BETA BLOCKERS Dr Reshmi Sameeth FIGHT OR FLIGHT

BETA BLOCKERS Dr. Reshmi Sameeth

FIGHT OR FLIGHT

SYMPATHETIC RECEPTORS BETA RECEPTORS β 1 β 2 β 3

BETA 1 HEART BETA 2 BRONCHUS GIT BLADDER UTERUS LIVER BLOOD VESSELS BETA 3 ADIPOSE TISSUE

BETA BLOCKERS Beta adrenergic receptor antagonists act on Β 1 or β 2 receptors or on both

SIR JAMES BLACK DEVELOPED BETA BLOCKER PROPRANOL IN 1958 AWARDED NOBEL PRIZE FOR MEDICINE IN 1988

CLASSIFICATION OF BETA BLOCKERS NON SELECTIVE BLOCKERS MIXED BLOCKERS

PROPRANOLOL TIMOLOL SOTALOL NADOLOL PINDOLOL OXPRENOLOL NON SELECTIVE BETA BLOCKERS

METOPROLOL ATENOLOL ESMOLOL ACEBUTOLOL CELIPROLOL BETAXOLOL BISOPROLOL NEBIVOLOL SELECTIVE β 1 BLOCKERS

BUTOXAMINE SELECTIVE β 2 BLOCKERS

LABETOLOL CARVEDILOL MIXED BLOCKERS---α+β BLOCKERS

NON SELECTIVE BLOCKERS • Blocks both β 1 and β 2 receptors • Eg: Propranolol

THERAPEUTIC USES

CARDIOVASCULAR USES BLOCK CARDIAC β 1 RECEPTORS HEART RATE MYOCARDIAL CONTRACTILITY CARDIAC OUTPUT BP

CARDIOVASCULAR USES • ESSENTIAL HYPERTENSION • CONGESTIVE HEART FAILURE • ANGINA PECTORIS • CARDIAC ARRHYTHMIAS • MYOCARDIAL INFARCTION

ESSENTIAL HYPERTENSION • Alone or in combination with diuretics • Rationale – Decrease in HR, CO , myocardial contractility. – Decrease renin release Dose: 20 -40 mg TDS

CANNOT PUMP SUFFICIENT BLOOD Congestive heart failure Useful in mild to moderate heart failure Introduced gradually Can antagonise damaging effect due to β 1 overactivity CI in severe heart failure

ANGINA PECTORIS DECREASES OXYGEN DEMAND INCREASES EXERCISE TOLERANCE SENSATION OF CHEST PAIN IMBALANCE BTW OXYGEN DEMAND SUPPLY CI: PRINZMETAL’S ANGINA

CARDIAC ARRHYTHMIAS • Used in SVT associated with thyrotoxicosis, • Digitalis toxicity Mechanism: • Membrane stabilising effect IRREGULAR HEARTBEAT TACHYCARDIA PALPITATIONS

MYOCARDIAL INFARCTION Decrease incidence, recurrence, mortality Prevent VF at the second attack of MI Dose: 40 -80 mg tds orally

NON CARDIOVASCULAR USES • Migraine Anxiety provoking situations • Glaucoma • Hyperthyroidism • Pheochromocytoma • Alcohol withdrawal • Oesophageal varices

NON CARDIOVASCULAR USES • MIGRAINE • Prophylaxis • Not for acute attack • Dose: 20 mg tds orally

ANXIETY Reduce anxiety Block peripheral manifestations of anxiety: tremors, sweating DOSE: 10 -20 MG TDS

GLAUCOMA Decrease intraocular pressure Propranolol not used Eg: Timolol topically

HYPERTHYROIDISM Reduces symptoms like tremor, sweating DOSE: 20 MG BD ORALLY

PHEOCHROMOCYTOMA GIVEN IN COMBINATION WITH α BLOCKER control tachycardia and arrythmia DOSE: 20 MG TDS FOR 3 DAYS BEFORE SURGERY

ALCOHOL WITHDRAWAL Reduces sympathetic overactivity during phase of withdrawal Dose: 20 mg BD orally

ADVERSE EFFECTS • • BRONCHOCONSTRICTION BRADYCARDIA COLD EXTREMITIES CNS SIDE EFFECTS HEART FAILURE HYPOGLYCEMIA REBOUND HYPERTENSION ADVERSE LIPID PROFILE

BRONCHOCONSTRICTION Contra indicated In ASTHMATICS COPD

BRADYCARDIA Can lower HR to 55 bpm BRADYARRHYTHMIA HEART BLOCK

COLD EXTREMITIES Loss of β 2 receptor mediated cutaneous vasodilataton in extremities CONTRA INDICATED IN REYNAUD’S DISEASE BLOOD VESSELS IN EXTREMITIES CONSTRICT IN RESPONSE TO TEMPERATURE: TURN BLUE OR WHITE

CNS SIDE EFFECTS SLEEP DISTURBANCES DEPRESSION NIGHTMARES

HEART FAILURE Cardiac patients need sympathetic drive to support heart to maintain proper cardiac output Beta blockers block this support Contraindicated in SEVERE HEART FAILURE

HYPOGLYCEMIA Beta blockers mask the symptoms of hypoglycemia like tremors , sweating and tachycardia CONTRAINDICATED IN PATIENTS ON INSULIN AND OHA

REBOUND HYPERTENSION CHRONIC THERAPY OF BETA BLOCKERS UPREGULATION IN NUMBER OF RECEPTORS NEWLY FORMED RECEPTORS ARE HYPER RESPONSIVE TO CATECHOLAMINES REBOUND HYPERTENSION ON STOPPING THE DRUG DOSE SHOULD BE GRADUALLY TAPERED

ADVERSE LIPID PROFILE LDL HDL

CARDIOSELECTIVE BLOCKERS • BLOCKS β 1 RECEPTORS • • • METOPROLOL ATENOLOL BISOPROLOL NEBIVOLOL ESMOLOL BETAXOLOL

Advantages over non-selective blockers • • Safer in asthmatics Safer in diabetes Safer in Reynaud’s disease Less deleterious effect on lipid profile

• Metaprolol: • Completely absorbed orally • BA less due to first pass metabolism Atenolol: Does not cross BBB Bisoprolol: Used in hypertension and angina

NEBIVOLOL New highly selective beta 1 blocker Rapid onset action Less deleterious effect on lipids

• ESMOLOL: • Ultra short acting beta 1 antagonist • Given IV in urgent settings when beta 1 blockade of short duration is desired. • Eg: • SVT, AF • completely withdrawn if adverse effects like bradycardia or heart failure occur

• BETAXOLOL • Used as eye drops in glaucoma • Less efficacious than Timolol • Safer in asthmatics and diabetics

NON SELECTIVE BLOCKERS WITH ISA PINDOLOL OXPRENOLOL ADVANTAGES: Lesser bradycardia and myocardial depression

SELECTIVE BLOCKERS WITH ISA • ACEBUTOLOL • CELIPROLOL • Celiprolol: • Partial agonist at beta 2 receptors • Used in hypertensives with asthma

Mixed antagonists • LABETALOL • CARVEDILOL

LABETELOL • Blocks alpha 1 and beta receptors • Fall in BP due to alpha 1 and beta 1 blockade • Uses: • Pheochromocytoma • Rebound hypertension after clonidine withdrawal

Carvedilol • • • Blocks alpha and beta receptors USES: Essential hypertension CHF Reduces mortality in MI

Selective β 2 blockers • BUTOXAMINE • EXPERIMENTAL • NO CLINICAL UTILITY

CLASSIFICATION OF BETA BLOCKERS NON SELECTIVE BLOCKERS MIXED BLOCKERS

PROPRANOLOL TIMOLOL SOTALOL NADOLOL PINDOLOL OXPRENOLOL NON SELECTIVE BETA BLOCKERS

NON SELECTIVE BETA BLOCKERS • • CARDIOVASCULAR USES 2 H 2 A MI Hypertension Heart failure Angina Arrhythmia Myocardial Infarction

NON CARDIOVASCULAR USES MIGRAINE ANXIETY GLAUCOMA HYPERTHYROIDISM PHEOCHROMOCYTOMA ALCOHOL WITHDRAWAL MAGH PAW

ADVERSE EFFECTS AND CI • • BRONCHOCONSTRICTION BRADYCARDIA COLD EXTREMITIES CNS SIDE EFFECTS HEART FAILURE HYPOGLYCEMIA REBOUND HYPERTENSION ADVERSE LIPID PROFILE • 2(BCH) RHAL

CARDIOSELECTIVE BETA BLOCKERS NEW BETA BLOCKERS ACTING EXCLUSIVELY AT MYO CARDIUM • • NEBIVOLOL BETAXOLOL BISOPROLOL ACEBUTOLOL ESMOLOL ATENOLOL METOPROLOL CELIPROLOL

BETA BLOCKERS WITH ISA • CELIPROLOL, OXPRENOLOL CONTAIN • PINDOLOL, PENBUTOLOL PARTIAL • ACEBUTOLOL AGONISTIC • ALPRENOLOL ACTIVITY

BETA BLOCKERS WITH MSA POSSESSES MEMBRANE STABILISING LOCAL ANAESTHETIC PROPERTY • • • PROPRANOLOL METOPROLOL LABETALOL ACEBUTOLOL PINDOLOL

LIPID INSOLUBLE BETA BLOCKERS • EXCRETED BY KIDNEY • LONG DOA • CI IN RF • • • NADOLOL SOTALOL ATENOLOL, ACEBUTOLOL BETAXOLOL, BISOPROLOL CELIPROLOL • NOT SOLUBLE ABC

• Longest acting beta blocker: NADOLOL • Shortest acting: ESMOLOL • Beta blocker with cardioselectivity, ISA, MSA and lipid solubility: ACEBUTOLOL • Most commonly used beta blocker in chronic CHF: CARVEDILOL

All are non selective beta blockers except: a)Propranolol b)Timolol c)Sotalol d)Carvedilol Ans: d Carvedilol alpha +beta blocker

All are cardioselective beta blockers except: a)Atenolol b)Esmolol c)Bisoprolol d)Labetalol Ans: d NEW BETA BLOCKERS ACTING EXCLUSIVELY AT MYO CARDIUM

Combined alpha and beta blockers are: a)Labetalol b)Prazocin c)Tamsulosin d)Milrinone Ans: a

Contraindication of beta blockers are: a)Asthma b)Angina c)Hypertension d)Arrhythmia Ans: a

Beta blockers with ISA are: a)Propranolol b)Oxprenolol c)Esmolol d)Butoxamine Ans: b

Beta blocker with cardioselectivity, membrane stabilsing property and ISA: a)Carvedilol b)Atenolol c)Acebutolol d)Metoprolol Ans: c

Propranolol can be used in all except: a)Hyperthyroidism b)Prinzmetal angina c)Migraine d)Hypertension Ans: b

Beta blockers are CI in Diabetes as it : a)Causes hyperglycemia b)Causes seizure c)Masks symptoms of hypoglycemia d)Causes hypotension Ans: c

An ultra short acting beta blocker: a)Esmolol b)Timolol c)Atenolol d)Pindolol Ans: a

Adverse effects of beta blockers include: a)Compensated heart failure b)Masking the features of hypoglycemia c)Bronchial asthma d)All the above Ans: d