Angiotensin Converting Enzyme inhibitor (ACEI)

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

• Release from juxtaglomerular cell of cortex

renin
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
5
(No Transcript)
6
(No Transcript)
7
Angiotensin converting enzyme inhibitors (ACEI)

• Inhibit enzyme ACE
• Decrease ATII
• Decrease the destroy of bradykinin
• Increase NO, PGI2 and PGE2

8
angiotensinogen
kinogen
renin
kallikrin
Angiotensin I
bradykinin
ACEI.
?PG syn.
Angiotensin II
inactive
? Aldosterone release
vasodilation
vasodilation
? NaH2O retention
? PVR
?PVR
? BP
?BP
9
Pharmacological effects
10

• Vascular smooth muscle

• Vasodilate venodilate
• Dilate afferent and efferent arteriole at renal
• Increase capillary compliance

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

14
Pharmacokinetic
15

• Divided into 3 groups
• 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

16
?????????????? ACE ????? 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 T1/2 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
ADR

• 1. Dry cough
• Common SE
• Cause by increase cough reflex, from the
  accumulation of bradykinin and others substance
  such as substance P, PG
• 2. Hypotensionesp. 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...?????????? ??? ???? ??????????
(??????) 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
ARB
vasoconstriction
Aldosterone release
Cardiac hypertrophy
Na reabsorption
27
Limitation of ACEI

1. Bilatery artery stenosis, unilatery artery
   stenosis
2. Pragnancy women.esp 1st trimester
3. Chronic cough
4. Black peoplelow renin activity

28
Drug interaction

• Beta-blocker decrease renin release
• K-sparing diureticincrease K
• NSAIDdecrease PG synthesis, bradykinin
• Probenecid.inhibit abs
• Antaciddecrease abs

29
Clinical uses

• Treatment HT with other condition Ex
• HT with Dyslipidemia, Gout, DM, renal
• CHF
• Atherosclerosis
• LVH