Beta blockers

16,345 views

Published on

Published in: Health & Medicine
4 Comments
101 Likes
Statistics
Notes
No Downloads
Views
Total views
16,345
On SlideShare
0
From Embeds
0
Number of Embeds
27
Actions
Shares
0
Downloads
903
Comments
4
Likes
101
Embeds 0
No embeds

No notes for slide

Beta blockers

  1. 1. Beta Receptor Blockers Dr. Ritu Budania MBBS, MD
  2. 2. Overview • Introduction • Classification • Pharmacological actions • Pharmacokinetics • Therapeutic uses • Adverse effects & Contraindications • Recent advances • Summary
  3. 3. Introduction Sympathetic Nervous System- Fight, Fear , Flight
  4. 4. Beta receptors β -1 β -2 β - 3
  5. 5. Beta Receptor Blockers
  6. 6. Classification: First Generation ( non-selective) • Propranolol • Timolol • Sotalol • Pindolol • Nadolol Second generation (Beta 1 selective) • Metoprolol • Atenolol • Acebutolol • Bisoprolol • Esmolol
  7. 7. Third Generation ( additional alpha blocking/ vasodilator property) • Labetalol • Carvedilol • Celiprolol • Nebivolol
  8. 8. Pharmacological Actions: 1. Heart: Sympathetic Stimulation Beta -1 receptors on myocardium Myocardial contractility Heart Rate Cardiac output Cardiac work Oxygen consumption Beta Blockers
  9. 9. • Increase refractory period • A-V conduction is delayed • Decreases automaticity
  10. 10. 2.Blood vessels Vasoconstriction Vasodilatation Alpha -1 receptors Beta -2 receptors
  11. 11. With continued treatment, resistance vessels gradually adapt to chronically reduced cardiac output so that t.p.r. decreases ,BP falls Total peripheral resistance (t.p r.) is increased initially (due to blockade of β mediated vasodilatation) Cardiac output is reduced Little change in BP β blockers
  12. 12. Other mechanisms for Anti- hypertensive action: (i) Reduced NA release from sympathetic terminals due to blockade of pre- synaptic β receptor mediated facilitation of the release process. (ii) Decreased renin release from kidney (iii) Decrease in Central sympathetic outflow
  13. 13. 3.Respiratory tract • Beta -2 receptors bronchi bronchodilation • Beta blockers broncho constriction • Asthmatics - severe attack may be precipitated Contraindicated in Asthma
  14. 14. 4.Metabolic Effects:  Hypoglycemia Adrenaline β- 2 receptors in liver glycogenolysis  Masks sympathetic manifestations of hypoglycemia  Plasma triglyceride levels increase  LDL/HDL ratio is increased Propranolol
  15. 15. 5.Eye  Ciliary epithelium – β -2 receptors -increases aqueous secretion Their blockade reduces Aqueous secretion Reduces Intra- ocular pressure
  16. 16. Pharmacokinetics • Well absorbed after oral administration • Propranolol- extensive first-pass metabolism- low oral bioavailability • Chronic use of propranolol - itself decreases hepatic blood flow- bioavailability of propranolol is increased
  17. 17. • Longest acting- Nadolol- 14-24 hrs • Shortest- Esmolol Ultra short acting blocker  inactivated by esterases in blood  plasma t1/2 < 10 min  Rapid onset, short lasting effect  Intravenous in emergency
  18. 18. Lipid insoluble( Atenolol, Sotalol) • Less CNS side effects • Less first pass metabolism • Long t ½- 6- 20 hrs
  19. 19. Drugs with partial agonistic activity • intrinsic sympathomimetic action • Pindolol, Acebutolol 1. Less Bradycardia preferred in those prone to severe bradycardia 2. Withdrawal is less likely to exacerbate hypertension or angina 3. Plasma lipid profile is not worsened
  20. 20. Advantages of Cardio selective Beta blockers over non -selective blockers: 1. safer in asthmatics 2. safer in diabetics 3 .Peripheral vascular disease 4. less deleterious effect on lipid profile 5. Less liable to impair exercise capacity
  21. 21. Therapeutic uses Cardiovascular uses Non-cardiovascular uses
  22. 22. Cardiovascular Uses
  23. 23. 1.Hypertension: • Past- recommended as first-line therapy • Present status - benefits have been overshadowed by their side-effect profile •sexual dysfunction •fatigue • depression • metabolic abnormalities
  24. 24. Consider Beta blocker if:  intolerance or contraindication to ACE inhibitors/angiotensin II receptor antagonists With increased sympathetic drive- HTN with tachycardia Tense young patient Post MI
  25. 25. • Atenolol 25–100 mg • Metoprolol 25–100 mg • Propranolol 40–160 mg • Labetalol 200–800 mg • Carvedilol 12.5–50 mg • Combined with Calcium channel blockers- check reflex tachycardia
  26. 26.  Atenolol -Most commonly used - Selective β-1 blocker - Low lipid solubility. -Does not cross BBB- CNS ADR are less -Longer duration of action, OD dosing  Metoprolol -Cardioselective Beta 1 blocker -Can be used in Diabetics with HTN, CHF
  27. 27. Hypertensive Emergency: Systolic BP >180 mm of Hg Diastolic BP > 120 mm of Hg Treatment: 1.Sodium nitroprusside- DOC 2.Glyceryl trinitrate 3. Esmolol 0.25-0.5 mg/kg IV over 1 min, then 0.05-0.1 mg/kg/min IV for 4 min 4.Labetalol
  28. 28. Labetolol • 3rd generation • Alpha -1 blocker • β -1 blocker • Partial agonist β -2 (Vasodilation,Bronchodilation) Uses: • Hypertensive emergencies • Pheochromocytoma • Pregnancy induced hypertension
  29. 29. 2.Congestive Heart Failure: Heart Failure Decreased Cardiac output Sympathetic activation Beta-1 receptors Myocardium myocyte hypertrophy, myocyte apoptosis detrimental remodelling JG cells kidney Renin release
  30. 30. β blocker in CHF -proper patient selection :  mild to moderate (NYHA class II, III ) cases of dilated cardiomyopathy with systolic dysfunction No place in decompensated patients.  Stopped during an episode of acute heart failure Starting dose -very low -then titrated upward
  31. 31. Drug Initial dose Maximum dose Carvedilol 3.125 mg BD 25-50 mg BD Bisoprolol 1.25 mg QID 10 mg QID Metoprolol 12.5–25 mg QID 200 mg QID
  32. 32. Carvedilol • Alpha 1, β1, β2 blocker • Anti oxidant property • Inhibits free radical induced lipid peroxidation, vascular smooth muscle mitogenesis • Use: cardioprotective in CHF Hypertension
  33. 33. 3. Angina Pectoris
  34. 34. Beta blockers Decrease cardiac work load Decrease myocardial oxygen demand  Angina of effort (Classical Angina)
  35. 35. Combined with nitrates for chronic prophylaxis Cardioselective- Metoprolol 25- 100 mg Atenolol 25- 100 mg Abrupt withdrawal- precipitate Angina / MI- up regulation of beta receptors Contraindicated in Prinzmetals angina
  36. 36. 4.Myocardial Infarction a. Myocardial salvage during evolution of MI β blockers- (i) limit infarct size by reducing oxygen consumption, prevents re- infarction (ii) prevent arrhythmias including ventricular fibrillation • Not given if- - Heart rate < 60/min - Systolic BP < 90 mm Hg - PR interval > 0.24 sec - LVF • Within 4-6 hrs Metoprolol- 5 mg i.v every 5 mins – 3 doses • Metoprolol 25–50 mg orally every 6 h
  37. 37. 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 • β- 1 selective antagonist –Atenolol , Carvedilol • Atleast for 2 years
  38. 38. 5. Cardiac Arrhythmias SA node - Decrease slope of phase - 4 depolarisation Decrease automacity in SA node, purkinje fibres Prolong ERP of AV node – impedes A-V conduction
  39. 39. Esmolol Intravenous It has been used to terminate:  Paroxysmal supraventricular tachycardia  episodic atrial fibrillation or flutter Adrenergically mediated arrhythmia Pheochromocytoma arrhythmia during anaesthesia intra operative, post operative hypertension  in early treatment of myocardial infarction
  40. 40.  Sotalol • Additional K channel blocking • Class III anti-arrhythmic Acebutolol- 20- 40mg Propranolol - 40 – 80 mg
  41. 41. 6.Dissecting aortic aneurysm • Intravenous Propranolol, Metoprolol- maintain heart rate of approximately 60 beats/min
  42. 42. 7.Hypertrophic obstructive cardiomyopathy  Subaortic region is hypertrophic  Forceful contraction of this region under sympathetic stimulation (exercise, emotion) increases outflow resistance 8. Mitral valve prolapse
  43. 43. Non- cardiovascular uses
  44. 44. 1.Hyperthyroidism • Thyroxine Up regulation of β-1 receptors in myocardium Tachycardia, palpitations • T 4 T 3
  45. 45. β blockers given - (i) with carbimazole or radioiodine (ii) with iodide preoperatively (iii) Thyroid storm (thyrotoxic crisis): emergency Propranolol- 1-2 mg slow i.v. 40-80 mg orally
  46. 46. 2.Glaucoma • Decrease aqueous secretion • chronic simple (wide angle) glaucoma
  47. 47. Advantages of topical β- blockers over Miotics No change in pupil size  myopia  headache fluctuations in i.o.t  convenient OD / BD dosing
  48. 48. Timolol • Non-selective • Action is smooth , well sustained • Effect on i.o.t. persists for 2-3 weeks following discontinuation • Dose – O.25% drops BD Levobunolol- Long duration, OD
  49. 49. Side effects • Redness and dryness of eye • Allergic blepharoconjunctivitis • Corneal hypoesthesia • Systemic side effects- threatening bronchospasm- asthmatics, bradycardia
  50. 50. Betaxolol • β- 1 selective blocker • Systemic side effects less • Protective effect in retinal neurones - reducing Na/Ca influx. • O.5 % 1 drop BD
  51. 51. 3. Pheochromocytoma: • Adrenal gland tumour Excess catecholamines hypertension, tachycardia • First alpha blocker is given then Beta blocker otherwise dangerous rise in BP can occur
  52. 52. 4. Migraine • Prophylaxis • severe migraine • Propranolol - most effective drug - reduces frequency, severity of attacks- in 70% patients - Effect seen in 4 weeks -Dose- 40 mg BD to 160 mg BD • Others- timolol, metoprolol,atenolol
  53. 53. 5.Anxiety - Stage fright, Nervousness, panic - Propranolol- 10- 20 mg BD
  54. 54. 6. Alcohol Withdrawal 7.Oesophageal variceal bleeding and portal hypertension -Nadolol + isosorbide mononitrate
  55. 55. Contraindications 1. Asthma, COPD 2. Prinzmetals angina 3. Bradycardia Heart Block Acute decompensated heart failure 4. Peripheral Vascular disease
  56. 56. Adverse Effects 1 . Adverse Lipid profile- total TG and LDL- cholesterol increase  HDL- cholesterol falls. Cardioselective β blockers - little/no deleterious effect on blood lipids 2.Fatigue and reduced exercise capacity
  57. 57. 3.CNS side effects sleep disturbance, bad dreams, sexual dysfunction 4.Hypoglycemia -Masks sympathetic symptoms of hypoglycemia 5.Rebound Hypertension -Chronic therapy up regulation of Beta receptors -sudden withdrawal rebound hypertension -Gradually tapered and Withdrawn 6. Miscellaneous: Labetalol- postural hypotension, Hepatoxicity
  58. 58. Beta blocker Overdose • Glucagon - specific antidote -positive inotropic action on the heart • Cardiac pacing • If bronchospasm occurs- Ipratopium • Other antidotes –Salbutamol and Isoprenaline
  59. 59. Celiprolol • Selective β1 blocker • Weak β2 agonistic activity • Nitric oxide release ,vasodilatation • No deleterious effects on lipid profile • Safe in asthmatics • Hypertension, Angina • Dose:200mg OD -400mg OD
  60. 60. Nebivolol • highly selective β1 blocker • Nitric oxide release, vasodilatation • Use: Hypertension • Dose - 2.5 mg OD
  61. 61. Newer uses: • Post traumatic stress disorder • Agoraphobia Uses under study: • Propranolol -for orbital , periorbital hemangiomas in infants • Breast cancer • Pindolol- depression
  62. 62. New β blockers: • Nipradilol (nonselective β-receptor and selective α1-receptor blocking properties, glaucoma) • Dilevalol ( stereoisomer of Labetalol)- HTN • Bopindolol
  63. 63. • Butoxamine -Selective β 2 blocker - Experimental drug
  64. 64. Summary • Therapeutically important class of drugs To summarise: • Heart failure- Carvedilol • Hypertension- Atenolol • Emergency - Esmolol • Migraine - Propranolol • Glaucoma - Timolol
  65. 65. References 1.T. Westfall, D. Westfall, Adrenergic agonists & antagonists, Goodman & Gilman’s The Pharmacological basis of Therapeutics, 12 th edition, 2006, Pg 237-296 2.HL, KK Sharma. Principles of Pharmacology. 2nd ed. Pg 185- 190 3.K. D. Tripathi, Adrenergic and Antiadrenergic drugs, Essentials of Medical Pharmacology,6th edition, 2008, Pg 134-148 4.Longo, Fausi, Kasper. Harrisons principles of Internal Medicine, 18TH ed. 5.NICE clinical guideline 127.Developed by the Newcastle Guideline Development and Research Unit and updated by the National Clinical Guideline Centre and the British Hypertension Society. Hypertension Clinical management of primary hypertension in adult
  66. 66. 6.Kenji Inoue,Kei Noguchi, Masato Wakakura,Goji Tomita .Effect of five years of treatment with nipradilol eye drops in patients with normal tension glaucoma 7.Lalonde RL, Tenero DM, Kazierad .Dilevalol: an overview of its clinical pharmacology and therapeutic use in hypertension

×