ACE inhibitors (angiotensin-converting enzyme inhibitors) prevent production of angiotensin II from angiotensin I. The angiotensin II receptor antagonists are more selective, and target angiotensin II type I (AT1) receptor, which is responsible for pressor actions of angiotensin
Angiotensin II is involved in renin-angiotensin-aldosterone system, which regulates blood pressure, sodium and water homoeostasis by kidneys, and cardiovascular function. Angiotensin II stimulates synthesis and secretion of aldosterone and raises blood pressure via a direct vasoconstrictor effect.
Angiotensin converting enzyme (ACE) is identical to bradykinase, so ACE inhibitors may additionally reduce degradation of bradykinin and affect enzymes involved in production of prostaglandins.
Many of interactions of ACE inhibitors and angiotensin II receptor antagonists involve drugs that affect blood pressure. Consequently in most cases result is either an increase in hypotensive effect (e.g. alcohol, ) or a decrease in hypotensive effect (e.g. indometacin,).
In addition, due to their effects on aldosterone, ACE inhibitors and angiotensin II antagonists may increase potassium concentrations and can therefore have additive hyperkalaemic effects with other drugs that cause elevated potassium levels. Furthermore, drugs that affect renal function may potentiate adverse effects of ACE inhibitors and angiotensin II antagonists on kidneys.
Most ACE inhibitor and angiotensin II receptor antagonist interactions are pharmacodynamic, that is, interactions that result in an alteration in drug effects rather than drug disposition, so in most cases interactions of individual drugs will be applicable to group. In vitro experiments suggest that role of cytochrome P450 isoenzymes in metabolism and interactions of angiotensin II receptor antagonists (candesartan, eprosartan, irbesartan, losartan and valsartan) is small, although losartan, irbesartan, and to a minor extent, candesartan, are metabolised by CYP2C9. Only losartan and irbesartan were considered to have a theoretical potential for pharmacokinetic drug interactions involving CYP2C9 enzyme.(See reference number 1)See Angiotensin II receptor antagonists + Azoles interaction. The ACE inhibitors do not appear to undergo interactions via cytochrome P450 isoenzymes.
table 1 below, (see below) lists ACE inhibitors and angiotensin II receptor antagonists. Although most of interactions of ACE inhibitors or angiotensin II receptor antagonists are covered in this section, if ACE inhibitor or angiotensin II receptor antagonist is affecting drug, interaction is dealt with elsewhere.
1. Taavitsainen P,Kiukaanniemi K, Pelkonen O. In vitro inhibition screening of human hepaticP450 enzymes by five angiotensin-II receptor antagonists. Eur J Clin Pharmacol (2000) 56, 135–40.
Benazepril,Captopril, Cilazapril, Delapril, Enalapril, Fosinopril, Imidapril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Spirapril, Temocapril, Trandolapril, Zofenopril
Candesartan,Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan
|Table 1 ACE inhibitors and Angiotensin II receptor antagonists|
|ACE inhibitors||Benazepril, Captopril, Cilazapril, Delapril, Enalapril, Fosinopril, Imidapril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Spirapril, Temocapril, Trandolapril, Zofenopril|
|Angiotensin II receptor antagonists||Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan|