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)

      • Effects of Anti-Retroviral Medications (continued)⁶

        • Administration of some nucleoside analogues which inhibit reverse transcriptase may result in fatal hepatomegaly with associated stenosis and lactic acidosis.⁶ 

           

          • Liver Biopsy Showing Macrovacuolar Steatosis¹¹

            "Liver biopsy from an HIV-infected patients who presented with zidovudine-related lactic acidosis (x500). "Marked macrovaculolar steatosis with rare lipid microvacuoles can be seen." Figure above corresponds to figure 2 of reference 11. Ogedegbe A-E O Thomas DL Diehl AM Hypertactataemia syndromes associated with HIV therapy (Review) Lancet Infectious Disease 3:  329-337, 2003.

          •  

            "Micrograph of Non-alcoholic fatty liver disease (NAFLD)."¹⁰

            Nephron  "Micrograph of non-alcoholic fatty liver disease (NAFLD). Masson's trichrome & Verhoeff stain" "The liver has a prominent (centrilobular) macrovesicular steatosis (white/clear round/oval spaces) and mild fibrosis (green). "The hepatocytes stain red. "Macrovesicular steatosis is lipid accumulation so large it distors the cell's nucleus. "Differential diagnosis of centrolobular (zone III) macrovescular hepatic steatosis: Diabetes Obesity Alcohol" http://en.wikipedia.org/wiki/Fatty_liver http://commons.wikimedia.org/wiki/File:Non-alcoholic_fatty_liver_disease1.jpg

          •  

            Computed Tomography (CT) image:  Liver steatosis (fatty liver)⁹ 

            Heilman J Liver steatosis (fatty liver):  CT image http://commons.wikimedia.org/wiki/File:Liversteatosis.png http://en.wikipedia.org/wiki/Fatty_liver

          • Examples of such drugs include zidovudine (AZT) and stavudine.

          • The association between lactic acidosis steatosis has been documented in clinical studies.⁷ 

            • One example study considered for clinical cases in which patients taking stavudine exhibited lactic acidosis, hepatic steatosis and myopathy.⁷ 

              • This was a small clinical study consisting of two men and two women, both HIV positive.

                • These individuals presented with lactic acidosis and elevated aminotransferase serum levels.

                  • Some patients underwent liver biopsy and muscle biopsy.

                    • Histologic findings from biopsy not only suggested that hepatic/muscle abnormality but also suggested mitochondrial injury.

              • For example, one patient, a 63-year-old obese HIV-infected woman presented with a 1-month history including nausea, abdominal pain with vomiting.⁷ 

                • The medical workup found severe metabolic acidosis with an arterial blood pH of 7.12, along with notably elevated serum lactate levels with hepatic steatosis and pancreatitis.

                  • The patient had been using stavudine and lamivudine for the prior six months.

                  • These agents were discontinued with the patient eventually recovering and new antiretroviral therapy consisting of nelfinavir, saquinavir and nevirapine substituting for previous antiretrovirals.

                    • The above described illness did not recur. The other patients followed a generally similar pattern.

              • The authors note that this type of life-threatening hepatic steatosis and lactic acidosis presentation, albeit uncommon, was identified in the early 1990s.⁷ 

                • By 1994, 40 cases had been reported to regulatory agencies.

                • In those instances zidovudine and didanosine were considered likely causative with the underlying mechanism proposed to be involving dysfunction of mitochondrial DNA replication.⁷

                 

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. 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). Miller KD Cameron M Wood LV Dalakas MC Kovacs JA Lactic Acidosis and Hepatic Steatosis Associated with Use of Stavudine:  Report of Four Cases (Brief Communication).  Annals of Internal Medicine 133(3) 192-196, 1 August 2000. Hepatic Steatosis http://en.wikipedia.org/wiki/Fatty_liver  ; http://en.wikipedia.org/wiki/File:Steatosis.jpg Heilman J Liver steatosis (fatty liver):  CT image http://en.wikipedia.org/wiki/Fatty_liver ;  http://commons.wikimedia.org/wiki/File:Liversteatosis.png Nephron  "Micrograph of non-alcoholic fatty liver disease (NAFLD). Masson's trichrome & Verhoeff stain" http://en.wikipedia.org/wiki/Fatty_liver  ; http://commons.wikimedia.org/wiki/File:Non-alcoholic_fatty_liver_disease1.jpg Ogedegbe A-E O Thomas DL Diehl AM Hypertactataemia syndromes associated with HIV therapy (Review) Lancet Infectious Disease 3:  329-337, 2003.

 

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