ADRENOCEPTOR

ANTAGONISTS
Dr. Amit M Shah
 Adrenoceptor
Antagonists

Alpha Receptor Beta Receptor

Antagonists Antagonists
Alpha Receptor
Antagonists
CLASSIFICATION
o Nonequilibrium type
 β-Haloalkylamines: Phenoxybenzamine
o Equilibrium type (competitive)
 Nonselective:
• Ergot alkaloids: Ergotamine, Ergotoxine
• Hydrogenated ergot alkaloids: Dihydroergotamine (DHE),
Dihydroergotoxine
• Imidazoline: Phentolamine
• Miscellaneous: Chlorpromazine
 α1 selective:
• Prazosin, Terazosin, Doxazosin, Alfuzosin, Tamsulosin
 α2 selective:
• Yohimbine
ADRENOCEPTORS
RECEPTOR SIGNAL TISSUE EFFECTS
Vascular smooth muscle Contraction
Genitourinary smooth mus. Contraction
α1 Gq/Gi Intestinal smooth muscle Relaxation
Heart ↑ Inotropy and excitability
Liver Glycogenolysis & gluconeogenesis
Pancreatic ß-cells ↓ Insulin secretion
Platelets Aggregation
α2 Gi
Nerve ↓ Norepinephrine release
Vascular smooth muscle Contraction
Heart ↑ Chronotropy and inotropy
ß1 Gs Heart ↑ AV-node conduction velocity
Renal juxtaglomerular cells ↑ Renin secretion
Smooth muscle Relaxation
ß2 Gs Liver Glycogenolysis & gluconeogenesis
Skeletal muscle Glycogenolysis and K+ uptake
ß3 Gs Adipose Lipolysis
GENERAL EFFECTS OF α BLOCKERS
o The important effects of α receptor stimulation:
 α1: vasoconstriction
 α2: decreases NA release from presynaptic neurons

o α1 blockade: inhibits vasoconstriction ⇒ vasodilation

⇒ decreases BP

o α2 blockade: enhance release of NA ⇒ stimulation of β

receptors ⇒ tachycardia and increase in CO
o Blockade of vasoconstrictor α1 receptors in blood
vessels ⇒ decrease in PVR ⇒ Pooling of blood in
capacitance vessels ⇒ decrease in venous returns and
CO ⇒ fall in BP
o Reflex tachycardia occurs due to fall in mean arterial
pressure and release of NA due to blockade of α2
receptors.
o Nasal stuffiness blockade of α receptor in nasal blood
vessels
o Miosis result from blockade of α receptor radial muscle
of Iris
o Increase in intestinal motility ⇒ diarrhoea
o Hypotension by α blockers can decrease renal blood
flow ⇒ decrease GFR ⇒ Na retention and expansion in
blood volume [so reflex increase in renin release β1]
o Tone of smooth muscle in bladder, trigone sphincter
and prostate is reduced by blockade of Alpha receptors
[α1A] ⇒ urine flow in patients with BPH is improved.
o Contraction of vas deferens and related organs
resulting in ejaculation are coordinated by α receptors
– α blockers can inhibit ejaculation ⇒ impotence
1. Hypotension and Postural hypotension
2. Nasal stuffiness
3. Increased intestinal motility
4. Reduced RBF & GFR- sodium retention
5. Improve urine flow in BPH
6. Inhibit ejaculation
PHENOXYBENZAMINE
o Irreversible, nonselective alpha blocker
o It cyclizes spontaneously in the body = Ethyleniminium
intermediate [reacts with α receptors] forms covalent
bond
o Effect is gradual even after i.v. administration and last
for 3-4 days
o High doses block of histamine, 5-HT, Ach receptors also
o Erratic oral absorption, i.m. & s.c. painful
o Cap 10 mg (20-60mg/day), Inj 50 mg/ml (1 mg/kg i.v.
infusion in 1 hr)
o Uses- Pheochromocytoma, PVD, Shock
PHENTOLAMINE
o Reversible, nonselective alpha blocker
o Quick & short acting α1 & α2 blocker – competitive
o Venodilatation, increase nor-adrenaline release

o Uses:
 For diagnosis & treatment of Pheochromocytoma
 Hypertension due to clonidine withdrawal and drug
interactions
 To counteract vasoconstriction due to extravasated NA/DA
during their i.v. infusion

o Inj 10 mg/ml, Dose 5 mg iv & as required

TOLAZOLINE
o Reversible, nonselective alpha blocker
o α blockade is modest & short lasting
o Block 5-HT, histamine like acid secretion & Ach like
motor action on intestine
o ADRs: Nausea, vomiting, cramps, diarrhea, chills
tachycardia, worsen CAD
o Rarely used
ERGOT ALKALOIDS & DERIVATIVES
o Adrenergic antagonists
o Ergotamine and ergotoxine are partial agonists and
antagonists at α adrenergic, 5HT, DA receptors
o Ergometrine has no α blocking activity
o ERGOTISM: Natural ergot alkaloids ⇒ long lasting
vasoconstriction ⇒ peripheral vascular insufficiency
and gangrene of toes and fingers
o Their principal uses:
 Ergotamine – Migraine
 Ergometrine – Induction of labor and abortion; PPH
 DH-ergotoxine – Cognition enhancer
PRAZOSIN
o Highly selective α1 blocker (α1 : α2 ⇒ 1000:1)
o Blocks sympathetic vasoconstriction ⇒ Arterioles and
venules are dilated ⇒ decrease PVR and CO.
o NA release is not increased due to absence of α2
blockade ⇒ mild tachycardia
o ‘First Dose Effect’
 Postural hypotension in the beginning of therapy ⇒
dizziness and fainting
 Marked fall in BP in standing because of antagonism of
compensatory vasoconstriction & unopposed β action
 Minimized by starting with a low dose and taking it at
bedtime
 Tolerance develops to this side effect
o Decreases central sympathetic outflow
o Inhibits vascular PDE (phosaphodiesterase) so
increase in CAMP ⇒ vasodilatation
o Relaxes smooth muscle in the prostate
o Decrease LDL,TG, increases HDL

o Effective orally, high Plasma Protein Binding & excreted

in bile
o T ½ 2-3 hrs, single dose acts for 6-8 hrs
o Therapeutic Uses:
o Hypertension: severe, not controlled by primary drugs
o Left ventricular failure (LVH) not controlled by
diuretics & other drugs
o Benign Prostatic hypertrophy (BPH): It relaxes the
urinary bladder neck and prostatic capsule, so used in
BPH to improves urine flow
o Raynaud’s disease
o Adverse effects:
o 1st dose hypotension
o Headache
o Dizziness
o Impaired ejaculation
TERAZOSIN
o Chemically & pharmacologically similar to prazosin
o Higher bioavailability (90%) and longer plasma t½
(~12 hr)
o Single daily dose lowers BP over 24 hrs
o Additional apoptosis promoting effect on prostate ⇒
retard the progression of prostatic hypertrophy
o More popular for use in BHP
DOXAZOSIN
o Long acting (t½ 18 hr) congener of prazosin
o Pharmacological profile similar to terazosin, including
the apoptosis promoting effect on prostate
o Used in hypertension and BHP
TAMSULOSIN
o Uroselective α1A/α1D blocker (α1A : α1B ⇒ 7–38 fold)
o α1A: Bladder base and prostate
o α1B: Blood Vessels
o Lacks the prostatic apoptosis promoting property
o As effective as terazosin in improving BHP symptoms
o Does not cause significant changes in BP or HR at doses
which relieve urinary symptoms
o Not used as an antihypertensive
o No increase in adverse cardiovascular events
o Postural hypotension is infrequent
o Plasma t½ is 6–9 hrs
o Modified release (MR) cap needs only once daily
o Better tolerated α1 blocker for BHP in patients who
continue to suffer postural hypotension with
terazosin/doxazosin.

o Adverse effects:
o Dizziness and retrograde ejaculation
o Problem of floppy iris has been encountered during
cataract surgery
USES OF α BLOCKERS
1. Pheochromocytoma
o Tumour of adrenal medullary cells ⇒ Excess CAs are
secreted ⇒ intermittent or persistent hypertension
o Phentolamine test:
 Inj. phentolamine 5 mg i.v. over 1 min in recumbent subject
 A fall in BP > 35 mm Hg systolic and/or > 25 mm Hg
diastolic is indicative of Pheochromocytoma
 Not very reliable
o Therapeutic:
 Phenoxybenzamine: Used as definitive therapy for
inoperable and malignant Pheochromocytoma
 Prazosin is an alternative
1. Pheochromocytoma (cont.…)
o Therapeutic (cont...):
 Phenoxybenzamine orally for 1–2 weeks preoperatively
and infuse it i.v. during surgical removal of the tumour
• Due to excess circulating CAs ⇒ blood volume is low
• Handling of the tumour during surgery may cause
outpouring of CAs in blood → marked rise in BP
• Removal of the tumour is often attended by marked fall in BP
as blood vessels dilate and the blood volume is low
2. Hypertension
o Non-selective α blockers are not useful as their effect
due to vasodilatation is compensated by cardiac
stimulation
o Selective α1 blocker (prazosin-like) may be useful in
the management of essential hypertension
o Drawbacks: Postural hypotension, impotence, nasal
blockage
o Phentolamine or phenoxybenzamine are of great value
in controlling episodes of rise in BP during clonidine
withdrawal and cheese reaction in patients on MAO
inhibitors
3. Benign Prostatic Hypertrophy of (BPH)
o Urinary obstruction caused by BPH due to:
 Static component: Increased size of prostate
 Dynamic component: Increased tone of bladder neck/
prostate smooth muscle
o Two classes of drugs are available:
 α1 adrenergic blockers (prazosin like): decrease tone of
prostatic/ bladder neck muscles
 5-α reductase inhibitor (finasteride): arrest growth/
reduce size of prostate
3. Benign Prostatic Hypertrophy of (BPH) (cont.…)
o α1 blockage in bladder trigone, prostate and prostatic
urethra ⇒ Relaxation of these structures ⇒ increase
urinary flow rate and complete emptying of bladder
o Voiding symptoms (hesitancy, narrowing of stream,
dribbling and increased residual urine) are relieved
better than irritative symptoms like urgency, frequency
and nocturia
o α1 blockers afford faster (~ 2 weeks) relief
o Provide only symptomatic relief
o More commonly used
o Terazosin, doxazosin, tamsulosin preferred
4. Secondary shock
o Shock due to blood or fluid loss is accompanied by
reflex vasoconstriction.
o Volume replacement fails to reverse this, therapy with
an α blocker (phenoxybenzamine i.v.) can help by:
 Counteracting vasoconstriction
 Shifting blood from pulmonary to systemic circuit
 Returning fluid from extravascular to the vascular
compartment so that cardiac output improves
5. Peripheral vascular diseases
o Reynaud's phenomenon, acrocyanosis: prazosin /
phenoxybenzamine produces good symptomatic relief

6. Papaverine/phentolamine induced penile

erection [PIPE]: Therapy for impotence
o In patients unable to achieve erection, inj of papaverine
[3 to 20 mg] with or without phentolamine [0.5 to 1
mg] in the corpus cavernosum produces penile
tumescence to permit intercourse
o Drawbacks: Priapism (in 2–15% cases), penile fibrosis
(on repeated injections), local haematoma, infection,
paresthesia and penile deviation
7. Congestive heart failure (CHF)
o Prazosin is used due to vasodilator action [ACEI
preferred]

8. Migraine:
o Ergotamine- Acute attack
Beta Receptor
Antagonists
CLASSIFICATION
o Nonselective (β1 and β2)
 Without intrinsic sympathomimetic activity:
• Propranolol, Sotalol, Timolol
 With intrinsic sympathomimetic activity:
• Pindolol
 With additional α blocking property:
• Labetalol, Carvedilol
o Cardioselective (β1)
 Metoprolol, Atenolol, Acebutolol, Bisoprolol, Esmolol,
Betaxolol, Celiprolol, Nebivolol
o β2 selective
 Butoxamine
 Third Generation
First Generation Second
(with additional α blocking
(older, Generation
and/or vasodilator
nonselective) (β1 selective)
property)

Metoprolol Labetalol
Propranolol
Atenolol Carvedilol
Timolol
Acebutolol Celiprolol
Sotalol
Bisoprolol Nebivolol
Pindolol
Esmolol Betaxolol
ADRENOCEPTORS
RECEPTOR SIGNAL TISSUE EFFECTS
Vascular smooth muscle Contraction
Genitourinary smooth mus. Contraction
α1 Gq/Gi Intestinal smooth muscle Relaxation
Heart ↑ Inotropy and excitability
Liver Glycogenolysis & gluconeogenesis
Pancreatic ß-cells ↓ Insulin secretion
Platelets Aggregation
α2 Gi
Nerve ↓ Norepinephrine release
Vascular smooth muscle Contraction
Heart ↑ Chronotropy and inotropy
ß1 Gs Heart ↑ AV-node conduction velocity
Renal juxtaglomerular cells ↑ Renin secretion
Smooth muscle Relaxation
ß2 Gs Liver Glycogenolysis & gluconeogenesis
Skeletal muscle Glycogenolysis and K+ uptake
ß3 Gs Adipose Lipolysis
PROPRANOLOL
o Nonselective β blocking agents
o Interacts with β1 and β2 receptors with equal affinity
o Lacks intrinsic sympathomometic activity
o Does not block alpha receptors
o Pure antagonist
PHARMACOLOGICAL ACTIONS
1. Heart:
o Decreases heart rate & force of contraction ⇒ decrease
cardiac output
o Retard the impulse conduction ⇒ Prolongs systole &
synergy of contraction of ventricular fibres is disturbed
o Effects are prominent under sympathetic overactivity
(exercise, emotion)
o Ventricular dilatation can occur in those with reduced
reserve ⇒ may precipitate/aggravate CHF
1. Heart:
o Improvement of O2 supply in angina patients:
 Reduce heart rate and aortic pressure ⇒ Reduce Cardiac
work and oxygen consumption
 Total coronary flow is reduced (blockade of dilator β
receptors), but this is largely restricted to the subepicardial
region
 Perfusion of the subendocardial area (which is the site of
ischaemia in angina patients) is not affected
 Exercise tolerance is increased
1. Heart:
o Antiarrhythmic/ Proarrhythmic effect:
 Shortens the refractory period of myocardial fibres and
decreases automaticity ⇒ Reduction of rate of diastolic
depolarization in ectopic foci
 More effect when it had been augmented by adrenergic
stimuli
 Delay the A-V conduction
 Direct depressant and membrane stabilizing (quinidine
like) action (high doses)
 Blocks cardiac stimulant action of adrenergic drugs but not
that of digoxin, methylxanthines or glucagon
2. Blood vessels & Blood pressure:
o No direct effect on blood vessels & no acute effect on BP
o Does not reduce BP in normotensives; but lowers BP in
hypertensive patients
o Gradual fall in SBP & DBP on prolong administration:
 Decrease renin release from kidney
 Cardiac actions like decrease in HR, FOC, CO
 Reduces Total Peripheral Resistance (TPR)
 Reduces neuronal NA release - β blockade
 Central action reduces sympathetic outflow
 Other minor mechanisms like: NO production, blockade of
Ca entry, opening of K channels, antioxidant property
3. Respiratory tract:
o Bronchoconstriction - β2 blockade, marked in
bronchial asthma patients

4. CNS:
o No effects- sometimes Behavioural changes, dreaming,
nightmares, forgetfulness on long term use

5. Eye:
o Local instillation reduces IOP
o Inhibit secretion of aqueous humor
o No effect on accommodation & pupil size
o Used in glaucoma (open angle)
6. Metabolic:
o Blocks adrenergically induced lipolysis ⇒ Increase in
plasma free fatty acid levels
o Increase in plasma triglyceride level and LDL/HDL ratio
o Inhibits glycogenolysis in heart, skeletal muscles and in
liver which occurs due to Adr release during
hypoglycaemia ⇒ Delayed recovery from insulin action
o Prolonged propranolol therapy may reduce
carbohydrate tolerance by decreasing insulin release

7. Uterus:
o No effect on normal uterine activity
8. Local anaesthetic:
o Potent local anaesthetic but it is not clinically because it
causes irritation at the injected site

9. Skeletal muscle:
o Inhibits adrenergically provoked tremor (directly on
the muscle fibres through β2 receptors)
o Reduce exercise capacity:
o Attenuating β2 mediated increase in blood flow to the
exercising muscles
o Limiting glycogenolysis and lipolysis which provide fuel to
working muscles
PHARMACOKINETICS
o Orally- High first pass metabolism (FPM)
o Oral: Parenteral ratio (40:1)
o Bioavailability is more after meals - Less FPM
o Individual oral dose variation- 20 fold
o Lipophilic → Penetrates brain
o 90 % bound to plasma proteins
o Chronic use decreases hepatic blood flow ⇒ Increase
oral bioavailability & t½
o Saturable Hepatic metabolism
o Dose: 40-160 mg/day.
o Start with low dose and increase gradually as required
o Not suitable for IM or SC inj. Slow IV can be given rarely
DRUG INTERACTIONS
o Depression of SA node & AV conduction with Digitalis &
verapamil ⇒ Cardiac arrest
o Delay recovery from hypoglycemia – Insulin & oral
hypoglycemics. Warning symptoms are suppressed (like
tachycardia, tremors)
o Marked BP rise with Nasal decongestants (unopposed α
action)
o NSAIDs reduce antihypertensive effect of β blockers:
local prostaglandins production at afferent and efferent
arterioles are essential for maintaining renal blood flow
o Propranolol reduces chlorpromazine & lignocaine
metabolism
ADVERSE DRUG REACTIONS & CONTRAINDICATIONS
o Accentuate myocardial insufficiency ⇒ precipitate/
worsen the CHF in decompensated heart (careful use in
CHF improves survival)
o Bradycardia: Patients of sick sinus are more prone
o Worsens chronic obstructive lung disease, can
precipitate life-threatening attack of bronchial asthma
⇒ contraindicated in asthmatics
o Exacerbates variant (vasospastic) angina due to
unopposed α mediated coronary constriction. In some
patients, even classical angina may be worsened
o Worsening of Peripheral vascular disease: cold hands
and feet, due to blockage of β2 receptors
o Withdrawal of propranolol after chronic use ⇒ rebound
hypertension, worsening of angina and sudden death
o Cardiac depressant effect: Cardiac arrest ⇒
Contraindicated in partial and complete heart block
o Impaired carbohydrate tolerance- in pre diabetics
o Raise triglyceride, LDL & reduce HDL- not seen with β1
blockers, less with agents having intrinsic
sympathomimetic action
o Tiredness & reduced exercise capacity- Vasoconstriction
in skeletal muscles & reduced fuel supply
o Sexual distress in male patients
o GI upset, lack of drive, nightmares, forgetfulness, rarely
hallucinations
COMPARATIVE PROPERTIES

Membrane Intrinsic
Drug Lipid Solubility
Stabilizing Activity Agonist Activity
Non-selective β blockers
Nadolol 0 0 Low
Penbutolol 0 + High
Pindolol + +++ Low
Propranolol ++ 0 High
Timolol 0 0 Low to moderate
Cardio Selective β blockers
Acebutolol + + Low
Atenolol 0 0 Low
Bisoprolol 0 0 Low
Esmolol 0 0 Low
Metoprolol + 0 Moderate
α + β blockers
Carvedilol ++ 0 Moderate
Labetalol + + Low
CARDIOSELECTIVITY (metoprolol, atenolol, acebutolol,
bisoprolol, nebivolol)
o Lower propensity to cause bronchoconstriction ⇒ Safer
in asthmatics and COPD patients
o Less interference with carbohydrate metabolism and
less inhibition of glycogenolysis during hypoglycaemia
⇒ safer in diabetics
o Lower incidence of cold hands and feet, less chances of
precipitating Raynaud’s phenomenon
o No/less deleterious effect on blood lipid profile.
o Less liable to impair exercise capacity
o Ineffective in suppressing essential tremor
INTRINSIC AGONIST (INTRINSIC SYMPATHOMIMETIC)
ACTIVITY (pindolol, celiprolol, acebutolol)
o Bradycardia and depression of contractility at rest are
not prominent, but exercise tachycardia is blocked; may
be preferred in those prone to severe bradycardia
(elderly patients; sick sinus) or with low cardiac reserve
o Continued agonistic action on β receptors prevents
development of supersensitivity ⇒ Withdrawal is less
likely to exacerbate hypertension or angina
o Plasma lipid profile is not/less worsened.
o Not effective in migraine prophylaxis—they dilate
cerebral vessels
o Not suitable for secondary prophylaxis of MI
MEMBRANE STABILIZING ACTIVITY (propranolol,
oxprenolol, acebutolol)
o Contribute to the antiarrhythmic action, but appears to
be significant only at high doses

LIPID INSOLUBILITY (atenolol, celiprolol, bisoprolol,

sotalol)
o Less likely to produce sleep disturbances and
nightmares
ELIMINATION HALF-LIFE
SOTALOL
o Nonselective β blocker with low lipid solubility
o Additional cardiac rectifier K+ channel blocking and
class III antiarrhythmic property

TIMOLOL
o Preferred for topical use in eye for glaucoma
o Orally it is a potent β blocker ⇒ was used in
hypertension, angina and prophylaxis of MI

BETAXOLOL, LEVOBUNOLOL, CARTIOLOL,

METIPRANOLOL
o Topical application to the eye for glaucoma
PINDOLOL
o Potent β blocker with prominent ISA
o Used primarily as antihypertensive: may be
advantageous in patients who develop marked
bradycardia with propranolol
o Rebound hypertension on withdrawal are less
o The effective dose range is rather narrow
METOPROLOL
o Cardioselective (β1) blockers
o Less likely to worsen asthma
o Preferred in diabetics receiving insulin or OHA
o Patients who complain of cold hands and feet while on
propranolol do better on metoprolol
o Side effects of metoprolol are milder
o Given orally for hypertension, angina and CHF
o IV injection (5–15 mg) has been used in myocardial
infarction provided bradycardia is absent
ATENOLOL
o Cardioselective (β1) blockers with low lipid solubility
o Longer duration of action ⇒ once daily dose
o Side effects related to CNS action are less
o No deleterious effects on lipid profile
o Most commonly used β blockers for hypertension and
angina

S(–) Atenolol
o Effective at half the dose and may be bettertolerated
ACEBUTOLOL
o Cardioselective agent with ISA and membrane
stabilizing properties
o Less effect on resting heart rate
o Side effect profile is like that of metoprolol
ESMOLOL
o Ultrashort acting β1 blocker
o Inactivated by esterases in blood
o Plasma t½ is < 10 min
o Action disappears 15–20 min after terminating i.v.
infusion ⇒ degree of β blockade can be titrated by
regulating the rate of infusion
o Used to terminate supraventricular tachycardia,
episodic atrial fibrillation or flutter, arrhythmia during
anaesthesia, to reduce HR and BP during and after
cardiac surgery, and in early treatment of MI
o A loading dose of 0.5 mg/kg is given followed by 0.05–
0.2 mg/kg/min infusion
NEBIVOLOL
o Highly selective β1 blocker also acts as a NO donor
o Produces vasodilatation and improve endothelial
function ⇒ May delay atherosclerosis
o Absence of deleterious effect on plasma lipids and on
carbohydrate metabolism
o Hypotensive response to nebivolol has a rapid onset
o It has been used in hypertension and CHF
USES OF β BLOCKERS
Cardiac & CVS Uses: Non-Cardiac Uses:
1. Hypertension 1. Thyrotoxicosis
2. Cardiac arrhythmias 2. Migraine
3. Angina pectoris 3. Anxiety
4. Myocardial infarction (MI) 4. Essential tremor
5. Congestive heart failure 5. Glaucoma
6. Pheochromocytoma
7. Dissecting aortic aneurysm
8. Hypertrophic obstructive
cardiomyopathy
1. Hypertension
o First-line drug therapy for HT with concomitant
disease like post MI
o Preferred in young non-obese hypertensive
o Reduce Blood Pressure by:
 Cardiac β1 receptor blockade ⇒ ↓ HR & Contractility
 JG cells β1 receptor blockade ⇒ ↓ Renin release
 Reduction in central sympathetic outflow
 Stimulation of prostacyclin synthesis in vascular beds
 ↑ secretion of natriuretic peptides
o Well tolerated
o Used in combination with diuretics, ACEIs and
vasodilators
2. Cardiac arrhythmias
o β blockers (mainly propranolol) suppress extrasystoles
and tachycardias, especially those mediated
adrenergically (during anaesthesia, digitalis induced)
o Used i.v. for this purpose
o Propranolol controls ventricular rate in atrial
fibrillation and flutter, but only occasionally restores
sinus rhythm
o Esmolol is an alternative drug for paroxysmal
supraventricular tachycardia
3. Angina Pectoris
o All β blockers benefit angina of effort
o Decrease frequency of attacks and increase exercise
tolerance
o High doses may worsen angina in some patients by
increasing ventricular size and reducing coronary flow
o Not suitable for variant (vasospastic) angina
4. Myocardial infarction (MI)
(a) Secondary prophylaxis of MI:
o Prevent reinfarction
o Prevent sudden ventricular fibrillation at the
subsequent attack of MI
o High risk patients (those who had large infarcts)
should be put on β blockers (if there are no
haemodynamic contraindications) for at least 2 years
o β blockers with ISA are less suitable for this purpose
4. Myocardial infarction (MI)
(b) Myocardial salvage during evolution of MI:
o Administered i.v. within 4–6 hours of an attack
followed by continued oral therapy
o May limit infarct size by reducing O2 consumption
o May prevent arrhythmias including VF

o β blockers can be given to only those patients

 Not in shock or cardiac failure
 Heart rate > 50/min with not higher than first degree heart
block (P-R interval < 0.24 sec)
5. Congestive heart failure
o β blockers can acutely worsen heart failure
o Long term use of metoprolol, bisoprolol, nebivolol,
carvedilol
o Retard the progression of CHF and prolong life
o Antagonism of deleterious effects of sympathetic
overactivity (reflexly by heart failure) on myocardium
o Metoprolol along with other measures, is now
established as standard therapy for most mild to
moderate CHF patients
o Should not be given to patients with marked fluid
retention and with vasodilators and inotropic drugs
6. Dissecting aortic aneurysm
o β blockers help by reducing cardiac contractile force
and aortic pulsation

7. Pheochromocytoma
o β blockers may be used to control tachycardia and
arrhythmia
o Suppress cardiomyopathy caused by excess CAs
o Never be administered unless an α blocker has been
given before, otherwise dangerous rise in BP can
occur
8. Hypertrophic obstructive cardiomyopathy
o Hypertrophy of subaortic region ⇒ Forceful
contraction of this region under sympathetic
stimulation (exercise, emotion) ⇒ Increases outflow
resistance
o β blockers improve CO in these patients during
exercise by reducing left ventricular outflow
obstruction
9. Thyrotoxicosis
o Propranolol rapidly controls the sympathetic
symptoms (palpitation, nervousness, tremor, fixed
stare, severe myopathy and sweating)
o Inhibits peripheral conversion of T4 to T3
o Use mainly preoperatively and while awaiting
response to antithyroid drugs/radioactive iodine.

10. Migraine
o Propranolol is the most effective drug for chronic
prophylaxis of migraine
11. Anxiety
o Blockade of peripheral manifestations of anxiety
(palpitation, tremor)
o Useful in the conditions which provoke nervousness
and panic, e.g. examination, unaccustomed public
appearance, etc.
o Ineffective in anxiety neurosis

12. Essential tremor

o Nonselective β1+β2 blockers have now an established
place in treating essential tremor
o No benefit in parkinsonian tremor
13. Glaucoma
o Used for chronic simple (wide angle) glaucoma
o Used as adjuvant in angle closure glaucoma
LABETALOL
o α + β adrenergic blocker
o β1 + β2 + α1 blocking and weak β2 agonistic activity
o β blocking potency is about 1/3 that of propranolol; &
α blocking potency is about 1/10 of phentolamine
o 5 times more potent in blocking β than α receptors
o α1 and β1 blockade as well as β2 agonism (vaso-
dilatation) ⇒ Fall in BP (both systolic and diastolic)
o Inhibit NA uptake by adrenergic nerve endings
o Orally effective but undergoes considerable first pass
metabolism
o Moderately potent hypotensive
o Used mainly in pheochromocytoma and clonidine
withdrawal
o Can also be used in essential hypertension
o Side effects:
 Postural hypotension
 Failure of ejaculation
 Rashes
 Liver damage
CARVEDILOL
o β1 + β2 + α1 adrenoceptor blocker
o Calcium channel blockade activity
o Antioxidant property
o Prevention of smooth muscle mitogenesis
o Reduce morbidity and mortality associated with HF
o Used in hypertension and is the β blocker especially
employed as cardioprotective in CHF