HYPERTENSION

Hypertension

mmHg 140 > mmHg 90 >

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Systolic Blood Diastolic Blood

Pressure (SBP) Pressure (DBP)
 Types of
Hypertension

Essential Secondary

A disorder of unknown origin affecting the

Secondary to other disease processes
Blood Pressure regulating mechanisms

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Environmental
Factors

Stress Na+ Intake Obesity Smoking

Risk factors: Hypertension: 7 classification

1. Age above 55 in Men and 65 in Woman

2. Family History
3. Smoking
4. Diabetes and Dyslipidemia
5. Hypertension
6. Obesity
7. Microalbuminuria
Treatment of Hypertension –
6 compelling Indications:
Heart failure
Coronary artery disease
H/o MI
H/o stroke
Diabetes
Chronic Renal failure
 Treatment – Why?
Symptomatic treatment is Mandatory:
Reduce premature cardiovascular morbidity and
mortality and microvascular disease affecting the
brain, kidney and retina.
Hypertension, even asymptomatic needs treatment
major risk factor for stroke, heart failure, renal
disease, peripheral vascular disease, and coronary
artery disease.
Factors inducing HTN include decreased vagal tone,
increased sympathetic tone, increased renin-
angiotensin activity, and excess water retention.
 MECHANISMS FOR CONTROLLING B.P
BP = CO x TPR
Cardiac output and peripheral resistance, are
controlled mainly by two overlapping control
mechanisms:
the baroreflexes and
the renin–angiotensin–aldosterone system

√ Most antihypertensive drugs lower blood pressure by

reducing cardiac output and/or decreasing peripheral
resistance
1. Baroreceptors and the sympathetic
nervous system
 A fall in blood pressure causes pressure-sensitive
neurons (baroreceptors in the aortic arch and
carotid sinuses) to send fewer impulses to
cardiovascular centers in the spinal cord.
 This prompts a reflex response of increased
sympathetic and decreased parasympathetic
output to the heart and vasculature, resulting in
vasoconstriction and increased cardiac output.
 These changes result in a compensatory rise in
blood pressure
2. Renin–angiotensin–aldosterone system
Baroreceptors in the kidney respond to reduced arterial
pressure (and to sympathetic stimulation of β1 adrenoceptors)
by releasing the enzyme renin.
Renin converts angiotensinogen to angiotensin I, which is
converted in turn to angiotensin II, in the presence of
angiotensin-converting enzyme (ACE).
Angiotensin II is a potent circulating vasoconstrictor,
constricting both arterioles and veins, resulting in ↑ B.P.
Angiotensin II exerts a preferential vasoconstrictor action on
the efferent arterioles of the renal glomerulus, increasing GFR.
Stimulation of angiotensin II type 1 (AT1) receptors leads to
aldosterone secretion, leading to increased renal sodium
reabsorption and increased blood volume, which contribute to
a further increase in blood pressure.
Pharmacotherapy
Non-drug treatment (Life-style changes)

 salt intake (2.5g/d --* 1 g/d)

 calorie intake, weight loss
 alcohol consumption
 physical activity
 stress factors
stop smoking,
caffeine intake
2020 International Society of Hypertension Global
Hypertension Practice Guidelines
 Pharmacotherapy
Goal of treating hypertension is a systolic B.P < 140 mm
Hg and a diastolic B.P of < 90 mm Hg.
Mild hypertension monotherapy, but most patients
require more than one drug to achieve B.P control.
Recommendation: initiate therapy with a thiazide
diuretic, ACEI, ARB, or calcium channel blocker.
Uncontrolled B.P a second drug should be added,
with the selection based on minimizing the adverse
effects of the combined regimen and achieving goal
blood pressure.
Patients with systolic B.P >160 mm Hg or diastolic B.P
>100 mm Hg should be started on two antihypertensives
simultaneously.
For patients with diabetes, goal B.P = < 140/80 mm Hg.
In patients with chronic kidney disease and
proteinuria, lower goals of < 130/80 mm Hg may be
considered.
Elderly patients less than 150/90 mm Hg.
Summary of antihypertensive drugs.
Drugs which lower blood pressure act through three
General Mechanisms:

1. Alter sympathetic activity

2. Relax vascular smooth muscle
3. Alter sodium and water balance

• Treatments for HTN aim to reduce sympathetic tone and

blood volume and/or relax vascular smooth muscle.
 Antihypertensive Drugs
Diuretics:
 Thiazides: Hydrochlorothiazide, chlorthalidone
 High ceiling: Furosemide
 K+ sparing: Spironolactone, triamterene and amiloride
MOA: Acts on Kidneys to increase excretion of Na and H2O –
decrease in blood volume – decreased BP
Angiotensin-converting Enzyme (ACE) inhibitors:
 Captopril, lisinopril, enalapril, ramipril and fosinopril
MOA: Inhibit synthesis of Angiotensin II – decrease in
peripheral resistance and blood volume
Angiotensin (AII) blockers:
 Losartan, candesartan, valsartan and telmisartan
MOA: Blocks binding of Angiotensin II to its receptors
 Antihypertensive Drugs
Centrally acting:
Clonidine, methyldopa
MOA: Act on central α2A receptors to decrease sympathetic outflow –
fall in BP
ß-adrenergic blockers:
Non selective: Propranolol (others: nadolol, timolol, pindolol,
labetolol)
Cardioselective: Metoprolol (others: atenolol, esmolol,
betaxolol)  
MOA: Bind to beta adrenergic receptors and blocks the activity
ß and α – adrenergic blockers:
Labetolol and carvedilol
α – adrenergic blockers:
Prazosin, terazosin, doxazosin, phenoxybenzamine and
phentolamine
MOA: Blocking of alpha adrenergic receptors in smooth muscles -
vasodilatation
 Antihypertensive Drugs
Calcium Channel Blockers (CCB):
Verapamil, diltiazem, nifedipine, felodipine,
amlodipine, nimodipine etc.
MOA: Blocks influx of Ca++ in smooth muscle cells
– relaxation of SMCs – decrease BP
K+ Channel activators:
Diazoxide, minoxidil, and nicorandil
MOA: Leaking of K+ due to opening – hyper
polarization of SMCs – relaxation of SMCs
Vasodilators:
Arteriolar – Hydralazine (also CCBs and K+
channel activators)
Arterio-venular: Sodium Nitroprusside
Angiotensin Converting Enzyme (ACE)
Inhibitors

What is Renin – Angiotensin-

Aldosterone System (RAAS)?
(Physiological Background)
 RAAS - Introduction
Renin is a proteolytic enzyme and also called
angiotensinogenase
It is produced by juxtaglomerular cells of kidney
It is secreted in response to:
Decrease in arterial blood pressure
Decrease Na+ in macula densa
Increased sympathetic nerve activity
Renin acts on a plasma protein – Angiotensinogen (a
glycoprotein synthesized and secreted into the
bloodstream by the liver) and cleaves to produce a
decapeptide Angiotensin-I
Angiotensin-I is rapidly converted to
Angiotensin-II (octapeptide) by ACE (present in
luminal surface of vascular endothelium)
Angiotensin-II stimulates Aldosterone secretion
from Adrenal Cortex.
RAAS – actions of Angiotensin-II.
1.Powerful vasoconstrictor, particularly arteriolar – direct
action and release of Adr/NA
Promotes movement of fluid from vascular to
extravascular
promotes Na+ and water reabsorption
It increases myocardial force of contraction (CA++ influx
promotion) and increases heart rate by sympathetic
activity, but reflex bradycardia occurs

2.Aldosterone secretion stimulation – retention of Na++ in

body
 Angiotensin-II
What are the chronic ill effects ?
Volume overload and increased T.P.R
Cardiac hypertrophy and remodeling
Coronary vascular damage and remodeling
Hypertension – long standing will cause ventricular
hypertrophy
Myocardial infarction – hypertrophy of non-infarcted
area of ventricles
Renal damage
Risk of increased CV related morbidity and mortality
ACE inhibitors reverse cardiac and vascular
hypertrophy and remodeling
 ACE inhibitors
Captopril, lisinopril, enalapril, ramipril and
fosinopril etc.
 ACE INHIBITORS
Recommended as first-line treatment of HTN in patients
with a variety of compelling indications, including high
coronary disease risk or history of diabetes, stroke, heart
failure, myocardial infarction, or chronic kidney disease
MOA
lower B.P by ↓PVR without reflexively ↑ CO, HR, or
contractility. (ACEI block conversion of AI to AII and inhibit
breakdown of bradykinin)
ACE is responsible for breakdown of bradykinin.
Bradykinin, is a peptide that ↑ production of nitric oxide
and prostacyclin by blood vessels, potent vasodilators
ACEIs block the enzyme ACE (which cleaves angiotensin I to
form the potent vasoconstrictor angiotensin II)
ACE inhibitors decrease angiotensin II and increase
bradykinin levels.
Vasodilation of both arterioles and veins occurs as a
result of decreased vasoconstriction (from
diminished levels of angiotensin II) and enhanced
vasodilation (from increased bradykinin).
By reducing circulating angiotensin II levels, ACE
inhibitors also decrease the secretion of aldosterone,
resulting in decreased sodium and water retention.
ACE inhibitors reduce both cardiac preload and
afterload, thereby decreasing cardiac work.
Therapeutic uses
Diabetic nephropathy Like the ARBs, ACEIs slow the
progression of diabetic nephropathy and ↓ albuminuria.
Beneficial effects on renal function may result from ↓
intraglomerular pressures, due to efferent arteriolar
vasodilation.
ACEIs used post myocardial infarction and first-line agents
in the treatment of patients with systolic dysfunction.
Chronic treatment achieves sustained B.P reduction,
regression of left ventricular hypertrophy, and prevention of
ventricular remodeling after a MI.
1st drugs for tx in HF, hypertensive patients with chronic
kidney disease, and patients at increased risk of CAD.
All equally effective in the tx of HTN at equivalent doses.
Adverse effects
Common: dry cough, rash, fever, altered taste,
hypotension and hyperkalemia.
dry cough( 10% of patients) due to increased levels of
bradykinin and substance P, resolves within a few days
of discontinuation.
Angioedema is a rare, due to ↑ bradykinin.
monitor K levels and use potassium supplements and
potassium-sparing diuretics cautiously.
ACE inhibitors can induce fetal malformations and
should not be used by pregnant women.
Effects of various drug classes on the Renin–Angiotensin–
Aldosterone system.
Blue = drug target enzymes; red = drug class.
ANGIOTENSIN II RECEPTOR BLOCKERS
E.g. Losartan, Irbesartan, are alternatives to the ACEIs.
block the AT1 receptors, decreasing the activation of
AT1 receptors by angiotensin II.
ARBs do not increase bradykinin levels.
Used as first-line agents for the tx of HTN especially in
patients with a compelling indication of diabetes, heart
failure, or chronic kidney disease
AE: similar to those of ACEIs, although the risks of
cough and angioedema are significantly decreased.
These agents are also teratogenic and should not be
used by pregnant women.
 BRADYKININ
Vasodilation
and vascular
permeability

Sites of action of drugs that interfere with the RAAS

 Thiazide diuretics
MOA: Block Na+/Cl- transporter in renal distal convoluted
tubule and decrease blood volume, which ultimately leads to
decreased blood pressure
used as initial drug therapy for hypertension unless CI.
effective in lowering blood pressure by 10–15 mm Hg.
E.g. Hydrochlorothiazide (HCT), lower B.P by increasing
sodium and water excretion.
This causes a decrease in extracellular volume, resulting in a
decrease in cardiac output and renal blood flow
useful in combo therapy with β-blockers, ACE inhibitors,
ARBs, and potassium-sparing diuretics.
 Loop diuretics
MOA: Block Na+/K+/2Cl- transporter in renal loop of Henle.
This site accounts for retention of approx. 20 % of filtered
sodium; therefore these are potent diuretics.
Furosemide, torsemide, bumetanide, and ethacrynic acid
act promptly by inhibiting reabsorption of sodium and
chloride
cause decreased renal vascular resistance and increased
renal blood flow.
unlike thiazides, loop diuretics increase the Ca 2+ content of
urine, whereas thiazide diuretics decrease it.
commonly used to manage symptoms of heart failure and
edema.
 Potassium-sparing diuretics
MOA: Inhibit sodium absorption by blocking aldosterone
receptor in renal collecting tubule.
oIncrease Na+ and water excretion and ↓ K+ excretion.
Amiloride and triamterene inhibit sodium reabsorption in
the distal tubule by blocking sodium channels. They
interfere with sodium/potassium exchange and reduce
urinary potassium excretion.
Aldosterone antagonists, e.g Spironolactone, have the
additional benefit of diminishing the cardiac remodelling
that occurs in heart failure
Potassium-sparing diuretics are sometimes used in
combination with loop diuretics and thiazides to reduce the
amount of potassium loss induced by these diuretics
β-ADRENOCEPTOR–BLOCKING AGENTS
MOA: Block β1 receptors reduce blood pressure primarily by
decreasing cardiac output.
Also decrease sympathetic outflow from the CNS and inhibit
the release of renin from the kidneys, thus decreasing the
formation of angiotensin II and the secretion of aldosterone.
Prototype = Propranolol acts at both β1 and β2 receptors.
Selective blockers of β1 receptors  Metoprolol and Atenolol
The selective β-blockers may be administered cautiously to
hypertensive patients who also have asthma.
The nonselective β-blockers, such as propranolol, are
contraindicated in patients with asthma due to their blockade of
β2-mediated bronchodilation.
use cautiously in the tx of patients with acute heart failure or
peripheral vascular disease
Beta-blockers Mode of action
Competitively block beta receptors in the
heart, peripheral vasculature, bronchi,
pancreas, uterus, kidney, brain and liver.
Beta-blockers reduce heart rate, BP and
cardiac contractility; also depress sinus node
rate and slow conduction through the AV node,
and prolong atrial refractory periods.
Actions of β-adrenoceptor–blocking agents.
Therapeutic uses
in hypertensive patients with concomitant heart
disease, such as supraventricular tachyarrhythmia (for
example, atrial fibrillation), previous myocardial
infarction, angina pectoris, and chronic heart failure.
Pharmacokinetics
Propranolol undergoes extensive and highly variable
first-pass metabolism.
Oral β-blockers may take several weeks to develop
their full effects.
Esmolol, metoprolol, and propranolol are available in
intravenous formulations.
Adverse effects
Common: Nausea, diarrhoea, bronchospasm, cold
extremities, may cause bradycardia, hypotension, and CNS
side effects such as fatigue, lethargy, and insomnia.
may decrease libido and cause erectile dysfunction,
which can severely reduce patient compliance.
Alterations in serum lipid patterns: Non cardioselective
β-blockers disturb lipid metabolism, decreasing high-
density lipoprotein cholesterol and increasing triglycerides.
Drug withdrawal: Abrupt withdrawal may induce angina,
myocardial infarction, and even sudden death in patients
with ischemic heart disease. Therefore, these drugs must
be tapered over a few weeks in patients with hypertension
and ischemic heart disease.
 α-/β-ADRENOCEPTOR–BLOCKING
AGENTS
Labetalol and Carvedilol block α1, β1, and β2
receptors.
Carvedilol, although an effective antihypertensive,
is mainly used in the treatment of heart failure.
Carvedilol, as well as metoprolol and bisoprolol
have been shown to reduce morbidity and
mortality associated with heart failure.
Labetalol is used in the management of
gestational hypertension and hypertensive
emergencies.
α-ADRENOCEPTOR–BLOCKING AGENTS
Prazosin, Doxazosin, and Terazosin produce a
selective block of α1 adrenoceptors in arterioles and venules.
They prevent sympathetic vasoconstriction.
They decrease PVR and lower arterial B.P by causing
relaxation of both arterial and venous smooth muscle.
cause only minimal changes in CO, renal blood flow, & GFR.
Are more effective when used in combo with other agents,
such as a β blocker and a diuretic, than when used alone.
primarily used in men with concurrent HTN & BPH.
a precipitous drop in standing blood pressure develops in
some patients shortly after the first dose is absorbed, thus
the first dose should be small and should be administered at
bedtime
CENTRALLY ACTING ADRENERGIC DRUGS
1. Clonidine acts centrally at alpha2 adrenoceptors in the
medulla of the brain and at imidazoline receptors.
Reduces sympathetic and increases parasympathetic tone,
resulting in blood pressure lowering and bradycardia.
This leads to reduced TPR and decreased B.P.
used primarily for the tx of HTN that has not responded
adequately to treatment with two or more drugs.
PK: absorbed well after oral admin. and excreted by kidney.
Also available in a transdermal patch.
AE: sedation, dry mouth, and constipation.
Rebound hypertension occurs following abrupt withdrawal of
clonidine. The drug should, therefore, be withdrawn slowly if
discontinuation is required.
2. Methyldopa
Methyldopa is a centrally acting alpha2 adrenoceptor agonist
that is converted to methylnorepinephrine centrally to
diminish adrenergic outflow from the CNS (sympathetic tone)
It lowers blood pressure chiefly by reducing peripheral
vascular resistance, with a variable reduction in heart rate
and cardiac output.
The most common side effects of methyldopa are sedation
and drowsiness.
Its use is limited due to adverse effects and the need for
multiple daily doses.
It is mainly used for management of hypertension in
pregnancy, where it has a record of safety.
 RENIN INHIBITOR
Inhibits enzyme activity of renin  Aliskiren
Aliskiren directly inhibits renin and, thus, acts earlier in
the RAAS than ACEIs or ARBs .
Reduces angiotensin I and II and aldosterone.
It lowers blood pressure about as effectively as ARBs,
ACE inhibitors, and thiazides.
should not be routinely combined with an ACEI or ARB.
AE: can cause diarrhea, especially at higher doses, and
can also cause cough and angioedema, but probably less
often than ACE inhibitors.
Contraindicated during pregnancy.
metabolized by CYP 3A4 and is subject to many DIs
Therapeutic uses
as an initial therapy or as add-on therapy.
useful in the treatment of hypertensive patients who also
have asthma, diabetes, and/or PVD, because unlike β-
blockers, they do not adversely affect these conditions.
Hypertension (all drugs), Angina (all
drugs),Antiarrhythmics- atrial fibrillation(verapamil,
diltiazem)
Pharmacokinetics
Most of these agents have short half-lives (3 to 8 hours)
following an oral dose.
SR preps are available and permit once-daily dosing.
Amlodipine has a very long half-life and does not require a
sustained-release formulation.
 Calcium Channel Blockers
MOA: block the inward movement of calcium by binding to
L-type calcium channels in the heart and in smooth muscle of
the coronary and peripheral arteriolar vasculature. This
causes vascular smooth muscle to relax, dilating mainly
arterioles.
Divided into three chemical classes, each with different
pharmacokinetic properties and clinical indications.
1. Diphenylalkylamines:
Verapamil : is the least selective of any calcium channel
blocker and has significant effects on both cardiac and
vascular smooth muscle cells.
It is also used to treat angina and SVT and to prevent
migraine and cluster headaches.
Mode of Action
Block inward current of Calcium into cells in vascular
smooth muscle, myocardium and cardiac conducting system
via L-type calcium channels.
Act on coronary arteriolar smooth muscle to reduce
vascular resistance and myocardial oxygen requirements,
relieving angina symptoms.
Dihydropyridines act mainly on arteriolar smooth muscle to
reduce peripheral vascular resistance and BP. They have
minimal effect on myocardial cells.
Non-dihydropyridines: Diltiazem and Verapamil act on
cardiac and arteriolar smooth muscle. They reduce cardiac
contractility, heart rate and conduction, with verapamil
having the greater effect. Diltiazem has a greater effect on
arteriolar smooth muscle than verapamil.
2. Benzothiazepines:
Diltiazem : affects both cardiac and vascular smooth
muscle cells, but it has a less pronounced negative inotropic
effect on the heart compared to that of verapamil. Diltiazem
has a favorable side effect profile.
3. Dihydropyridines:
Nifedipine, Amlodipine Felodipine, Nicardipine.
act mainly on arteriolar smooth muscle (vascular calcium
channels) to reduce peripheral vascular resistance and BP.
Their affinity for vascular calcium channels rather than for
calcium channels in the heart, makes them particularly
beneficial in treating hypertension.
All differ in their PK, approved uses, and DIs.
Adverse effects
First-degree atrioventricular block and constipation are
common dose dependent side effects of Verapamil.
Verapamil and diltiazem should be avoided in patients with
heart failure or with atrioventricular block due to their
negative inotropic (force of cardiac muscle contraction) and
dromotropic (velocity of conduction) effects.
Dizziness, headache, and a feeling of fatigue caused by a
decrease in blood pressure are more frequent with
dihydropyridines.
Peripheral edema is another commonly reported side
effect.
Nifedipine and other dihydropyridines may cause gingival
hyperplasia.
Reflex tachycardia ("-dipine"s)
DIRECT-ACTING VASODILATORS
Hydralazine and Minoxidil are direct-acting smooth
muscle relaxants.
Hydralazine : Causes nitric oxide release, ↓ TPR via
arteriolar dilation.
Minoxidil : metabolite opens Potassium channels in
vascular smooth muscle causing hyperpolarization of smooth
muscle, results in arteriolar vasodilation.
Decreased arterial resistance and mean arterial blood
pressure elicit compensatory responses reflex stimulation
of heart, resulting in the competing reflexes of increased
myocardial contractility, heart rate, and oxygen
consumption.
also ↑ plasma renin conc, resulting in NA &H 2O retention.
HYDRALAZINE
Predominantly an arteriolar vasodilator with little effect on
venous smooth muscle
Arteriolar vasodilation results in reflex sympathetic stimulation,
leading to tachycardia and fluid retention.
Increases cGMP and this will lead to smooth muscle relaxation.
Also reduces the afterload and has a greater effect to dilate the
arterial
Uses
Severe HTN and congestive heart failure
First line htn in pregnancy with methyldopa.
Why is hydralazine co-administered with beta blocker?
oTo prevent reflex tachycardia.
These actions may prompt angina pectoris, myocardial
infarction, or cardiac failure in predisposed individuals.
Hydralazine is mostly admin in combo with a β-blocker,
such as propranolol, metoprolol, or atenolol (to balance the
reflex tachycardia) and a diuretic (to decrease sodium
retention).
Together, the three drugs decrease cardiac output, plasma
volume, and peripheral vascular resistance.
Indication: B.P in pregnancy induced hypertension.
AE: headache, nausea, anorexia, palpitations, sweating,
and flushing, lupus erythematosus-like syndrome.
Tx with Minoxidil causes hypertrichosis (the growth of
body hair), thus Topical minoxidil (as Rogaine) is used to
treat male pattern baldness.
one person’s toxicity another person’s therapy.
Includes the oral vasodilators, hydralazine and minoxidil, which are used for long-term
outpatient therapy of hypertension; the parenteral vasodilators, nitroprusside, diazoxide,
and fenoldopam, which are used to treat hypertensive emergencies; the calcium channel
blockers, which are used in both circumstances; and the nitrates, used mainly in angina
 Sodium Nitroprusside
Powerful vasodilator: releases nitric oxide.
↓ TPR via dilation of both arterioles and venules.
Use: hypertensive emergencies (DOC used IV)
The action occurs as a result of activation of guanylyl
cyclase, either via release of nitric oxide or by direct
stimulation of the enzyme.
The result is increased intracellular cGMP, which relaxes
vascular smooth muscle.
metabolized rapidly (half-life of minutes) and requires
continuous infusion to maintain its hypotensive action.
Adverse effects: All are due release of cyanides
(thiocyanate) – palpitation, pain abdomen, disorientation,
psychosis, weakness and lactic acidosis.
DIAZOXIDE
Diazoxide is an effective and relatively long-acting
parenterally administered arteriolar dilator that is
occasionally used to treat hypertensive emergencies.
prevents vascular smooth muscle contraction by
opening potassium channels and causing powerful
vasodilation.
FENOLDOPAM
Fenoldopam is a peripheral arteriolar dilator used for
hypertensive emergencies and postoperative
hypertension.
It acts primarily as an agonist of dopamine D 1 receptors,
resulting in dilation of peripheral arteries and natriuresis
 HYPERTENSIVE EMERGENCY
rare but life-threatening situation characterized by severe
elevations in blood pressure (systolic >180 mm Hg or
diastolic >120 mm Hg) with evidence of impending or
progressive target organ damage (for example, stroke,
myocardial infarction).
B.P should be lowered by about 25%, maintaining diastolic
blood pressure at no less than 100–110 mm Hg.
Parenteral meds lower B.P rapidly (within a few hours)&
achieve reasonable B.P control, then use oral meds over
several weeks  smoother long-term mgx of HTN.
Most commonly used: Sodium Nitroprusside.
Other parenteral drugs include fenoldopam, nitroglycerin,
labetalol, CCBs, diazoxide, and hydralazine.
hydralazine 5 mg bolus intravenously over 5 minutes and
repeated every 10 minutes up to a maximum of 20 mg, followed
by intravenous infusion of hydralazine
OR
labetalol (100 mg per 20 mL); initial dose of 20–40 mg given
intravenously over 1–2 minutes and repeated at intervals of 5–
10 minutes until 200 mg have been given.
Alternatively, labetalol may be given as a continuous
intravenous infusion at a rate of 2 mg per minute

Once the BP is stabilised, the patient should be changed to oral

treatment for maintenance.
 RESISTANT HYPERTENSION
defined as blood pressure that remains elevated
(above goal) despite administration of an optimal three-
drug regimen that includes a diuretic.
The most common causes of resistant hypertension
are poor compliance, excessive ethanol intake,
concomitant conditions (diabetes, obesity, sleep apnea,
hyperaldosteronism, high salt intake, and/or metabolic
syndrome), concomitant medications
(sympathomimetics, nonsteroidal anti-inflammatory
drugs, or antidepressant medications), insufficient dose
and/or drugs, and use of drugs with similar mechanisms
of action.
 COMBINATION THERAPY
Combination therapy with separate agents or a fixed-dose
combination pill may lower blood pressure more quickly
with minimal adverse effects.
A variety of combination formulations of the various
pharmacologic classes are available to increase ease of
patient adherence to treatment regimens that require
multiple medications to achieve the blood pressure goal.