Special considerations
– Dose adjustment for renal dysfunction
3 Topical Agents
• Penciclovir (Denavir)
– 1% cream, for oral herpes lesions
– Apply every 2 hours while awake for 4 days – Headache, local skin reactions
• Docosanol (Abreva)
– 10% cream, available OTC, for oral herpes lesions
– Rub in a thin layer gently but completely 5 times daily until healed
• May apply cosmetics over this product
• Trifluridine (Viroptic)
– 1% ophthalmic solution, for primary keratoconjunctivitis and recurrent epithelial keratitis caused by HSV
– Dose de-escalation procedure
CMV
– DNA virus
– Typically result from reactivation in immunocompromised patients
• HIV, transplant
– Dissemination results in end-organ disease
• Retinitis, colitis, esophagitis, CNS disease, pneumonitis
• Treatments are virustatic
– Arrest DNA synthesis by inhibiting viral DNA polymerase
• Completely different regimens than used for HSV or VZV
– Increased toxicity
Ganciclovir (Cytovene)
replaced with valganciclovir
– Converted to ganciclovir triphosphate
• Incorporated into viral DNA
• Inhibits viral DNA polymerase • Terminates viral replication
– Does exhibit activity against HSV, VZV, EBV • Too toxic to be used for those viruses
Ganciclovir (Cytovene)
• Adverse effects
– Black box warning: bone marrow toxicity
• Special considerations
– Hydrate aggressively
– Monitor renal function and adjust accordingly – Avoid direct contact with skin
• Extremely alkaline solution, teratogenic and carcinogenic
Valganciclovir (Valcyte)
DRUG OF CHOICE for Tx and Px! (oral)
• Special considerations – PO only
– Look-alike/sound-alike names
• Valganciclovir and valacyclovir
Foscarnet (Foscavir)
Mechanism of action
– Binds noncompetitively to viral DNA polymerase to form an inactive complex and prevents pyrophosphate cleavage
• Results in termination of viral DNA chain elongation – Broad spectrum of activity
• Covers HSV, VZV
– Reserved for acyclovir-resistant strains
• Covers CMV, influenza, HIV
– Not used for the latter 2
– Used as second-line to valganciclovir for CMV
Hepatitis B Virus (HBV) Infection
- Agents utilized – PO
- Adefovir, lamivudine, entecavir, telbivudine, tenofovir – Subcutaneous
- Interferon alfa
Tenofovir (Viread)
1st line treatment
• Special considerations
– Maintains activity against lamivudine- and entecavir-resistant isolates
– Reduced activity against adefovir-resistant isolates – Significantly higher rate of response than adefovir
• Less likely to develop resistance • Fewer adverse effects
Entecavir (Baraclude)
1st line treatment
• Mechanism of action
– Carbocyclic analog of guanosine – Phosphorylated to its active form
• Then inhibits viral polymerase and halts HBV DNA synthesis
– Effective for lamivudine-resistant HBV
Adverse effects
– Black box warning: severe acute exacerbations of hepatitis upon discontinuation
– Dizziness, fatigue, headache, nausea
Lamivudine (Epivir HBV)
Special considerations for HBV – Dosing is 100 mg PO daily • Epivir HBV dosage form – Very rapid and potent HBV suppression • HOWEVER, resistance is quite common
HCV Infection goals of therapy
Goals of therapy
– Eradicate the virus
– Achieve sustained virologic response (SVR)
• Undetectable viral load for 6 months after completion of therapy
– Improve liver histology
– Reduce risk of hepatocellular carcinoma
Interferons for HCV Infection
Products available – Pegasys – Peg-Intron • Adverse effects Interferons for HCV Infection – Flu-like syndrome • Headache, myalgias, arthralgias, fatigue. malaise, fever, chills • Improves as treatment continues • Special considerations – Contraindications to therapy • Hepatic decompensation • Autoimmune disease • History of arrhythmia • Pregnancy
Ribavirin (Rebetol, Copegus)
• Adverse effects
– Hemolytic anemia (must monitor CBC q4 weeks)
– GI upset
– Depression
– Teratogenic!!
• Special considerations
– Handling capsules, pregnancy precautions
Sofosbuvir (Sovaldi)
• Special considerations – $1000 per tablet!! – Pan-genotypic activity – Makes it possible to treat some patients without interferon! Polymerase inhibitor
Simeprevir (Olysio)
• Dosing – 150 mg PO daily with food • Adverse effects – Rash – Itching – Nausea • Special considerations – Assessment of Q80K mutation – Drug interactions!!
Influenza virus
Single stranded RNA virus • Influenza A and Influenza B • Influenza A – Two surface antigens: – hemagglutinin (H1 to H16) and neuraminidase (N1 to N9)
Complications of Influenza
Viral Pneumonia
Complications of Influenza
• Secondary bacterial pneumonia, sinusitis, otitis
• Exacerbates other medical conditions – Especially cardiac/pulmonary disease
• Also uncommonly associated with: – encephalopathy, transverse myelitis
– myositis, myocarditis, pericarditis
– Reye’s syndrome
Antiviral Therapy treating with 48 hrs if?
Treat if high risk group within 48 hrs
children younger than 2 years old
adults 65 years and older
pregnant women and women up to 2 weeks postpartum
persons with certain chronic medical or immunosuppressive conditions
Antiviral Prophylaxis
Chemoprophylaxis if
– persons at higher risk for influenza-related complications have significant contact with flu.
– Early treatment is alternative to chemoprophylaxis after a suspected exposure.
• If clinical signs or symptoms develop, then treat
• Best method of routine prevention: inactivated influenza vaccine!!
Amantadine (Symmetrel)
• Adverse effects
– Dry mouth, nausea, anorexia
– CNS toxicity (increased risk in elderly)
Mechanism of action
– Inhibits viral replication by interfering with viral attachment and uncoating
• Special considerations
– No longer recommended for influenza prophylaxis
– Role in treatment in 2012
– Teratogenic
– Used to treat Parkinson Disease and drug-induced EPS
Rimantadine (Flumadine)
• Adverse effects
– As with amantadine
• Less CNS adverse effects
MOA is same as amantadine
Oseltamivir (Tamiflu)
• Mechanism of action
– Neuraminidase inhibitor
– Active against both influenza A and B
• Adverse effects
– Nausea, vomiting, abdominal pain
– CNS adverse effects
– Approved for use in ages 1 and over – Dose adjust for renal insufficiency
Zanamivir (Relenza)
• Adverse effects
– Cough, bronchospasm
– Reversible decrease in pulmonary function – Transient nasal and throat discomfort
• Special considerations
– Avoid use in patients with asthma and COPD
– Puncture Rotadisk only when ready to use
– FDA alert 10/9/2009!
Disinfectants
– Chemicals that inhibit or kill microorganisms (not spores)
• Used on inanimate surfaces
– Regulated by EPA
Disinfectants and Antiseptics can become contaminated with spores and bacteria
Antiseptics
– Disinfecting agents that can be applied to skin, mucus membranes, wounds due to low toxicity to host cells
• To prevent infection
– Regulated by FDA
Sterilants
– Kill both cells and spores when applied for certain duration of time/temperature
– Regulated by EPA
