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ALISHA SHARMA
MBBS 2006
PharmacologyCMC2008
Angiotensinase
PharmacologyCMC2008
ANGIOTENSIN CONVERTING ENGYME is a dipeptidyl carboxypeptidase located on the luminal surface of the vascular endothelial cells, especially in the lungs ACE is responsible for the conversion of angiotensin I to angiotensin II
PharmacologyCMC2008
Action of Angiotensin II
1. CVS
a. Vasoconstriction
Occurs in both arterioles and venules, but less marked in cerebral, skeletal muscles, pulmonary & coronary vessels b. Increased force of myocardial contraction by promoting calcium influx
c. On chronic use hypertrophy, hyperplasia and increased inter cellular matrix production in the myocardium and vascular smooth muscles
PharmacologyCMC2008
2 Smooth muscles
Angiotensin II cause visceral smooth muscle contraction
Adrenal Cortex
Tropic action on zona glomerulosa
4 Kidney
sodium, chloride & bicarbonate reabsorpiton Na+/H+ exchange in PCT
PharmacologyCMC2008
CNS
1. Induces drinking behaviour and ADH release both resulting in plasma volume expansion
PharmacologyCMC2008
ACE inhibitors are those drugs which inhibit the angiotensin converting enzyme, hence preventing the conversion of angiotensin I to angiotensin II, hence disrupting RAS.
PharmacologyCMC2008
Action of Inhibitors
Angiotensinogen Rennin Angiotensin I ACE Angiotensin II Production Decreases ACE Inhibitor
1. 2. 3. 4. output from sympathetic nervous system relaxation of vascular smooth muscles Retention of sodium & water levels of bradykinin contributing to the in preload & afterload cardiac output
PharmacologyCMC2008
vasodilation
Fall in BP
1.
Hypertension
First line of drugs for all grades of hypertension They offer the following advantages Lack of postural hypotension, electrolyte disturbance, feeling of weakness and CNS side effects Safety in asthmatics, diabetics, peripheral vascular disease patients Prevent secondary hyperaldosteronism and potassium loss due to diuretics Renal blood flow is well maintained
PharmacologyCMC2008
1.
2. 3. 4.
1.
5.
Hypertension (cont..)
Reverse left ventricular hypertrophy and increased wall to lumen ratio of blood vessels that occurs in hypertensive patients No hyperuricemia or any deleterious effects on plasma lipid profile No rebound hypertension on withdrawl Minimum worsening of quality of life parameters
6.
7. 8.
PharmacologyCMC2008
2.
CHF
Cause both arteriolar & venodilation Reduces both preload and afterload They can provide both symptomatic relief as well as disease modifying benefits by retarding or reversing ventricular hypertrophy and remodeling
MI
If the ACE inhibitors are administered within 24 hours of an attack and then continued for 6 weeks, the early and long term mortality can be reduced
PharmacologyCMC2008
Prophylaxis in high risk cardiovascular subjects Risk of developing cardiac failure on diabetes is reduced Protecting effect exerted on both myocardium as well as the vasculature
PharmacologyCMC2008
5 Diabetic nephropathy
i. Delay or prevent end stage renal disease in type I and II DM ii. Albuminuria remains stable iii. Higher creatinine clearance, hence require less dialysis and life expectancy increases iv. These benefits are mainly because of the haemodynamic and mesengial cell growth attenuating effects v. Controls micro and macrovascular complications produced by RAS vi. Retards deterioration of retinopathy
PharmacologyCMC2008
6.
Non-Diabetic Nephropathy
Prevent doubling of creatinine levels or end stage renal disease
7.
Scleroderma crisis
ACE inhibitors can bring down BP and retard the deterioration renal function
8.
Captopril Test
This test is done to obviate the need for renal angiography for diagnosis of renovascular hypertension
PharmacologyCMC2008
PharmacologyCMC2008
Actions
Abolishes pressor effect of angiotensin I but not that of AII Increases plasma kinin levels Potentiates hypotensive action of bradykinin Lowers the TPR by dilation of arterioles and increases compliance of larger arterioles Both SBP and DBP decrease with no fall in CO Cardiovascular reflexes not interfered with Renal blood flow not compromised
PharmacologyCMC2008
II Pharmacokinetics
Oral bioavailability 40% Presence of food in stomach reduces BA Poor penetration in brain Plasma half life =2hrs. Action lasts for 6-12hrs
PharmacologyCMC2008
Adverse Effects
Hypotension Hyperkalemia Cough Rashes, urticaria Angioedema Dysgeusia Fetopathic Headache, dizziness, nausea, bowel upset Granulocytopenia & proteinuria Acute renal failure
PharmacologyCMC2008
IV Interactions
1. 2. 3. 4. With Indomethacin (other NSAIDS) accentuate hypotension K+ supplements/ K+ sparing diuretics precipitate hyperkalemia Antacids reduce BA of captopril. ACE inhibitors reduce lithium clearance and predispose to its toxicity
PharmacologyCMC2008
PharmacologyCMC2008
CONTRAINDICATIONS
Bilateral renal artery stenosis Pregnancy(later half) Patients on potassium sparing diuretics,NSAIDS
PharmacologyCMC2008
Enalapril
1. 2. 3. 4. 5. 6. 7. It is a producing converted to enalaprilat Not used orally because of poor absorption More potent, effective dose 5-20mg OD or BD Absorption not affected by food Slower onset of action Longer duration of action Rashes and loss of taste is less frequent
PharmacologyCMC2008
PharmacologyCMC2008
PharmacologyCMC2008