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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].
Show detailsOVERVIEW
Antihypertensive medications are some of the most important and commonly used drugs in medical practice. Hypertension affects at least 50% of persons over the age of 60 and is an important cause of morbidity and mortality from cardiovascular and cerebrovascular disease.
More than 50 medications are used in the therapy of hypertension. The drugs can be categorized into seven major classes: (1) diuretics, (2) sympatholytic drugs, (3) calcium channel blockers, (4) angiotensin converting enzyme [ACE] inhibitors, (5) angiotensin II receptor antagonists/blockers [ARBs], (6) direct renin antagonists, and (7) various vasodilators.
Overall, the antihypertensive agents are rare causes of drug induced liver injury, the exceptions being two agents that have been in use for more than 50 years and are now not commonly used: methyldopa and hydralazine. The other antihypertensive drugs have been linked to drug induced liver injury only in isolated case reports and are rarely listed in large case series of acute liver failure or clinically apparent liver injury with jaundice due to medications.
The diuretics can be categorized into four groups: thiazides, loop diuretics, potassium-sparing diuretics, and carbonic anhydrase inhibitors. Some of these agents have been implicated in causing liver injury in rare single case reports.
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Sympatholytic drugs include alpha- and beta-adrenergic receptor antagonists (alpha blockers and beta blockers) as well as centrally acting agents such as clonidine, guanabenz, methyldopa, minoxidil, and reserpine. These agents rarely cause liver injury, the exception being methyldopa which can cause acute or chronic hepatitis, that can be severe, resulting in acute liver failure or cirrhosis.
Calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin inhibitors are some of the most potent and well tolerated antihypertensive agents and are widely used. Many of these agents have been implicated in causing clinically apparent liver injury, but only in isolated case reports.
Finally, various arterial and venous vasodilators are useful for managing hypertension in special situations. Guanfacine, minoxidil and nitroprusside have not been implicated in causing liver injury. In contrast, hydralazine is a well known cause of clinically apparent liver injury, often presenting with autoimmune features.
Heart Failure Agent
ANNOTATED BIBLIOGRAPHY
References updated: 20 July 2017
- Zimmerman HJ. Antihypertensive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd edition. Philadelphia: Lippincott Williams & Wilkins, 1999. p. 654-60.(Expert review of drug induced liver injury due to antihypertensive agents published in 1999 discusses captopril, hydralazine and methyldopa).
- De Marzio DH, Navarro VJ. Antihypertensives. Hepatotoxicity of cardiovascular and antidiabetic drugs: antihypertensives. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 522-5.(Review of hepatotoxicity of antihypertensive agents discusses hydralazine, diuretics, ACE inhibitors, ARBs, beta blockers, calcium channel blockers and methyldopa).
- Michel T, Hoffman BB. Treatment of myocardial ischemia and hypertension. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 745-88.(Textbook of pharmacology and therapeutics).
- Drugs for hypertension. Treat Guidel Med Lett 2014; 12 (141): 31-8. [PubMed: 24759265](Concise summary recommendations for treatment of hypertension and current understanding of indications, efficacy and safety).
- Drugs for hypertension. Med Lett Drugs Ther 2017; 59 (1516): 41-8. [PubMed: 28263286](Concise summary recommendations for treatment of hypertension and current understanding of indications, efficacy and safety).
- PubMedLinks to PubMed
- Review Development and trends in the drug treatment of essential hypertension.[J Hypertens Suppl. 1992]Review Development and trends in the drug treatment of essential hypertension.van Zwieten PA. J Hypertens Suppl. 1992 Dec; 10(7):S1-12.
- Review Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis.[BMJ. 2013]Review Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis.Wu HY, Huang JW, Lin HJ, Liao WC, Peng YS, Hung KY, Wu KD, Tu YK, Chien KL. BMJ. 2013 Oct 24; 347:f6008. Epub 2013 Oct 24.
- Review First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension.[Cochrane Database Syst Rev. 2015]Review First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension.Xue H, Lu Z, Tang WL, Pang LW, Wang GM, Wong GW, Wright JM. Cochrane Database Syst Rev. 2015 Jan 11; 1:CD008170. Epub 2015 Jan 11.
- Review [Are all antihypertensive drugs renoprotective?].[Herz. 2004]Review [Are all antihypertensive drugs renoprotective?].Wolf S, Risler T. Herz. 2004 May; 29(3):248-54.
- Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes: A Comparative Effectiveness Study.[Clin J Am Soc Nephrol. 2018]Add-On Antihypertensive Medications to Angiotensin-Aldosterone System Blockers in Diabetes: A Comparative Effectiveness Study.Schroeder EB, Chonchol M, Shetterly SM, Powers JD, Adams JL, Schmittdiel JA, Nichols GA, O'Connor PJ, Steiner JF. Clin J Am Soc Nephrol. 2018 May 7; 13(5):727-734. Epub 2018 Mar 23.
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