Download - B blockers
BETA BLOCKERS
Dr. RENJU.S.RAVI MD
OVERVIEW Introduction MOA Classification Actions Adverse effects Drug interactions Uses Contraindications Overdose
BETA BLOCKERS
Drugs which inhibit adrenergic response mediated by beta receptors
BETA RECEPTORSReceptors Sites actionsβ1 Heart
JG cells-kidneyPosterior pituitaryAdipose tissue
stimulatoryRenin release ADH releaselipolysis
β2 BronchiBlood vessels of skeletal muscleSmooth muscle(Uterus ,intestine , detrusor)Liver, MuscleAdipose tissueEye
BronchodilationVasodilatationRelaxation
GlycogenolysisLipolysisEnhanced aqueous secretion
β3 Adipose tissue Lipolysis
Professor Raymond P Ahlquist
Classified adrenoreceptors. (1948)
HISTORY
1st β blocker –DICHLORO ISOPROTERENOL-1958
PRONETHALOL---1962
PROPRANOLOL--1963
NEWER β BLOCKERS
James Black
MOA
Ac
PKA
α
GTP
ATP cAMP
+GDP
α βγ
MECHANISM OF ACTION Via GPCR
Antagonist binding to receptor
No stimulation of G protein
No change in cAMP conc
No EFFECT
PROPERTIES Receptor Blockade
Nonselective β blockade Selective β1 blockade Β+α blockade
Intrinsic sympathomimetic property-ISA (partial agonistic action) Membrane stabilising action-MSA
(Local anaesthetic action-Na channel block)
CLASSIFICATION
Beta blockers1st generation
ClassicalNon
selective
2nd generation
ClassicalBeta 1
selective
3rd generationNewer
Non selective & beta1 selective + Add. properties
1ST GENERATION – NON SELECTIVE
With ISA only Penbutolol
With MSA only Propranolol With ISA & MSA
Pindolol
Without ISA &MSATimolol
Nadolol Sotalol
2ND GENERATION – SELECTIVE Β1 AGENTS
With MSA only Metoprolol
With ISA & MSA
Acebutolol
Without ISA &MSAAtenolol
Bisoprolol
Esmolol
3RD GENERATION
Non-selective Selective
With ISACarteolol
With ISACeliprolol
With MSABetaxolol
With MSACarvedilol
With MSA & ISALabetalol
Β BLOCKERS
With ISAPenbutololCarteololCeliprolol
BothPindolol
AcebutololLabetalol
With MSAPropranololMetoprolol
BetaxololCarvedilol
Without ISA & MSATimolol, Sotalol, NadololAtenolol, Bisoprolol, Esmolol
PROPERTIES OF Β1 SELECTIVITY
Less broncho constriction Less interference with CHO metabolism less
hypoglycemia preferred in diabetics Less chances of Raynaud's phenomenon Less deleterious effect on blood lipid profile Less impairment of exercise capacity Less effect on tremor
PROPERTIES OF ISA
Less bradycardia Less rebound effect on withdrawal Less deleterious effect on blood lipid
profile Not effective in migraine prophylaxis Not suitable for secondary prophylaxis of
MI
ACTIONS
On CVS Heart
Negative Ionotropy Chronotropy Dromotropy Bathmotropy
ACTIONS….
On CVS Blood vessel
Vasoconstriction in prone individuals Direct
Vasodilatation due to additional properties
Precipitates Reynaud's disease
•α1 blockade•β2 agonism•Ca ++ channel block•K+ channel opening•NO production
ACTIONS….
On CVS Antihypertensive action
Decreased CO Decreased TPR on long term
administration Decreased renin release
BETABLOCKERS WITH VASODILATOR PROPERTY
Alpha blockadeLabetalolCarvedilolBucindololBevantololNipradilol
Beta2 agonismCeliprololCarteololBopindolol
CCB actionBetaxolol BevantololCarvedilol
K+ Channel openingTilisolol
NO productionCeliprololCarteololBopindololNipradilolNebivolol
Anti oxidantCarvedilol
ACTIONS -CNS
Anti anxiety Behaviour changes Forgetfulness Night mares Increased dreaming
Non-selective lipid soluble
ACTIONS -METABOLIC
CHO metabolism Hypoglycemia
Inhibits muscle glycogenolysis Hypoglycemic unawareness
Lipid Increases VLDL(TG) levels Alters HDL/LDL ratio
Less with β 1 selectiveagents
ACTIONS - EYE
Decrease secretion of aqueous
Decrease IOT No effect on pupil size or
accommodation
Ciliary body
ACTIONS- BRONCHUS
Increases airway resistance
Less with beta 1 selectiveagents
SKELETAL MUSCLES
o Decrease exercise capacity By decreasing blood flowInhibit glycogenolysis and
lipolysis.
MISCELLANEOUS
oAntagonise catecholamine induced Tremor Inhibition of mast cell
degranulation oPrevent platelet aggregation and
promote fibrinolysis
Water soluble
Lipid solubleBy LiverBy Kidney
100% 80 60 40 20 0
0 20 40 60 80 100%
PROPRANOLOL TIMOLOL PINDOLOL BISOPROLOL ACEBUTOLOL ATENOLOLCARVEDILOL NADOLOLMETOPROLOL SOTALOLLABETALOL CARTEOLOLPENBUTOLOL
Pharmacokinetics
ADVERSE EFFECTS - CVS
Bradycardia Exacerbation of
angina Precipitation of CHF
ADVERSE EFFECTS…
Increased air way resistance worsening of bronchial asthma
ADVERSE REACTIONS
Impairment of carbohydrate tolerance Alteration of lipid profile Rebound hypertension on withdrawal Cold hands and feet, worsening of PVD
ADVERSE EFFECTS…
Nightmares Decreased exercise capacity
TirednessLack of drive
DRUG INTERACTIONS
PHARMACOKINETIC
• Al salts, CholestyramineDecrease absorption• Enzyme inducersDecrease plasma conc.• Cimitidine, HydralazineIncrease BA• They impair clearance of
lidocaine
PHARMACODYNAMIC
Digoxin CCB (Verapamil) CCB (DHP) NSAIDs Adrenaline & other α
agonists
USES
CARDIOVASCULAR
Hypertension Angina Myocardial infarction Arrhythmia Cardiomyopathy CCF Dissecting aneurysm of
aorta
NON - CARDIOVASCULAR
Thyrotoxicosis Pheochromocytoma Migraine prophylaxis Essential tremor Glaucoma Anxiety Portal hypertension Anti psychotic induced
akathesia
HYPERTENSION
Cardioselective beta blockers Rationale
Decrease in HR,CO, myocardial contractility.
Decrease renin release Decrease central sympathetic
out flow
ANGINA
Metoprolol Atenolol Bisoprolol
ProphylaxisTreatment
Contraindication•Variant angina
ANGINA - RATIONALE
Decrease HR & contractility
Decrease myocardial oxygen demand
Antianginal action
MI
o Prophylaxiso Treatment Anti anginal action
Reduce infarct size Prevents arrhythmia
Prevents reinfarction Prevents arrhythmia
MetoprololEsmololTimolol
ARRYTHMIAS
Propranolol Esmolol Acebutolol Sotalol
Decreases AV conduction
Inhibits impulses from atria to ventricle controls ventricular rate
Mainly effective inArrhythmias precipitated by catecholamines
Sotalol K+ channel block class3 anti arrhythmicEsmolol ultra short acting supraventricular tachycardia
ARRHYTHMIA
Control ventricular rate in atrial flutter and fibrillation.
Suppress extrasystole and tachycardia especially mediated adrenergically .
HOCM
↓ contractility
↓ LV outflow obstruction
Improve cardiac output in exercise
CHF
ONLY in compensated CHF Antagonise sympathetic overactivity
on myocardium
Prevents myocyte apoptosis
↓ cardiac remodelling
Retard progression of CHF Metoprolol BisoprololCarvedilol
DISSECTING AORTIC ANEURYSM
↓ cardiac contractility, and aortic pulsation.
NON - CARDIAC USES
o Pheochromocytoma Used after an α blocker To control tachycardia and arrhythmia Suppress cardiomyopathy due to excess
catecholamineso Thyrotoxicosis
Control sympathetic symptoms Inhibit peripheral conversion of T4 to T3 Preoperative use
MIGRAINE PROPHYLAXIS
Propranolol Nadolol Metoprolol
PORTAL HYPERTENSION
To Decrease Portal Vein Pressure in Patients with Cirrhosis
Decrease variceal bleeding
Propranolol
GLAUCOMA
Decrease aqueous humour secretion
Attenuating neuronal Ca and Na influx Protection to retinal neurons
Inhibit ganglion cell death
TimololCarteololBetaxololLevobetaxololLevobunololMetipranolol
CNS
Anxiety Essential tremor Akathisia induced by
antipsychotics Alcohol withdrawal
3RD GENERATION AGENTSDrug MSA ISA Beta blockade Other properties
Labetalol + + Non selective α1 blockade
Carvedilol + Non selective α1 blockade,CCBAntioxidant
Bucindolol + Non selective α1 blockade,β2,β3 agonismIncreases HDL cholesterol
Celiprolol + β1 selective β2 agonismNO release
Nebivolol β1 selective •NO release•Inhibits platelet aggregation
Bevantolol Nonselective α1 blockadeCCB
CONTRAINDICATIONS
Absolute
1. Severe Bradycardia
2. Pre-existing High Grade Heart Block
3. Overt Untreated Heart Failure
4. Cardiogenic Shock
5. Severe Bronchospasm
6. Severe Depression
7. Active Raynaud’s Phenomenon
CONTRAINDICATIONSRelative
1. Prinzmetals Angina
2. Concomitant Use Of :Verapamil/ Diltiazam/Digoxin
3. Mild Asthma
4. Insulin Requiring DM
OVERDOSAGEManifestations extension of pharmacological properties
Hypotension
Bradycardia
Prolonged Conduction Times
Widened QRS Complexes
SIGNS AND SYMPTOMS
Seizures Depression Hypoglycemia Bronchospasm
TREATMENT
Atropine Initially
Cardiac Pacemakers Required
Large amt of Isoproterenol / Agonist
Glucagon
Thank you