Beta blockers were first developed in the 1950s and propranolol was the first clinically useful beta blocker introduced in 1962 for treatment of angina. Beta blockers are classified based on selectivity for beta1/beta2 receptors and other properties. They are used clinically for cardiovascular conditions like hypertension, angina, arrhythmias, and heart failure as well as non-cardiac uses for conditions like migraine, anxiety, and glaucoma. Common side effects include fatigue, bronchospasm, hypoglycemia, and depression. Newer generations of beta blockers have additional properties like alpha-1 receptor blockade.

1. ΒETA ADRENERGIC RECEPTOR BLOCKER
ADRENO
RECEPTORS
ANTAGONISTS

2. HISTORY
 Dichloroisoprenaline was first β #  1958
(partial agonistic action)
 Pronethalol  J.W.Black
 Black & Stephenson (1962) – Propranolol for
Angina
 First clinically useful β #
ADRENO
RECEPTORS
ANTAGONISTS
SIR JAMES WHYTE BLACK (1924-2010)
NOBEL PRIZE FOR MEDICINE - 1988

3. ADRENO
RECEPTORS
ANTAGONISTS

4. ADRENO
RECEPTORS
ANTAGONISTS

5. ADRENO
RECEPTORS
ANTAGONISTS

6. ADRENO
RECEPTORS
ANTAGONISTS
CLASSIFICATION OF β BLOCKERS
 BASED ON :
1. SELECTIVITY FOR β1 & β2 RECEPTORS
2. INTRINSIC SYMPATHETIC ACTIVITY
3. BLOCKADE OF α RECEPTORS
4. DIFFERENCES IN LIPID SOLUBILITY
5. MEMBRANE STABILIZING ACTIVITY
6. CAPACITY TO INDUCE VASODILATION
7. PHARMACOKINETIC PARAMETERS

7. ADRENO
RECEPTORS
ANTAGONISTS
CLASSICAL NON-SELECTIVE β # : FIRST GENERATION
NADOLOL
PENBUTOLOL
PINDOLOL
PROPRANOLOL
TIMOLOL
β1 SELECTIVE # : SECOND GENERATION
ACEBUTOLOL
ATENOLOL
BISOPROLOL
ESMOLOL
METOPROLOL
NON-SELECTIVE β # WITH ADDITIONAL ACTIONS : THIRD GENERATION
LABETOLOL
CARVEDIOLOL ALPHA + BETA
CARTEOLOL
BUCINDOLOL
CELIPROLOL
BETAXOLOL VASODIALATOR
NEBIVOLOL

8. INTRINSIC SYMPATHETIC ACTIVITY
ADRENO
RECEPTORS
ANTAGONISTS
MNEMONIC DRUG
COntain Celiprolol, Oxprenolol
Partial Pindolol, Penbutolol
Agonistic Alprenolol
Activity Acebutolol
- Prevent profound bradycardia
- Preferred in those prone to severe
bradycardia
- Withdrawal less likely to exacerbate HTN
- Lipid profile not worsened
- Not effective for migraine prophylaxis –
dilate cerebral vessels

9. LIPID SOLUBILTY – INSOLUBLE BETA #
ADRENO
RECEPTORS
ANTAGONISTS
MNEMONI
C
DRUG
Not Nadolol ( longest acting)
Soluble Sotalol
A Atenolol
Acebutolol
B Betaxolol
Bisoprolol
C Celiprolol
 LIPID SOLUBLE – readily cross BBB (Propranolol,
Metaprolol, Labetalol)
 ATENOLOL – lowest lipid soluble – fewer S/E
 Forgetfulness, increased dreaming, nightmares &
depression
 Propranolol alters mood – used in anxiety states

10. MEMBRANE STABILIZING ACTIVITY
ADRENO
RECEPTORS
ANTAGONISTS
MNEMONIC DRUG
Possess Propranolol (max)
Membrane
stabilizing or
Metoprolol
Local Labetalol
Anaesthetic Acebutolol
Property Pindolol
Variable direct depressant effect
Local anaesthetic action (Na+ channel #)
Demonstrated experimentally in isolated
neurons, heart, skeletal muscle
membrane
Seen at higher doses

11. CAPACITY TO INDUCE VASODILATION

13. VASODILATORY ACTIVITY
ADRENO
RECEPTORS
ANTAGONISTS

14. ALPHA BLOCKER ACTIVITY
ADRENO
RECEPTORS
ANTAGONISTS

15. PHARMACOLOGICAL ACTIONS DUE TO BETA # - CVS
ADRENO
RECEPTORS
ANTAGONISTS
Blood vessels :
- PVR Increase  PVR decrease
- With continued Rx, TPR adapt to chronically
reduced COTPR decrease
-Beta # with Alpha1 # - Labetalol, carvedilol  CO
maintained with great fall in TPR
Mechanisms for Anti-HTN action:
1. Reduced NA release – Beta2#
2. Decreased renin release from kidney
3. NO production
4. Beta2 activation
5. Alpha1 #
6. Ca++ entry #
7. K+ channel opening
8. Antioxidant property

16. ADRENO
RECEPTORS
ANTAGONISTS
RESPIRATORY TRACT

17. METABOLIC EFFECTS
DYSLIPIDEMIA – BETA2 #
MASK SYMPATHETIC
MANIFESTATIONS OF
HYPOGLYCAEMIA !!
INSULIN SENSITIVITY :
DECREASED – NONSELECTIVE
INCREASED – CELIPROLOL, NIPRADILOL, CARTEOLOL

18. EYE & SKELETAL MUSCLE

19. PHARMACOKINETICS
 PROPRANOLOL – Extensive first pass metabolism – low oral BA
 Chronic – Propranolol – decrease hepatic blood flow – BA increased
 Metabolised by CYP2D6 – metabolite – 4 hydroxypropranolol
 LONGEST ACTING – NADOLOL 14 – 24hrs
 SHORTEST ACTING – ESMOLOL – ultra short acting, rapid onset
- Intravenous emergency
- Class 2 anti arrhythmic agent in SVT

20.  Calcium channel blockers – additive depressive effect
 NSAIDS – attenuate anti-HTN effect of Beta blocker
 Delays recovery from hypoglycaemia due to insulin & oral
antidiabetics
 Lidocaine metabolism retarded by reducing hepatic blood
flow
DRUG INTERACTIONS

21. CLINICAL USES BETA BLOCKERS
ADRENO
RECEPTORS
ANTAGONISTS
CARDIOVASCULAR ( DUE TO BETA1 BLOCKADE )
1. ESSENTIAL HTN
2. ANGINA PECTORIS
3. SUPRAVENTRICULAR ARRHYTHMIAS
4. PREVENTION OF MYOCARDIAL INFARCTION
EARLY ADMINISTRATION
LATE ADMINISTRATION
5. CARDIAC FAILURE
6. PORTAL HTN
7. AORTIC DISSECTION – MARFAN’S SYNDROME
8. SUBARACHNOID HAEMORRAGE
9. TOF, MITRAL VALVE PROLAPSE
10. HOCM

22. CARDIOSELECTIVE BETA BLOCKERS
ADRENO
RECEPTORS
ANTAGONISTS
MNEMONIC DRUG
New Nebivolol (Most cardioselective)
Beta Betaxolol
Blockers Bisoprolol
Acting Acebutolol
Exclusively Esmolol
At Atenolol
Myo Metoprolol
Cardium Celiprolol
WHY ??
SAFER IN ASTHMATIC
SAFER IN DIABETICS
PERIPHERAL VASCULAR DISEASE
LESS DELETERIOUS EFFECT ON LIPID PROFILE
LESS LIABLE TO IMPAIR EXERCISE CAPACITY

23. CARDIOVASCULAR USES( DUE TO BETA1 BLOCKADE )
 ESSENTIAL HTN :
Past recommended – benefits have overshadowed side-effects
(sexual dysfunction, fatigue, depression)
Consider Beta blocker if – ACE inhibitors /angiotensin II receptor
antagonists -intolerance or C/I
- With increased symp.drive – HTN with tachycardia
- Post MI, angina, heartfailure

24. HYPERTENSIVE CRISIS
 Rx :
1. Sodium nitroprusside – DOC
2. Glyceryl trinitrate
3. Esmolol 0.25-0.5mg/kg IV 1min, then 0.05-0.1mg/kg/min for 4min
4. Labetalol 20-80mg IV bolus every 10min to max total dose of
300mg

25. ATENOLOL METOPROLOL
 Most commonly used
 Selective Beta1 blocker
 Low lipid solubility
 HTN Rx – initial dose
50mg/day OD several weeks
 increase upto 100mg
 Excreted primarily in urine
 T1/2 – 8hrs
 Cardioselective Beta1 blocker
 Can be used in diabetics with
HTN, CHF
 HTN Rx – initial dose
100mg/day  increased
weekly until reduction of BP

26. LABETOLOL
 First adrenergic, antagonist – ALPHA & BETA
 Partial agonist Beta2 ( Vasodilation, Bronchodilation)
 USES:
1. Chronic HTN – start with 50mg BD, increase to 100-200mg TDS
2. Hypertensive emergencies (20-4-mg iv every 10min)
3. Pheochromocytoma & Clonidine withdrawal
4. Pregnancy induced hypertension
 S/E : Postural hypotension
Failure of ejaculation

27. CONGESTIVE HEART FAILURE

 Beta blockers arrest or reverse disease
progression and prolong survival rate
 Mild to moderate ( NYHA II, III ) cases of dilated
cardiomyopathy with systolic dysfunction
 No place in decompensated patients
 Stopped during Acute heart failure –
further worsen the situation
 Starting dose –very low –then titrated upward

28. CARVEDILOL
 ALPHA 1 , BETA 1, BETA 2 blocker
 Anti oxidant & anti-inflammatory property
 Inhibits - free radical induced lipid peroxidation
- vascular smooth muscle mitogenesis
- Inhibits ROS mediated stress induced hypertrophy
 USES : cardioprotective in CHF
HTN
LVF following MI

29. ANGINA PECTORIS :
• BETA Blockers - decrease cardiac workload
- decrease myocardial oxygen demand
• BETA Blockers reduce the frequency of angina episodes and improve exercise
tolerance
• ABRUPT WITHDRAWAL – precipitate Angina / MI – up regulation of beta
receptors
• C/I in Prinzmetal angina / vasospastic angina

30. MYOCARDIAL INFARCTION
A)Myocardial salvage during evolution of MI
i) Beta blockers limit infarct size by reducing oxygen consumption, prevents
re-infarction
Prevent arrhythmias including ventricular fibrillation
NOT GIVEN IF HR <60/min
SBP <90mmhg
PR interval >0.24sec
Within 4-6hrs Metoprolol – 5mg IV every 5min – 3doses
Metoprolol 25-50mg orally every 6 hrly

31. MYOCARDIAL INFARCTION
B) Secondary prophylaxis of MI :
Decrease subsequent mortality by 20%
i) By preventing re-infarction
ii) By preventing sudden ventricular fibrillation at the second
attack of MI

32. CARDIAC ARRHYTHMIAS
 Effective in both Supraventricular and Ventricular arrhythmias
 Decrease automaticity in SA node, purkinje fibres
 Increase AV nodal refractory period – Slow ventricular response
rates in atrial flutter & fibrillation
 Reduce ventricular ectopic activity

33. ESMOLOL
 IV
 USED TO TERMINATE : Paroxysmal supraventricular tachycardia
Episodic atrial flutter or fibrillation
Adrenergic mediated arrhythmias in
pheochromocytoma
Intra / post operative HTN
SOTOLOL
 Additional K+ channel blocking
 Class III anti-arrhythmic
 USES : Ventricular tachycardia & Ventricular fibrillations

34. DISSECTING AORTIC ANEURYSM
- By reducing cardiac contractile force and aortic pulsation
HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY
- Subaortic region is hypertrophic
- Forceful contraction (under symp. Stimulation like exercise,
emotion) –increase outflow resistance
- Beta blockers improve cardiac output in these patients
during exercise by reducing left ventricular outflow
obstruction

35. • NON-CARDIAC ( DUE TO BETA2 BLOCKADE)
1. CNS – MIGRAINE
ANXIETY
ESSENTIAL TREMORS
ALCOHOL & OPIOD DEPENDENCE
AKATHISIA
2. ENDOCRINE – PHEOCHROMOCYTOMA
HYPERTHYROIDISM
3. OPHTHALMIC – GLAUCOMA
(TIMOLOL & BETAXOLOL)
CLINICAL USES BETA BLOCKERS

36. HYPERTHYROIDISM
BETA BLOCKERS GIVEN :
1) with carbimazole or radioiodine
2) with iodide pre-operatively
3) Thyroid storm ( Thyrotoxicosis ) – Emergency
PROPRANOLOL 1-2mg slow IV  40-80mg orally

37. GLAUCOMA
 ADVANTAGES OF TOPICAL BETA BLOCKERS OVER MIOTICS :
No
 Change in pupil size
 Myopia
 Headache
 Fluctuations in IOT
 Convenient OD / BD dosing

38. SIDE EFFECTS
ADRENO
RECEPTORS
ANTAGONISTS
1. CVS – HEART BLOCK
COLD EXTREMITIES
HYPOTENSION – AFTER MI
HTN – PHEOCHROMOCYTOMA
METABOLISM REDUCED BY LIVER & KIDNEY
2. BRONCHOCONSTRICTION
3. METABOLIC – HYPOGLYCEMIA
DYSLIPIDEMIA
4. FATIGUE
5. CNS – SEDATION, INSOMNIA, DEPRESSION,
NIGHTMARES / BAD DREAMS
6. OVERDOSE / TOXICITY - ATROPINE (1-2mg IV 1-2 BOLUS)  CARDIAC PACING
GLUCAGON (50-150mcg/kg 5% glucose)
7. ABRUPT WITHDRAWAL

39. NEWER BETA BLOCKERS
 NIPRADILOL – NON SELECTIVE BETA # & SELECTIVE ALPHA 1 #  GLAUCOMA
 DILEVALOL ( stereoisomer of Labetalol )  HTN
TO SUMMARISE :
HEART FAILURE – CARVEDILOL
HYPERTENSION – ATENOLOL, METOPROLOL
EMERGENCY - ESMOLOL
MIGRAINE - PROPRANOLOL
GLAUCOMA - TIMOLOL

40. ADRENO
RECEPTORS
ANTAGONISTS
Thank You..