Medicinal chemistry of drugs used in diabetic cardiomyopathy

Curr Med Chem. 2010;17(6):517-51. doi: 10.2174/092986710790416281.

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.

Publication types

  • Review

MeSH terms

  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / therapeutic use
  • Cardiomyopathies / drug therapy*
  • Cardiomyopathies / etiology
  • Diabetes Complications / drug therapy*
  • Diabetes Mellitus / drug therapy*
  • Endothelin-1 / antagonists & inhibitors
  • Endothelin-1 / metabolism
  • Fenofibrate / analogs & derivatives
  • Fenofibrate / chemistry
  • Fenofibrate / therapeutic use
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / therapeutic use
  • Peroxisome Proliferator-Activated Receptors / antagonists & inhibitors
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Receptors, Angiotensin / metabolism

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Calcium Channel Blockers
  • Endothelin-1
  • Hypoglycemic Agents
  • Peroxisome Proliferator-Activated Receptors
  • Receptors, Angiotensin
  • fenofibric acid
  • Fenofibrate