Transcript hypertension

Hypertension or arterial hypertension is a chronic medical
condition in which the blood pressure in the arteries is persistently
elevated.
 Hypertension is present  Hypertension is classified
if the blood pressure is
persistently at or above
140/90 mmHg
as either primary
(essential) hypertension
(90–95%) or secondary
hypertension (5–10%).
 Primary hypertension is
high blood pressure with no
obvious underlying cause.
 Secondary hypertension is
hypertension due to an
identifiable cause
Complications of Hypertension
Hypertensive crisis -severely elevated blood pressure (equal
to or greater than a systolic 180 or diastolic of 110).
 Hypertensive crisis is categorized as :
 Hypertensive urgency
There is no evidence of end organ damage resulting from the
elevated blood pressure. In these cases, oral medications are
used to lower the BP gradually over 24 to 48 hours.
 Hypertensive emergency
There is evidence of direct damage to one or more organs.The
most affected organs include the brain, kidney, heart and
lungs, producing symptoms which may include confusion,
drowsiness, chest pain and breathlessness. In hypertensive
emergency, the blood pressure must be reduced rapidly to stop
ongoing organ damage.
CLASSIFICATION
1. Diuretics
Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
High ceiling: Furosemide, etc.
K+ Sparing: Spironolactone, Amiloride
2. ACE inhibitors
 Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Fosinopril, etc.
3. Angiotensin (AT1 receptor) blockers
 Losartan, Candesartan, Irbesartan, Valsartan, Telmisartan
4. Direct renin inhibitor
 Aliskiren
5. Calcium channel blockers
 Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine, Nitrendipine, Lacidipine, etc.
6. β Adrenergic blockers
 Propranolol, Metoprolol, Atenolol, etc.
7. β + α Adrenergic blockers
 Labetalol, Carvedilol
8. α Adrenergic blockers
 Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxybenzamine
9. Central α2 Adrenomimetics
 Clonidine
10. Vasodilators
 Arteriolar: Hydralazine, Minoxidil, Diazoxide
 Arteriolar + venous: Sodium nitroprusside

Sympatholytics (Reserpine, Guanethidine, etc.) and ganglion blockers (Pentolinium, etc.) are only of
historical importance.
DIURETICS
 Only the thiazide and thiazide-like diuretics should
usually be the first choice when selecting a diuretic to
treat hypertension.

The reason why thiazide-type diuretics are better than the others is (at least in part) thought to be
because of their vasodilating properties.
 Loop diuretics should be used only in case of severely
elevated blood pressure (hypertensive crisis).
 Potassium sparing diuretics are used only in
conjunction with a thiazide diuretic to prevent K+ loss.
ANGIOTENSIN CONVERTING
ENZYME (ACE) INHIBITORS
 inhibit the activity of angiotensin-converting enzyme
(ACE), an enzyme responsible for the conversion of
angiotensin I into angiotensin II, a potent
vasoconstrictor.
ACE-INHIBITORS
ACE-INHIBITORS
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Captopril
Enalapril
Lisinopril
Ramipril
Perindopril
Clinical use:
1) Hypertension
2) Cardiac conditions such as congestive heart failure
3) Myocardial infarction
Adverse effects:
 Hypotension
 Cough: a persistent brassy cough is caused by inhibition of
bradykinin breakdown in the lungs
 Hyperkalemia
 Teratogenicity
 Acute renal failure
Angiotensin II receptor antagonists
 Angiotensin II receptor antagonists also known
as angiotensin receptor blockers (ARBs), AT1receptor antagonists or sartans
 Work by antagonizing the activation of angiotensin
receptors.
Losartan
Telmisartan
Irbesartan
Valsartan
Mechanism of action
Blockage of AT1 receptors directly causes:
 Vasodilation
 Reduce production and secretion of aldosterone
Medical uses
 primarily for the treatment of patients that is intolerant of
ACE inhibitor therapy
 They do not inhibit the breakdown of bradykinin ⇒ there are no the
persistent dry cough or angioedema that limit ACE inhibitor therapy.
Adverse effects:
 Hypotension
 Hyperkalemia
 Headache
 Dizziness
Calcium channel blockers (CCB)
Block the entry of Ca2+ into:
 Smooth muscle cells in artery walls
 SA, A-V node, atrial and ventricular cardiac
fibres
Classes of calcium channel blockers:
Dihydropyridines :
Amlodipine
Felodipine
Isradipine
Nicardipine
Nifedipine
Nimodipine
Non-dihydropyridines:
Verapamil
⇒
Diltiazem
⇒
Act only on arteries
⇒reduce systemic
vascular resistance and
arterial pressure
selective for myocardium
Act both on arteries and
heart
Comparative properties of representative
calcium channel blockers
Nifedipine
Vascular smooth muscle
relaxation
++++
Cardiac effects :
Heart rate ↓
AV conduction velocity↓
Contractility↓
-
Clinical use in
Hypertension
Angina
ADR
Hypotension
Tachycardia
Edema
Verapamil
Diltiazem
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++
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++
Arrhythmia
Angina
(Hypertension)
Arrhythmia
Hypertension
Angina
Bradycardia
A-V block
CHF
Cardiac arrest
Hypotension
A-V block
β-ADRENERGIC BLOCKERS
Nonselective (β1 and β2)
a. Without intrinsic sympathomimetic activity:
 Propranolol
 Sotalol
 Timolol
b. With intrinsic sympathomimetic activity:
 Pindolol
Cardioselective (β1):
 Metoprolol
 Atenolol
 Acebutolol
 Bisoprolol
 Esmolol
 Betaxolol
 Nebivolol
α and β blockers (with additional vasodilator property):
 Labetalol
 Carvedilol
αβ ADRENERGIC BLOCKERS
 Labetalol
 acts faster than pure β blockers. It has been used i.v.
for rapid BP reduction in hyperadrenergic states,
cheese reaction, clonidine withdrawal, eclampsia, etc.
Oral labetalol therapy is restricted to moderately
severe hypertension not responding to a pure β
blocker.
 Carvedilol
 produces vasodilatation and has additional
antioxidant/free radical scavenging properties.
Carvedilol is a frequently selected drug for long-term
treatment of CHF, and is approved as an
antihypertensive as well.
α-ADRENERGIC BLOCKERS
A. Nonselective
 Phentolamine
 Phenoxybenzamine
B. α1 selective— Prazosin, Terazosin, Doxazosin,
Alfuzosin
Central α2 Adrenomimetics
 Clonidine
Use
 Clonidine was a popular antihypertensive in the late
1960s and 1970s, but frequent side effects, risk of
withdrawal hypertension and development of tolerance
have relegated it to a 3rd or 4th choice drug. There is no
data on prognostic benefits, if any, of clonidine. At
present, it is occasionally used in combination with a
diuretic.
 Clonidine has also facilitated alcohol withdrawal and
smoking cessation.
ADR:
 Orthostatic hypotension
 Sedation
 Rebound effect
VASODILATORS
 Vasodilators act directly on the smooth muscle of arteries and veins
to relax their walls
 They are only used in hypertensive emergencies or when other
drugs have failed.
Arteriolar: Hydralazine, Minoxidil, Diazoxide
Hydralazine and its derivatives are used in the treatment of severe
hypertension, although they should be avoided in emergencies. They
are no longer indicated as first-line therapy for high blood pressure
due to side effects and safety concerns.
Arteriolar + venous: Sodium nitroprusside
Sodium nitroprusside, a very potent, short-acting vasodilator, is most
commonly used for the quick, temporary reduction of blood pressure
in emergencies (such as malignant hypertension or aortic dissection).
VASODILATORS
Adverse effects of vasodilators
 Facial flushing, throbbing headache, dizziness,
palpitation, nasal stuffiness, edema, CHF, weakness,
disorientation
 Angina and MI may be precipitated in patients with
coronary artery disease.
 Postural hypotension
 Paresthesias, tremor, muscle cramps, rarely peripheral
neuritis.
TREATMENT OF HYPERTENSION
 4 groups of first choice antihypertensive drugs:
A—ACE inhibitor/ARB
B—β-blocker
C—CCB
D—diuretic
 A and B are preferred in younger patients (<55 years),
C and D are preferred in the older (> 55 years)
Combination therapy
 Though guidelines emphasise on single drug therapy,
the addition of a second (and third or even fourth)
drug is also highlighted when monotherapy fails.
 In practice, a large majority of hypertensives ultimately
require 2 or more drugs (70% patients who achieved
target BP were being treated with 2 or more drugs)
The preferred combinations
 Thiazide diuretic and ACE inhibitor
 Thiazide diuretic and angiotensin receptor antagonist
 Calcium antagonist and ACE inhibitor
 Calcium antagonist and angiotensin receptor
antagonist
 Calcium antagonist and thiazide diuretic
 β-blocker and calcium antagonist (dihydropiridine)
Combinations to be avoided
1. An α adrenergic blocker with clonidine: apparent
antagonism of clonidine action has been observed.
2. Hydralazine with a DHP or prazosin; because of
similar pattern of haemodynamic action (huge risk of
orthostatic hypotension and collapse).
3. Verapamil or diltiazem with β blocker, because
marked bradycardia, A-V block can occur.
4. Any two drugs of the same class.
Hypertensive emergencies and
urgencies
Oral therapy
 Nifedipine (10 mg orally or s.l. every 30 min). Adverse
consequences - abrupt fall in BP.
 Captopril (25 mg oral every 1–2 hours) - risk of
excessive hypotension.
 Clonidine (100 mg every 1–2 hours oral) acts mostly in
30–60 min, but produces sedation and rebound rise in
BP on stopping the drug.
Parenteral therapy
 1. Sodium nitroprusside (slow i.v. injection) is the drug of
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choice for most hypertensive emergencies.
2. Hydralazine (i.m. or slow i.v. injection) acts in 20–30
min and keeps BP low for 4–8 hours, but is less predictable,
and not a first line drug. It has been especially used in
eclampsia. It causes tachycardia and should be avoided in
patients with myocardial ischaemia.
3. Phentolamine .This nonselective α1 + α2 blocker is the
drug of choice for hyperadrenergic states, e.g. hypertensive
episodes in pheochromocytoma, cheese reaction or
clonidine withdrawal. Injected i.v.
4.Furosemide (oral or i.v.)
Nicardipine and clevidipine (parenteral DHPs),
Enalaprilat (a parenteral ACE inhibitor)
Trimethaphan (a ganglion blocker)