Angiotensin Converting Enzyme
inhibitor (ACEI)
Vilasinee Hirunpanich
B. 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.
2.
3.
4.
BP drop
Beta-adrenergic receptor stimulation
The stimulation of sympathetic system
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
kinogen
renin
Angiotensin I
kallikrin
ACEI.
Angiotensin II
vasodilation
inactive
 Aldosterone
release
 Na+&H2O
retention
 PVR
 BP
bradykinin
PG
syn.
vasodilation
PVR
BP
1. Vascular smooth muscle
•
•
•
Vasodilate & venodilate
Dilate afferent and efferent arteriole
at renal
Increase capillary compliance
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
กลไกการยับยั้ง ACE ของยา 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
Benazepril
Cilazapril (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 stenosis
Severe single renal artery stenosis
Need
ATII
7. Angioedema...บวมของจมูก ปาก ลิ้น กล่องเสี ยง (พบน้อย)
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
vasoconstric
tion
Cardiac
hypertrophy
ARB
Aldosterone
release
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