18.antihypertensives

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 : 1
st
line agents

Renin

ACE



(vasoconstriction)


BP
ACEIs

Bradykinin
PG
Vasodilation
Blood vessel Aldosterone
release
Cardiac hypertrophy
& remodelling
Angiotensinogen
Angiotensin I
Angiotensin II
PVR Na
+
& H
2
O 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 AT
1
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
+
,
H
2
O 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 1
st
line agents in mild to moderate
hypertension
blocks β
1
receptors on heart – HR,

FOC, CO - BP
β-blockers
blocks β
1
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 α
2A

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 α
2
-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 α
1 & α
2- receptors Block selectively α
1-
in the blood vessels vascular receptors
Vasodilation & fall in BP Arterial & venodilation
(due to α
1
-blockade)
Noradrenaline release Fall in BP
(due to presynaptic α
2-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 1
st
dose

26. VI. Vasodilators :
activates








Minoxidil
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
+
& H
2O retention with
edema
Diazoxide:
•Use – treatment of hypertensive emergencies
•AE - reflex tachycardia, Na
+
& H
2O 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
O
2
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