By: Abdurazak J
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Introduction cont…
Hypertension is a sustained systolic blood pressure (SBP)
of greater than 140 mm Hg or a sustained diastolic blood
pressure (DBP) of greater than 90 mm Hg
mmHg 140 > mmHg 90 >
Hypertension
SBP DBP
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Introduction cont…
Although hypertension occur secondary to other disease
processes, ˃90% are essential hypertension, a disorder of
unknown origin affecting BP regulating mechanism.
A family history of hypertension increases the likelihood
that an individual will develop hypertensive disease.
The incidence of essential hypertension is four-fold more
frequent among blacks than among whites
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Introduction cont…
It occurs more often among middle-aged male than among
middle-aged female & prevalence ↑ with age & obesity.
Environmental factors, such as a stressful lifestyle, high
dietary intake of sodium & smoking, further predispose
individual to the occurrence of hypertension
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Introduction cont…
Environmental
Factors
Stress Na+ Intake Obesity Smoking
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Introduction cont…
Reference is made to stages of hypertension according to
recommendations of the Sixth Joint National Committee
on the Detection, Evaluation & Treatment of High BP
Blood Pressure (mm Hg)
Classification Systolic Diastolic
Normal <120 and <80
Pre-hypertension 120–139 or 80–89
Hypertension, stage 1 140–159 or 90–99
Hypertension, stage 2 ≥160 or ≥100
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Normal Blood Pressure Regulation
According to hydraulic equation, arterial blood pressure
(BP) is directly proportionate to the product of blood flow
(cardiac output) & resistance to passage of blood through
precapillary arterioles (peripheral vascular resistance, PVR):
BP = CO × PVR
Physiologically (in normal, hypertensive), BP is maintained
by moment-to-moment regulation of CO & PVR, exerted at
three anatomic sites: arterioles, postcapillary venule & heart.
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Normal Blood Pressure Regulation cont..
A fourth control site, kidney, contributes to maintenance of
blood pressure by regulating volume of intravascular fluid
Baroreflex, mediated by autonomic nerve act in combination
with humoral mechanisms including renin angiotensin-
aldosterone system), to coordinate function at these four
control sites & maintain normal blood pressure.
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Normal Blood Pressure Regulation cont..
Local release of vasoactive
substances from vascular
endothelium also involved in
regulating vascular resistance:
endothelin-1 constricts & NO
dilates blood vessels.
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Normal Blood Pressure Regulation cont..
Arterial blood pressure is regulated within a narrow range
to provide adequate perfusion of tissues without causing
damage to vascular system, particularly arterial intima
CO & PR controlled mainly by two overlapping control
mechanisms: baroreflexes, w/c mediated by sympathetic
neuron & renin-angiotensin-aldosterone system
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Normal Blood Pressure Regulation cont..
1. Baroreceptor reflex: moment-to-moment BP regulation
─ Central sympathetic neurons arising from vasomotor area of
medulla are tonically active
─ fall in BP causes pressure-sensitive neurons (baroreceptors
in aortic arch & carotid sinuses) to send impulses to
cardiovascular centers in spinal cord, this prompts a reflex
response of ↑sympathetic & ↓parasympathetic output to
heart & vasculature → vasoconstriction & ↑cardiac output.
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Normal Blood Pressure Regulation cont..
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Normal Blood Pressure Regulation cont..
1. Renin-angiotensin-aldosterone system
Kidney provides for long-term control of blood pressure by
altering the blood volume.
Baroreceptor in kidney respond to reduced arterial pressure
(sympathetic stimulation of β-receptor) by releasing renin
Low Na intake & greater sodium loss also ↑renin release
Renin convert Angiotensinogen to AgI→ AgII (ACE)
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Normal Blood Pressure Regulation cont..
Angiotensin II potent vasoconstrictor, constricting both
arterioles and veins, causing an increase in blood pressure.
─ preferential vasoconstrictor action on efferent arterioles of
renal glomerulus, increasing glomerular filtration.
─ stimulates aldosterone secretion, leading to increased renal
sodium reabsorption & increased blood volume, which
contribute to a further increase in blood pressure
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Blood Pressure Regulation in Hypertension
BP in hypertensive patient is controlled by same mechanism
that are operative in normotensive subjects.
Regulation of blood pressure in hypertensive patients differs
from healthy patients in that baroreceptors & renal blood
volume-pressure control systems appear to be ‘set’ at a
higher level of blood pressure.
Antihypertensive drugs lower BP by reducing CO and/or
decreasing peripheral resistance
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Hypertension Treatment Strategies
Goal of antihypertensive therapy is to reduce cardiovascular
and renal morbidity/mortality
Newly added classification of prehypertension emphasizes
need for decreasing blood pressure in general population by
education & adoption of blood pressure lowering behaviors
Mild hypertension can be controlled with a single drug;
however, most patients require more than one drug to
achieve blood pressure control. 16
Hypertension Treatment Strategies cont..
Current recommendation is to initiate therapy with thiazide
unless compelling reasons to employ other drug classes.
BP inadequately controlled, a second drug added, with
selection based on minimizing SE of combined regimen.
β-blocker is added if initial drug was diuretic, or a diuretic
is added if first drug was a β-blocker
Vasodilator added as a third step if failed to respond
ACEIs, ARB & CCB can also be used to initiate therapy
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Antihypertensive Drugs
1. Diuretics:
Thiazides: hydrochlorothiazide, chlorthalidone
High ceiling: furosemide
K+ sparing: spironolactone, triamterene, amiloride
MOA: acts on kidneys to increase excretion of Na & H2O
– decrease in blood volume – decreased BP
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Antihypertensive Drugs cont..
2. ACEIs: captopril, lisinopril, enalapril, ramipril, fosinopril
MOA: inhibit synthesis of Angiotensin II – decrease in
peripheral resistance & blood volume
3. Angiotensin (AT1) blockers: losartan, candesartan,
valsartan, irbesartan, eprosartan, olmesartan, telmisartan
MOA: blocks binding of Angiotensin II to receptors (AT1)
─ decrease in peripheral resistance & blood volume
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Antihypertensive Drugs contd..
4. Centrally acting sympathoplegics: clonidine, methyldopa
MOA: act on central α2A receptors to decrease sympathetic
outflow – fall in BP
5. ß-adrenergic blockers:
─ Nonselective: propranolol, nadolol, timolol, pindolol
─ Cardioselective: metoprolol, atenolol, esmolol, betaxolol
MOA: bind to beta adrenergic receptors & blocks the activity
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Antihypertensive Drugs contd..
6. ß and α – adrenergic blockers: labetolol & carvedilol
7. α – adrenergic blockers: prazosin, terazosin, doxazosin,
phenoxybenzamine and phentolamine
MOA: block alpha receptor in smooth muscle-vasodilatation
8. Calcium Channel Blockers (CCB): verapamil, diltiazem,
nifedipine, felodipine, amlodipine, nimodipine etc.
MOA: blocks influx of Ca2+ in smooth muscle cells →
relaxation of SMCs → decrease BP
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Antihypertensive Drugs contd..
9. KC activator: diazoxide, minoxidil, pinacidil, nicorandil
MOA: Leaking of K+ due to opening – hyper polarization of
SMCs – relaxation of SMCs
10.Vasodilator: diazoxide, minoxidil, hydralazine, fenoldopam
a) Arteriolar – Hydralazine (CCBs & K+ channel activators)
b) Arterio-venular: Sodium Nitroprusside
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Treatment of Hypertension – General principles
Stage I: start with a single appropriate drug with a low dose
preferably start with thiazides, others: BBs, CCBs, ARBs & ACE
inhibitors may also be considered. CCB – in case of elderly &
stroke prevention, if required increase the dose moderately
Partial response or no response – add from another group of drug,
but remember it should be a low dose combination
If not controlled – change to another low dose combination
In case of SE lower the dose or substitute with other group
Stage 2: start with 2 drug combination – one should be diuretic
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Treatment of Hypertension – combination therapy
In clinical practice patients require combination therapy that must
be rational & from different patterns of haemodynamic effects
Sympathetic inhibitors (not BBs)& vasodilators + diuretics
Diuretics, CCBs, ACEIs & vasodilator+ BBs(block renin release)
Hydralazine & CCBs + beta-blockers (tachycardia countered)
ACE inhibitors + diuretics
Three Drug combinations: CCB+ACE/ARB+diuretic; CCB+Beta
blocker+ diuretic; ACEI/ARB+ beta blocker+diuretic
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Treatment of Hypertension – contd.
Never combine:
─ Alpha or beta blocker & clonidine - antagonism
─ Nifedepine and diuretic synergism
─ Hydralazine with DHP or prazosin – same type of action
─ Diltiazem and verapamil with beta blocker – bradycardia
Hypertension & pregnancy: no drug is safe in pregnancy
─ Avoid diuretic, propranolol, ACEIs, Na nitroprusside
Safe: hydralazine, methyldopa, cardioselective BBs, prazosin
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Hypertensive Emergencies
Cerebrovascular accident or head injury with high BP
Left ventricular failure with pulmonary edema due to HTN
Eclampsia and Hypertensive encephalopathy
Acute renal failure, Angina or MI with raised BP
Pheochromocytoma, cheese reaction and clonidine withdrawal
Drugs:
─ Na Nitroprusside (20-300 mcg/min) – dose titration &
monitoring
─ GTN (5-20 mcg/min) – cardiac surgery, LVF, MI and angina
─ Esmolol (0.5 mg/kg bolus) and 50-200mcg/kg/min - useful in
reducing cardiac work
─ Phentolamine – pheochromocytoma, cheese reaction and
clonidine withdrawal (5-10 mg IV) 26
