Antihypertensive Drugs Guide

Antihypertensive Drugs
Prepared By – Undhad Tushar C.
Masters Of Pharmacy Sem – 1 (Pharmacology) R.K.
University
Under The Guidance Of – ujjval vaghela
M. Pharm - Pharmacology,
Professor, School Of Pharmacy, RK University
1
Prepared By – Undhad Tushar C.
Masters Of Pharmacy Sem – 1 (Pharmacology)
Antihypertensive Drugs

CONTENTS
 1.Introduction
 2.Types of Hypertension
 3.Risk factors
 4.Classification of Anti-hypertensive
Drugs
 5.Pharmacology of Antihypertensive
drugs
 6.Reference
2

1.INTRODUCTION
 Hypertension is an elevation of systolic
and diastolic BP above 140/90 mm of Hg.
 Hypertension the heart is working harder
than normal putting extra strain on the
heart and vessels.
3

1.INTRODUCTION
 Systolic blood pressure :- The
amount of pressure against the artery
walls each time the heart contract
 Diastolic blood pressure :- The
amount of pressure inside the artery when
heart is at rest, in between heartbeats.
4

1.INTRODUCTION
 Blood pressure is determined by cardiac
output (CO) and total peripheral
vascular resistance (PVR).
 Prolonged hypertension damages the
blood vessels of the heart, brain and
the kidneys and may result in several
complications like stroke, coronary
artery disease or renal failure.
5

1.INTRODUCTION
 Blood pressure is controlled by
baroreceptor reflexes acting through
autonomic nervous system along with
the renin-angiotensin-aldosterone
system.
6

Low blood pressure
Baroreceptor sense low BP
Parasympathetic sympathetic
Vasoconstriction Vasoconstriction
Increase cardiac output, BP
Release of Renin of kidney
Angiotensinogen Angiotensin-1
ACE
Vasoconstriction Angiotensin -2
7

2.Type Types of Hypertension
 1.Primary (Essential) Hypertension:-
where the cause is not known.
 2.Secondary:-
 Cause are known kidney problem,
Adrenal gland tumor - aldosteronism,
Thyroid problem - increase ca+
8

3.Risk factors:
 Risk with increase age (above 65
years)
 Family history
 Tobacco
 Smoking
 Diet-High salt and oil intake and
alcohol
 Stress condition
9

4.Classification of Anti-hypertensive
Drugs
1.Diuretics :-
(a)Thiazides :-
Hydrochlorothiazide, Chlorthalidone,
Indapamide
(b)Loop diuretics :-
Furosemide, Bumetanide, Torasemide
(c)Potassium sparing diuretics :-
Spironolactone, Amiloride,
10

Drugs
2. ACE inhibitors :-
Captopril,, Lisinopril, Enalapril, Ramipril,
3. Angiotensin blockers :-
Losartan, Candesartan ,Valsartan
4. Renin inhibitors :-
Aliskiren , Remikiren
11

Drugs
5. β-adrenergic blockers :-
(a)Non selective :- Propranolol, Metoprolol
Timolol,
(b)Selective :- Bisoprolol, Metoprolol,
Atenolol
12

Drugs
6. α-adrenergic blockers :-
(a)Selective :- Prazosin, Terazosin,
Doxazosin
(b)Non Selective :- Phentolamine,
Phenoxybenzamine
13

Drugs
7. α-β, adrenergic blockers :-
Labetalol, Carvedilol
8. Calcium channel blockers :-
(a)L Type –Verapamil, Diltiazem, Efonidipine,
(b)Dihydropyridine -Nifedipine, Nicardipin,
Lacidipine
14

Drugs
9. Potassium channel openers :-
Minoxidil, Diazoxide,
10. Vasodilators :-
(a)Arteriolar dilator:- Hydralazine, Minoxidil,
(b)Arteriolar venodilator :- Sodium
Nitroprusside
15

Drugs
11. Centrally acting sympatholytics :-
Clonidine, α- methyldopa,
16

1.Diuretics :-
(a)Thiazides :-
 Hydrochlorothiazide,
Chlorthalidone, Indapamide
MOA:
 Diuretics enhance the excretion of
sodium and water.
17

(a)Thiazide diuretics :-
 Acts on early part of
distal tubules.
 Inhibit Na+-Cl-
symporter at the
luminal membrane.
 Increase NaCl
excretion.
 Na+ exchanges with K+
in the DT.
18

(a)Thiazide diuretics :-
 1. ↓ Plasma volume →
↓ cardiac output → ↓
BP
 2. ↓ Body sodium →
relaxation of vascular
smooth muscles (due
to Na+ depletion in
the vascular smooth
muscle) - ↓ PVR → ↓
BP
.
19

(a)Thiazides diuretics :-
Pharmacokinetic action :
 Extensively protein-bound
 All are excreted in the urine, mainly by
tubular secretion
 Their action starts within 1 hrs but the
duration varies from 8-12hrs
20

ADR:
 Hypokalaemia
 Hyperuricemia
 Hyperglycemia
 Hypercalcemia
21

Therapeutic uses:
 CHF
 Hypertension
 Edema
22

 Furosemide,
Bumetanide, Torasemide
MOA:
 The major site of action
is the thick AscLH,
 Inhibits Na+ - K+ -2Cl-
cotransport
23

 Absorbed orally ( 1 hrs. )
 Bioavailability is 60%
 Lipid solubility is low
 Highly bound to plasma proteins
24

ADR:
 Hypokalaemia.
 Excessive Na+ and water loss are
common.
 Metabolic alkalosis.
25

Therapeutic uses:
 These agents are rarely used alone to
treat hypertension, but they are
commonly used to manage symptoms
of heart failure and edema.
 Hypercalcaemia and renal calcium
stones.
26

 Spironolactone, Amiloride
MOA:
 Amiloride inhibitors of epithelial sodium
transport at the late distal and collecting
ducts.
 spironolactone are aldosterone receptor
antagonists.
 All of these agents reduce potassium loss
in the urine.
27

 Oral bioavailability of 70%
 Highly bound to plasma proteins.
 Completely metabolized in liver.
 Plasma half - 10 min.
28

ADR:
 Hyperkalaemia
 Gastrointestinal upset
 menstrual disorders
29

Therapeutic uses:
 Potassium-sparing diuretics are
sometimes used in combination with
loop diuretics and thiazides to reduce
the amount of potassium loss induced
by these diuretics.
 Heart failure.
 Primary Hyperaldosteronism.
30

Ras system 31
Angiotensinogen
Angiotensin-1
Liver secretion
Angiotensin-2
Angiotensin-2
Type 1 receptor
Kidney secretion
ACE Inhibitor
Kidney
↑Na+ reabsorption
↑Aldosterone effect
↑vasoconstriction
CNS
↑sympathetic
activity
Vessels
↑vasoconstriction
↑atherosclerosis
Renin
ACE
Direct renin inhibitor

32
Bradykinin
Nitric oxide prostaglandin
(PGE2&PGI2)
vasodilation
Blood pressure

 Captopril, Lisinopril, Enalapril, Ramipril
MOA:
 Angiotensin II is a powerful
vasoconstrictor.
 Aldosterone also raises the BP by
increasing the plasma volume
33

 ACE inhibitors prevent the formation of
angiotensin II and (indirectly)
aldosterone.
 There is vasodilation and decrease in
PVR resulting in a fall in BP.
 As ACE also degrades bradykinin, ACE
inhibitors raise the bradykinin levels
which is a potent vasodilator. This also
contributes to the fall in BP
34

 Better oral bioavailability
 t½ is 2 hrs.
ADR:
 Hypotension, Acute renal failure
 Proteinuria, Angioedema, Hyperkalaemia
36

Therapeutic uses:
 Hypertension
 Coronary artery disease
 Chronic renal failure
 Congestive heart failure
 Left ventricular systolic dysfunction
37

3. Angiotensin receptor blockers
(ARBs) :-
 Losartan, Candesartan ,Valsartan
MOA:
 Angiotensin II receptors— AT1 and
AT2 .
 Losartan has high affinity for AT1
receptors when compared to AT2
receptors. By blocking AT1 receptors,
losartan blocks the effect of
angiotensin II.
38

(ARBs) :-
 It cause relaxes vascular smooth muscles,
promotes salt and water excretion and
reduces plasma volume.
 Angiotensin converting enzyme is not
inhibited cause increase in bradykinin levels
and its associated adverse effects like dry
cough and angioedema.
39

(ARBs) :-
 High first pass metabolism
 Highly bound to plasma proteins
 Absorption is not affected by food
 t½ -6 hrs.
40

(ARBs) :-
ADR:
 Risks of cough and angioedema
 Hypotension and hyperkalaemia
Therapeutic uses:
 Hypertension
 Cardiac failure
 Diuretic
41

4. Renin inhibitors
 Aliskiren , Remikiren
MOA:
 Renin inhibitors bind to active site of
renin and prevent the formation of
ang1 and age 2.
 Resulting decrease blood pressure.
42

4. Renin inhibitors 43
Mechanism of action:

4. Renin inhibitors
 It is orally active,
 t½ is about 24 hrs.
 It is reduce plasma renin activity by 50-
80%,
 It is metabolised by liver and excreted
by the kidneys.
44

4. Renin inhibitors
ADR:
 Diarrhea ,cough and angioedema
 Hyperkalaemia
Therapeutic uses:
 Heart attacks,
 Kidney failure
45

Doxazosin
Phenoxybenzamine
46

MOA:
 Blockade of cardiac β1 receptors results
in decreased myocardial contractility and
cardiac output.
 They reduce the BP due to a fall in the
cardiac output.
 They also lower plasma renin activity and
have an additional central
antihypertensive action.
47

5. β-adrenergic blockers :- 48
Mechanism of action:

 β-blockers are orally active
 Metabolised in the liver
 t½ is 3-7 hrs.
49

ADR:
 Bradycardia
 Fatigue
 Insomnia
 Sexual Dysfunction
 Hypotension
50

Therapeutic uses:
 Previous myocardial infarction,
 Angina pectoris
 Chronic heart failure
 Hypertension
51

Doxazosin
Phenoxybenzamine
52

MOA:
 Blocks alpha
adrenergic
receptors -
vasodilatation &
decrease in BP
53

 It is orally bioavailability is 60%,
 Highly bound t plasma proteins,
 Metabolised in liver and excreted
primarily in bile,
 t½ is 2-3 hrs
54

ADR:
 Palpitation,
 Nasal blockade
 Hypotension
 Reflex tachycardia
55

Therapeutic uses:
 Used in hypertension
 CHF
 It may be added to a diuretic + blocker
in those not achieving target BP.
56

Labetalol, Carvedilol
MOA:
 Blocking both α and β receptors.
Fall in bp ( both systolic and diastolic ) is
due to α1 and β2 blocked as well as β2
agonism (vasodilation ).
57

 Alpha-blockers work on
norepinephrine or noradrenaline, while
beta-blockers work on epinephrine or
adrenaline.
 Alpha-blockers affect only blood
pressure levels, while beta-blockers
affect both the heart and blood
pressure.
58

(a)L Type:- Verapamil, Diltiazem,
Efonidipine,
(b)Dihydropyridine:- -Nifedipine,
Nicardipin, Lacidipine
59

MOA:
 The intracellular concentration of
calcium plays an important role in
maintaining the tone of smooth muscle
and in the contraction of the
myocardium.
 Calcium enters muscle cells through
special voltage sensitive calcium
channels.
60

 This triggers release of calcium from
the sarcoplasmic reticulum and
mitochondria, which further increases
the cytosolic level of calcium.
 Calcium channel blocker block L-type
calcium channels in the heart and in
smooth muscle of the coronary and
peripheral arteriolar.
61

 This causes vascular smooth muscle to
relax, dilating mainly arterioles.
Calcium channel blockers do not dilate
veins
62

 Most of these agents have short half-
lives (3 to 8 hours)
 Metabolized in liver
 Excreted in urine
63

ADR:
 Dizziness, headache, and a feeling of
fatigue caused by a decrease in blood
pressure
 Peripheral edema is another commonly
reported side effect of this class.
64

Therapeutic uses:
 Hypertension
 Treatment of angina
 Arrhythmias
65

Minoxidil, Diazoxide,
MOA:
Opening these channels
hyperpolarizes the smooth
muscle, which closes
voltage-gated calcium
channels and decreases
intracellular calcium.
This leads to relaxation and
vasodilation.
66

9. Potassium channel openers :- 67

ADR:
 Headaches, flushing,
 Reflex tachycardia
 Fluid and salt retention
68

Therapeutic uses:
 Hypertension
 Smooth muscle relaxing activity
 Vasodilator to treat angina
69

10. Vasodilators :-
(a)Arteriolar dilator:- Hydralazine,
Minoxidil,
(b)Arteriolar venodilator :- Sodium
Nitroprusside
70

10. Vasodilators :-
MOA:
Hydralazine molecules combine with
receptors in the endothelium of arterioles
– NO release – relaxation of vascular
smooth muscle – fall in BP
71

10. Vasodilators :-
ADR:
 Hypotension, salt & water retention
 It may precipitate angina in some patients
because increased o2 demand due to reflex
tachycardia and decreased myocardial blood
supply due to peripheral vasodilatation
 Headache (caused by cerebral vasodilation)
72

10. Vasodilators :-
Therapeutic uses:
 Heart failure
 Angina and myocardial infarction
 Ability to inhibit platelet aggregation
73

11. Centrally acting sympatholytics
:-
 Clonidine, α- methyldopa,
MOA:
 Centrally acting sympatholytic block
sympathetic activity by binding to and
activating alpha (α2) adrenoceptors
74

 This reduces sympathetic outflow to
heart thereby decreasing cardiac
output by decreasing heart rate and
contractility ,which causes vasodilation
and reduced systemic vascular
resistance, which decreases arterial
pressure.
75

ADR:
 Bradycardia (not good for emergency),
 Dryness of mouth,
 Vertigo Bradycardia (not good for
emergency),
 Dryness of mouth,
76

Therapeutic uses:
 Preferred for pts. with chronic renal
disease & hypertensive emergencies
 Now used only in HTN associated with
pregnancy since it is safe.
77

Advance drugs in hypertension
 Genericart Amlodipine+Atenolol
5mg/50mg Tablet (01-Oct-2021)
 Prescription Required
 MANUFACTURER
 Swast Aushadhi Seva Generic Medicine
Store
 SALT COMPOSITION
 Amlodipine (5mg) + Atenolol (50mg)
78

Combination antihypertensives
 Combination antihypertensives include
combined agents from the following
pharmacologic classes: diuretics and
potassium-sparing diuretics, beta
blockers and diuretics, angiotensin-
converting enzyme (ACE) inhibitors and
diuretics, angiotensin-II antagonists and
diuretics, and calcium channel blockers
and ACE inhibitors.
79

agent
 The recommendation for first-line therapy for
hypertension remains a beta blocker or
diuretic given in a low dosage. A target blood
pressure of less than 140/90 mm Hg is
achieved in about 50 percent of patients
treated with monotherapy; two or more
agents from different pharmacologic classes
are often needed to achieve adequate blood
pressure control
80

agent
81
 Diuretic combinations
 Brand name - Moduretic
 Amiloride and hydrochlorothiazide (5 mg/50 mg)
 Beta blockers and diuretics
 Brand name - Tenoretic
 Atenolol and chlorthalidone (50 mg/25 mg, 100 mg/25 mg)
 ACE inhibitors and diuretics
 Brand name - Lotensin HCT
 Benazepril and hydrochlorothiazide (5 mg/6.25 mg, 10 mg/12.5
mg, 20 mg/12.5 mg, 20 mg/25 mg)

References:
 Essentials Of Medical Pharmacology 8th Edition
2018 By KD Tripathi
 Lippincott's pharmacology
 Padmaja Uday Kumar Professor and Head
Department of Pharmacology Fr. Muller Medical
College, Mangalore Karnataka India
 Goodman and Gilman’s The Pharmacological Basis of
Therapeutics, 11th -Edition 2006
 Rang & Dale’s Pharmacology, Eighth edition
82

Antihypertensive Drugs Guide

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Antihypertensive Drugs Guide

Similar to Antihypertensive Drugs Guide (20)

Recently uploaded

Recently uploaded (20)

Antihypertensive Drugs Guide