Adrenergic blocking drugs [Beta blockers]

Dr.Rathnakar U.P.
16
MD.DIH.PGDHM

 Receptors - distribution
1 -Heart, JG cells in kidney 2 -Blood vessels, sk.muscles, eye.Bronchi
[Uterus, liver, GIT, GUT]

Blockade- beneficial effects and adverse effects

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Beta blockers-classification

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Nonselective (1 and 2) a. Without intrinsic sympathomimetic activity PROPRANOLOL, Sotalol, Timolol. b. With intrinsic sympathomimetic activity Pindolol c. With blocking property Labetalol, Carvedilol Cardioselective (1) METOPROLOL, Atenolol, Acebutolol, Bisoprolol, Esmolol, Betaxolol, Celiprolol, Nebivolol

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Beta blockers
Beneficial effects Antihypertensive In myocardial ischemia Antiarrhythmic In CHF Anxiety Migraine Glaucoma ADEs Bronchospasm Blunts symptoms of hypoglycemia and delays recovery Muscle fatigue

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Beta blockers [Prototype-propranolol]

Antihypertensive
1. 2. 3. Only in hypertensive C.O. [1] renin release from JGA[1] Initially-TPR [2, unopposed 1 in BV] 4. Long term- TPR???] 5. Reduced NA release [Presynaptic 2 blockade] 6. Central sympathetic outflow Vasodilation [some blockers]
production of nitric oxide blockade of 1 blockade of Ca2+ entry antioxidant activity opening of K+ channels

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Beta blockers [Prototype-propranolol]

Antiangina [prophylaxis] Not in vasospastic angina. O2 consumption [HR] Sudden withdrawal ppt angina Decrease cardiac work [upregulation of rec.] related to ex. 2 blockade reduce subepicardial coronary flow! Only subepicardial Subendocardial [site of ischemia] not affected Subendocardial [Redistribution-improved flow!] Redistribution

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Beta blockers [Prototype-propranolol]

MI
Acute-Limits infarct size [Pt should not have HB, HR should be more than 50] Long term-Protects heart from arrhythmias [VF and sudden death] Antiarrhythmic Decrease ERP Decreases automaticity Decreases AV conduction Membrane stabilizing[LA] K channel block [Sotalol]
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CHF [carvedilol, metoprolol, bisoprolol]

Symp.overactivity Acute- blockers worsen Stable CHF- long term benefits by reducing 1activity Reverse remodeling, improve patient symptoms, prevent hospitalization, and prolong life

Beta blockers [Prototype-propranolol]

Glaucoma Reduces intraocular tension by reducing aqueous humor formation Timolol[non-selective], beaxolol [1 selective] Pheochromacytoma [after blockade] Anxiety & tremors
Hyperthyroidism & thyrotoxic crisis

Reduce symptoms Inhibit peripheral conversion of T4 [propranolol]

Beta blockers [Prototype-propranolol]

Bronchospasm Airway resistance least Metabolic Blunt recognition of hypoglycemia & delay recovery from insulin-induced hypoglycemia Adverse serum lipid profile

affected in normal subjects

In asthmatics & COPD severe bronchospasm

Beta blockers [Prototype-propranolol]

PK Well absorbed Drug interactions Additive with digoxin & verapamil-CI Decongestants- BP With antidiabetics NSAIDs antihypertensive effect Lignocaine metabolism BA of Chlorpromazine

High First pass[Hepatic

blood flow dependent] Long term-reduces hepatic

blood flow
BA more with food

Beta blockers [Prototype-propranolol]

ADEs
Worsen CHF in uncompensated heart Bradycardia Worsens COPD Delay recognition & recovery of

ADEs
Sudden withdrawalexacerbation of angina Reduced ex.capacity Worsening of PVD Not related to beta blockadeG.I.T, nightmares, insomnia, loss of memory, sexual distress in males Practolol bannedocculomucocutaneous syndrome

hypoglycemia
Exacerbates variant angina Adverse lipid profile [cardio selective & Pindolol safe]
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Beta blockers [With special features]

Cardioselective [Metoprolol. Atenolol]
Intrinsic sympathomimetic activity [Pindolol]

1 selective Safe in COPD Safe in diabetics Less peripheral action on BV[safe in pts with PVD] Lipid profile not affected Cannot suppress tremors Less effect on ex.capacity

Less bradycardia at rest Less withdrawal effect [ continued agonistic action] Not effective in migraine[dilate cerebral vessels] Not in MI

Beta blockers [With special features]

Lipid insoluble [bisoprolol. Atenolol] Less absorbed from GIT Undergo slower metabolism-long duration Do not cross BBB-insomnia and nightmares less With K channel blockade Sotalol
3

Membrane stabilizing

[Propranolol]
Better arrhythmic activity???????

With blockade
Labetolol & Carvedilol [also antioxidant]

Ultra short acting

Esmolol [10 mts]

Clinical applications of blockers

Hypertension
Angina pectoris MI SVT CHF HCM Migraine prophylaxis

Muscle tremors
Thyrotoxic crisis

Glaucoma