1. BETABLOCKERS THIRUMURUGAN E MSC CVT

2. SYMPATHETIC NERVOUS SYSTEM  FIGHT  FEAR  FLIGHT

5. Do you stay and fight or you turn and run away?

6.  In these type of situations, your sympathetic nervous system called into actions-it uses energy  Bp increases  Hr increases  Body temperature  Sweating  Pupil dilation

7. Beta 1 Beta 2 BETA RECEPTORS

9. Beta receptor blockers  First generation (non selective): Propranolol Pindolol Sotalol Timolol Second generation (beta 1 selective ): Metoprolol Atenolol esmolol

10. Pharmacological actions Heart sympathetic stimulation beta-1 receptors on myocardium BETABLOCKERS Myocardial contractility Heart rate Cardiac output Cardiac work

11. PROPERTIES OF BETABLOCKERS Depress all cardiac properties 1-negative chronotropic effect 2-negative inotropic effect 3-decrease cardiac output 4-depress SA node and AV nodal activity 5-Increased refractory period of AV node 6-Decrease co

12. Non selective beta adrenergic blockers(1 st generation )  Propranolol  Non selective beta blocker  Highly lipid soluble  Bioavailability of drug is low because of extensive first pass metabolism  Crosses bbb  Short duration of action  Large dose-local anaesthetic property.  Dose- 20-400 mg  Route-iv/oral.  Excreated in urine

13. Beta-1 selective adrenergic blockers Esmolol  Ultra short acting blocker (t1/2=mins)  Route-iv, used in emergency  Dose-0.5mg/kg  Rapid onset of action  Useful for control of ventricular rate in svt  Also used in hypertensive emergencies  Lipid solubility-low

14. Beta-1 selective adrenergic blockers Atenolol:  Route-oral  Dose-25-200mg  Longer duration of action-given once daily  Side effects are rare  Lipid solubility-low  Metoprolol  Used in diabetics with HTN AND CHF

15. Indications for use of beta blockers Strongly indicated  Systolic heart failure  Post MI (ventricular arrhythmias) Other indications  STEMI / NSTEMI /HTN / HCM  MS / MVP  MARFAN SYNDROME (AORTIC ROOT INVOLVEMENT )  AORTIC ANEURYSM / TOF  Inherited arrhythmogenic disorders.

16. CLINICAL USES

17. ANGINA PROPHYLAXIS AND MI BETA BLOCKERS Decrease HR, Myocardial contractility Reduce myocardial oxygen demand Reduce the frequency of anginal episodes

18. ANGINA PROPHYLAXIS AND MI  Combined with nitrates for chronic prophylaxis  Use of beta blockers early in acute phase of MI may limit infarct size.  Long term use may reduce reinfarction.

19. Hypertension  Past-recommended as initial therapy.  Present: 1- benefits of drug overshadowed by side effects 2- Moderately stopped due to clinical trials Side effects:  Fatigue  Depression  Metabolic abnormalities  Sexual dysfunction

20. Hypertension  Trial suggest that – for same degree of bp control, most antihypertensive drugs provide the same degree of cardiovascular protection.  eg: trials like CAPPP,STOP-HYPERTENSION-2  Found little over all difference in outcomes between the older (beta blocker ) and newer (ACE inhibitors, ARB’S)  Outcome difference were noted, drug providing better outcomes had better blood pressure control.  Eg- amlodipine arm was superior to atenolol, mean bp was significantly lower in patients taking amlodipine.

21. BMJ –LARGEST META ANALYSIS FOR ANTIHYPERTENSIVES (2009)  Effect of bp lowering drugs in reducing the risk of disease is entirely or largely due to bp reduction.  Proportional reduction in coronary heart disease events and stroke for a given reduction in bp- is same in people with and without a history of vascular disease and in people without high bp as well as in those with high bp.

22. Congestive heart failure Heart failure Decreased cardiac output Sympathetic activation Beta-1 receptors Myocardium Myocyte hypertrophy Myocyte apoptosis Detrimental remodelling

23. Congestive heart failure  Betablocker in CHF- proper patient selection  Mild to Moderate (NHYA CLASS-II, III,) Cases of dcm with systolic dysfunction  Stopped during an exposide of acute heart failure  Started dose-very low-then titrated upward.

24. Congestive heart failure

25. Cardiac arrhythmias  Mainly used in  Atrial arrhythmias  Atrial fibrillation  Atrial flutter  Psvt  Rarely for ventricular arrhythmias

26. Hypertrophic obstructive cardiomyopathy  Subaortic region is hypertrophic  Forceful contraction of this region under sympathetic stimulation (exercise, emotion ) - increase outflow resistance  Propranolol decreases outlow resistance.

27. Contra indications  Asthma, copd  Bradycardia  Heart block  Pheripheral vascular disease  Acute heart failure

28. NITROGLYCERIN(NTG)

29. ORGANIC NITRATES  Organic nitrates are prodrugs  They release nitric oxide (NO)  Nitrates are mainly venodilators, also cause arteriolar dilatation and reduce preload and afterload.  Nitrates-nitroglycerin, isosorbide dinitrate

30. Pharmacological actions  Nitroglycerin is prototype drug.  Nitrates has no direct effects on heart  Vascular smooth muscle:  Quickly relieves anginal pain by decreasing the oxygen requirement and increasing oxygen delivery to myocardium.

31. Pharmacokinetics  Readily absorbed from oral mucous membrane, skin and GIT  Extensive first pass metabolism  Oral bioavailability of nitrates is very low  Sublingual route produces rapid onset (2-5 mins )but short duration of action  Transdermal route is used for prolonged effect  Metabolities are excreted in urine.

32. Adverse effects  Adverse effects are due to extensive vasodilatation  Headache,  tachycardia,  Hypotension  Palpitation  Weakness  Flushing  Rarely syncope  Overdosage –methaemoglobinaemia.

33. Therapeutic uses of nitrates  Acute attack of angina:  Nitroglycerin is the drug of choice.  Commonly administered sublingually with initial dose of 0.5mg that relieves pain in 2-3 mins  Patient is advised to spit out the tablet as soon as the pain is relieved,to avoid side effects (hypotension and headache)  If the pain is not relieved,the tablet can be repeated after 5mins but not more than three tablets in 15mins.

34. Nitroglycerin action in patients with chest pain Stable angina Dilation of veins Decreased oxygen consumption

35. Nitroglycerin action in patients with chest pain  Heart failure  Dilation of conduit arteries  dilation of veins (decreased preload )  reduced LVEDP

36. Nitroglycerin action in patients with chest pain ACS Dilation of conduit arteries increased oxygen suppy

37. Indications  Control of HF in setting of acute MI,  angina pectoris- who have not responded to sublingual NTG  Perioperative HTN

38. Contra indications  Allergic patients  Severe anaemia  Hypotension  Iv nitroglycerin contraindicated in patients with these conditions  Pericardial tamponade  RCM  Constrictive pericarditis  Where cardiac output is dependent upon venous return

39. Warnings  Use of PVC (POLYVINYL CHLORIDE) tubing in infusion sets may lead to loss of active ingredient,  Due to absorption of nitroglycerin to pvc tubing,therefore dosage is affected.  Relatively non-adsorptive iv administration sets are avaiable.  If IV NITROGLYCERIN is administered through non adsorptive tubing,doses based upon reports will be generally high.

40. conclusion EffectNitratesBeta blockers Heart rateIncreaseDecreases AfterloadDecrease PreloadDecreaseIncrease ContractilityIncreaseDecrease