Antihypertensive

1. Antihypertensive
drugs

2. • Primary or essential hypertension (95%)
No specific underlying cause
• Secondary hypertension (5%)
Due to specific disease or drug

3. Blood Pressure
• Systolic blood pressure (SBP) : maximum
pressure recorded during ventricular systole
• Diastolic blood pressure (DBP) : minimum
pressure recorded during ventricular diastole
• Pulse pressure (PP) : SBP - DBP
• Mean arterial pressure : DBP + 1/3 PP

4. Classification of BP for adults
Category SBP (mmHg) DBP (mmHg)
Normal < 120 < 80
Prehypertension 120 - 139 80 - 89
Hypertension
Stage 1 (mild) 140 - 159 90 - 99
Stage 2 (moderate) 160 - 179 100 - 109
Stage 3 (severe) ≥ 180 ≥ 110

5. Classification:
1.Angiotensin Converting Enzyme inhibitors (ACEIs) :
Captopril, enalapril, lisinopril
2. Angiotensin-II receptor blockers (ARBs) :
Losartan, candesartan, irbesartan
3. Calcium channel blockers (CCBs) :
Verapamil, diltiazem, nifedipine, nimodipine
amlodipine, felodipine

6. 4. Diuretics :
a) Thiazides & related agents – Hydrochlorothiazide
chlorthalidone
b) Loop diuretics – Furosemide, bumetanide
c) Potassium sparing diuretics – Amiloride
triamterene
spironolactone
5. Sympatholytic drugs:
a) Centrally acting agents – Clonidine, α-methyldopa
b) Ganglion blockers – Trimethaphan
c) Neuronal blockers – Reserpine

7. d) α-Adrenergic blockers:
(i) Non-selective: Phenoxybenzamine
phentolamine
(ii) Selective: Prazosin, terazosin
e) β-Adrenergic blockers:
(i) Non-selective: Propranolol, timolol
(ii) Selective: Atenolol, metoprolol
6. Vasodilators:
a) Arteriolar – Hydralazine, minoxidil, diazoxide
b) Arterial and venodilator – Sodium nitroprusside

8. I. ACEIs : 1st
line agents
Renin
ACE
(vasoconstriction)
BP
ACEIs
Bradykinin PG
Vasodilation
Blood vessel Aldosterone
release
Cardiac hypertrophy
& remodelling
Angiotensinogen
Angiotensin I
Angiotensin II
PVR Na+
& H2O retention
Inactive

9. Mechanism of action:
• Inhibit the generation of angiotensin II – a potent
vasoconstrictor
• Inhibit the degradation of bradykinin – a potent
vasodilator
• Stimulate the synthesis of PGs
• Reduce sympathetic nervous system activity
• Reduce aldosterone production
• Dilates both arteries & veins – afterload and preload

10. Therapeutic uses:
 Hypertension
 Congestive cardiac failure (CCF)
 Myocardial infarction
 Diabetic nephropathy
 Scleroderma renal crisis

11. Adverse effects:
• Dry cough & angioedema
• Taste alteration, proteinuria
• Teratogenicity – growth retardation & neonatal death
• Severe hypotension, neutropenia
• Hyperkalaemia

12. Drug interactions :
• ACEI x Potassium sparing diuretics –
hyperkalaemia
• ACEI x Lithium – Li toxicity
Contraindicated in pregnancy
Preferred drug in younger age group,
diabetics – delay or prevent the
progression of renal complications

13. II. ARBs :
MOA : competitevely inhibits the binding of
angiotensin II to AT1 receptors
- do not affect bradykinin production
Therapeutic uses:
• Hypertension
• Diabetic nephropathy
• CCF
Adverse effects:
• Dry cough & angioedema - less

14. III. Diuretics:
Thiazide diuretics –
MOA:
On chronic therapy
Thiazides
Inhibit Na+
-Cl-
symport in the
early distal tubule
Promote Na+
,
H2O excretion
CO
BP
Na+
concentration in
the vascular smooth vessels
PVR

15. Advantages:
• Long duration of action
• Cheaper
• Well tolerated in elderly patients
• Decreases the incidence of fracture in elderly
patients by reducing urinary calcium excretion
Can not be given in patients with gout and
hyperlipidaemia

16. Loop diuretics:
Furosemide – not preferred in uncomplicated
primary HT because of shorter
duration of action
- used in presence of renal failure,
CCF or hypertensive emergency

17. IV. CCBs:
• Dihydropyridines (DHPs) – preferred among CCBs -
more selective action on blood vessels
• Particularly useful in elderly patients and also in
patients with angina, asthma, pvd, migraine,
hyperlipidaemia, diabetes and renal dysfunction
DHPs
Relaxes vascular
smooth muscle
PVR
BP

18. V. Sympatholytics :
a) β-adrenergic blockers –
often used as 1st
line agents in mild to moderate
hypertension
blocks β1 receptors on heart – HR,
FOC, CO - BP
β-blockers
blocks β1 receptors on kidney –
renin release - BP
sympathetic outflow - BP

19. β-adrenergic blockers are mainly useful in
–
• Young hypertensives with high renin
levels
• Patients with associated conditions such
as angina, post MI, migraine and
psychosomatic disorders
• Patients receiving vasodilators
Avoided in pts with asthma, pvd, diabetes,
hyperlipidaemia

20. b) Centrally acting agents:
Clonidine –
MOA:
to
Heart
Blood
vessel
HR, CO
PVR
BP
Clonidine stimulates α2A
receptors in VMC
sympathetic outflow
from VMC

21. Adverse effects:
 Dryness of mouth & eyes
 Sedation, depression, nausea, dizziness
 Bradycardia, impotence, pain
 Swelling of parotid gland
 Sudden stoppage after prolonged use - withdrawal
syndrome –
headache, nervousness, tachycardia, sweating,
tremors, palpitation & rebound hypertension

22. α-Methyldopa:
MOA – α-methyldopa
α-methyldopamine
α-methylnoradrenaline (false NT)
stimulates α2-VMC
sympathetic outflow
HR,PVR
BP

23. • Preferred antihypertensive during pregnancy
Adverse effects:
• Nasal stuffiness, dryness of mouth
• Headache, sedation, mental depression
• Bradycardia, EPS
• Impotence, gynaecomastia

24. c) α-Adrenergic blockers:
α-blockers
Nonselective blockers Selective blockers
Block both α1 & α2- receptors Block selectively α1-
in the blood vessels vascular receptors
Vasodilation & fall in BP Arterial & venodilation
(due to α1-blockade)
Noradrenaline release Fall in BP
(due to presynaptic α2-blockade)
Reflex tachycardia

25.  Non-selective drugs – not preferred for
essential hypertension
 Used in special conditions –
• Pheochromocytoma
• Clonidine withdrawal
• Cheese reaction
 Prazosin – first dose phenomenon – postural
hypotension after the 1st
dose

26. VI. Vasodilators :
activatesMinoxidil
Diazoxide
K+
channel (K+
channel
openers)
K+
efflux
Hyperpolarization of
vascular smooth muscle
Vasodilatation
BP

27. Minoxidil:
• Use – promote hair growth in male-type baldness
• AE – reflex tachycardia, Na+
& H2O retention with
edema
Diazoxide:
• Use – treatment of hypertensive emergencies
• AE - reflex tachycardia, Na+
& H2O retention,
hyperglycaemia

28. Sodium nitroprusside:
• A powerful arteriolar & venodilator
MOA: Sodium nitroprusside
generates nitric oxide (NO)
relaxes vascular smooth muscles
Vasodilation
CO, BP

29. myocardial work
O2 demand
Uses :
 Hypertensive crisis
 CCF
 Acute aortic dissection
AE: anorexia, nausea, vomiting, fatigue, disorientation,
toxic psychosis

30. Treatment of Hypertension
Non-pharmacological approaches:
• Weight reduction
• Sodium restriction
• Alcohol restriction
• Aerobic exercises
• Mental relaxation
• Smoking cessation
• Consumption of potassium-rich diet

31. Selection of antihypertensive drugs in
individual patients depends on:
• Comorbidity
• Associated complications
• Age
• Sex
• Cost of the drug
• Concomitant drugs

32. Combination therapy
• Hydralazine/ DHPs & beta blockers
• ACEI/ ARBs & Diuretics
• Vasodilators & diuretics
• ACEI & clonidine/ beta blocker
• CCB + ACEI + Diuretic
• CCB + beta blocker + diuretic
• ACEI + beta blocker + diuretic
Used for severe / non responsive / malignant
HT

33. Thank you