Antivirals Flashcards
what are the DNA viruses
- adenovriuses
- herpesviruses
- papillonaviruses
- Varciella-Zoster
what are the RNA viruses
-ortho and paramyxoviruses, rubella, viruses and retroviruses
what is used to treat Herpes and Varicella-Zoster Infections
Acyclovir
what are the symptoms of Acyclovir toxicity
- nausea, headache, diarrhea and vomiting
- transient renal dysfunction at high doses and when given to dehydrated patients by IV
what is the therapeutic use of Ganciclovir
- treatment of CMV retinitis in immunocompromised pats
- prevention of CMV disease in transplant pts
what is the toxicity of Ganciclovir
dose-dependent neutropenia, CNS effects (headache, behavioural changes, convulsions, coma), carcinogenic
patients with Ganciclovir toxicity present with
- blurred vision
- floaters
- loss of central or peripheral vision
what is the plasma half life of acyclovir
2.5 hrs
what is the plasma half life of Ganciclovir
> 24 hrs
Ganciclovir triphosphate [ ] are 10x of acyclovir
what is the therapeutic use of Foscarnet
- IV treatment for CMV retinitis in HIV-infected patients who are resistant to ganciclovir.
- Herpes patients who are resistant to acyclovir.
Toxicity of Foscarnet
Nephrotoxicity, anemia, nausea, fever, hypocalcemia and hypomagnesemia.
what is the therapeutic effect of Trifluridine
HSV keratoconjunctivitis and keratitis.
Replaced the drug Idoxuridine
what is the toxicity of Trifluridine
Inflammation of the cornea
what is the therapeutic effect of Fomivirsen
CMV retinitis in patients who do not respond to other drugs. Do not give to patients who have taken cidofovir in past month-may increase inflammation of the eye.
what is the toxicity of Fomivirsen
Iritis, increased intraocular pressure and vision changes.
see mnemonic on slide 13
see mnemonic on slide 13
what are the Neuraminidase Inhibitors
zanamivir, oseltamivir
what is the therapeutic use of Neuraminidase Inhibitors
-shortens the duration and may be used to prevent flu
what is the toxicity of Zanamivir
nasal and throat discomfort and headaches
-bronchospasm in asthma patients
what is the toxicity of oseltamivir (TAMIFLU)
- nausea, vomiting and headaches
- when taken with food there is less nausea
what can Zanamivir be used for
treatment of H1N1
what is Oseltamivir used for
Influenza A and B, H1N1
what are interferons
Interferons alpha and beta are made in response to viral infection
what is the MAO of interferons
IFNs bind to cellular receptors and activate the JAK-STAT signal transduction pathway
IFNs induce many proteins, including 2’-5’-oligoadenylate synthetase and a kinase, that inhibit protein synthesis.
what is the therapeutic use of interferons
genital warts, chronic hepatitis B and C, Kaposi’s sarcoma in HIV-infected patients, multiple melanomas and multiple sclerosis.
Peg-interferon 2A with Ribavirin is the treatment of choice for
chronic hepatitis C
what is the toxicity of interferons
- IM or SC injection may produce flu-like symptoms
- High dose or chronic therapy may be limited due to bone marrow suppression, fatigue, increased susceptibility to bacterial infections, anorexia, diarrhea and psychiatric syndrome (depression and anxiety)
what is the MOA of Ribavirin
inhibits viral mRNA synthesis
what is the therapeutic use of Ribavirin
- Ribavirin with interferon is the standard treatment for hepatitis C
- Given to treat infants and young children with Respiratory Syncytial Virus infections that cause bronchiolitis and pneumonia.
- Influenza A and B, Parainfluenza, Paramyxovirus, Arenaviruses and HIV.
what is the toxicity of Ribavirin
Aerosol is well tolerated, but systemic doses may cause anemia
Teratogenic therefore do not give to pregnant women.
what does HAART stand for
Highly Active Anti-Retroviral Therapy
what are the possible side effects of HAART
liver problems diabetes lipodystrophy syndrome high cholesterol increased bleeding hemophiliacs decreased bone density skin rash
what is the therapeutic use of Zidovudine (AZT)
HIV patients, protects fetuses from becoming infected in HIV-infected pregnant women.
Zidovudine resistance
Mutated reverse transcriptase that has a lower affinity for the AZT-TP
what is the toxicity of Zidovudine
Bone marrow (anemia and leukopenia) and headaches
what drugs increase the toxicity of Zidovudine
Probenecid, Acetaminophen Lorazepam (benzodiazepine), Indomethacin (anti-inflammatory), and Cimetidine (H2-receptor antagonist)
“I am a PAL I Care”
what is the therapeutic use of Didanosine (ddI)
-patients with AZT-resistant HIV infections
what s the toxicity of Didanosine
- Pancreatitis that may be fatal, gastrointestinal disturbances and a dose-limiting peripheral neuropathy
- toxicity increases when combined with Stavudine
what is the therapeutic Zalcitabine (dec)
-Given in conjunction with AZT or alone for those who cannot tolerate AZT- treatment
what is the toxicity of Zalcitabine
Peripheral neuropathy, rash and stomatitis on initial treatments
what is the toxicity of Stavudine
peripheral neuropathy
what is the toxicity of both AZT and Stavudine treatment
Potentially fatal lactic acidosis, peripheral lipoatrophy, central fat accumulation and hyperlipidemia
what is the therapeutic use of Lamivudine (3CT) and Emtricitabine
Patients with HIV in combination with AZT (resistance to AZT develops more slowly when used in combination)
and hepatitis B patients.
what is the toxicity of Lamivudine
Pancreatitis often develops in pediatric patients
what is the therapeutic use of Abacavir
: HIV infected adults and children in combination with AZT and Lamivudine or a protease inhibitor
what is the toxicity of Abacavir
Hypersensitivity resulting in fever, gastrointestinal distress, malaise and rash
what is the MOA of Tenofovir
Inhibits reverse transcriptase and terminates DNA chain elongation.
what is the therapeutic use of Tenofovir
HIV infected patients and chronic hepatitis B infections.
see slide 32
see slide 32
what is the toxicity of Tenofovir
- well tolerated except for flatulence, some renal toxicity
- do not give as didanosine, lamivudin or abacavir combo
see mnemonic on slide 33
see mnemonic on slide 33
what is the MOA of Efavirenz
alters the conformation of reverse transcriptase
what the therapeutic use of Efavirenz
Used in combination with AZT and Lamivudine
what is the toxicity of Efavirenz
Dizziness, headache, insomnia, rash
what is the drug interactions of Efavirenz
Efavirenz decreases concentration of Phenobarbital, Phenytoin, Carbamazepine, Methadone and Rifabutin.
Co-administration of Rifampin will reduce levels of Efavirenz
what is the MOA of Nevirapine
alters the conformation of reverse transcriptase
what is the therapeutic use of Nevirapine
used in combo with Didanosine or Stavudine
what is the toxicity of Nevirapine
Rash, fever, nausea, severe dermatologic effects and fatal hepatotoxicity
what are the drug interactions of Nevirapine
Must warn patients not to take St. John’s Wort which lowers the concentration of Nevirapine.
Nevirapine induces CYP3A4 and therefore it may lower the concentration of drugs metabolized by this enzyme.
Nevirapine lowers plasma concentrations of Ethinyl estradiol and therefore patients should be given alternate methods of birth control
what is the MOA of Delavirdine
binds and inhibits reverse transcriptase
what is the therapeutic effect of Delavirdine
Used in combination with Zidovudine and Didanosine, least potent NNRTI
what are the drug interactions of Delavirdine
Delavirdine inhibits CYP3A4 and may thus alter the metabolism of Rifampin, Rifabutin, Ergot derivatives, Triazolam, Midazolam and Cisapride.
Delavirdine also inhibits CYP2C9.
Drugs that induce CYP3A4, such as Carbamazepine, Penobarbital, Phenytoin, Rifabutin and Rifampin, may decrease Delavirdine levels.
see mnemonic on slide 37
see mnemonic on slide 37
what are the protease inhibitors
Atazanavir Indinavir Ritonavir Lopinavir Nelfinavir Amprenavir Saquinavir
see mnemonic on slide 39
see mnemonic on slide 39
what is the therapeutic use of protease inhibitors
HIV patients must take the drugs continuously in combination with AZT and Lamivudine or other nucleoside reverse transcriptase inhibitors.
what is the toxicity of protease inhibitors
Well tolerated
Sometime- nausea, vomiting, diarrhea, lipodystrophy and hyperglycemia
what is the resistance of protease inhibitors
Cross-resistance often occurs among the protease inhibitors, but the HIV strains may still be susceptible to Amprenavir.
what are the pharmacokinetics of Lopinavir/Ritonavir
is metabolized by CYP3A. Ritonavir is an inhibitor of CYP3A4 activity and, therefore, raises the Lopinavir plasma levels
what is the therapeutic use of Lopinavir/Ritonavir
The combination of drugs is used to treat HIV strains that are resistant to multiple protease inhibitors
what is the toxicity of Lopinavir/Ritonavir
Well tolerated.
Diarrhea, nausea, fatigue, headache, hyperlipidemia, hyperglycemia, and altered body fat
what are the drug interactions of Lopinavir/Ritonavir
Inhibit the activity of CYP3A4 and CYP2D6 and therefore may increase or prolong the therapeutic or adverse effects of drugs metabolized by these pathways
what the Fusion Inhibitor
Enfuvirtide
Macaviroc
what is the therapeutic use of Enfuvirtide
Injected twice daily in HIV patients. Used with other drugs
what is the toxicity of Enfuvirtide
Pain, redness, nodules and cysts formation at the site of injection
what is the therapeutic use of Maraviroc
HIV patients
what is the MOA of Maraviroc
The drug blocks the CCR5 chemokine receptor. HIV uses CCR5 as a co-receptor to bind and enter macrophages
what is the toxicity of Maraviroc
- most common are cough, fever, dizziness, headache, lowered blood pressure, nausea, and bladder irritation
- May cause liver problems and cardiac events, an increased risk for some infections, and a slight increase in cholesterol levels
see slide 47
see slide 47
