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36 Cards in this Set
- Front
- Back
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Name examples of DNA viruses
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adenoviruses (conjunctivitis, sore throat), hepadnaviruses (hepatitis B), herpesviruses (herpes), papillomaviruses (warts), Varicella-Zoster (chickenpox and shingles)
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RNA viruses
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arboviruses (yellow fever, arthropod-borne encephalitis), arenaviruses (meningitis, Lassa fever), orthomyxoviruses (influenza), paramyxoviruses (measles, mumps), rhabdoviruses (rabies) and rubella viruses (German measles), retroviruses (AIDS, T-cell leukemias)
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HSV 1 and HSV 2
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HSV I causes diseases of the mouth, face, skin, esophagus, and brain. HSV 2 causes infections of the genitals, rectum, skin, hands and meninges.
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MOA and clinical use of acyclovir
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MOA: The viral thymidine kinase gene phosphorylates the drug producing acyclovir triphosphate. This competes with dGTP and is incorporated into DNA where it causes premature chain termination.
Therapeutic use: Acyclovir is used to treat patients with herpes and VZV infections. In immunocompetent patients the drug works best on the initial herpes infection and in immunocompromised patients it works even better because of the severity of the infection. Systemic administration (oral or IV) is much more effective than topical administration of the drug for genital herpes |
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Resistance and toxicity of acyclovir
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Resistance: Drug resistance is due to altered or deficient viral thymidine kinase or polymerase. Toxicity: Oral administration infrequently produces nausea, headache, diarrhea and vomiting. Transient renal dysfunction may occur when the drug is given high doses and when given to dehydrated patients by IV.
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Gancyclovir
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is a guanine nucleoside analog. MOA: The drug competitively inhibits viral DNA polymerase and may be incorporated into DNA to block elongation. Therapeutic use: Ganciclovir is used to treat cytomegalic retinitis in immunocompromised patients and for prevention of CMV disease in transplant patients. Toxicity: Toxicities include myelosuppression, dose-dependent neutropenia, CNS effects (headache, behavioral changes, convulsions, coma), and it may be carcinogenic.
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Foscarnet
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is an inorganic pyrophosphate analog. MOA: Foscarnet reversibly inhibits viral DNA and RNA polymerases. Therapeutic use: Foscarnet may be given by IV to treat cytomegalic retinitis in immunocompromised HIV-infected patients who are resistant to ganciclovir and to herpes patients resistant to acyclovir. Toxicity: Nephrotoxicity, anemia, nausea, fever, hypocalcemia and hypomagnesemia, headaches (there is more toxicity associated with it than gancyclovir) and genital ulceration are toxicities associated with Foscarnet treatment.
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Trifluridine
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is a pyrimidine analog. MOA: Trifluridine inhibits viral DNA synthesis. Therapeutic use: Trifluridine is used to treat primary keratoconjunctivitis and recurrent epithelial keratitis from HSV infection. Toxicity: Trifluridine may cause inflammation of the cornea.
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Fomivirsin
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is an antisense oligonucleotide and the first FDA approved gene therapy. Therapeutic use: Fomivirsen is injected directly into the eye. It is used to treat CMV retinitis in HIV patients who do not respond to other drugs. Fomivirsen should not be given to patients who have taken Cidofovir in past month. Toxicity: Iritis, vitritis, increased intraocular pressure and vision changes are associated with Fomivirsen treatment.
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Idoxuridine
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is an iodinated thymidine analog MOA: Idoxuridine inhibits viral DNA synthesis and is incorporated into viral and cellular DNA, making it more susceptible to breaks. This leads to error-prone transcription. Therapeutic use: Idoxuridine is used as a topical treatment of HSV keratitis. Toxicity: Idoxuridine may cause pain, inflammation or edema of eyes or lids.
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Neuraminidase Inhibitors MOA
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Viral respiratory infectionsr. MOA: These drugs inhibit neuraminidases, which results in decreased release of virus from infected cells, increased formation of viral aggregates and decreased viral spread. Neuraminidase inhibitors are active against influenza A and B.
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Zanamivir
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Neuraminidase InhibitorTherapeutic use: When taken within 30 hours of onset of flu symptoms, Zanamivir can shorten the duration of the illness and decrease the incidence of respiratory complications. In addition, it may be used once daily to prevent a person from getting the flu. Toxicity: Zanamivir may cause nasal and throat discomfort, headaches and bronchospasms in asthma patients.
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Treatment Of Herpes, Varicella-Zoster And Megalovirus Infections
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acyclovir, ganiclovir, foscarnet, trifluridine, fomivirsen, idoxurine
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Oseltamivir (TAMIFLU)
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Therapeutic use: When taken within 36 hours of onset of symptoms, Oseltamivir can shorten the duration of the flu and decrease the incidence of respiratory complications. Oseltamivir may be used once or twice daily to prevent the flu. Toxicity: Oseltamivir may cause nausea, vomiting and headache. When Oseltamivir is taken with food, there is less nausea.
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Treatment for hepatitis viral infection
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Interferon, ribavirin
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MOA and clinical use of interferon
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Interferons alpha and beta are made by most cells in response to viral infection. Interferon gamma is produced by T lymphocytes and natural killer cells and has less antiviral activity but more immunoregulatory effects. MOA: 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. Therapeutic use: IFNs are used to treat condyloma acuminatum (genital wart), chronic hepatitis B and C, Kaposi's sarcoma in HIV-infected patients, other malignancies, and multiple sclerosis. Peg-interferon 2A with Ribavirin is the treatment of choice is for chronic hepatitis C infections
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Interferon toxicity
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Toxicity: IM or SC injection may produce flu-like symptoms. High dose or chronic therapy of IFNs may be limited because it causes bone marrow suppression, fatigue, increased susceptibility to bacterial infections, anorexia, diarrhea and psychiatric syndrome (depression and anxiety).
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Ribaviron
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Ribavirin is a synthetic guanosine analog. MOA: Ribavirin alters the intracellular nucleotide pools and inhibits viral mRNA synthesis. Therapeutic use: Ribavirin combined with pegIFN alpha is the standard treatment for Hepatitis C infections. Ribivarin may be given as an aerosol to treat infants and young children with respiratory syncytial virus (RSV) infections. Ribavirin may also be used to treat influenza A and B, parainfluenza, paramyxovirus and HIV. Toxicity: Since Ribavirin is given as an aerosol, it may cause conjunctival irritation and transient wheezing. Systemic doses of Ribavirin may cause anemia and bone marrow suppression. Ribavirin may be teratogenic, therefore pregnant women should not use it.
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HIV treatment
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HAART Therapy (Highly Active Anti-Retroviral Therapy)
A. Nucleoside Reverse Transcriptase Inhibitors- These drugs must be converted to their nucleotide form to be effective. The 3' position of the deoxyribose moiety of the drugs either lacks a hydroxyl group or is blocked. |
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Zidovudine (AZT, 3'-Azido-3'-Deoxythymidine), MOA, clinical use
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MOA: Mammalian thymidine kinase converts the drug to AZT-TP which is incorporated into viral DNA and terminates chain elongation. AZT affects viral replication more than cellular replication since the viral reverse transcriptase is less discriminating than cellular DNA polymerases. Therapeutic use: AZT is the drug most frequently given to HIV patients. AZT protects fetuses from becoming infected in HIV-infected pregnant women.
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Zidovudine (AZT, 3'-Azido-3'-Deoxythymidine): resistance and toxicity
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Resistance: Patients often become resistant to the drug because the reverse transcriptase becomes mutated and then has a lower affinity for AZT-TP. Toxicity: The main toxicity is associated with bone marrow problems including anemia and leucopenia. In addition, patients who take AZT often have headaches. Other toxicities include peripheral lipoatrophy, central fat accumulation and hyperlipidemia. NEW: Trizivir: Zidovudine, Lamivudine and Abacavir is a single pill with 3 drugs that makes it easier for the patients to be compliant with taking their medications.
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Didanosine (ddI)
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MOA: Didanosine inhibits reverse transcriptase and terminates DNA chain elongation. Therapeutic use: Didanosine is given to patients with AZT-resistant HIV infections. Resistance: Patients become resistant to the drug because the reverse transcriptase becomes mutated. Toxicity: Didanosine may cause pancreatitis that may be fatal. Pancreatitis may be indicated by abdominal pain that penetrates to the back. It is important for the doctor to monitor serum amylase levels that rise on the first days of illness but then return to normal. Patients taking Didanosine may also experience a dose-limiting peripheral neuropathy.
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Zalcitabine (ddC)
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MOA: Zalcitabine inhibits reverse transcriptase and terminates DNA chain elongation. Therapeutic use: Zalcitabine is given in conjunction with AZT or alone for those who cannot tolerate AZT- treatment. Resistance: Patients become resistant to the drug because the reverse transcriptase becomes mutated. Toxicity: Peripheral neuropathy, rash and stomatitis on initial treatments are toxicities associated with the use of Zalcitabine.
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Stavudine (d4T)
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MOA: Stavudine inhibits reverse transcriptase and terminates DNA chain elongation.
Therapeutic use: Stavudine is given for HIV infections. Toxicity: Stavudine may cause peripheral neuropathy, potentially fatal lactic acidosis, peripheral lipoatrophy, central fat accumulation and hyperlipidemia. |
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Lamivudine (3TC)
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MOA: Abacavir inhibits reverse transcriptase and terminates DNA chain elongation. Therapeutic use: Abacavir is given to HIV infected adults and children in combination with Zidovudine and Lamivudine or a protease inhibitor. Toxicity: Abacavir may cause hypersensitivity resulting in fever, gastrointestinal distress, malaise and rash.
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Tenofovir
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MOA: Inhibits reverse transcriptase and terminates DNA chain elongation. Therapeutic use: HIV infected patients and chronic hepatitis B infections. Women using a vaginal gel of Tenofovir prophylactically before and after having sex had a 39% reduced risk of becoming infected by the virus compared to those who were given a placebo.In 2010 the Pre-Exposure Prophylaxis Initiative published results that showed there was a 44-92% reduction. In 2010 the Pre-Exposure Prophylaxis Initiative published results that showed there was a 44-92% reduction
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Non-nucleoside Reverse Transcriptase Inhibitors
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Efavirenz, Nevirapine, Delaviridine,
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Efavirenz: MOA and clinical use
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MOA: Efavirenz binds next to the reverse transcriptase activation site, altering the conformation of the enzyme and thereby inhibiting its activity. Therapeutic use: Efavirenz is used in combination with Zidovudine and Lamivudine. Toxicity: Efavirenz may cause dizziness, headache, insomnia and rash. In addition the drug will occasionally cause nightmares and hallucinations.
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Drug interactions and toxicity of efavirenz
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Drug interactions: There are a lot of drug interactions you need to consider when using this drug. Efavirenz decreases the concentration of Phenobarbital, Phenytoin, Carbamazepine, Methadone and Rifabutin. Coadministration of Rifampin will reduce levels of Efavirenz. Please see table for interactions with HIV protease inhibitors. Atripla is single pill that contains Efavirenz, Emtricitabine, Tenofovir is available. Toxicity: Efavirenz may cause headaches, dizziness, abdominal pain, nausea, vomiting, rash, lactic acidosis, liver toxicity, renal impairment and severe depression. Do not give Efavirenz to patients with chronic Hepatitis B infection since it may produce a hypersensitivity reaction.
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Nevirapine
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MOA: Nevirapine inhibits the reverse transcriptase. Therapeutic use: Nevirapine is used in combination with Didanosine and Stavudine to treat HIV. Toxicity: Nevirapine may produce a rash, fever, nausea, severe dermatologic effects and fatal hepatotoxicity Drug interaction: St. John's Wort lowers the concentration of Nevirapine. Nevirapine induces CYP3A4 and therefore it may lower the concentration of drugs metabolized by this enzyme. Rifampin and Ketoconazole should not be administered to patients receiving Nevirapine. Also, Nevirapine lowers plasma concentrations of Ethinyl estradiol and therefore patients should be given alternate methods of birth control.
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Delaviridine
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MOA: Delaviridine binds and inhibits reverse transcriptase. Therapeutic use: Delaviridine is used in combination with Zidovudine and Didanosine to treat HIV. Toxicity: Rash is less frequent and severe with Delaviridine compared to other nnRTIs. Drug interactions: Delaviridine inhibits CYP3A4 and may thus alter the metabolism of Rifampin, Rifabutin, Ergot derivatives, Triazolam, Midazolam and Cisapride. Delaviridine also inhibits CYP2C9. Drugs that induce CYP3A4, such as Carbamazepine, Penobarbital, Phenytoin, Rifabutin and Rifampin, may decrease Delaviridine levels.
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Protease Inhibitors
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Atazanavir, Indinavir, Ritonavir, Lopinavir, Nelfinavir, Amprenavir, Saquinavir
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MOA and clinical use of protease inhibitors
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MOA: These drugs interfere specifically with proteolysis of the gag-pol precursor and thereby lead to nonfunctional virions.
Therapeutic use: HIV patients must take the drugs continuously in combination with AZT and Lamivudine or other nucleoside reverse transcriptase inhibitors. Atazanavir may be taken orally once per day. Toxicity: Protease inhibitors are well tolerated, however sometimes nausea, vomiting, diarrhea, lipodystrophy and hyperglycemia may occur with the use of protease inhibitors. |
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Drug interactions and toxicity of protease inhibitors
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Drug interactions: Atazanavir has less of an effect on the patient’s lipid profile than other protease inhibitors. Ritonavir interacts with benzodiazepines, antiarrhythmic agents, narcotics and some antibiotics often given to AIDS patients. Since protease inhibitors are metabolized by the P450 system, inducers (Rifampin and Rifabutin) and inhibitors (Ketoconazole and Itraconazole) should be avoided. Amprenavir inhibits CYP3A4 activity and therefore should not be given with Midazolam, Triazolam, Bepridil, Ergotamine, or Dihydroergotamine. In addition, drug interactions may occur when a patient is taking protease inhibitors and any of the following drugs: Cisapride, Amiodarone, systemic Lidocaine, Warfarin, tricyclic antidepressants, Rifabutin, statins and Sildenafil (Viagra). Rifampin induces 3A4 and therefore may lower Amprenavir levels dramatically. Efavirenz lowers serum levels of Amprenavir, while Ritonavir increases levels. St. John's wort lowers the concentration of Indinavir, Ritonavir and Saquindvir. Resistance: Cross-resistance often occurs among the protease inhibitors. When cross-resistance occurs the HIV strain may still be susceptible to Amprenavir.
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Lopinavir/Ritonavir
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is a combination of protease inhibitors often given together. Pharmacokinetics: Lopinavir is metabolized by P450 CYP3A. Ritonavir is an inhibitor of CYP3A4 activity and therefore it raises Lopinavir plasma levels. Therapeutic use: The combination of drugs is used to treat HIV strains that are resistant to multiple protease inhibitors. Toxicity: The combination of the two drugs is well tolerated but it may cause diarrhea, nausea, fatigue, headache, hyperlipidemia, hyperglycemia, and altered body fat. Drug interactions: The combination of the two drugs inhibits the activity of CYP3A4 and CYP2D6 and therefore may increase or prolong the therapeutic or adverse effects of drugs metabolized by these pathways.
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Fusion Inhibitors- Enfuvirtide and Maraviroc
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MOA: The HIV viral envelope glycoprotein undergoes a conformational change when it binds to the host cell surface. Enfuvirtide binds to the glycoprotein and prevents the conformational change. Maraviroc is a chemokine receptor 5 (CCR5) inhibitor. Therapeutic use: Enfuvirtide is injected twice daily in HIV patients. Maraviroc is used in adults with CCR5-tropic HIV-1. CCR5 is a co-receptor for viral entry into the cell. Toxicity: Enfuvirtide may cause pain, erythema, nodules and cysts formation at the site of injection. Maraviroc may cause respiratory infection, rash, musculoskeletal symptoms, abdominal pains and postural dizziness. In addition, hepatotoxicity may occur with Maraviroc. Drug interactions: Inducers and inhibitors of CYP3A may effect Maraviroc
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