Medicinal chemistry of drugs used in diabetic cardiomyopathy

E. Adeghate, H. Kalasz, G. Veress, K. Tekes

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)

Abstract

Diabetes mellitus is a common disease and contributes to a high degree of morbidity and mortality. Cardiovascular complications, including diabetic cardiomyopathy are major causes of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy is a condition that affects the myocardium, primarily. It is not necessarily associated with ischemic heart disease, high blood pressure, valvular or congenital anomalies. The pathology of diabetic cardiomyopathy includes interstitial fibrosis, apoptosis of cardiomyocytes, abnormal energy utilization, small vessel disease and cardiac neuropathy. These pathologies are induced by hyperglycemia and oxidative stress. Biochemical as well as electrolyte changes, especially reduced calcium availability also occurs in the myocardium of diabetic patients. The abnormal structure and biochemistry of the myocardium result in functional problems such as diastolic and systolic dysfunctions, which may cause symptoms of dyspnea and inability to tolerate exercise. No single specific therapeutic agent can treat diabetic cardiomyopathy because once the disease is overt, the management may require a variety of approaches such as risk factors and lifestyle modification, glucose control (insulin, alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones and dipeptidyl peptidase 4 (DPP-4) inhibitors); hormones (IGF-1); ACE inhibitors (captopril, enalapril); angiotensin II receptor antagonists (losartan, olmesartan); beta adrenoreceptor antagonists (acebutolol, carvedilol); peptides (adrenomedullin); endothelin-1 receptor antagonists (bosentan, tezosentan); calcium channel blockers (amlodipine, verapamil); antioxidants (methalothionein, alpha tocopherol, alpha lipoic acid) and antihyperlipidemic drugs (simvastatin, fenofibrate, ezetimibe) to effectively treat patients with diabetic cardiomyopathy.

Original languageEnglish
Pages (from-to)517-551
Number of pages35
JournalCurrent Medicinal Chemistry
Volume17
Issue number6
DOIs
Publication statusPublished - Feb 2010

Keywords

  • ACE inhibitors
  • Angiotensin II receptor antagonists
  • Antidiabetic drugs
  • Antioxidants
  • Beta adrenoreceptor blockers
  • Calcium channel blockers
  • Cardiomyopathy
  • Diabetes mellitus
  • Endothelin-1 receptor antagonists
  • Fenofibrates
  • Heart failure
  • PPAR-receptor antagonists
  • Peptides
  • Statins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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