1. Angiotensin Converting Enzyme inhibitor (ACEI) Vilasinee Hirunpanich B. Pharm(Hon), M.Sc in Pharm(Pharmacology)

2. Renin angiotensin system (RAS) Control the balance of electrolyte, blood volume, BP renin Release from juxtaglomerular cell of cortex

3. Factors which stimulate renin release 1.BP drop 2.Beta-adrenergic receptor stimulation 3.The stimulation of sympathetic system 4.The decrease of Na + -load

4. Function of renin

7. Angiotensin converting enzyme inhibitors (ACEI) Inhibit enzyme ACE Decrease ATII Decrease the destroy of bradykinin Increase NO, PGI 2 and PGE 2

8. angiotensinogen Angiotensin I Angiotensin II vasodilation  PVR  BP renin  Aldosterone release  Na + &H 2 O retention kinogen bradykinin inactive  PG syn. vasodilation  PVR  BP kallikrin ACEI.

10. Vasodilate & venodilate Dilate afferent and efferent arteriole at renal Increase capillary compliance 1.Vascular smooth muscle

11. 2. Cardiovascular effect Decrease both preload and afterload Increase cardiac out put Decrease left ventricular hypertrophy (LVH) No reflex tachycardia

12. 3. renal Increase renal blood flow Decrease excretion of protein in urine which good for pts with DM Inhibit the secretion of aldosterone

13. 4. CNS Decrease NE release Increase parasympathetic system so not increase reflex tachycardia May increase cerebral blood flow

15. Divided into 3 groups 1.Direct action but internalized metabolite to disulfide group Ex. captopril 2. Prodrug (esterdicarboxylic acid) They have the effects when they are changed to active metabolized Ex enalapril, benazepril, cilazapril 3. Soluble in water and not change in the body Ex lisinopril

16. กลไกการยับยั้ง ACE ของ ยา ACEI

17. structure

18. Drugs captoril Contain sulhydril (SH) in the structure Bioavailability 70% Food interfere with absorption …AC Metabolized into disulfide group

19. Enalapril The first prodrug which was used in clinic It is metabolized into dicarboxylic group … enalaprilat which is the active metabolized. Elanaprilat has long T 1/2 than parent drug.

20. Lisinopril Direct action in the body Excrete by renal

21. Other drugs Benazepril Cilazapril (Inhibace) Delapril (Cupressin) Fosinopril (Monopril) Perindopril (Coversyl) Ramipril (Ramace, Tritace)

22. 1. Dry cough Common SE Cause by increase cough reflex, from the accumulation of bradykinin and others substance such as substance P, PG 2. Hypotension…esp. first dose 3. Hyperkalemia esp. used with K + sparing diuretic 4. Fetopathic category X…….not use in pregnant women

23. ADR (cont) 6. Renal failure bilateral renal artery stenosis Severe single renal artery stenosis Need ATII 7. Angioedema... บวมของจมูก ปาก ลิ้น กล่องเสียง ( พบน้อย ) 8. Rash ……..SH group, bradykinin accumulation 9. loss of taste….most in captopril 10. Protein in urine (less)

24. Angiotensin receptor blocker(ARB) Lorsartan Valsartan Candesartan Eprosartan Irbesartan telmisartan

25. Mechanism of action Direct inhibit at angiotensin II receptor (type I) More selective than ACEI No or less Side effect of dry cough and angioedema

26. Angiotensin I ACEI Angiotensin II Cellular response vasoconstric tion Cardiac hypertrophy Aldosterone release ARB Na + reabsorption

27. Limitation of ACEI 1.Bilatery artery stenosis, unilatery artery stenosis 2. Pragnancy women….esp 1 st trimester 3.Chronic cough 4.Black people…low renin activity

28. Drug interaction 1.Beta-blocker…decrease renin release 2.K + -sparing diuretic……increase K + 3.NSAID……decrease PG synthesis, bradykinin 4.Probenecid….inhibit abs 5.Antacid……decrease abs

29. Clinical uses Treatment HT with other condition Ex 1.HT with Dyslipidemia, Gout, DM, renal 2.CHF 3.Atherosclerosis 4.LVH