Renin-angiotensin system agents

Tricyclic Antidepressants Renin-Angiotensin System Agents... 

A summary of the agents that inhibit the renin-angiotensin system and their sites of action is provided in Figure 18.3. 

In view of the importance of the renin-angiotensin system in cardiovascular disease, considerable effort has been directed to developing drugs that inhibit the system. A wide variety of agents that block the formation or action of Ang II is now available. Some of these drugs block renin secretion, but the newer ones inhibit the conversion of Ang I to Ang II, block angiotensin AT receptors, or inhibit the enzymatic action of renin. 

Drug Interactions Agents increasing serum potassium Diuretics Drugs which act on the renin-angiotensin system ... 

The release of renin is altered by a wide variety of pharmacologic agents. Renin release is stimulated by vasodilators (hydralazine, minoxidil, nitroprusside), (3-adrenoceptor agonists (isoproterenol), ft-adrenoceptor antagonists, phosphodiesterase inhibitors (theophylline, milrinone, rolipram), and most diuretics and anesthetics. This stimulation can be accounted for by the control mechanisms just described. Drugs that inhibit renin release are discussed below in the section on inhibition of the renin-angiotensin system. 

Agents that interact with the renin-angiotensin system... 

Hypertensive patients with normal or high renin levels can benefit from treatment with agents which affect the renin-angiotensin system. 

If the blood pressure is still not controlled, a second agent should be added, using the opposite pair to the first drug e.g. if the patient is on an ACE inhibitor add a Calcium channel blocker or thiazide Diuretic (A+C or A+D), since both vasodilatation or diuresis will stimulate the renin-angiotensin system and turns nonrenin-dependent hypertension into renin-dependent hypertension). The combination B+D is associated with increased risk of diabetes and should be avoided in at-risk patients (obesity, family history). The combinations A+B or C+D usually produce a less than additive effect on blood pressure, but should be tried in patients still uncontrolled on more standard combinations. 

Thus far, no reports have been published on membranous glomerulopathy or acute interstitial nephritis in relation to the use of angiotensin It receptor antagonists. Whether this is due to the relatively short experience with these agents, or the fact that these ACET induced side effects are specific for ACEl and thus not related to the interference in the renin angiotensin system in general, cannot be concluded as yet. 

Introduction - The search for new antihypertensives and for a better understanding of existing ones remains quite intense with emphasis this past year on 3-blockers (see Chapter 9) and on agents that affect the renin-angiotensin system. Diuretics were reviewed last year and are not included in this chapter. Structures of drugs mentioned in this review are shown or may be found in recent volumes of Annual Reports in Medicinal Chemistry. 

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