Nursing Pharmacology:  Antiviral Drugs

• Antiviral Drugs

  • Anti-viral drugs with activity against HIV (Human Immunodeficiency Virus)

    • HIV-1 Pathophysiology/Pathogenesis:  HIV Disease Presentations

      Hepatobiliary Dysfunction in HIV (continued)

      • In addition to hepatitis B and hepatitis C viruses, numerous other infectious agents can contribute to hepatic pathologies such as hepatocellular necrosis or granulomatous inflammation.⁹

        • Hepatocellular Necrosis¹⁶

          Kleiner DE Acute Hepatic necrosis (due to acetominophen) "A few viable hepatocytes are left near the vein, but most are present as hepatocyte ghosts. "Macrophages (arrows) have infiltated into the necrotic zone. "Hepatocytes around the edges of the necrosis show ballooning injury and steatosis*." *steatosis:  fatty degeneration

        •  

          Granulomatous inflammation¹⁷

          Greenson JK Granulomatous inflammation PBC:  primary biliary cirrhosis

        • Hepatocellular pathologies may be caused by:

          • Cytomegalovirus (CMV)

          • Epstein-Barr virus (EBV)

          • Adenovirus

          • Herpes simplex virus (HSV)⁹ 

        • Mycobacterial and fungal organisms may also promote granulomatous inflammations.⁹ 

          • The most common opportunistic hepatic pathogen in the mycobacterial group is Mycobacterium avium complex (MAC).

            • M. avium complex infection may result in disseminated disease.

              • Symptoms associated with disseminated disease may include fever, sweats, weight loss and anemia.

        • Extrapulmonary Mycobacterium tuberculosis (M. tuberculosis) may cause hepatic disease in about 5%-10% of HIV-related cases.⁹ 

          • Mycobacterium tuberculosis¹⁵

            Ewing Jr EP/CDC Mycobacterium tuberculosis,  1994

          • Widespread fungal infections by a number of pathogens may cause hepatic granulomatous reactions.  Such pathogens include:⁹

            • Cryptococcus neoformans (C. neoformans)

              • Cryptococcus neoformans¹⁴

                Beards G Cryptococcus neoformans, an encapsulated years, stained by Gram's method (Demers T, preparation), Feb. 18, 2012 http://en.wikipedia.org/wiki/Cryptococcus_neoformans http://commons.wikimedia.org/wiki/File:Cryptococcus_Gram_film.jpg

            • Histoplasma capsulatum (H. capsulatum)

              •  

                Histoplasma capsulatum¹³ 

                Ajello L/CDC (Centers for Disease Control and Prevention) Histoplasmosis capsulatum "Note the histopathologic changes seen in histoplasmosis due to Histoplasma capsultum using methenamine silver stain. "Note the presence of typical yeast cells, some of which are undergoing replication by 'budding'.  Histoplasmosis can be confined to the lungs, or become systemically disseminated,  thereby, producing a fatal outcome."

            • Coccidioides immitis (pathogenic fungus)

              • Coccidioides immitis¹²

                Hardin/CDC Arthrocondia of Coccidioides immitis, 1965

            • Penicillium marneffei

              • Penicillium marneffei¹¹

                Gathany J (Centers for Disease Control and Prevention, CDC) The surface of a Penicillium marneffei colony http://en.wikipedia.org/wiki/Penicillium_marneffei http://commons.wikimedia.org/wiki/File:Penicillium_marneffei_colony.jpg

            • Candida albicans (C. albicans)

              • Candida albicans¹⁰

                Colm  G Candida albicans http://commons.wikimedia.org/wiki/File:Candida_albicans_2.jpg

                 

        • Pneumocystis jirovecii (P. jirovecii, PCP) is another cause of liver infection and may be more often observed during pentamidinec prophylaxis.⁹ 

        • Bartonella henselae infection may result in peliosis hepatitis.

          • Peliosis hepatitis is more likely associated with profound immunodeficiency.

      • Finally, prior to generalized use of cART (combination anti-retroviral treatment), the most frequently observed hepatic malignancy was Kaposi's sarcoma.⁹

References

Flexner C Antiretroviral Agents and Treatment of HIV Infection, Chapter 59  in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition (Brunton LL Chabner BA Knollmann BC, eds; Brunton LL, ed; Blumenthal DK  Murri N Hilal-Dandan R, assoc eds, Knollmann BC, consulting ed, on-line edition) The McGraw-Hill Companies, 2011. Fauci AS Lane HC Chapter 189, Human Immunodeficiency Virus Disease:  AIDS and Related Disorders, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Longo DL Fauci AS  188, The Human Retroviruses, in Harrison's Online   (Dan L. Longo, Anthony S. Fauci, Dennis L. Kasper, Stephen L. Hauser, J. Larry Jameson, Joseph Loscalzo, Eds.),  Harrison's Principles of Internal Medicine, 18th edition, The McGraw-Hill Companies, Inc. 2012. Woster PM Chapter 43:  Antiviral Agents and Protease Inhibitors in Foye's Principles of Medicinal Chemistry 6e, Lemke, TL Williams DA, eds; Roche VG Zito SW, asst eds) Wolters Kluwer|Lippincott Williams & Wilkins 1214, 2008. Knox TA Wanke C Gastrointestinal Manifestations of HIV and AIDS  Chapter 397, pp 2196-2199 Goldman's Cecil Medicine 24e (Goldman L and Schafer AI, eds) Elsevier/Saunders, 2012. Public Domain:  Digestive system diagram. http://commons.wikimedia.org/wiki/File:Digestive_system_showing_bile_duct.png Emannuelm Opened gall bladder containing numerous gallstones. http://en.wikipedia.org/wiki/Gallstone; http://commons.wikimedia.org/wiki/File:Gallstones.jpg . Heilman J "A 1.9 cm gallstone impacted in the neck of the gallbladder and leading to cholecystitis. http://commons.wikimedia.org/wiki/File:Gallstones.PNG Haines C Sulkowski MS Gastrointestinal, Hepatobiliary and Pancreatic Manifestations of Human Immunodeficiency Virus Infection.  Chapter 126, 1567-1573 in Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8e, Bennett, JE Dolin R Blaser MJ, eds, 2015). Colm  G Candida albicans http://commons.wikimedia.org/wiki/File:Candida_albicans_2.jpg ; http://en.wikipedia.org/wiki/Candida_albicans Gathany J (Centers for Disease Control and Prevention, CDC) The surface of a Penicillium marneffei colony http://commons.wikimedia.org/wiki/File:Penicillium_marneffei_colony.jpg ; http://en.wikipedia.org/wiki/Penicillium_marneffei   Hardin/CDC Arthrocondia of Coccidioides immitis, 1965 http://commons.wikimedia.org/wiki/File:Arthroconidia_of_Coccidioides_immitis_39G0040_lores.jpg ; http://phil.cdc.gov/PHIL_Images/11121998/00004/39G0040_lores.jpg Ajello L/CDC (Centers for Disease Control and Prevention) Histoplasmosis capsulatum; http://en.wikipedia.org/wiki/Histoplasmosis ; http://commons.wikimedia.org/wiki/File:Histoplasmosis_capsulatum.jpg Beards G Cryptococcus neoformans, an encapsulated years, stained by Gram's method (Demers T, preparation), Feb. 18, 2012; http://en.wikipedia.org/wiki/Cryptococcus_neoformans ; http://commons.wikimedia.org/wiki/File:Cryptococcus_Gram_film.jpg Ewing Jr EP/CDC Mycobacterium tuberculosis,  1994; http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis ; http://commons.wikimedia.org/wiki/File:Mycobacterium_tuberculosis_Ziehl-Neelsen_stain_640.jpg Kleiner DE Acute Hepatic necrosis LiverTox:  Clinical and Research Information on Drug-Induced Liver Injury, United States National Library of Medicine ; http://livertox.nih.gov/Phenotypes_ahn.html#top Greenson JK Granulomatous inflammation http://www.pathology.med.umich.edu/greensonlab/M2liverlecture.html .

 

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