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Angiotensin Converting Enzyme inhibitor (ACEI)
Vilasinee HirunpanichB. Pharm(Hon), M.Sc in Pharm(Pharmacology)
Renin angiotensin system (RAS)
Control the balance of electrolyte, blood volume, BP
renin
Release from juxtaglomerular cell of cortex
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
Function of renin
Angiotensin converting enzyme inhibitors (ACEI)
• Inhibit enzyme ACE
• Decrease ATII
• Decrease the destroy of bradykinin
• Increase NO, PGI2 and PGE2
angiotensinogen
Angiotensin I
Angiotensin II
vasodilation
PVR
BP
renin
Aldosterone release
Na+&H2O retention
kinogen
bradykinin
inactive
PG syn.
vasodilation
PVR
BP
kallikrin
ACEI.
• Vasodilate & venodilate
• Dilate afferent and efferent arteriole at renal
• Increase capillary compliance
1. Vascular smooth muscle
2. Cardiovascular effect
Decrease both preload and afterload
Increase cardiac out put
Decrease left ventricular hypertrophy (LVH)
No reflex tachycardia
3. renal
• Increase renal blood flow
• Decrease excretion of protein in urine which good for pts with DM
• Inhibit the secretion of aldosterone
4. CNS
• Decrease NE release
• Increase parasympathetic system so not increase reflex tachycardia
• May increase cerebral blood flow
Divided into 3 groups
1. Direct action but internalized metabolite to disulfide group
Ex. captopril
2. Prodrug (ester dicarboxylic 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
กลไกการยั�บยั�ง ACE ของ ยัา ACEI
structure
Drugs
captoril•Contain sulhydril (SH) in the structure
•Bioavailability 70%
•Food interfere with absorption …AC
•Metabolized into disulfide group
Enalapril
• The first prodrug which was used in clinic
• It is metabolized into dicarboxylic group …enalaprilat which is the active metabolized.
• Elanaprilat has long T1/2 than parent drug.
Lisinopril
• Direct action in the body• Excrete by renal
Other drugs
BenazeprilCilazapril (Inhibace)Delapril (Cupressin)Fosinopril (Monopril)Perindopril (Coversyl)
Ramipril (Ramace, Tritace)
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
ADR (cont)6. Renal failure
bilateral renal artery stenosisSevere single renal artery stenosis
Need ATII
7. Angioedema...บวมของจม�ก ปาก ล�น กล�องเสี�ยัง (พบน�อยั)
8. Rash ……..SH group, bradykinin accumulation
9. loss of taste….most in captopril
10. Protein in urine (less)
Angiotensin receptor blocker(ARB)
Lorsartan
Valsartan
Candesartan
Eprosartan
Irbesartan
telmisartan
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
Angiotensin I
ACEI
Angiotensin II
Cellular response
vasoconstriction Cardiac
hypertrophy
Aldosterone release
ARB
Na+ reabsorption
Limitation of ACEI
1. Bilatery artery stenosis, unilatery artery stenosis
2. Pragnancy women….esp 1st trimester
3. Chronic cough
4. Black people…low renin activity
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
Clinical uses
Treatment HT with other condition Ex
1. HT with Dyslipidemia, Gout, DM, renal
2. CHF
3. Atherosclerosis
4. LVH