This document provides information on antihypertensive drugs. It begins by listing the specific learning objectives, which include defining hypertension, discussing types and drugs for treatment, mechanisms of action, adverse effects, and considerations for use in various conditions. It then covers primary and secondary hypertension, urgency vs emergency, and mnemonics for drug classes. Individual drug classes are discussed in detail, including diuretics, ACE inhibitors, ARBs, calcium channel blockers, arteriolar vasodilators, and beta blockers. Mechanisms, advantages, disadvantages, and special considerations are provided for each class.

1. ANTIHYPERTENSIVE DRUGS
PH 1.27
DR MONICA JAIN

4. Specific Learning objective
• At the end of session student would able
• Define hypertension
• Discuss types of hypertension
• Enlist drugs used for hypertension
• Explain mechanism of action and adverse effect
of each class of drugs
• Will be able to choose drug of choice in specific
condition
• Distinguish between emergency and urgency
types of hypertension

5. Specific learning objective
• Describe advantages and disadvantages of
each class of drugs
• Explain the drugs preferred and avoided with
justification in hypertension during pregnancy
• Discuss Hypertension treatment in
angina,CHF,diabetes,bronchial
asthma,gout,obesity ,migraine,osteoporosis

8. Primary or idiopathic or essential
hypertension
Most adults with hypertension are in this
category.
It is combination of genetics, diet, lifestyle, and
age.
• Lifestyle factors include smoking, drinking too
much alcohol, stress, being overweight, eating
too much salt, and not getting enough
exercise.

9. Secondary Hypertension
• Secondary hypertension is when there’s an identifiable— and
potentially reversible— cause of your hypertension.
• 30 percent of those ages 18 to 40 with hypertension have
secondary hypertension.
The underlying causes of secondary hypertension include:
• narrowing of the arteries that supply blood to your kidneys
• adrenal gland disease
• side effects of some medications, including birth control pills, diet
aids, stimulants, antidepressants, and some over-the-counter
medications
• obstructive sleep apnea
• hormone abnormalities,thyroid abnormalities ,constriction of the
aorta

10. Difference between urgency and
emergency
• Hypertensive urgency has no associated target organ
damage, whereas hypertensive emergency can feature
neurologic, aortic, cardiac, renal, hematologic, and/or
pregnancy-related damage
• Hypertensive urgency is defined as having a systolic
blood pressure over 180 mmHg or a diastolic blood
pressure over 110 mmHg.
• Hypertensive emergency is defined as elevated blood
pressure consistent with hypertensive urgency, plus
evidence of impending irreversible hypertension-
mediated organ damage (HMOD).

11. Mnenomic
• 3A- alpha blockers,ACE inhibitors,ARB blockers
• Beta blockers
• 2C calcium channel blockers, central
sympatholytics
• 2D diuretics, dialators

12. Non Pharmacological measure

13. Classification
• 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

14. • 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 sympatholytics Clonidine, Methyldopa
• 10. Vasodilators Arteriolar: Hydralazine, Minoxidil,
Diazoxide
• Arteriolar + venous: Sodium nitroprusside

16. ACE inhibitor status in hypertension
• First line drug
• Useful for all grades of hypertension
• Well tolerated
• Indicated specially as antihypertensives in
• -hypertension with hypertrophy of heart
• With DM as they slow development of nephropathy
• With renal disease slow progression of chronic renal
disease
• Coexisting IHD and post MI
• Can be combined with other antihypertensives like
beta blockers,CCBs,Diuretics

18. Mechanism of action
• Reduces BP by
• Reduction in peripheral arterial resistance
• Inhibition of AngII formation and raised
bradykinin levels
• Fall in aldosterone level
• Increase in renin activity
• Suitable for young patient, also patient with
gout, PVD, dyslipidemic,with LVH

19. Advantages
Free of postural hypotension, electrolyte
disturbances, feeling of weakness and CNS
effects.
• Safety in asthmatics, diabetics and peripheral
vascular disease patients.
• Long-term ACE inhibitor therapy has the potential
to reduce incidence of type 2 diabetes in high risk
subjects.
• Secondary hyperaldosteronism and K+ loss due to
diuretics is prevented.
• Renal blood flow is well maintained.

20. Contd
• Left ventricular hypertrophy and increased wall-
to-lumen ratio of blood vessels that occurs in
hypertensive patients is reversed.
No hyperuricaemia, no deleterious effect on
plasma lipid profile.
• No rebound hypertension on withdrawal.
• Minimum worsening of quality of life parameters
like general wellbeing, work performance sleep,
sexual performance

22. Special points
• Captopril and lisniopril active drug
• Extensive tissue distribution-ramipril

25. ARB blockers
Do not interfere with degradation of bradykinin
and so cough is rare.
• They result in more complete inhibition of AT1
receptor activation, because responses to Ang II
generated via alternative pathways and
consequent AT1 receptor activation (which
remain intact with ACE inhibitors) are also
blocked.
• They result in indirect AT2 receptor activation.

26. Contd
Due to blockade of AT1 receptor mediated
feedback inhibition—more Ang II is produced
which acts on AT2 receptors that remain
unblocked.
• ARBs cause little increase in the level of Ang
(1-7) which is raised by ACE inhibitors, since
Ang (1-7) is partly degraded by ACE.

27. Advantages
• No cough
• Losartan has antiplatelet effect and
metabolite of losartan reduces PG synthesis
• Effective in portal hypertension due to
cirrhosis of liver
• also reduces proliferation of arteriolar intima
• Except losartan all are longer acting

29. Calcium channel blockers
• The common property of all three subclasses
of CCBs is to inhibit Ca2+ mediated slow
channel component of action potential (AP) in
smooth/ cardiac muscle cell.
• The two most important actions of CCBs are:
(i) Smooth muscle (especially vascular)
relaxation.
• (ii) Negative chronotropic, inotropic and
dromotropic action on heart.

30. Classification
• Three important classes of calcium channel
blockers are examplified by:
• Verapamil—a phenyl alkylamine, hydrophilic
papaverine congener.
• Nifedipine—a dihydropyridine (lipophilic).
• Diltiazem—a hydrophilic benzothiazepine.

31. Dihydropyridines (DHP)
• Ultra short acting- clevidipine
• Short acting –nifedipine,
nicardipine,nimodipine
• Intermediate acting-
nisoldipine,niterndipine,isradipine,lacidipine,
Cilnidipine,lercanidipine
Longer acting –felodipine,benidipine and
amlodipine

32. Important features
• Nifedipine – have intrinsic natriuretic effect so
does not need diuretic
• Ankle edema due to dilation and reflex post
capillary constriction leading increase hydrostatic
pressure
• Lacidipine cause least ankle edema and slows
progression of carotid atherosclerosis, limits
development of new metabolic syndrome ,good
vasoprotection
• Nicardipine – more coronary dialator

33. Important features
• Cilnidipine –more renoprotective
• Nimodipine –lipid soluble and crosses blood
brain barrier ,cerbroselective
• Clevidipine –t1/2 ultra short acting L type
CCBwith terminal t1/2 less than 15 min

37. CALCIUM CHANNEL BLOCKERS
1. Do not compromise haemodynamics: no
impairment of physical work capacity.
2. No sedation or other CNS effects; cerebral
perfusion is maintained.
3.Not contraindicated in asthma, angina (especially
variant) and PVD patient: may benefit these
conditions.
4. Do not impair renal perfusion.
5. Do not affect male sexual function.

38. Contd
6. No deleterious effect on plasma lipid profile,
uric acid level and electrolyte balance.
7. Shown to have no/minimal effect on quality
of life.
8. No adverse foetal effects; can be used during
pregnancy (but can weaken uterine
contractions during labour).

39. Arteriolar vasodialators
• Include hydralazine,minoxidil,diazoxide and
fenoldapam
• They act by increase in K ion conduction
causing hyperpolarization of cell membrane
which causes relaxation of vascular smooth
muscle
• Should be combined with beta blockers or
diuretics

40. Hydralazine dose 25 to 50mg B.D
• Needs intact endothelium
• Activates k channel
• Generation of nitric oxide and stimulation of
cGMP
• Max response in 30 min to 1 hr
• Duration 6hrs
• Prolong use cause DLE as it undergoes N-
acetylation
• Adverse effect due to vasodialation

41. Minoxidil 2.5-5mg daily
• Orally effective
• Potent longer acting
• Converts into active metabolite minoxidil sulphate
which opens potassium channel
• Maximum effect within 1-2 minutes but
antihypertensive effect last for 12 to 24 hrs
• Indicated in severe HT or HT associated with chronic
renal failure
• Typical adverse effect hirsuitism in women as it
activates a specific gene that regulates the hair shaft
protein

42. Diazoxide
• Related to thiazide but causes fluid retention
• Long lasting arteriolar dialatory
• BP lower in 3-5 min after I.V injection
• Long term causes
hyperuracemia,hyperglycemia and fluid
retention
• Used in treatment of malignant hypertension
,hypertensive encephalopathy and eclampsia

43. Diuretics
• Studies shows hydrochlorothiazide is to be
used as 12.5 mg and in combination it can be
combined with vasodilators or sympatholytics
• Effective in elderly and with systolic
hypertension
• They reduce calcium excretion so useful in
osteoporosis
• Not effective in chronic kidney disease,
metazoline and indapamide effective

44. Fenoldopam dose 0.1 to 1.5
microgms/kg/min
• Agonist at D1 leading to natriuresis and dilatation of
peripheral arteries
• Rapid onset ,short half life
• Given I>V infusion for short term management of
hypertensive emergencies
• Urine output, creatinine clearence and Na excretion
increases so indicated in hypertensive emergency with
renal impairment
• Concomitant use of beta blocker or diuretic not needed
• ADR-HYPOKALEMIA,RAISED IOP

45. Sodium Nitroprusside
• Activates guanylyl cyclase either directly or
through release of NO
• Causes increase incGMP-vascular smooth
muscle relaxation
• Powerful,parenterally administered arteriolar
veno dialator
• Onset 30 sec after IV infusion
0.3microgm/kg/min and disaapear in ten min
after stopping

46. Contd
• Indicated in severe HT with acute MI and LVF
• Aqueous solution of sodium nitroprusside are
unstable and sensitive to light so solution
freshly made before each administration and
bottle covered with black paper
• Apart from headache nausea and vomiting
cynaide and thiocynate accumulation cause
toxicity

47. Contd
• Sodium nitroprusside in erythrocytes to cynaide
and in liver convert into thiocynate half life of
which is 3 days
• In renal insufficiency it accumulates causing
metabolic acidosis and arrhythmias
• Thiocynate toxicity manifested as psychosis
,disorientation and convulsion
• Delayed hypothyroidism may also occur as
thiocyanate inhibit iodine uptake
• Treatment – sodium thiosulfate and
hydroxycobalamine

48. Thiazides (hydrochlorothiazide,
chlorthalidone)
• Chlorthalidone is longer acting (~ 48 hours)
than hydrochlorothiazide (< 24 hours) and
may have better round-the-clock action

50. Proposed action
• 1. Initially, the diuresis reduces plasma and
e.c.f. volume by 5–15%, and this decreases
c.o. 2.
• Subsequently, compensatory mechanisms
operate to almost regain Na+ balance and
plasma volume; c.o. is restored, but the fall in
BP is maintained by a slowly developing
reduction in t.p.r

51. Proposed action
• Small persistent deficit of Na+ concentration
in the vascular smooth muscle may reduce
stiffness of vessel wall, increase their
compliance and dampen responsiveness to
constrictor stimuli (NA, Ang II).
• Has vasodilator action by opening potassium
channel K+ATP
• Thiazides are mild antihypertensives, average
fall in mean arterial pressure is ~10 mm Hg

52. Desirable properties of thiazide
diuretics as antihypertensives are:
• 1. Once a day dosing and flat dose-response
curve permitting simple standardized regimens.
• 2. No fluid retention, no tolerance.
• 3. Low incidence of postural hypotension and
relative freedom from side effects, especially
CNS, compared to sympatholytics.
• 4. Effective in isolated systolic hypertension (ISH).
5. Lessened risk of hip fracture in the elderly due
to hypocalciuric action of thiazides.
• 6. Low cost.

53. Features
• Thiazides have no effect on capacitance vessels,
sympathetic reflexes are not impaired: postural
hypotension is rare.
• In combination, they are useful in any grade of
hypertension.
• They are more effective in the elderly and
maximal antihypertensive efficacy is reached at
25 mg/day dose
• Their antihypertensive action is attenuated by
NSAIDs.

54. Indapamide
• It is a mild diuretic, chemically related to
chlorthalidone
• reduces BP at doses which cause little diuresis.
Electrolyte disturbances and K+ loss are minimal
at antihypertensive doses.
• It probably has additional vasodilator action
exerted through alteration of ionic fluxes across
vascular smooth muscle cell.
• Indapamide is well absorbed orally, has an
elimination t½ of 16 hr. Single daily dose (2.5 mg)
is enough

55. High ceiling diuretics
• Antihypertensive efficacy does not parallel
diuretic potency.
• Furosemide is a weaker antihypertensive than
thiazides: fall in BP is entirely dependent on
reduction in plasma volume and c.o.
• The natriuretic action lasting only 4–6 hr after
the conventional morning dose is followed by
compensatory increase in proximal tubular
reabsorption of Na

57. Proposed mechanism
• They are indicated in hypertension only when
it is complicated by:
(a) Chronic renal failure: thiazides are
ineffective, both as diuretic and as
antihypertensive.
(b) Coexisting refractory CHF.
(c) Resistance to combination regimens
containing a thiazide, or marked fluid
retention due to use of potent vasodilators.

58. Adverse effects
• Hypokalaemia—muscle pain, fatigue and loss of energy.
Erectile dysfunction in males.
• Carbohydrate intolerance: due to inhibition of insulin release
(probably secondary to K+ depletion which interferes with
conversion of proinsulin to insulin), precipitation of diabetes.
• Dyslipidemia: rise in total and LDL cholesterol and triglycerides
with lowering of HDL. This could increase atherogenic risk, but
no direct evidence has been obtained.
• Hyperuricaemia: by inhibiting urate excretion—increased
incidence

59. Beta blockers
• They are mild antihypertensives
• do not significantly lower BP in
normotensives.
• Used alone they suffice in 30–40% patients—
mostly stage I cases
• Response develop in one to three weeks
• Nebivolol reduces t.p.r. by generating NO

60. Mechanism of action
• central inhibition of sympathetic nervous system
outflow
• inhibition of the renin–angiotensin system by
decreasing renin release from the juxtaglomerular
apparatus
• decreasing heart rate and myocardial contractility, and
a resetting of the baroreceptors
• Stimulation of prostacyclin synthesis in vascular bed
• Reduce NA release from sympathetic terminal due to
blockade of beta receptor mediated facilitation of
release process

62. Cardioselective beta blockers
• 1. Lower propensity to cause bronchoconstriction
• . 2. Less interference with carbohydrate metabolism and
less inhibition of glycogenolysis during hypoglycaemia—
safer in diabetics.
• However, tachycardia in response to hypoglycaemia is
blocked.
• 3. Lower incidence of cold hands and feet, less chances of
precipitating Raynaud’s phenomenon
• . 4. No/less deleterious effect on blood lipid profile.
• 5. Ineffective in suppressing essential tremor (it occurs
through β2 action on muscle fibres).
• 6. Less liable to impair exercise capacity

63. Beta blockers
• Indication
• 1. Stable heart failure
• Post MI
• CAD
• Suitable for
• young patient,anxious
• Low cost therapy

64. β+α ADRENERGIC BLOCKERS- Labetalol
• It is a combined α and β blocker
• reduces t.p.r. and 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, because side effects of both α blocker
and β blocker occur with it

65. Carvedilol
• This nonselective β + weak selective α1
blocker 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.
• Side effects are similar to labetalol; liver
enzymes may rise in some.

66. α-ADRENERGIC BLOCKERS- Prazosin
alpha antagonist
• dilates both resistance and capacitance
vessels; more on resistance
• little reflex cardiac stimulation and renin
release during long-term therapy.
• postural hypotension and fainting may occur
in the beginning—called ‘first dose effect’, and
with dose increments so given at bed time
with low dose then increased

67. Advantages
• Does not impair carbohydrate metabolism;
suitable for diabetics, but not if neuropathy is
present, because postural hypotension is
accentuated.
• • Has a small but favourable effect on lipid
profile: lowers LDL cholesterol and triglycerides
• increases HDL.
• • Affords symptomatic improvement in coexisting
benign prostatic hypertrophy.

68. Adverse effect
• Headache, drowsiness, dry mouth, weakness,
palpitation, nasal blockade, blurred vision and
rash.
• Ejaculation may be impaired in males:
especially with higher doses.
• Fluid retention attending prazosin
monotherapy may precipitate CHF.
• It may be added to a diuretic + β blocker in
those not achieving target BP

69. Why Nonselective α blockers (Phentolamine,
Phenoxybenzamine) is not used as HT
• because fall in t.p.r. is compensated by
increased HR and c.o.
• They are reserved for special situations like
pheochromocytoma, clonidine withdrawal,
cheese reaction, etc., where circulating CAs
are responsible for the rise in BP

70. CENTRAL SYMPATHOLYTICS
• Clonidine –dose Dose: Start with 100 µg OD or
BD, max. 300 µg TDS, orally or i.m.
• imidazoline derivative
• High affinity to alpha2 receptor especially α2A
subtype in brainstem and stimulates imidazole
receptor present in brain and periphery
• α2A receptors present mainly postjunctionally in
medulla (vasomotor centre). This decreases
sympathetic out flow → fall in BP and
bradycardia.

71. • Enhanced vagal tone contributes to
bradycardia.
• Plasma NA declines.
• Though clonidine is capable of reducing NA
release from peripheral adrenergic nerve
endings (release inhibitory prejunctional α2
action but not manifest at clinically used
doses)

72. Important point
• Rapid i.v. injection of clonidine raises BP
transiently due to activation of peripheral
postsynaptic vasoconstrictor α2B receptors at
the high concentration
• At low dose cause because clonidine has lower
intrinsic activity on α2B receptors which
predominate in vascular smooth muscle
• Therapeutic window - 0.2–2.0 ng/ml optimum
control

73. Adverse effect
• mouth, nose and eyes (secretion is decreased
by central action), constipation (antisecretory
effect on the intestines).
• • Impotence, salt and water retention,
bradycardia.
• • Postural hypotension occurs, but is mostly
asymptomatic.

74. Clonidine withdrawl
• Features
• Alarming rise in BP, in excess of pretreatment level,
with tachycardia, restlessness, anxiety, sweating,
headache, nausea and vomiting occur in some patients
when doses of clonidine are missed for 1–2 days.
• This is due to: (a) Sudden removal of central
sympathetic inhibition resulting in release of large
quantities of stored CAs.
• (b) Supersensitivity of peripheral adrenergic structures
to CAs that develops due to chronic reduction of
sympathetic tone during clonidine therapy.

75. Other uses
• 1. Opioid withdrawal: Opioid and α2 adrenergic
systems converge on the same effectors in many
systems; both activate the Gi regulatory protein.
Clonidine suppresses sympathetic overactivity of
opioid withdrawal syndrome and reduces craving
to some extent. Clonidine has also facilitated
alcohol withdrawal and smoking cessation.
2. Clonidine has analgesic activity. It has been used
to substitute morphine for intrathecal/epidural
surgical and postoperative analgesia.

76. Other uses
• 3. Clonidine attenuates vasomotor symptoms
of menopausal syndrome.
• 4. Clonidine has been used to control loose
motions due to diabetic neuropathy. It may be
acting by α2 receptor mediated enhancement
of salt absorption in gut mucosa

77. Methyldopa – used in pregnancy
induced hypertension
• precursor of dopamine (DA) and NA
• α methyl-NA (a selective α2 agonist) formed
in the brain from methyldopa acts on central
α2 receptors to decrease efferent sympathetic
activity.
• Because methyldopa decreases t.p.r. more
than HR or c.o., it may be acting on a different
population of neurones in the vasomotor
centre than clonidine

79. Adverse effect
• CNS- Sedation, lethargy and reduced mental capacity
are common side effects. Cognitive impairment may
develop.
• Dryness of mouth, nasal stuffiness, headache, fluid
retention, weight gain, impotence are the other side
effects. Postural hypotension is generally mild.
• Positive Coomb’s test occurs in 1/6 patients, few
develop haemolytic anaemia. Fever, rash, hepatitis,
‘flu’ like illness, thrombocytopenia and rarely lupus
syndrome occur. Rebound hypertension on sudden
withdrawal of methyldopa is mild and less common.

80. Hydralazine – arteriolar dialator dose -
25–50 mg OD–TDS;
• reduces t.p.r. and causes greater decrease in
diastolic than in systolic BP. Reflex compensatory
mechanisms are evoked which cause tachycardia,
increase in c.o. and renin release → increased
aldosterone → Na+ and water retention.
• Cardiac stimulation is due augmentation of NA
release
• hyperdynamic circulatory state is induced—
angina may be precipitated

81. contd
• Tolerance to the hypotensive action develop
so other drugs are to added
• Mechanism of action
• Interference with Ca2+ release, opening of
certain K+ channels and/or NO generation
may be involved

82. Important points
• metabolic pathway is acetylation which exhibits a
bimodal distribution in the population:
• there are slow and fast acetylators. Bioavailability
is higher in slow acetylators, but these patients
are more prone to develop the lupus syndrome
• , t½ 1–2 hours. However, hypotensive effect lasts
longer (12 hours), probably because of its
persistence in the vessel wall.

83. Adverse effect
• Vasodilatation induce
• • Facial flushing, conjunctival injection,
throbbing headache, dizziness, palpitation,
nasal stuffiness, fluid retention, edema, CHF.
• • Angina and MI may be precipitated in
patients with coronary artery disease.

84. Avoided during pregnancy
• ACE inhibitors, ARBs: Risk of foetal damage,
growth retardation.
• Diuretics: Tend to reduce blood volume—
accentuate uteroplacental perfusion deficit (of
toxaemia)—increase risk of foetal wastage,
placental infarcts, miscarriage, stillbirth.
Nonselective β blockers: Propranolol has been
implicated to cause low birth weight, decreased
placental size, neonatal bradycardia and
hypoglycaemia.
• Sod. nitroprusside: Contraindicated in eclampsia.

85. Safe drugs
• Hydralazine ,Methyldopa (a positive Coombs’ test
occurs, but has no adverse implication).
Dihydropyridine CCBs: if used, they should be
discontinued before labour as they weaken
uterine contractions
• . Cardioselective β blockers and those with ISA,
e.g. atenolol, metoprolol, pindolol, acebutolol:
may be used if no other choice.
• Prazosin and clonidine—provided that postural
hypotension can be avoided.

86. Hypertensive emergencies and
urgencies
• Emergency – there is high BP Systolic BP > 220
or diastolic BP > 120 mm Hg
• End organ damage present – is emergency
• Mean BP should be lowered by no more than
25% over a period of minutes or a few hours
and then gradually to not lower than 160/100
mm Hg. Drugs employed are:

87. Sodium nitroprusside
• predictable, instantaneous, titratable and
balanced arteriovenous vasodilatory action
which persists without tolerance till infused,
nitroprusside (20–300 μg/min) is the drug of
choice for most hypertensive emergencies.
• Continuous monitoring and infusion pump
required
• If MI or LVF then nitroglycerine

88. Glyceryl trinitrate
• Given by i.v. infusion (5–20 μg/min) GTN also
acts within 2–5 min and has brief titrat
• able action, but is a less potent hypotensive.
• Its predominant venodilator action makes it
particularly suitable for lowering BP after
cardiac surgery and in acute LVF, MI, unstable
angina, but not in other conditions.
• Tolerance starts developing after 18–24 hours
of continuous infusion

89. Hydralazine
• 10–20 mg 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 or
aortic dissection.

90. Esmolol
• This β blocker given as 0.5 mg/kg bolus followed
by slow i.v. injection (50–100 μg/kg/min) acts in
1–2 min; action lasts for 10–20 min. It is
particularly useful when cardiac contractility and
work is to be reduced, such as in aortic
dissection.
• Nitroprusside is given concurrently, because the
BP lowering action is weaker.
• It is a useful hypotensive and bradycardiac drug
during and after anesthesia
• . Excess bradycardia is to be guarded

91. 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. (5–10 mg) it
acts in 2 min and action lasts 5–15 min.

92. labetalol
• Injected i.v., it is an alternative to an α blocker
+ a β blocker combination for lowering BP in
pheochromocytoma, etc. but has only weak α
blocking action.
• It has been used to lower BP in MI, unstable
angina, eclampsia as well. It is also good for
patients with altered consciousness, because
it does not cause sedation or increase
intracranial pressure.

93. Hypertensive emergencies
• Mean BP should fall up to 25% over few
minutes or hour to gradually 160/100mmHg
• If reduce too quickly then perfusion of vital
organs
• Vasodilators and adrenergic blockers will serve
the purpose

94. Drugs
• Nicardipine – DHP most popular drug for
variety of hypertensive emergencies replacing
nitroprusside
• Highly Vasoselective
• Dilates arteriolar
• Reflex tachycardia can be blocked beta blocker
can be added
• Target BP reaches in an hour

95. Nicardipine
• Fall in BP is predictable and dose related
• Elimination half life 45 minutes effect last for 3-4
hrs
• Beneficial in both haemorrhagic stroke and
ischaemic, arotic dissection,acute heart failure
and preclamsia
• Less toxic than sodium nitroprusside
• Dose -5mg/hr also used hypertension attending
cardiac surgery and neurosurgeryas well as to
facilitate percutaneous coronary intervention

96. Sodium nitroprusside
• Instantaneous
• Potent
• Combined arterio and venodialator
• Main indication in arotic dissection along with
esmolol
• In acute hypertensive heart failure can be
combined with loop diuretic
• Rapid acting so used precise infusion pump
• And BP monitoring , it produce cyanide and
thiocyanate

97. Glyceryl trinitrate
• Infused IV 5-20mg microgram /min act in 2to
5min but not a potent hypotensive
• Venodialtoe useful in patient associated with
MI or ACS
• Needs to be combined with labetalol or
nicardipine
• If used continuously greater than 12 hours
tolerance develop

98. Labetalol
• This alpha and beta blocker
• Used in pheochromocytoma, cheese reaction
and cocaine abuse
• Also in arotic dissection, MI,ACS and
preeclampsia
• Good for patient with altered mental function
as it does not cause sedation
• Dose 20 to 40 mg i.v. every ten minutes till
response or increase up to 20mg/hr

99. Esmolol
• Ultra short acting beta blocker given in dose of
0.5mg/kg bolus i.v followed by 50 to
200microgram /kg/min acts in 1-2 min and
last for 10 -20min
• Useful cardiac contractility and heart rate
need to be reduce
• use in combination of nicardipine or
nitroprusside as BP lowering action low