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Cardio-vascular
Pharmacology
Professor Doctor:
Abd Al Rahman Abd Al
Fattah Yassin
Professor and head of clinical
pharmacology department
Mansura university
HYPERTENSION
• Hypertension is a persistent elevation of blood
pressure above 140/90 mm. Hg.
• Classification of Hypertension
According to etiology: essential and secondary
(e.g. thyrotoxicosis).
• According to type: systolic, diastolic and mixed
(more dangerous).
• According to degree:
N.B:
• Borderline hypertension: Hypertensive cases
with blood pressure always at the upper limits
of normal.
• Labile hypertension: In which blood pressure
is only occasionally elevated.
THERAPY OF HYPERTENSION
A) Non-Drug Therapy
• It includes decrease sodium intake,
weight reduction in obese, stop
smoking, coffee and alcohol drinking;
exercise program and control
diabetes
mellitus
and
hyperlipideamia.
Avoid agents that increase blood pressure as
Sympathomimetics.
Steroids.
NSAIDs.
Carbenoxolone,oral
contraceptives,cyclosporine,
recombinant
human erythropoietin, and products that
contain large quantities of sodium. Such as
effervescent solutions.
B) Drug Therapy (Antihypertensives)
There are many groups of drugs available for
treatment of hypertension
Commonly used drugs:
• Angiotensin converting enzyme inhibitors.
• Beta-blockers.
• Calcium channel blockers.
• Diuretics.
N.B: Beta blockers nowadays restricted to the
presence of other associated diseases (angina
arrhthymia and thyrotoxicosis)because of their
diabetogenic effect
Other groups of drugs
1. Direct vasodilators e.g. hydralazine.
2. Centrally acting agents interfering with
adrenergic function e.g. alphametyldopa,
clonidine and guanfacine
3. Alpha adrenergic blockers e.g. prazocin.
4. Concurrent alpha and beta blockers e.g.
labetalol, carvedilol.
5.Adrenergic neurone blockers e.g. reserpine
and alpha methyldopa.
6.Serotonine antagonists e.g. ketanserine.
7.Ganglion blockers e.g. trimetaphan.
8.Potassium channel openers e.g. cromakalim,
pinacidil.
9.Imidazoline receptors agonist e.g.
moxonidine and rilminidine.
DIURETICS
Mechanisms of Diuretics as an Antihypertensive
• Decrease peripheral vascular resistance due to
vasodilator action possibly through:
• Direct vasodilator effect.
• Decreased vascular receptor sensitivity to
vasopressin agents (adrenaline, angiotensin II by
decreasing Na+ content in the cells of vascular
wall.
• Increase synthesize of the vasodilator PGs.
• Diminished cardiac output due to decrease
blood volume by the diuretic action.
Indications of Diuretics in Hypertension
Thiazides:
• Initial therapy in most hypertensive patients.
• Part of most combined antihypertensive regimen.
Loop diuretics
• Hypertensive crises.
• Chronic renal failure.
• Resistant hypertension where there is marked
sodium retention due to other antihypertensives,
cardiac failure or liver cirrhosis
Spironolactone: Primary hyperaldosteronism
BETA BLOCKERS
Indications of beta-blockers in hypertension:
• Hypertensive
patient
with
stable
angina,
supraventricular or ventricular arrhythmias.
• In patients with increased adrenergic activity e.g.
younger age group, hyperkinetic circulation, alcohol
withdrawal hypertension, with labile hypertension and
palpitation.
• Hyperrenenimic hypertension.
• As a part of combined therapy.
• N.B. Beta-blocker of choice in treatment of
hypertension should be cardioselective 1 blocker and
with a long duration of action e.g. atenolol.
CALCIUM CHANNEL BLOCKER (C.C.Bs)
Definition: These are drugs,
which block the slow calcium
influx occurring during the
terminal phase of depolarization
and during the plateau phase of
the action potential.
Classification according to the therapeutic
effects:
• Calcium channel blockers with cardiac
effects e.g. verapamil and diltiazem.
• Calcium channel blockers with vascular
effects e.g. nifedipine, isradipine and
clvedipine
• Calcium channels blockers with tissue
protection: e.g. flunarizine, nifedipine.
Pharmacokinetics
• Absorption of these agents is nearly complete
after oral administration. Their bioavailability is
reduced in some cases because of the first pass
hepatic metabolism. The effects of theses drugs
are evident within 30 to 60 minutes of an oral
dose, with the exception of the more slowly
absorbed and longer acting agents e.g.
amlodipine. Peak effects of verapamil occur
within 15 minutes of its intravenous
administration.
• These agents are bound to plasma proteins (70 to
98%). Their elimination half-lives are widely
variable. Some of them have metabolites e.g.
diltiazem, verapamil which have a vasodilator
effect. The metabolites of the dihydropyridines
are inactive or weakly active.
• In patients with hepatic cirrhosis the
bioavailabilites and half-lives of the Ca2+ channel
blockers may be increased and dosage should be
decreased. The half-lives of these agents may also
be longer in older patients.
Pharmacological Effects:
Smooth muscle
• They cause relaxation of vascular smooth
muscle, bronchiolar, gastrointestinal, and
uterine smooth muscle. In the vascular
system arterioles appear to be more
sensitive than veins. Dihydropoyridines
have a greater ratio of vascular smooth
muscle effects relative to cardiac effects
than do dilitazem and verapamil
Cardiac muscle
• These drugs reduce cardiac contractility in a
dose dependent fashion. This reduction in
mechanical function is another mechanism
by which the calcium channel blockers may
reduce the oxygen requirement in patients
with angina.
• The calcium channel blockers have been
demonstrated to protect against the
damaging effects of calcium.
They block tachycardia in calcium dependent
cells, e.g. the atrioventricular node, more
selectively than do the dihydropyridine. On
the other hand, the dihydropyridines appear
to block smooth muscle calcium channels at
concentrations below those required for
significant cardiac effects; they are therefore
less depressant on the heart than verapamil
or diltiazem.
Other pharmacological effects
• They may ↓ platelet aggregability.
• They interfere with stimulus secretion
coupling in gland and nerve terminals
e.g. verapamil inhibits insulin release.
• They inhibit calcium influx across
nervous membranes, so they are
effective in limiting the spread of
seizure activity.
Therapeutic Indications
A) Cardio-selective CCBs are used in treatment of:
• Ischemic heart disease: all types of angina and
myocardial infarction.
Mechanisms of action in Ischemic heart diseases
• Decrease arterial blood pressure, contractility and
heart rate so they decrease myocardial oxygen
demand.
• Decrease Coronary vascular resistance so increases
blood flow to the myocardium.
• Dilatation of epicardial coronary arteries
• Decrease Ca++ load, which improve myocardial
relaxation and decrease myocardial cell necrosis.
Cardiac
arrhythmias
e.g.
paroxysmal
supraventricular tachycardia because they prolong
intranodal conduction time and slow AV conduction
and lengthen the ERP of the AVN.
Hypertrophic
obstructive
cardiomyopathy:
because they produce:
• Reducing contractile force during systole, this leads
to decrease O2 consumption and increase exercise
tolerance.
• Enhance relaxation during diastole resulting in
improving coronary flow.
Arterial hypertension: due to vasodilatation of the
blood vessels.
B) Vascular selective CCBS are used in:
• Arterial hypertension: due to vasodilatation
of the blood vessels.
• Cerebral vasospasm (nimodipine).
• Peripheral vascular disease.
• Chronic renal failure to minimize ischemia
• Re-perfusion injury in the myocardium.
• Migraine.
Adverse Effects
Aggravation of congestive heart
failure (with verapamil or diltiazem).
• A.V. block in-patients with pre-existing
disease or when combined with betablockers (with verapamil or diltiazem).
• Nausea, vomiting, constipation and
reversible hepatotoxicity.
•
• Interference with normal glucose
insulin-response and worsen diabetes
mellitus.
• Hypotension, flushing, nasal
congestion, tinitus and occasional
aggravation of angina (with
nifedipine).
• Ankle edema (with nifedipine or
verapamil).
Drug Interactions
• Verapamil with digitalis or with betablockers may cause A-V block due to
additional effect on conducting system
(nifedipine would be the drug of choice
if B-blockers are to be used with CCBs).
• CCBs and direct vasodilators may cause
profound hypotension.
Contraindications and precautions
•
Verapamil should be used with
great caution in the presence of
heart failure, unstable AV block, sick
sinus syndrome, low blood pressure
states e.g. cardiogenic shock & with
beta blockers.
• Verapamil and diltiazem are contraindicated in
Wolf-Parkinson-White syndrome complicated by
A.F. & A. flutter.
• Nifedipine is contraindicated in idiopathic
hypertrophic subaortic stenosis, severe
myocardial depression and unstable angina.
Dose and Preparations
Verapamil: 80-160 mg /8 hours
orally
Nifedipine: 10-40 mg/8 hour
orally or S.L.
Diltiazem: 30-90 mg/8 hours oral.
RENNIN ANGIOTENSIN
ALDESTERON SYSTEM
RENIN
• It is a proteolytic enzyme secreted by the kidney
into the blood stream.
• Kidney and blood contain also (inactive renin) i.e.
pre-renin which is converted to active renin by
tissue kallekrein.
• It has a t½ 80 minutes
There are two pathways for converting
Angiotensin I to Angiotensin II, the first is
the enzymatic pathway by Angiotensin
converting enzyme (ACE) and the second
is the non-ACE enzymes (Cathepsin,
Chymase). So to prevent formation of
Angiotensin II from Angiotensin I, these
two pathways must be blocked.
RENIN ANGIOTENSIN SYSTEM
• ACE inhibitors only block the ACE pathway
leaving the other pathway working to produce
Angiotensin II. This may explain failure of these
drugs to control some cases of hypertensive
patients and necessitates addition of diuretics to
ACE inhibitors in these cases.
Stimuli that increase renin secretion:
Sodium depletion, diuretics,
hypotension, hemorrhage, upright
posture, dehydration, constriction of
renal artery, heart failure and Cirrhosis
• Inhibitors of renin secretion: Increased
Cl- or Na+ reabsorption, angiotensin II,
vasopressin and increased blood
pressure.
•
Actions of Angiotensins
• Angiotensin I (precursor of angiotensin II): It has
no pharmacological action.
•
•
•
•
Angiotensin II: It acts on two receptors; AT1 and AT2
Its action on AT1 receptor produces the following:
CVS:
Arteriolar constriction leading to increase systolic and
diastolic blood pressure (4-8 times as active as
epinephrine).
• Angiotensin II produces positive inotropic and
chronotropic effects which are primarily due to central
and peripheral sympathetic stimulation. In addition,
angiotensin II has a weak direct inotropic effect.
Endocrine:
• Increase secretion and synthesis of
aldosterone.
• Facilitate catecholamine synthesis and release.
• Increase pituitary vasopressin and ACTH.
Renal:
• Suppress renin release
• V.C of renal efferent arterioles,
increases proximal tubular Na+
reabsorption
C.N.S
• Increase H2O intake and vasopressin
secretion.
• Stimulate
central
sympathetic
discharge.
Its action on AT2 receptor produces
the following:
• Antiproliferation.
• Apoptosis (normal cell death).
• Vasodilatation and increase local
bradykinin.
Inhibitors of Renin Angiotensin System:
• Inhibition of renin release: by beta-blockers, clonidine,
•
•
•
•
alpha methyl dopa and prostaglandin inhibitors e.g.
indomethacin.
Renin activity inhibitors e.g. enalakrine , pepstatin and
aliskirin.
Angiotensin converting enzyme inhibitors (ACEIs):
Sulph-hydryl containing ACEIs: e.g. Captopril, Alacepril,
Zofenopril
ACEIs without sulph-hydryl group: e.g. Enalapril,
Lisinopril, Prindopril, Ramipril, Cilazapril, Benzapril,
Quinapril.
• ACEIs inhibitors which contain phosphinate group e.g.
Fosinopril is the only ACE that contains a phosphinate
group that binds to active site of ACE. It is a prodrug which
is transformed to fosinoprilat, an ACE inhibitor which is
more potent than captopril yet less potent than
enalaprilat. It is metabolised and excreted into both the
urine and bile. It is has a plasma half-life 11.5 hours. The
oral dosage of fosinopril ranges form 10 to 80 mg. daily.
• Angiotensin II receptor blockers e.g. Saralasin, Losartan,
Valsartan.
Mechanism of Action of ACEIs
•
Interrupt Renin-Angiotensin-Aldosterone pathway through
inhibition of peptidyl dipeptidase enzyme that converts
angiotensin I to angiotensin II. These drugs prevent ang-II
formation in the tissues (heart, blood vessels).
• Prevent inactivation of kinins lead to increase the
concentration of bradykinins which is a potent vasodilator.
Pharmacokinetics of ACEIs
• Captopril: is rapidly absorbed from GIT. It is
distributed to most tissues except the CNS. The
primary route of excretion is the kidney; 50% is
eliminated as unchanged drug.
• Enalapril: it is inactive. It undergoes hepatic
hydrolysis to the active diacid form enalaprila it is
more slowly absorbed and the active metabolite
has a long half-life and duration of action. Thus,
enalapril is given usually once daily.
• Lisinopril: it is not a prodrug it is not metabolized
by the liver it is given once daily.
Pharmacological Effects
• They decrease peripheral resistance but little change in heart
rate, cardiac output or pulmonary wedge pressure.
• Do not modify cardiovascular responses to autonomic
reflexes. And don’t cause tachycardia inspite of hypotension
due to: reset of baroreceptors reflex sensitivity downward.,
Venodilatation offered by ACEIs. and modification
parasympathetic activity.
• They increase renal blood flow; Cerebral and
coronary blood flow are maintained even when
systemic blood pressure is reduced.
• In congestive heart failure, ACEIs increase the
cardiac output, cardiac index, and decrease the
heart rate.
• They decrease the left ventricular mass and wall
thickness and prevent ventricular enlargement
after myocardial infraction.
Clinical Uses
•
•
•
•
•
Hypertension.
Heart failure.
Postinfarction ventricular remodeling.
Renal diseases in cases of Scleroderma.
Possible new uses: Insulin resistance Arteriosclerosis - Rheumatoid arthritis.
Adverse Effects
•
First dose hypotension specially in sodium
depleted person.
• Cough and bronchospasm due to accumulation of
bradykinin and prostaglandin (treated by NSAIDs).
• Angiedema: secondary to change in bradykinin
metabolism, it may cause respiratory arrest and
death.
• Proteinuria in patients with compromised renal
function.
• Neutropenia: especially in patient who
have impaired renal function or serious
autoimmune diseases.
• Skin rashes.
• Hyperkalaemia.
• Temporary loss of taste.
• Headache, dizziness and fatigue.
Contraindications
•
•
•
•
•
ypotension: systolic pressure less than 95 mm Hg.
Severe renal failure.
Hyperkalaemia.
Severe anaemia.
Bilateral renal artery stenosis or stenosis in a
solitary kidney because angiotensin II, by
constricting the efferent arteriole, helps to
maintain adequate glomerular filtration when
renal perfusion pressure is low. Consequently
inhibition of ACE can induce acute renal
insufficiency.
• Immune problems, in particular due to collagen
vascular, autoimmune disease or with
immunosuppressive drugs.
• Patients’ known to have neutropenia or
thrombocytopenia.
• Pregnancy and breast-feeding because ACE
inhibitors can cause fetal pulmonary hypoplasia,
fetal growth retardation and fetal death.
Precautions during Use of ACEIs
• Initial dose should be low.
• Diuretic use with caution.
• Measurement of blood urea and
creatinine before and one week after
treatment then every 3 months.
• Electrolyte assay specially potassium.
ANGIOTENSIN II RECEPTOR BLOCKERS
Losartan and valsartan were the first
marketed blockers of the angiotensin II type 1
(AT1) receptor. More recently candesartan,
eprosartan, irbesartan, and telmisartan have
been released. They have no effect on
bradykinin metabolism and are therefore more
selective blockers of angiotensin effects than
ACE inhibitors.
• They also have the potential for more
complete inhibition of angiotensin action
compared with ACE inhibitors because there
are enzymes other than ACE that are
capable of generating angiotenin II. The
adverse effects are similar to those
described for ACE inhibitors, including the
hazard of use during pregnancy. Cough and
angioedema can occur but are less common
with angiotensin receptor blockers than with
ACE inhibitors.
VASODILATORS
Classifications
Arteriolar vasodilators: e.g. nifedipine, hydralazine, minoxidil.
Directly relaxes arteiolar smooth muscles and thus decrease peripheral
vascular resistance and arterial blood pressure so they are used in systemic
hypertension, forward congestive heart failure or in low C.O.P state.
Venodilators: e.g. nitrates.
Chiefly used in congestive heart failure or in acute pulmonary edema.
Mixed arterio and venodilators:
e.g. sodium nitroprusside,
prazocin, ACEIs and Trimetaphan. They can be used in heart failure as they
act on both pre-and afterload.
General Consideration as Regard Arteriolar V.D
• Beneficial effect on peripheral vascular
resistance can be partially antagonized by
increased reflex sympathetic activity which
can result in increase heart rate, stroke
volume, C.O.P. and plasma renin activity. It
can be counteracted by beta-blockers.
• They can cause salt and water retention.
Therefore they should be used in conjunction
with diuretics.
• They preserve renal and cerebral blood flow.
• They almost completely devoided of CNS
side effect.
• They don't cause orthostatic hypotension or
sexual dysfunction.
• Best indicated in hypertensive heart failure
and renal hypertension.
HYDRALAZINE
• It directly relaxes small arteries and arterioles.
• It decreases arterial blood pressure
• It is absorbed from GIT, acetylated in the liver.
Uses
• Combination therapy for hypertension.
• Primary pulmonary hypertension.
Dose: 10 mg 2-3 times/day.
Adverse effects
• Systemic Lupus-like syndrome in slow acetylators.
• Nasal congestion, flushing, lacrimation, drug fever,
skin rash.
• Headache, palpitation, tachycardia, anginal pain,
anorexia, nausea, dizziness.
MINOXIDIL
• It is arteriolar vasodilator, which cause activation of potassium
channel result in hyperpolariziation of the cell membrane,
which will causes relaxation of vascular smooth muscle.
• It is absorbed from GIT, metabolized by conjugation with
glucoronic acid in the liver, excreted in the urine.
• Uses
• Severe hypertension in combination therapy.
• Azotemic hypertensive patients.
DIAZOXIDE
• It is related to chlorothiazide but produces sodium retention rather than
diuresis.
• It has a direct vasodilator action on the arterioles through activation of
potassium channels.
• The drug is 90% bound to plasma albumin.
• Uses
• Hypertensive emergencies e.g. hypertensive encephalopathy, and toxaemia
of pregnancy.
• Hypoglycaemia due to hyperinsulinism.
• Dosage: it is given by I.V. injection. Start with small dose 50-75 mg rapidly.
The dose can be repeated after 10-15 minutes intervals.
• Adverse effects
• Tachycardia which can precipitate angina.
• Hyperglycaemia due to inhibition of insulin release.
• Sodium and water retention.
• Hyperuricemia.
• Others: nausea, vomiting, constipation.
• Dose: The effective dose range is 10-40 mg/day
/orally.
• Adverse effects
• Palpitation, tachycardia, anginal pain, headache.
• Fluid retention and edema.
• Hypertrichosis
• Pericardial effusion.
SODIUM NITROPRUSSIDE
• It has a vasodilator effect on the smooth muscle of the
venoarteriolar beds, through activation of guanylate
cyclase which bring about an increase in cGMP .
• It is rapidly metabolized in red cells to cyanide, which is
then metabolized to thiocyanate prior to renal excretion.
• Uses
• Hypertensive encephalopathy
• Refractory cases of congestive heart failure
Dosages: It is given by IV infusion in 5% dextrose.
The initial dose is 0.5 g/kg/minute and may be
increased up to 10 g/kg/min as necessary to
control blood pressure.
Adverse effects
• Nausea, vomiting, sweating, restlessness
headache, palpitation and substernal pain and
may be increased up to 10 g/kg/minute as
necessary to control blood pressure.
• Prolonged therapy may lead to accumulation of
cyanide (metabolic acidosis, arrhythmias,
death) or thiocyanate (delirium and psychosis).
Precautions
• Infusion must not stop abruptly to avoid rebound
hypertension.
• In liver disease, cyanide doesn’t convert to
thiocyanate and hence more toxic.
• Higher rates of infusion may result in toxicity.
CENTRALLY ACTING ANTIHYPERTENSIVES
CLONIDINE
It is an agonist to central postsynaptic 2 adrenoceptors
suppressing sympathetic outflow and reduces blood
pressure. It has been postulated that they it is also partly
due to effects of imidazoline receptors which act in CNS
to reduce sympathetic outflow to the heart and vascular
smooth muscles.
 It decreases synthesis of NE by decreasing dopamine hydroxylase and N-methyl transferase enzymes.
 It acts on peripheral presynaptic 2 adrenoceptors
inhibiting N.E release.

 It reduces plasma renin activity, decrease renal
vascular resistance and renal blood flow is
maintained.
 Reduction of cardiac output due to decrease
heart rate.
 Pressor effects of clonidine are not observed
after ingestion of therapeutic dose but overdose
may induce severe hypertension due to
stimulation of postsynaptic adrenoceptors.
Dose: 0.2-1.2 mg/day orally.
Therapeutic uses
• Moderate and severe hypertension 0.1 - 0.2 mg twice/day
• Prophylaxis in migraine 0.025 mg twice /day.
• In opiate withdrawal to reduce signs of sympathetic
overactivity.
• Sedation and reduction of anxiety in preanaesthetic medication
Adverse effects
• Dry mouth and sedation.
• Salt and water retention
• Withdrawal syndrome leads to hypertensive crisis. It is treated
with reinstitution of clonidine or administration of both alpha
and beta-blockers. So clonidine withdrawal, if indicated, should
be done gradually with substitution by other antihypertensive.
Drug interactions
• Tricylic antidepressant may block the
antihypertensive effect of clonidine
• Beta-blockers
may
aggravate
the
hypertensive crises following sudden
clonidine withdrawal.
• CNS depressants may cause excessive
drowsiness with clonidine.
ALPHA METHYL DOPA
1-It stimulate central postsynaptic alpha 2 receptor so, decrease central
sympathetic outflow.
2-it inhibits renin release.
3-it cause formation of false chemical transmitter.
*It can be used in treatment of hypertension with
pregnancy.
GUANFACINE
• Has a mechanism of action similar to clonidine.
• Hypotensive effect is associated with a fall in peripheral resistance, HR and COP.
• Most common side effects are dry mouth, somnolence, dizziness and asthenia.
ALPHA-ADRENERGIC BLOCKERS
* Prazocin and trimazocin are selective alpha 1 blockers
*Indoramine
 Selective blocker to postsynaptic 1receptors.
 First dose phenomenon does not occur.
 It causes sedation, lethargy, drowsiness and dizziness.
 Contraindicated in renal failure and depressive states.
 Dose 25 mg twice /day.
CONCURRENT ALPHA AND BETA ADRENOCEPTOR
BLOCKERS
LABETALOL
 It blocks both alpha (selective 1 blocker) and betareceptors (non-selective -blocker).
 It lowers blood pressure by reducing peripheral resistance
without affecting cardiac output.
 It reduces plasma renin activity.
 It has a rapid onset of action as an antihypertensive.
 It is used for emergency control of severe hypertension
with pheochromo-cytoma, and hypertensive response
during abrupt clonidine withdrawal.
Carvedilol
1-Block both alpha and beta receptors.
2-Has vaodliator effect.
3- Has antioxiodant effect.
4- Can be used in treatment of heart failure.
KETANSERIN
 It is a selective antagonist of 5-HT2 receptors in smooth muscles of
arteries, bronchi and platelets.
 It also blocks alpha adrenoceptors.
 It lowers the BP without postural hypotension or reflex tachycardia
and the effect is greater on the diastolic blood pressure.
 It does not affect glomerular filteration rate or renal blood flow
 Side effects: Dizziness, fatigue and polyuria.
 Potential uses
 Orally: hypertension and peripheral vascular diseases.
 I.V.: asthmatic attack, thrombophlebitis, and pulmonary emboli.
 Effective dose: 20 mg 2-3 times/day
Dopamine (D1) receptor agonist e.g. Fenoldopam
• Pharmacokinetics:
• Given by continuous intravenous administration.
• Metabolized in the liver by conjugation (t 1/2 10 minutes).
• Pharmacological Effects:
• ++ Dl receptors in peripheral arteries leading to arterio-dilatation
& natriuresis.
• Therapeutic uses:
• Treatment of hypertensive emergency.
• Treatment of post-operative hypertension.
• Adverse effects:
• Reflex tachycardia, headache & flushing.
• ↑ IOP (avoided in patient with glaucoma).
HYPERTENSIVE EMERGENCIES
• These include hypertensive encephalopathy, cerebral stroke, acute left
ventricular failure, aortic dissection, epistaxis, and severe renal failure.
• Patient should be hospitalised.
• Reduction of blood pressure should be in hours and not in minutes.
• Sublingual nifedipine or captopril may be effective in reducing blood pressure.
• Parenteral therapy:
• Diuretics (frusemide, Bumetanide) I.V.
• Reserpine 1-2 mg I.M (never I.V.)
• Diazoxid 300 mg I.V. very rapidly
• Sodium nitroprusside infusion 2-5 g/kg/min. according to blood pressure
• Hydralazine 20 mg I.V. slowly diluted.
• Beta blocker (Propranolol) 1-2 mg I.V. slowly diluted.
• Methyl dopa I.V. diluted
• Nifedipine I.V., diluted.
• Nitroglycerin I.V. 1-10 g/kg/min.