Drugs that Affect Cardiac Metabolism: Focus on Perhexiline.
Approaches to the pharmacotherapy of angina pectoris have previously centred on the concept that a transient imbalance between myocardial oxygen "demand" and supply within the myocardium can best be addressed by reducing demand (for example, with β-adrenoceptor antagonist) or by increasing availability of blood (via coronary vasomotor reactivity adjustment or coronary revascularization). However, this principle is potentially challenged by the emergence of cases of angina unsuitable for such therapies (for example because of concomitant severe systolic heart failure) and by the recognition that impaired myocardial energetics may precipitate angina in the absence of fixed or variable coronary obstruction (for example in hypertrophic cardiomyopathy). The past 20 years have seen the re-emergence of a class of anti-anginal agents which act primarily by improving efficiency of myocardial oxygen utilization, and thus can correct impaired energetics, simultaneously treating angina and heart failure symptoms. We review the principles underlying the safe use of such agents, beginning with the prototype drug perhexiline maleate, which despite complex pharmacokinetics and potential hepato- or neuro-toxicity has emerged as an attractive management option in many "complicated" cases of angina pectoris.
Cardiology Unit, The Queen Elizabeth Hospital, 28, Woodville Road, Woodville South, SA, 5011, Australia.|Clinical Pharmacology Department, The Queen Elizabeth Hospital, Basil Hetzel Institute, Woodville South, SA, 5011, Australia.|School of Medicine, University of Adelaide, Adelaide, Australia.
Cher-Rin
CR
Chong
Clinical Pharmacology Department, The Queen Elizabeth Hospital, Basil Hetzel Institute, Woodville South, SA, 5011, Australia.|School of Medical Science, University of Adelaide, Adelaide, Australia.
Benedetta
B
Sallustio
Cardiology Unit, The Queen Elizabeth Hospital, 28, Woodville Road, Woodville South, SA, 5011, Australia. john.horowitz@adelaide.edu.au.|Clinical Pharmacology Department, The Queen Elizabeth Hospital, Basil Hetzel Institute, Woodville South, SA, 5011, Australia. john.horowitz@adelaide.edu.au.|School of Medicine, University of Adelaide, Adelaide, Australia. john.horowitz@adelaide.edu.au.
John D
JD
Horowitz
D000787:Angina Pectoris / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010480:Perhexiline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D002317:Cardiovascular Agents; D005227:Fatty Acids; D005947:Glucose; C023470:perhexiline maleate; D010480:Perhexiline
Angina; Myocardial metabolism; Perhexiline