O slideshow foi denunciado.
Utilizamos seu perfil e dados de atividades no LinkedIn para personalizar e exibir anúncios mais relevantes. Altere suas preferências de anúncios quando desejar.
Beta Receptor Blockers
Dr. Ritu Budania
MBBS, MD
Overview
• Introduction
• Classification
• Pharmacological actions
• Pharmacokinetics
• Therapeutic uses
• Adverse effects...
Introduction
Sympathetic Nervous System- Fight, Fear , Flight
Beta receptors
β -1 β -2 β - 3
Beta Receptor
Blockers
Classification:
First Generation ( non-selective)
• Propranolol
• Timolol
• Sotalol
• Pindolol
• Nadolol
Second generation...
Third Generation ( additional alpha blocking/
vasodilator property)
• Labetalol
• Carvedilol
• Celiprolol
• Nebivolol
Pharmacological Actions:
1. Heart:
Sympathetic Stimulation
Beta -1 receptors on myocardium
Myocardial contractility
Heart ...
• Increase refractory period
• A-V conduction is delayed
• Decreases automaticity
2.Blood vessels
Vasoconstriction Vasodilatation
Alpha -1 receptors Beta -2 receptors
With continued treatment, resistance vessels
gradually adapt to chronically reduced cardiac
output so that t.p.r. decreas...
Other mechanisms for Anti- hypertensive action:
(i) Reduced NA release from sympathetic terminals
due to blockade of pre- ...
3.Respiratory tract
• Beta -2 receptors bronchi bronchodilation
• Beta blockers broncho constriction
• Asthmatics - severe...
4.Metabolic Effects:
 Hypoglycemia
Adrenaline
β- 2 receptors in liver
glycogenolysis
 Masks sympathetic manifestations o...
5.Eye
 Ciliary epithelium – β -2 receptors
-increases aqueous secretion
Their blockade reduces Aqueous
secretion
Reduce...
Pharmacokinetics
• Well absorbed after oral administration
• Propranolol- extensive first-pass metabolism-
low oral bioava...
• Longest acting- Nadolol- 14-24 hrs
• Shortest- Esmolol
Ultra short acting blocker
 inactivated by esterases in
blood
...
Lipid insoluble( Atenolol, Sotalol)
• Less CNS side effects
• Less first pass metabolism
• Long t ½- 6- 20 hrs
Drugs with partial agonistic activity
• intrinsic sympathomimetic action
• Pindolol, Acebutolol
1. Less Bradycardia
prefer...
Advantages of Cardio selective Beta
blockers over non -selective blockers:
1. safer in asthmatics
2. safer in diabetics
3 ...
Therapeutic uses
Cardiovascular uses Non-cardiovascular uses
Cardiovascular
Uses
1.Hypertension:
• Past- recommended as first-line therapy
• Present status - benefits have been
overshadowed by their side...
Consider Beta blocker if:
 intolerance or contraindication to ACE
inhibitors/angiotensin II receptor antagonists
With in...
• Atenolol 25–100 mg
• Metoprolol 25–100 mg
• Propranolol 40–160 mg
• Labetalol 200–800 mg
• Carvedilol 12.5–50 mg
• Combi...
 Atenolol
-Most commonly used
- Selective β-1 blocker
- Low lipid solubility.
-Does not cross BBB- CNS ADR are less
-Long...
Hypertensive Emergency:
Systolic BP >180 mm of Hg
Diastolic BP > 120 mm of Hg
Treatment:
1.Sodium nitroprusside- DOC
2.Gly...
Labetolol
• 3rd generation
• Alpha -1 blocker
• β -1 blocker
• Partial agonist β -2
(Vasodilation,Bronchodilation)
Uses:
•...
2.Congestive Heart Failure:
Heart Failure
Decreased Cardiac output
Sympathetic activation
Beta-1 receptors
Myocardium
myoc...
β blocker in CHF -proper patient selection :
 mild to moderate (NYHA class II, III ) cases of
dilated cardiomyopathy with...
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 Q...
Carvedilol
• Alpha 1, β1, β2 blocker
• Anti oxidant property
• Inhibits free radical induced lipid
peroxidation, vascular ...
3. Angina Pectoris
Beta blockers Decrease cardiac work load
Decrease myocardial oxygen demand
 Angina of effort (Classical Angina)
Combined with nitrates for chronic prophylaxis
Cardioselective-
Metoprolol 25- 100 mg
Atenolol 25- 100 mg
Abrupt withdr...
4.Myocardial Infarction
a. Myocardial salvage during evolution of MI
β blockers-
(i) limit infarct size by reducing oxygen...
b. Secondary prophylaxis of MI :
Decrease subsequent mortality by 20%.
(i) By preventing re-infarction
(ii) By preventing ...
5. Cardiac Arrhythmias
SA node - Decrease slope of phase - 4
depolarisation
Decrease automacity in SA node, purkinje
fib...
Esmolol
Intravenous
It has been used to terminate:
 Paroxysmal supraventricular tachycardia
 episodic atrial fibrillat...
 Sotalol
• Additional K channel blocking
• Class III anti-arrhythmic
Acebutolol- 20- 40mg
Propranolol - 40 – 80 mg
6.Dissecting aortic aneurysm
• Intravenous Propranolol, Metoprolol-
maintain heart rate of approximately 60
beats/min
7.Hypertrophic obstructive cardiomyopathy
 Subaortic region is hypertrophic
 Forceful contraction of this region under
s...
Non- cardiovascular
uses
1.Hyperthyroidism
• Thyroxine
Up regulation of β-1 receptors in myocardium
Tachycardia, palpitations
• T 4 T 3
β blockers given -
(i) with carbimazole or radioiodine
(ii) with iodide preoperatively
(iii) Thyroid storm (thyrotoxic cri...
2.Glaucoma
• Decrease aqueous secretion
• chronic simple (wide angle) glaucoma
Advantages of topical β- blockers over
Miotics
No
change in pupil size
 myopia
 headache
fluctuations in i.o.t
 conve...
Timolol
• Non-selective
• Action is smooth , well sustained
• Effect on i.o.t. persists for 2-3 weeks following
discontin...
Side effects
• Redness and dryness of eye
• Allergic blepharoconjunctivitis
• Corneal hypoesthesia
• Systemic side effects...
Betaxolol
• β- 1 selective blocker
• Systemic side effects less
• Protective effect in retinal neurones -
reducing Na/Ca i...
3. Pheochromocytoma:
• Adrenal gland tumour
Excess catecholamines
hypertension, tachycardia
• First alpha blocker is given...
4. Migraine
• Prophylaxis
• severe migraine
• Propranolol
- most effective drug
- reduces frequency, severity of attacks- ...
5.Anxiety
- Stage fright, Nervousness, panic
- Propranolol- 10- 20 mg BD
6. Alcohol Withdrawal
7.Oesophageal variceal bleeding and
portal hypertension
-Nadolol + isosorbide mononitrate
Contraindications
1. Asthma, COPD
2. Prinzmetals angina
3. Bradycardia
Heart Block
Acute decompensated heart failure
4. Pe...
Adverse Effects
1 . Adverse Lipid profile-
total TG and LDL- cholesterol increase
 HDL- cholesterol falls.
Cardioselect...
3.CNS side effects
sleep disturbance, bad dreams, sexual dysfunction
4.Hypoglycemia
-Masks sympathetic symptoms of hypogly...
Beta blocker Overdose
• Glucagon
- specific antidote
-positive inotropic action on the heart
• Cardiac pacing
• If broncho...
Celiprolol
• Selective β1 blocker
• Weak β2 agonistic activity
• Nitric oxide release ,vasodilatation
• No deleterious eff...
Nebivolol
• highly selective β1 blocker
• Nitric oxide release, vasodilatation
• Use: Hypertension
• Dose - 2.5 mg OD
Newer uses:
• Post traumatic stress disorder
• Agoraphobia
Uses under study:
• Propranolol -for orbital , periorbital hema...
New β blockers:
• Nipradilol (nonselective β-receptor and
selective α1-receptor blocking properties,
glaucoma)
• Dilevalol...
• Butoxamine
-Selective β 2 blocker
- Experimental drug
Summary
• Therapeutically important class of drugs
To summarise:
• Heart failure- Carvedilol
• Hypertension- Atenolol
• Em...
References
1.T. Westfall, D. Westfall, Adrenergic agonists & antagonists, Goodman &
Gilman’s The Pharmacological basis of ...
6.Kenji Inoue,Kei Noguchi, Masato Wakakura,Goji Tomita .Effect of five years of
treatment with nipradilol eye drops in pat...
Beta blockers
Beta blockers
Beta blockers
Próximos SlideShares
Carregando em…5
×

Beta blockers

53.718 visualizações

Publicada em

Publicada em: Saúde e medicina
  • If you’re struggling with your assignments like me, check out ⇒ www.HelpWriting.net ⇐.
       Responder 
    Tem certeza que deseja  Sim  Não
    Insira sua mensagem aqui
  • Hello! I have searched hard to find a reliable and best research paper writing service and finally i got a good option for my needs as ⇒ www.WritePaper.info ⇐
       Responder 
    Tem certeza que deseja  Sim  Não
    Insira sua mensagem aqui
  • Why men leave "perfect" women: what EVERY woman needs to know ➽➽ https://dwz1.cc/LOSfnztD
       Responder 
    Tem certeza que deseja  Sim  Não
    Insira sua mensagem aqui
  • Boyfriend More Responsive. I don't know how to say this, but ever since I've been using your program, I've seen my breasts grow by 1 cup size and my boyfriend seems to be a lot more affectionate towards me now! He cuddles me longer every night and buys me flowers every week. It's as if he's just been turned into a super-lover by my breast growing. I love it. ☺☺☺ https://dwz1.cc/aRWJhQS6
       Responder 
    Tem certeza que deseja  Sim  Não
    Insira sua mensagem aqui
  • Hi there! I just wanted to share a list of sites that helped me a lot during my studies: .................................................................................................................................... www.EssayWrite.best - Write an essay .................................................................................................................................... www.LitReview.xyz - Summary of books .................................................................................................................................... www.Coursework.best - Online coursework .................................................................................................................................... www.Dissertations.me - proquest dissertations .................................................................................................................................... www.ReMovie.club - Movies reviews .................................................................................................................................... www.WebSlides.vip - Best powerpoint presentations .................................................................................................................................... www.WritePaper.info - Write a research paper .................................................................................................................................... www.EddyHelp.com - Homework help online .................................................................................................................................... www.MyResumeHelp.net - Professional resume writing service .................................................................................................................................. www.HelpWriting.net - Help with writing any papers ......................................................................................................................................... Save so as not to lose
       Responder 
    Tem certeza que deseja  Sim  Não
    Insira sua mensagem aqui

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

×