13 Beta Adrenoceptor Blockers
Transcript of 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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&linical uses of blockers contd:
;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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&linical uses of blockers contd:
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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&linical uses of blockers contd:
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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&linical uses of blockers contd:
9ypertension
Reduce renin secretion
Reduce cardiac output
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&linical uses of blockers contd:
9yperthyroidism
Reduce symptoms + signs
/nhibit peripheral con%ersion of ,
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&linical uses of blockers contd:
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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&linical uses of blockers contd:
&(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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Ad%erse effects of blockers contd''
/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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Ad%erse effects of blockers contd''
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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Ad%erse effects of blockers contd''
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