13 beta adrenoceptor blockers

7/23/2019 13 Beta Adrenoceptor Blockers

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Beta adrenoceptor blockers

DR S. A Jayaratne

Dept of Pharmacology


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Most blocking drugs can be 1 or receptor

blockers

Some are partial agonists ie intrinsicsympathomimetic effects ! o"prenolol#

pindolol. acebutalol$

Some blockers ha%e membrane stabilising

effect !local anaesthetic effect$ &linicallyinsignificant


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receptor'blocking drugs ha%e relati%e affinities

for 1and receptors Some of these

antagonists ha%e a higher affinity for 1than

for receptors

(one of the clinically a%ailable receptor

antagonists are absolutely specific for 1

receptors# the selecti%ity is dose'related) it

tends to diminish at higher drug concentrations


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(on selecti%e blockers

*lock both 1 +receptors

Propranolol

(adololSotalol,imololAlprenolol-"prenololPindolol


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Selecti%e blockers ! cardioselecti%e$

Predominantly 1blocking effect Selecti%ity relati%e

ess bronchoconstriction

/n diabetics'ess masking of hypoglycaemic effects#less effect on counter regulatory hypoglycaemic

effects

Acebutolol MetoprololAtenolol *isoprolol

Practolol


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/ntrinsic sympathomimetic acti%ity

Partial agonist acti%ity

Sympathetic acti%ity through 1receptors

accelerate the heart

&auses less falling resting heart rate than pure

antagonists. ess effecti%e in se%ere angina


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/ntrinsic sympathomimetic acti%ity contd''

ess likely to cause cold e"tremities

Abrupt 0ithdra0al less rebound effectess up'regulation of receptors


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Pharmacokinetics of Receptor blockers

Most drugs 0ell absorbed orallySome are lipid soluble.

,hey readily cross cell membranes + ha%e high

apparent %olume of distribution

,hy also enter the &(S readily+ produce &(S

ad%erse effects ! bad dreams$

Sub2ected to e"tensi%e hepatic first pass metabolism

. 3hich is mainly dependent on hepatic blood flo0

eg' propranolol# metaprolol# o"prenolol# labetalol


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Pharmacokinetics of Receptor blockers contd''

Some are 0ater soluble

ess sub2ected to hepatic metabolism

4"creted unchanged in urine. !t15prolonged in renal

failure$

ess 0idely distributed

More predictable plasma concentration

ess readily enters the brain. ess &(S side effects

eg atenolol# sotalol# nadolol


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4ffects of blockers

&ardio%ascular effect

Primarily reduction in sympathetic dri%e

Reduce automaticity !rate$

Reduce myocardial contractility

Reduce renin secretion from 2u"taglomerular

apparatus

Reduced cardiac output + reduce o"ygen

consumption


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4ffects on respiratory system

*lockade of receptors cause

bronchoconstriction. 61selecti%e blockers ha%e

some benefit o%er non specific blockers. *ut

effect is relati%e


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4ffects on the eye

Reduce intra'ocular pressure in glaucoma by

reducing the formation of a7ueous humor by

the ciliary body. 4g timolol # beta"olol.

,hey are topically applied.

May cause some systemic A54


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&linical uses

&ardio%ascular uses8' /schaemic heart disease8' Angina !stable +

unstable$# M/

&ardiac arrhythmias

9ypertension

&hronic heart failure


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&linical uses of blockers contd:

Action of receptor antagonists in angina

Acting on 1 receptors

!'$ %e chronortropic effect'reduce heart rate

!'$ %e inotropic effect'reduce force of contraction

Reduce cardiac out put

ess 0ork on %entricles Reduce myocardial o"ygen demand !reduce

9R# + contractility$


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receptor antagonists in angina contd''

Reduce the fre7uency of anginal episodes

/mpro%e e"ercise tolerance duration of

e"ercise before the onset of anginal pain

Reduce mortality useful in secondary

pre%ention

/mpro%es sur%i%al after M/

commonly used drugs'atenolol# propranolol#

metoprolol # bisoprolol


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;nstable angina + Mycardial infarction

Pathophysiology

Rupture of atheromatous plaque with

overlying thrombus ACS

Acute Unstable

Myocardial infarction Angina

!S,4M 5(S,4M/$


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use of blockersin A&S contd:

;sed during the acute stage !1st< hrs$

Reduce 9R + contractility Reduce -demand

Start 0ithin 1st< hrs + continued about 1yr

post M/ Reduce myocardial damage + infarct si=e if

used >?hrs

Protect against cardiac rupture

Reduce reinfarction // rypre%ention+ sudden

death


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use of blockers in A&S contd:

Reduce mortality# increase sur%i%al

Reduce *P

Reduce risk of post infarction angina

Reduce the risk of arrhythmias

Drugs'atenolol#

@i%en to all patients 0ith A&S if there are no

contraindications8'9eart failure# bradycardia#

heart block# bronchial asthma# hypotension


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Arrhythmias

&lass // antiarrhythmic drug

Reduce SA + A nodal conduction

Most effecti%e in arrhythmias caused by increased

sympathetic acti%ity

,hyroto"icosis# acute M/

;sed in supra %entricular + %entricular

arrhythmias Slo0s %entricular rate in atrial flutter + fibrillation


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9eart failure

*enefit by blocking ad%erse effects due to

high concentration of catecholamines

;sed in chronic heart failure

Reduce mortality + morbidity

Drugs'car%edilol# metaprolol# bisoprolol


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9ypertension

Reduce renin secretion

Reduce cardiac output


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9yperthyroidism

Reduce symptoms + signs

/nhibit peripheral con%ersion of ,


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Portal hypertension

Pre%ent %ariceal bleeding

*y propranolol

Reducing portal blood flo0

Reduce cardiac output

&onstrict splachnic %essels

! blockade + unopposed C adrenergic

%asoconstriction$


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&(S

Migraine prophyla"is

*enign essential tremor

An"iety disorders! reduce palpitation + tremors$

@laucoma!open angle$

Reduce formation of a7ueous humor


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Ad%erse effects of blockers

Respiratory bronchospasm

/s of little importance in normal people

&an be life threatening in asthmatic

4%en eye drops can be fatal

@reater 0ith non selecti%e blockers


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Ad%erse effects of blockers contd''

&ardio%ascular

&ardiac failure

-ccur in patients 0ith high sympathetic dri%e

Dose is reduced in at risk patients

&5/ in uncontrolled heart failure

*radycardia

9ypotension


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/ncapacity for %igorous e"ercise

Due to inability to respond to sympathetic

dri%e

Reduced peripheral blood flo0

Results in cold e"tremities

3orsens intermittent claudication Raynauds phenomenon


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9ypoglycaemia

4specially in diabetics 0ith non selecti%e

blockers. Due to the impairment of

sympathetic mediated homeostatic

mechanisms.

Reco%ery from hypoglycaemia is delayed

Symptoms of hypoglycaemia !an"iety#

palpitations$ are masked


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Plasma lipoproteins

&hronic blockade 0ith nonselecti%e

blockers' 9D + triglycerides

Abrupt 0ithdra0al

&an cause angina

Due to up'regulation of receptors

3ithdra0al should be gradual


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A54 not due to blockade

oss of general 0ell being

Eatigue # tiredness# insomnia# bad dreams

feeling of 0eakness Rashes


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Carvedilol

antagonist F C antagonist Fantio"idant

properties. effect is more than the C

blocking effect

&linical uses 8' chronic heart failure

Most blockers are &5/ in heart failure because

of their negati%e inotropic effects


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&ar%edilol

&hronic heart failure is influenced by 8'

acti%ation of sympathetic ner%ous

system

acti%ation of renin angiotensin

aldosterone system


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Action of car%edilol in heart failure8'

Slo0 the progression of heart failure reduce mortality


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&ar%edilol is administered 0ith

diuretics

A&4 inhibitors F5' digo"in

&5/ in se%ere decompensated heart failure


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abetolol

Racemic mi"ture of isomers a$ !non selecti%e blocker$ adrenoceptor

blocker

b$ C adrenoceptor blockers blockade is

13 beta adrenoceptor blockers

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