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Adrenoceptor Blocking Agents

To explain mechanisms and physiological consequences of alpha 1, alpha2, beta1,

and beta2 receptor blockade
Phentolamine, prazosin and yohimbine are competitive (reversible binding with
receptors) -adrenergic antagonists.
In contrast, phenoxybenzamine binds covalently to -adrenergic receptors to produce an
irreversible and insurmountable type of -receptor blockade. Once blockade has been
established with phenoxybenzamine, even massive doses of sympathomimetic agents
are ineffective until the effect of phenoxybenzamine is terminated by metabolism and
regeneration of receptors.
Phentolamine and phenoxybenzamine are non selective -antagonists acting at
postsynaptic 1 and presynaptic 2 receptors.
Prazosin is 1 selective, and yohmibine is 2 selective.
-adrenergic receptor antagonists exhibit selective affinity for -adrenergic receptors,
where they act by competitive inhibition.
Binding of antagonist drugs to -adrenergic receptor is reversible such that the drug
can be displaced from the occupied receptor if sufficiently large amounts of agonist
becomes available.
Competitive antagonism causes a rightward displacement of the dose-response
curve for the agonist, but the slope of the curve remains unchanged,
Chronic administration of -blockers is associated with an increase in the number of receptors.
-adrenergic receptors are G-protein coupled receptors and their occupancy by agonists
stimulates G proteins that in turn activates adenylate cyclase to produce cAMP.
cAMP activates protein kinases which phosphorylate proteins including L-type
voltage dependent calcium channels and troponin C in a variety of tissues (especially
The net effect of -adrenergic stimulation in the heart is to produce positive
chronotropic, inotropic and dromotropic effects and these are the responses that are
blunted by -adrenergic receptor antagonists
It is estimated that about 75% of receptors in the myocardium are 1, and about
20% are 2.

To classify alpha and beta receptor blocking agents according to their

pharmacokinetic and pharmacodynamic properties
Non selective blockers
4 main groups
Imidazoline eg, Tolazoline, phentolamine
Benzodioxan eg piperoxan (not used clinically)
Chorloethylamine eg Phenoxybenzamine
Ergot alkaloids and dihydro derivatives eg Ergotamine, dihydroergotamine
1 receptor blocking agents
2 receptor blocking agents
Non selective blockers
Labetalol and carvedilol are mixed and blocking drugs, though effect
1 receptor blocking agents
2 receptor blocking agents
Nil selective 2 blockers clinically available (undesirable to have selective
bronchoconstriction): but butoxamine is known.

To describe the pharmacology of alpha receptor blocking agents and apply this to
their clinical use
Imidazoline derivatives
Competitive antagonist eg phentolamine and tolazine
Phentolamine - short acting duration of 10-15 minutes
3-5 x more potent in blocking 1 vs 2
10x more potent than tolazoline
These drugs cause a fall in MAP (block of mediated vasoconstriction) and postural
CO and HR increase
Reflex tachycardia in response to fall in MAP, if concomitant block of 2 then this
enhances the reflex tachycardia (increased nor-adrenaline release).
Diagnosis and perioperative management of patients with phaeochromocytoma
Acute treatment of hypertension during anaesthesia
treatment of left ventricular failure complicating myocardial inharction
Previously used in pulmonary hypertension
Role in assessment of sympathetically mediated chronic pain
Injection into the corpus cavernosum has been used to treat impotence due to erectile
Clear solution for injection of 10mg/mL of phentolamine mesilate.
Main Actions
Hypotension, positive inotropism, chronotropism
Mode of Action
Acts by transient competitive adrenergic blockade (1:2 3-5:1)
Also has some adrenergic agonist and anti 5-HT activity
Route of Administration/Doses
IMI 5-10mg
IV infusion (diluted in dextrose or saline) at 0.1-0.2mg/min
Onset of action in 1-2 minutes, duration of action 5-20 minutes
Absorption - given parenterally. Oral bioavailability 20%
50% protein bound
Extensive metabolism
10% excreted unchanged in the urine.
Plasma half life 10-15 minutes

1 blockade - vasodilatation and hypotension, reduced SVR
2 blockade - reflex tachycardia, increased CO. Indirect effect of inotropism
Coronary blood flow is increased
Drug also has class I antiarrhythmic effects.
In patients with heart failure, phentolamine causes an increase in the HR and CO,
with a concomitant decrease in PAP, SVR and LVEDP.
Increases vital capacity, FEV1, and maximum breathing capacity in normal subjects.
Prevents histamine induced bronchoconstriction
Respiratory secretions increased.
Pulmonary arterial vasodilator.
The presence of sulphites in phentolamine ampoules may lead to hypersensitivity
reactions, which are manifest as acute bronchospasm in susceptible asthmatics.
Increases salivation, gastric acid and pepsin secretion, and GIT motility
May precipitate hypoglycemia secondary to increased insulin secretion
Generally well tolerated, may cause orthostatic hypotension, dizziness, abdominal
discomfort and diarrhoea.
Cardiovascular collapse and death have followed the administration of phentolamine
when it is used as a diagnostic test for phaeochromocytoma.
Special points
Phentolamine causes marked congestion of the nasal mucosa and this may make nasal
instrumentation more traumatic if topical vasoconstrictors are not used.

Chloroethylamine derivatives - Phenoxybenzamine

Haloalkalamine that undergoes spontaneous cyclization to ethylenimimium ion which
binds to the alpha receptor by van der Waal forces. Receptor then becomes alkylated to
form a strong covalent bond resulting in a non-competitive block
most antagonists are competitive: except for aspirin, clopidogrel, phenoxybenzamine.
Non-competitive antagonists have long half lives!!
100x more potent in blocking 1 compared to 2
Other effects: also antihistamine, anticholinergic, antiserotonin effects.
Side effects: sedation, nausea and vomiting, nasal congestion (mucosal vasodilitation
and swelling), postural hypotension, anhidrosis
po10mg daily 1 wk, then 10mg bd 1 wk, 10mg tds 1 wk. Need plenty of fluids.
If given IV - sudden vasoconstriction: need arterial and CVP monitoring.
Pre-Op for Phaeo - How do you know that there is adequate -blockade before starting blocker?
postural hypotension (main criteria)
symptoms of -blockade: insomnia, nasal stuffiness
Pre-operative management of phaeochromocytoma (to allow expansion of intravascular
perioperative management of some neonates undergoing cardiac surgery
hypertensive crises
Rayauds phenomenon
sometimes as an adjunct to the treatment of severe shock.
Tertiary amine which is a halo-alkylamine
Capsules 10mg
Clear colourless solution for injection 100mg/2mL phenoxybenaxmine hydrochloride with
ethyl alcohol, hydrochloric acid and propylene glycol.
Main Action
Vasodilation (predominantly arterial)
Mode of Action
Phenoxybenzamine acts via a highly reactive carbonium ion derivative (reactive
intermediate) that forma a strong covalent bond to the -adrenergic receptor to produce
irreversible blockade.
The drug increases the rate of peripheral turnover of noradrenaline and the amount of
noradrenaline released per impulse by blockade of pre-synaptic 2 receptors.
Haloalkylamines also inhibit the response to serotoninergic, histaminergic and
cholinergic stimulation.
Routes of Administration/Doses
Oral as above 10mg upwards.
IV infusion (diluted in dextrose saline) over 1 hr of 10-40mg. After IV administration, the
drug acts in 1 hr, and has a duration of action of 3-4 days.

Incompletely absorbed after oral administration - bioavailability 20-30%
Highly lipophilic
Liver - deacetylation
Urine and bile, half life 24 hrs. Effects may persist for 3 days while new -receptors
are synthesised.
Decrease in peripheral vascular resistance DBP, and pronounced orthostatic
Reflex tachycardia and CO
Inhibits catecholamine induced cardiac dysrhythmias
Fluid shift from interstitial to the vascular compartment due to vasodilation of pre and
post-capillary resistance vessels
CBF only if marked hypotension occurs
Usually causes sedation, although convulsions have been reported after rapid IV
infusion. Meiosis also seen.
Little change in GIT tone or splanchnic blood flow
Little alteration in renal blood flow, decreases motility of non-pregnant uterus.
Toxicity/Side Effect
Overdose should be treated with noradrenaline
Dizziness, sedation, dry mouth, paralytic ileus and impotence can result
Contact dermatitis
Special points
Systemic administration of the drug may lead to an increase in the systemic absorption
of co-administered local anaesthetic agents.
Causes marked congestion of nasal mucosa and this may make nasal instrumentation
more traumatic if topical vasoconstrictors are not used.

Prazosin - Selective 1 blocker

Specific post junctional 1 blocker
Pre-junctional 2 receptor not blocked and there fore inhibits further release of
noradrenaline at nerve ending
No tachyphylaxis, renin release not increased
Well absorbed, but high first pass
t 1/2 4 hrs
Side effects
1st dose phenomenon- with high first dose - orthostatic hypotension
dry mouth
Raynauds phenomenon
Congestive cardiac failure
aortic and mitral regurgitation
bladder neck obstruction
benign prostatic hypertrophy
Quinazoline derivative
tablets 0.5/1/2/5mg of prazosin hydrochloride
Main Action
Arterial and venous vasodilation
Mode of Action
Highly selective competitive antagonist of 1 adrenoreceptors (post-synaptic) thereby
causing relaxation of vascular smooth muscle.
Routes of Administration
0.5mg tds increasing upto 20mg total daily
Oral absorption is variable: bioavailability 40-80%
92% protein bound to plasma mainly to acid glycoprotein
VD 0.5-0.89L/kg
Liver - dealkylation and conjugation. The metabolites are active
Bile and faeces. - thus can be used in patient with renal impairment
<10% excreted unchanged.
CLearance is 3.5-4mL/kg/min,
Elimination half life 3 hrs.

Dilates coronary arteries, peripheral arterioles and veins, Pulmonary and
systemic vascular resistance and MAP.
Relatively little reflex tachycardia occurs
Drug may have direct negative chronotropic effect on the SA node.
CO may in patient with heart failure, due to reduced filling pressures

Clinically insignificant bronchdilatation in some asthamatic patients


Little effect on renal blood flow or GFR

Relaxation of bladder trigone and sphincter muscle
Increase in plasma noradrenaline concentration
Generally well tolerated.
Postural hypotension, drowsiness, fatigue, nausea and urinary urgency may occur.
First-dose phenomenon consists of dizziness and faintness, possibly accompanied
by palpitations, occurring as a result of profound hypotension, bradycardia and
decreased venous return.
Special Points
False positive results may occur in patients undergoing screening test for
Additive hypotensive effect should be expected with co-administered volatile anaesthetic
Drug is not removed by dialysis.
Doxazosin and Terazosin are similar drugs with longer half lives, allowing for once-daily
Tamsulosin an 1A-receptor antagonist shows some selectivity for the bladder and causes
less hypotension than drugs such as prazosin, which also act on 1B - receptors to control
vascular tone. It is believed that 1A - receptors play a part in the pathological hypertrophy
not only of prostatic and vascular smooth muscle, but also in cardiac hypertrophy that
occurs in hypertension, and the use of selective 1A - receptor antagonists to treat these
chronic conditions is under investigation.
Yohimbine - selective 2 blockade
Plant alkaloid - bark of yohmibe tree formulated as the hydrochloride
Used experimentally, not clinically (IV anaesthesia for horses).
Variable effect on CVS system - HR and BP, but may preciptiate orthostatic
In vitro it blocks the hypotensive response of clonidine
Has an antidiuretic effect and can cause anxiety and manic reactions.
Contraindicated in renal or hepatic disease

To describe the pharmacology of beta blockers with particular reference to

propanolol, atenolol, metoprolol, esmolol, carvedilol, sotalol, labatalol
2 subtypes of receptors
1 = cardiac effects, heart rate and contractility
2 = bronchodilation, vasodilation especially skeletal muscle arterioles, uterine relaxation
Metabolic = glycogenolysis (2 receptor, some blockers can result in hypoglycemia)
Structure-Activity Relationships
All beta-blockers are derivatives of the beta-agonist drug isoproterenol.
1. Substituted benzene ring with alkyl amino side chain
2. Increasing length on alkyl group increases potency
3. OH group to carbon - optical isomer - levorotation, levo compounds are active.
Non selective - propranolol, nadalol, timolol, pindolol
Cardioselective (for 1 receptor)- metoprolol, atenolol, betaxolol, esmolol, bisoprolol
Cardioselectivity is dose dependent and is lost when large doses of antagonist are
Pharmacodynamic Effects
Non selective
No agonist activity eg propanolol (short acting); nadolol (long acting)
with agonist activity eg oxyprenolol, alprenolol (short acting), pindolol (long acting)
with agonist activity - acebutolol (short acting)
no agonist activity eg metoprolol (short acting), atenolol (long acting)
Agonist activity (Intrinsic sympathetic activity)
Theoretically may provide advantages by decreasing myocardial depression, less
bronchospasm and less peripheral vasoconstriction eg Raynauds phenomenon
In practice not important
Occurs due to shape of b-blockers - binds to b-receptors.
Membrane stabilising effect
In high concentrations some beta blockers have potent local anaesthetic effects.
Doses are higher than those used clinically
eg propanolol, acebutolol

Table 12-10 --Pharmacokinetics and Pharmacology of Selected -Adrenoceptor

Proprietary name




Labetalol Esmolol











Relative sensitivity +

Intrinsic sympathetic 0











Hydrolysis by


Membranestabilizing activity

Predominant route of RE (mostly



RBC esterase

Drug accumulation







6 to 9

3 to 4

3 to 4

9 min

2 to 8

50-100mg qd


60mg qid




in renal disease
Elimination half-life
Usual oral
maintenance dose
Usual intravenous
dose (caution)

g qid



mg bid


1-2mg/kg 50 to 300 g/kg/

15 mg

q5min 3 (maximum)

min infusion

HM, hepatic metabolism; N/A, not applicable; RBC, red blood cell; RE,
renal excretion; 0, no effect; +, mild effect; ++ moderate effect.
Non selective blocker without ISA.
Racemic mixture, the S-isomer conferring most of its effects, although the R-isomer is
responsible for preventing the peripheral conversion of T4 to T3
Essential tremor
Prophylaxis for migraine
blocker of choice for thyrotoxicosis, as it inhibits the effects of thyroid hormones, as
well as preventing the peripheral conversion of T4 to T3.
IV 0.5-10mg titrated to effect
Oral 160-320mg daily, but due to increased clearance in thyrotoxicosis even higher
doses may be required.
High lipid solubility it is well absorbed from the GIT.
High first pass metabolism reduces oral bioavailablility to 30%.

Highly protein bound, this may be reduced by heparin.

Hepatic metabolism of the R-isomer is more rapid than the S-isomer and one of their
metabolites, 4-hydroxypropranolol, retains some activity.
Elimination dependent on hepatic metabolism, but is impaired by unknown mechanism in
renal failure.
Duration of action is longer than its half life of 4 hrs suggests.
Cardioselective blocker: tablets 25-100mg, syrup 5mg/mL and IV solution of 5mg in 10
25-100mg daily
IV 2.5mg slowly upto 10mg which then may be followed by an infusion
Incompletely absorbed from the gut. Oral bioavailability 45%
Not significantly metabolsied
5% protein bound
Excreted unchanged in the urine, thus dose should be reduced in renal impairment.
Elimination half life 7hrs, although actions appear to persist for longer than would
Relatively cardioselective, with no ISA.
Early use of metoprolol in AMI reduces infarct size and incidence of ventricular fibrillation
Adjunct in thyrotoxicosis
Migraine prophylaxis
25-200mg daily in bd
Up to 5-10mg IV for arrhythmias and AMI
Absorption - rapid and complete, but hepatic first pass metabolism makes oral
bioavailability 50%. This increases to 70% during continuous administration, and also
increases when taken with food.
High lipid solubility - can cross BBB, and also get into breast milk
20% protein binding
Hepatic metabolism exhibits genetic polymorphism resulting in 2 different half-life profiles
of 3 and 7 hrs.
Highly lipiophilic, cardioselective blocker with rapid onset and offset.
Clear liquid of either 2.5g (diluted for infusions) or 100mg in 10mLs.
Infusion 50-200 g/kg/min

Bolus 10mg titrated to effect

Short term management of tachycardia and HT in perioperative period
Acute supraventricular tachycardia.
mixed - and -antagonist, has been introduced as therapy for
mild or moderate hypertension, for the
management of stable or unstable angina, and after acute MI.
Clinical trials of carvedilol for the treatment of controlled CHF (New York Heart
Association class II to IV) suggest a significant reduction in mortality, especially for
patients with diabetes.
Non-selective -blocker with no ISA
Class III anti-arrhythmic properties
Racemic mixture
D isomer - class III activity
L isomer - class III and class II (-blocking) actions.
Prophylaxis of paroxysmal supraventricular tachycardias following direct current (DC)
Ventricular rate is also well controlled if SR degenerates back into AF.
Should not be used for angina, hypertension, thyrotoxicosis, or peri-myocardial infarction
Oral 80-160mg bd
IV 50-100mg over 20 minutes
Other effects
Precipitation of torsades de points which is rare, occurring in less than 2% of those being
treated fro sustained ventricular tachycardia or fibrillation.
COmmon with higher doses, a prolonged QT interval and electrolyte imbalance.
May precipitate heart failure.
Completely absorbed from GIT.
Oral bioavailability >90%
Not protein bound or metabolised
90% excreted unchanged in urine, remainder in bile.
Renal impairment significantly reduces clearance.
and adrenoceptor antagonist
blockade is specific to 1
blockade is non specific.
Has 2 asymmetric centres and exists as a mixture of four stereoisomers present in equal
(SR)-stereoisomer is probably responsible for the 1 effects

(RR)-stereoisomer probably confers the -blockade.

Ratio of 1: blocking effect depends on the rout of administration: 1:3 for oral, and 1:7
for IV.
Presentation and Uses
Available as 50-400mg tablets and as a colourless solution containing 5mg/mL.
HT crises
Facilitate hypotension during anaesthesia
IV - 5-20mg titrated to a maximum of 200mg
Oral form is used to treat HT associated with angina and during pregnancy, where the
dose is 100-800mg bd but may be increased to a maximum of 2.4g/day
Mechanism of Action
Selective 1 blockade produces peripheral vasodilitation
blockade prevents tachycardia
Myocardial afterload and oxygen demand are decreased providing favourable conditions
for those with angina.
Well absorbed from the GIT, but due to extensive 1st pass metabolism oral bioavailability
This may be increased with increasing age, and when adminstered with food.
50% protein bound
Metabolism occurs in the liver and produces several inactive conjugates.


To describe the clinical uses of beta receptor blocking agents and their potential
adverse effects
Clinical Uses
Treatment of Essential Hypertension
Chronic therapy results in a gradual reduction in systemic blood pressure
Antihypertensive effect is largely dependent on decreases in cardiac output due to
decreased heart rate.
Large doses of -blockers may decrease myocardial contractility as well
In many patients SVR remains unchanged.
Absence of orthostatic hypotension (cf prazosin)
Often -blocker used in combination with vasodilator to minimise reflex baroreceptor
mediated tachycardia and increased CO.
Release of renin from the juxtaglomerular apparatus that occurs in response to
stimulation of 2 receptors is prevented by nonselective beta blockers eg propranolol.
THis may account for a portion of the antihypertensive effect of propranolol especially in
patients with high circulating plasma concentrations of renin.
As drug induced decreases in secretion of renin, -blockers also will lead to a decrease
in release of aldosterone, and hence prevent the compensatory sodium and water
retention that accompanies treatment with a vasodilator.
Management of Angina Pectoris
Drug induced decreases in myocardial oxygen requirements secondary to reduced HR
and contractility.
Effective dose usually decreases resting HR <60
Treatment of Acute Coronary Syndrome
All patients who experience AMI receive IV -blocker as early as possible.
Contraindications to treatment are severe bradycardia, unstable left ventricular failure,
AV heart block.
Relative contraindications are asthma, reactive airway disease, mental depression,
peripheral vascular disease.
Diabetes is not a contraindication, there has to be recognition that the symptoms of
hypoglycemia may be masked.
The incidence of non fatal reinfarction and recurrent myocardial ischaemia was reduced
in patients who received oral metoprolol within 6 days following AMI.
Peri-operative beta-adrenergic blockade
Role is controversial at the moment
In the late 1990s, two important studies established the value of perioperative blockade in patients at risk for coronary ischemia who were undergoing noncardiac
Patients are labeled as at risk if they fit into one of two categories:
they are undergoing high-risk vascular surgery and have no evidence of inducible
coronary ischemia, or
they are undergoing a nonvascular procedure but have traditional risk factors for
coronary artery disease (elderly, high cholesterol, hypertension, cigarette
smoking, family history of coronary disease, or diabetes).
The Multicenter Study of Perioperative Ischemia Research Group[215] enrolled 200
patients about to undergo surgery who had risk factors for coronary artery disease
and randomized them to receive placebo or atenolol before and after surgery. Their
results demonstrated that although there was no improvement in in-hospital
outcomes (cardiac death or MI) in the atenolol-treated group, the treated group did

have a lower incidence of cardiac events at the 6- to 8-month follow-up and a marked
decrease in all-cause mortality that persisted at 2-year follow-up (survival rate at 2
years: 68% in the placebo group and 83% in the atenolol-treated group).
The second study enrolled patients with known ischemic disease demonstrated on
preoperative stress echocardiography.
Treatment group in this study was given bisoprolol and the dose was titrated to
achieve a heart rate below the patients ischemic threshold.
The results of this study, whose participants were at much higher risk for ischemic
events than those of the previous study, demonstrated a 10-fold decrease in
perioperative cardiac death and MI (3.4% versus 34%).
These powerful demonstrations that -blockade could decrease perioperative cardiac
risk and improve survival out to 2 years led to tremendous political and administrative
pressure to increase the use of -blockers perioperatively.
Unfortunately, more recent research has brought the value of routine perioperative blockade into question.
POBBLE study results showed no reduction in 30-day cardiovascular morbidity in
patients undergoing vascular surgery (one of the at-risk groups from previous
studies). Similarly, the
DIPOM study showed no benefit of -blockade in diabetics (another at-risk group)
undergoing major noncardiac operations.
Finally, a large retrospective study looking at in-hospital mortality in more than
780,000 patients demonstrated a neutral or even negative effect of perioperative blockade in patients without clear-cut coronary artery disease. -Blockade was
associated with a reduced mortality rate in only the 3% of patients who had three or
more risk factors (based on the revised Cardiac Risk Index) for coronary ischemia.
Thus, until larger studies are completed, the only strong indication for initiating blockade preoperatively is for patients undergoing vascular surgery who are at high
cardiac risk as a result of the finding of ischemia on preoperative testing.
When perioperative -blocker therapy is initiated, it should be titrated to a nonischemiainducing heart rate (usually 60 to 70 beats per minute) and not given as a standard fixed
dose to all patients. -blockers should be continued in patients who are already taking
them as treatment of their angina, symptomatic arrhythmia, or hypertension.
The safety of continuing -blockade perioperatively is well established, and initial
concerns regarding interaction with general anesthesia have not been confirmed.
Attempts to discontinue -blockers increase the risk for rebound tachycardia (with or
without atrial fibrillation) and myocardial ischemia in patients with coronary disease.
These drugs should be given up to the time of surgery, and intravenous forms in
appropriate dosages should be used whenever gastrointestinal absorption may be in
If -blockers have been omitted from the preoperative regimen, esmolol or labetalol may
be used acutely to blunt tachycardia and hypertension.
Cardioselective and nonselective -blockers appear to be effective in blocking the
chronotropic effects of endotracheal intubation and surgical stress.[231]

Treatment of intra-operative myocardial ischaemia

Appearance of ECG changes or wall motion abnormalities on the TOE may benefit from
treatment with -blocker.
IV titrated to desired HR (about 60bpm) to attenuate ischaemia.
Suppression of cardiac dysrhythmias
Effective in the treatment of cardiac dysrhythmias associated with enhanced sympathetic
nervous system stimulation (thyrotoxicosis, phaeochromocytoma, perioperative stress).

Esmolol, Metoprolol have been used for rapid AF and atrial flutter to control ventricular
response rate
Management of congestive cardiac failure
Metoprolol, carvedilol, bisoprolol improve ejection fraction and increase survival in
patients with chronic heart failure.
Sustained release metoprolol is associated with improved survival
Carvedilol a nonselective beta blocker with vasodilator and antioxidant properties has
been shown to decrease mortality associated with congestive heart failure.
Introduce slowly, and gradually increase dose.
Prevention of excessive sympathetic nervous system activity
-blockade is associated with attenuated HR and BP changes in response to direct
laryngoscopy and tracheal intubation.
Hypertophic obstructive cardiomyopathies are often treated with -adrenergic
Tachycardia, and cardiac dysrhythmias associated with phaeochromocytoma and
hyperthyroidism are effectively suppressed with propranolol.
Likelihood of cyanotic episodes in patients with Tetralogy of Fallot is minimised by blockade.
Preoperative preparation of hyperthyroid patients
Thyrotoxic patients can be prepared for emergency surgery by IV administration of
propranolol or esmolol or electively by oral administration of propranolol.
Treatment of migraine headache
Treatment of glaucoma - timolol - reduces aqueous humour production, can have systemic
side effects.
Essential tremor
Panic disorder
Adverse effects
negative inotropic and chronotropic effect
can precipitate worsening of heart failure
av block in patients with pre-existing disease
Excessive bradycardia and/or decreases in cardiac output due to drug induced blockade should be treated initially with atropine in incremental doses of 7g/kg IV.
Atropine is likely to be effective by blocking vagal effects on the heart and thus
unmasking any residual sympathetic nervous system stimulation.
If Atropine is ineffective, drugs which produce direct positive chronotropic and
inotropic effects are indicated eg isoproterenol (if non-selective blocker used) or
dobutamine (if selective -blocker was used).
Glucagon administered 1-10mg IV followed by 5mg/hr IV effectively reverses
myocardial depression produced by -adrenergic receptors at normal doses as it
does not exert its effect at receptors.
Calcium may also be effective
In the presence of bradycardia that is unresponsive to pharmacologic therapy
transvenous pacing or external pacing may be required
worsening of peripheral vascular disease

patients with peripheral vascular disease do not tolerate well the peripheral
vasoconstriction associated with 2 blockade by non-selective blockers.
Vasospasm associated with Raynauds disease is accentuated by propranolol.
Nonselective blockers consistently increase airway resistance bronchoconstriction.
More common in those with pre-existing airway disease
Selective blockers are less likely to cause this.
Nausea, vomiting, diarrhoea
Lipid soluble -blockers (eg propranolol) can cross the BBB, and produce fatigue,
lethargy, vivd dreams.
Atenolol is less lipid soluble and may be associated with less CNS effects.
blockers alter carbohydrate and fat metabolism
Non selective blockers prevent glycogenolysis that usually occurs in response to the
release of adrenaline in response to hypoglycemia.
Mask the tachycardia associated with hypoglycemia in diabetics on treatment.
Interaction with Anaesthetics
Generally well tolerated
Exception is timolol where profound bradycardia has been observed in the presence of
inhaled anaesthetics.
Acute Withdrawal
Acute discontinuation can result in excess nervous activity which manifests in 24-47
Presumably, this enhanced activity reflects an increase in the number of receptors (upregulation) during chronic therapy with blockers.