3.Anti-Hypertensive drugs.pdf

Scope: This subject is intended to impart the fundamental knowledge on various aspects
(classification, mechanism of action, therapeutic effects, clinical uses, side effects and
contraindications) of drugs acting on different systems of body and in addition,emphasis
on the basic concepts of bioassay. Objectives: Upon completion of this course the student should be able to
1. Understand the mechanism of drug action and its relevance in the treatment of
different diseases
2. Demonstrate isolation of different organs/tissues from the laboratory animals by
simulated experiments
3. Demonstrate the various receptor actions using isolated tissue preparation

1. Course:Pharmacology II
Unit 1:Pharmacology of Drugs Acting on
Cardiovascular System
Topic: Anti-Hypertensive Drugs
CO -503T.1: Explain pharmacology of the drugs acting on
various Cardiac complications
BY
Mr. Bhagwat H. Garje (M.Pharm).
Asst. Professor
Department of Pharmacology
SCOPER, Kopergaon.

2. 2
Content
•Introduction
•Classification
•Mechanism of action
•Therapeutic Effects
•Clinical Uses & Side effects
•Contraindications

3. •Definition: Antihypertensive are a class of drug that
used to treat of hypertension (High BP)
•Anti-hypertensive therapy seeks to prevent the
complication of high blood pressure, such as stock &
myocardial infractions.
•BP more than 140 mm HG systolic and 90 mm HG
diastolic.
•High Blood Pressure: blood forced through the arteries
at an increased rate.
•Severe hypertension may cause headache, sleepiness,
confusion or coma. 3
Introduction

4. Etiology of Hypertension
• A specific cause of hypertension established in only 10-15% of
patients.
• Patients in whom no specific cause of hypertension are said to have
essential or primary hypertension.
• Patients with a specific etiology are said to have secondary
hypertension.
• Genetic factors, psychological stress, and environmental and
dietary factors as contributing to the development of hypertension.
The heritability of essential hypertension is estimated to be about
30%.
4

5. 5

6. Symptoms of Hypertension
Most of the time, there are no symptoms.
Symptoms that may occur include:
▪Confusion
▪Earnoiseorbuzzing
▪Fatigue
▪Headache
▪Irregularheartbeat
▪Nosebleed
▪Visionchanges
6

7. 7
Classification
•A) Diuretics :
1) Thiazoles-Hydrochlorothiazide
2) Loop Diuretics-Furasemide
3) Osmatic-Mannital, Urea
•B) ACE Inhibitor-
eg . Captopril, Enalapril, Fosinopril
•C) Angiotensin(A1Receptor) Blockers-
eg. Losartan, Candesartan, Valsartan
•D) B adrenergic Blockers-
eg. Propranolol ,Atenolol, Metoprolol

8. •E) Calcium channel blockers :
eg . Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine, Nitrendipine, Lacidipine,
etc.
•F) B + a Adrenergic blockers:
eg . Labetalol, Carvedilol
•G) Alpha Adrenergic blockers:
eg . Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxybenzamine
•I) Central sympatholytics :
eg . Clonidine, Methyldopa
•J) Vasodilators :
-Arteriolar: Hydralazine, Minoxidil, Diazoxide
-Arteriolar + venous: Sodium nitroprusside
•K) Others :
eg . Adrenergic neurone blockers (Reserpine, Guanethidine, etc.), Ganglion blockers
(Pentolinium, etc.)
Pnemonic: ABCDA(ACEI, ARBSs, alpha blockers) B(beta blockers) C (CCB, centrally acting)
D (Diuretics, direct renin inhibitors, dilators)
8

9. A.Diuretics
Examples:
■Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
■High ceiling : Furosemide
■K+ sparing: Spironolactone, Triamterene, Amiloride
9

10. Mechanism of antihypertensive action: (Thiazides)
Act on Kidneys to increase excretion of Na and H2O → decrease
in blood volume decrease in COP & hence decrease in BP.
■After 4 -6 weeks, compensatory mechanisms operate to regain
Na+ balance, plasma volume and Cardiac output but BP remains
low. Why?
■Answer:Even after the compensatory mechanisms, there exists
a small deficit of Na+ in the vessel wall. This Na deficit reduces
stiffness of vessel wall leading to vasodilation. This leads to
decrease in TPR and fall in BP. So, the initial fall in BP due to
thiazides is due to fall in COP but fall in BP is sustained due to fall
in TPR.
10
A.Diuretics

11. A.Diuretics
Mechanism of antihypertensive action (high ceiling diuretics)
Fall in BP is dependent only on reduction in plasma volume &
Cardiac output (similar to the initial fall in BP due to thiazides) but
unlike thiazides the Na deficit is not persistent due to short action of
high ceiling diuretics. Hence no fall in t.p.r and no sustenance of BP
fall.
11

12. Therapeutic & Clinical Uses
1. In Hypertension
2. In CHF
3. In Osteoporosis
4. In Renal Insufficiency
5. In High BP
6. In Liver Disease
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13. Adverse Effects
1.Hypokalemia :
Thiazide and Loop Diuretics lead to decrease in serum potassium
level due to their kaliuretic effect.
2. Dyslipidemia :
Diuretic should not be used in increases in Triglyceride (TG) level, low
density lipoprotein cholesterol (LDL) and total cholesterol.
3. PPT of Diabetes :
Thiazide and loop diuretics inhibit insulin release thereby produce
Glucose intolerance.
4. Hyperuricemia :
Thiazide Diuretics increases the serum uric acid levels due to
inhibition of uric acid excretion.
13

14. Contraindications
1. Diuretic should not be used in Gout patients.
2. Diuretic should not be used in patients suffering from
Hyperlipidemia.
3. They are contraindicated in pregnancy induced hypertension.
4. Thiazide and loop diuretics are contraindicated in hypersensitivity
and severe Hepatic Dysfunction.
14

15. B. ACE Inhibitors
Examples :
Captopril, Lisinopril., Enalapril, Ramipril, Fosinopril
Mechanism of antihypertensive action :
■Inhibit the Renin Angiotensin Aldosterone system (RAAS).
■Inhibit synthesis of Angiotensin II by inhibiting ACE-> decrease in
(tpr) and blood volume →fall in diastolic and systolic BP.
WHAT IS RAAS???
Next slide…..
15

16. RAAS
■Renin is produced by JG cells of kidney in response to
-Fall in BP or blood volume
-Decrease Na+ in macula densa
■Renin acts on a plasma protein Angiotensinogen to convert it to Angiotensin-l
■Angiotensin-l is rapidly converted to Angiotensin-II by ACE(present in
luminal surface of vascular endothelium)
■Angiotensin-II is degraded by peptidases to produce Angiotensin-III
■Angiotensin II causes vasoconstriction (increased TPR) leading to rise in
diastolic BP.
■Both Angiotensin-II and Angiotensin-III stimulates Aldosterone secretion
from Adrenal Cortex. Aldosterone promotes Na+ & water reabsorption by the
kidneys leading to increased blood volume & increased COP & systolic BP.
16

17. RRAS Diagram
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18. Therapeutic & Clinical uses
■Anti Hypertensive Agent
■Congestive Heart Failure
■Myocardial Infarction
■Prophylaxis of high CVS risk subjects
■Diabetic Nephropathy
■Scleroderma crisis
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19. Adverse Effects
■Cough: persistent brassy cough due to inhibition of bradykinin breakdown
in lungs
■Hyperkalaemia (in renal failure patients, those with K+ sparing diuretics,
NSAID and beta blockers (routine check of K+ level))
■First dose Hypotension: sharp fall may occur
■Angioedema: swelling of lips, mouth, nose etc.
■Rashes, urticaria
■Dysgeusia: loss or alteration of taste
■Fetopathy: hypoplasia of organs, growth retardation etc
■Neutropenia
■Proteinuria
■Acute renal failure (occurs in patients with bilateral renal artery stenosis)
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20. ■Captopril can produces morbidity and mortality in fetus when
administered by pregnant women.
■It is contraindicated in patients of renal artery stenosis.
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Contraindications

21. C. Angiotensin Receptor Blockers (ARBS)
Examples : Losartan, Candesartan, Valsartan, Telmisartan
Mechanism of antihypertensive action :
Angiotensin Receptors (AT1 & AT2) are present on target cells. Most
of the physiological actions of angiotensin are mediated via AT1
receptor.
■ARBs are competitive antagonists and inverse agonist of AT1
receptor. Blocks all the actions of A-II mediated by AT1 like
vasoconstriction, aldosterone release and renal actions of salt & water
reabsorption.
21

22. D. Beta blockers
Examples:
-Non selective: Propranolol
-Cardio selective: Metoprolol, Atenolol
Mechanism of antihypertensive action :
■Decreases heart rate, contractility, conduction velocity, cardiac output
(inverse agonist on 31 ). Total peripheral resistance increases initially.
■Initial phase: COP decreases (systolic BP decreases), t.p.r increases (diastolic
BP increases) overall little BP change.
■With prolonged use resistance vessels adapt to decreased COP so that t.p.r
decreases both systolic & diastolic BP decrease
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23. 1. Irregular heart rhythm (arrhythmia)
2. Heart failure.
3. Chest pain (angina)
4. Heart attacks.
5. Migraine.
6. Certain types of tremors.
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Therapeutic & Clinical uses

24. 1. Bradycardia
2. Chronic Obstructive Lungs Diseases
3. Disturbance In Lipid Profile
4. Coronary Artery Diseases
5. Reduces Exercise Capacity
24
Adverse Effects

25. Non selective B Blockers are Contraindicated in :
1. Bronchial Asthma
2. COPD
3. Heart Failure
4. In Peripheral Vascular Diseases
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Contraindications

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