pharma fouda 2_p55-56.pdf

█ Angiotensin--convertin ng enzym me inhibittors (ACE EIs) ▌Back kground ▌The rrenin-angiotensin-aldosteron ne (...

█ Angiotensin--convertin ng enzym me inhibittors (ACE EIs) ▌Back kground ▌The rrenin-angiotensin-aldosteron ne (RAAS) system  Whe ccurs, therre is ↓ RBF and ↓ GFR. This m en renal isschemia oc may lead to acute olig guria that may m develo op to acutee tubular necrosis.  As a compensatory me echanism, rrenin is re eleased fro om the juxttaglomerular cells of the kidney as a rescu ue messag e to initiate e stimulation of RAA AS as follow ws:  Ang g-II acts on n AT1 rece eptors in th he efferent arterioles s of the kid dney causing their VC and thus maintains m adequate a GFR in spiite of the ↓ RBF. G  Unffortunatelyy, Ang-II ac 1 receptorrs in other vascular beds and tissues cts on AT1 cau using systemic VC, cell hyp pertrophy, and apoptosis ((i.e. degen nerative cha anges). 152 Should we inhibit the RAAS?! Inhibitors of RAAS  Inhibition of the RAAS will  Inhibitors of renin release: β-blockers, correct the hypertension but α-methyldopa, and clonidine. also will ↓ GFR and aggravate  Inhibitors of plasma renin activity: RF if renal ischemia was grave. aliskiren.  Normal S. creatinine is 0.3-1.2  Inhibitors of Ang-2 formation: ACEIs mg/dl. If S. creatinine is up to 3  AT1 receptor blockers (ARBs) e.g. mg/dl (i.e. mild renal impairm- losartan, valsartan ent) → you can block RAAS.  If S. creatinine >3 mg/dl (i.e. severe renal impairment) → blocking the RAAS is dangerous and will aggravate RF. █ Angiotensin converting enzyme inhibitors Classification  SH-containing drugs: Captopril, zofenopril, alacepril  Non SH-containing drugs: Enalarpril, fosinopril, lisinopril, benazepril, ramipril Pharmacological properties of some ACEIs Captopril Fosinopril Enalapril Lisinopril Benazepril SH group + – – – – Immune S/E + – – – – Prodrug – + + – + Metabolism Liver, Liver, Liver No Liver, kidney kidney metabolism kidney Onset 1–4h Frequency of /8 h /12 h /12 h /24 h /24 h administration SL dose 25 mg None None None None Mechanism of action They inhibit Ang-converting enzyme (ACE) in the vascular endothelium leading to: – Inhibition of both Ang-II formation and aldosterone release (→ ↓ both VC and salt & water retention). – Prevent degradation of bradykinin which is a potent VD. – Most ACEIs have direct VD action to both arteries (i.e. ↓ afterload) and veins (i.e. ↓ preload). 153