Angina for medical bds students class ppt

Angina for medical bds students class ppt

1. Angina Pectoris Dr. Ramnarayanreddy

2. Chest pain due to transient myocardial ischemia. Cardiac ischemia is due to imbalance between: Angina Pectoris Definition Coronary flow = O2 supply Cardiac work = O2 needs

3. Angina Pectoris Types of Angina Pectoris Coronary V.D. 1- Angina of Effort ( Exertional , Stable, Classic): - Most common type. Occurs on exertion and relieved by rest. - Due to coronary atherosclerosis Coronary lumen is narrowed & fixed. - Treatment by  Cardiac work .

4. Angina Pectoris 2- Variant ( Prinzmetal , Vaso -spastic) Angina: a- Occurs at rest, usually accompanied by arrhythmia. b- Due to reversible coronary V.C. = Supersensitive coronary. c- Treatment by Coronary V.D.

5. Angina Pectoris 3- Unstable Angina (Pre-infarction, Crescendo): - Emergency case  a- Progressive worsening  Occurs on mild exertion then on rest. b- Progressive occlusion of coronary artery on top of atherosclerosis. c- Treatment : Hospitalization + Coronary V.D. +  Cardiac work + Anti- thrombotics

6. Management Of Angina Pectoris 1- Change life style : Stop smoking Gradual exercise Weight reduction I- General Measures

7. 2- Avoid : Exertion Emotions Eating heavy fatty meals Exposure to cold.

8. 3-Treat

9. II-Drug Treatment of Angina

10. Treatment of angina Organic nitrates 1- Nitrates a- Glyceryl Trinitrate (GTN, Nitroglycerin ). C- Isosorbid Mononitrate . b- Isosorbid Dinitrate . Organic nitrite: Inorganic nitrite: Sodium nitrite Amyl nitrite

11. Treatment of angina Pharmacokinetics: 1- Absorbed from Buccal & Intestinal mucosa, and skin.

12. Treatment of angina 2- Extensive hepatic first pass metabolism (90 %)  10 % Oral bioavailability. 3- Excreted as Glucuronide conjugates  Isosorbide dinitrate is converted into isosobide 5-mononitrate (active metabolite)

13. Drug Treatment of angina Pharmacodynamics Nitrates cGMP Nitric Oxide (NO) Endothelial cells Guanylate Cyclase Soluble Guanylate Cyclase cGTP Myosin-LC b-  Platelet aggregation a-Myosin-LC-PO 4 Relaxation Contraction S-H

14. Treatment of angina Pharmacological Actions of Nitrates :

15. 1- Blood Vessels V.D. of Veins more than arterioles - Powerful Veno -V.D.   V.R.   E.D.V.    Pre-Load.   Pulmonary vascular pressure and heart size  C.O.P. Systolic B.P.

16. 1- Blood Vessels b- Some Arterio -V.D.   T.P.R.    After-load.  Diastolic B.P. c- V.D. of big epicardial normal coronaries  Redistribution to ischemic area .

17. 2- Heart a - Decrease Cardiac work (  Preload >  Afterload) &  Oxygen consumption . b - Powerful Veno-Dilator   V.R.   E.D.V.  -  Pre-load -  Contractility   Pressure on Sub-endocardial coronaries. c - Some Arterio-V.D.   T.P.R.   Afterload.

18. - Hypotension  Reflex  Sympathetic   Contractility &Tachycardia  Shorten Diastolic Coronary Perfusion Time 3-Blood pressure  S.Bl.p. > D.Bl.p. Hypotension:

19. So the beneficial effects of nitrate are: - Decreased O 2 requirement due to decreased B.P., deceased ventricular volume and ejection time. - Increased O 2 supply by dilating epicardial coronary vessels and increased collateral flow and decreased left ventricular diastolic pressure. O2 supply O2 needs O2 supply O2 needs

20. 4-Smooth muscle Spasmolytic on smooth muscles of Bronchial, biliary , GIT , Urinary bladder & Uterus.

21. 1- All Types of Angina Pectoris :  Acute attacks : nitroglycerin or isosorbide dinitrate sublingual or oral spray.  Repeat the drug every 5 min. till disappearance of pain or maximum 3 doses, otherwise  Acute M I. In Immediate Prophylaxis  Drugs are taken 5 minutes before exertion. Th. Uses of Nitrates

22.  In Long Term Prophylaxis  Long Acting Nitrates: Oral S.R. (Large dose to overcome Hepatic First Pass Effect) , Trans-dermal patch or Ointment  Slow release Oral preparations Therapeutic Uses of Nitrates 2- Acute myocardial infarction (A.M.I.), Acute Pulmonary Edema (Acute Left Ventricular Failure) & Refractory H.F.  I.V.nitroglycerin  coronary resistance,  oxygen consumption,  Pulmonary congestion& may  the size of infracted area .

23. 3- Congestive heart failure with high preload to  pulmonary congestion. 4- Cyanide poisoning : Use Na nitrites I.V. or amyl- nitrite inhalation to produce meth- Hb and so compete with cyanide. Therapeutic Uses of Nitrates

24. Precautions :  - 8-10 Hours nitrate-free period or alternate every 2 weeks to avoid tolerance with long acting nitrate.  - Never Stop nitrate therapy Suddenly  Rebound ischemia & infarction.  - Do NOT take double dose. If a dose is missed  wait for the next dose.  Do Not use after expiry date  No effect.  - Not combined with Sildenafil  Severe Hypotension  May be Fatal

25. - Postural hypotension & tachycardia  - Tolerance & cross-tolerance between nitrites & nitrates: Adverse Effects of Nitrates : b- Avoid by daily 8-10 hours nitrate free or alternate with other Anti-anginals every 2 weeks a- Due to depletion of group required for denitration S-H & activation .

26. Adverse Effects of Nitrates : - Headache, Flush, dizziness & weakness . - Met- Hb and cyanosis especially by Nitrites > Nitrates. - Dangerous interaction with sildenafil severe hypotension. - Hypersensitivity reaction as skin rash .

27.  - Oral V.D.   Preload & Afterload : a- Nitrate-like  Release NO = Arterio-venodilator . b- Opens ATP-dependent K+-Channel .  - V.D. of Normal Large Epicardial coronaries.  - Useful in Angina & Heart failure.  - No tolerance.  - Headache. Other Anti- Anginal Drugs Nicorandil

28.  -Blockers 3- Desirable Effects  - Long use  Anti-hypertensive   After-load.  -  Contractility -  Cardiac work &  O2-Consumption: -  H.R.  Resting HR 50-60 b/min or Max HR 100-120 b/min.

29. 4- Undesirable effects: Bradycardia  a- Long diastole   E.D.V.   Preload. -  O2-needs  Partially offset the beneficial effects of B-Blockers. This can be balanced by concomitant use of nitrates.  -Blockers

30. Calcium Channel Blockers C.C.B Classification:

31. L- type voltage sensitive Ca²+ channel Ca²+ Na + Na + Ca²+ K + Na +- K + ATPase exchange Na +- Ca²+ exchange Mechanism of Action: Pharmacodynamics CCB Types of calcium channels are L, N, T & P.

32. Pharmacodynamics I- Mechanism of Action: 1- They block Voltage-dependent L-type calcium channels present in Heart, Blood vessels and Smooth muscles . 2- They  Ca2+ influx into: Cardiac muscle  Cardiac inhibition Blood vessels  Arteriolar VD a- b-

33. Pharmacological Action: I-C.V.S action II-Other actions I-C.V.S action: 1- Verapamil ( Effect on Heart ˃ V.D.) Pharmacokinetics Absorbed orally, extensively metabolized in liver with 20-35% oral bioavailability & excreted in urine.

34. Pharmacological Action: Pharmacodynamics It affects cardiac tissue more than vascular smooth muscle, so it decreases B.P., H.R., C.O. Uses :  - Antiarrhythmic in supraventricular arrhythmia (class IV )  -Prophylactic treatment of all types of angina. - Hypertension. - Hypertrophic cardiomyopathy, cerebrovascular accidents and premature labour.

35. Pharmacological Action: Adverse Effects Headache, dizziness, flushing Bradycardia Heart block Heart failure Hypotension Constipation Diltiazem : is similar to verapamil but less potent less effect on contraction .

36. Pharmacological Action: 2-Nifedipine Pharmacokinetics Absorbed orally, and has about 45-70% oral bioavailability Pharmacodynamics It affects smooth muscles of arterioles  V.D. and has less effect on heart It decreases TPR. And B.P. It reflexly  H.R., and myocardial contractility due to reflex increase in sympathetic stimulation

37. Pharmacological Action: Uses :  Hypertension.  Migraine headache  Hypertrophic cardiomyopathy  Raynaud’s disease Adverse Effects Hypotension, headache, flushing, nausea, vomiting, Steal phenomenon may occure . ankle edema

38. Other Calcium Channel Blockers  - Nitrendipine : it is similar to nifedipin but more potent and has longer duration.  - Nimodipine : is used to reduce morbidity following subarachnoid haemorrage probably by preventing vasospasm.  - Bepridil : affects heart more than B.V., used in angina.  Amiodarone : ClassIII antiarrhythmic C.C.B

39. II- Other Actions of CCB : a-  Platelet aggregation. b- Smooth muscle relaxation e.g. Bronchial, Biliary , GIT, Urinary & Uterine. c- Skeletal muscle: No effect, they depend on intracellular calcium pool. d- Endocrine: Verapamil  insulin release Pharmacological Action:

40. -ve Inotropic  Heart failure. -ve Chronotropic  Bradycardia. -ve Dromotropic  Heart Block. Contraindication of CCB. I - Verapamil & Diltiazem - Angina - Hypotension II- Nifedipine

41. a- Verapamil  Renal excretion of Digoxin. b- Verapamil +  -Blocker  Severe Cardiac depression. c- Nifedipine + Nitrates  Severe Hypotension & Tachycardia Drug interactions of CCB.

42. 1- Dipyridamol :  Phosphodiesterase enzyme   cAMP   Platelet aggregation   Heart  + ve Inotropic effect. B.P.   Blood vessels  V.D. 2- Aspirin in SD : (75–150 mg)    Platelet TXA-2. Also treats Nitrate-induced headache 3- ADP-Receptors Blockers : Ticlopidine & Clopidogrel . 4- GP IIb / IIIa -Receptors Blockers : Abciximab & Tirofiban IV- Anti-Platelet Drugs

43. Management Of Angina Pectoris 1- Change life style : Stop smoking Gradual exercise Weight reduction I- General Measures A) Angina of Effort (Classic, Stable) : 2- Avoid : Exertion, emotions, eating heavy meals & exposure to cold. 3- Treat

44. A) Acute Attacks (Present Pain) & Immediate Prophylaxis : Rapidly acting Nitrates: 1. Nitroglycerine: S.L. 0.5 mg / Buccal Spray 0.4 mg 2. Isosorbid Dinitrate : S.L. 5 mg / Buccal Spray 1.25 mg II-Treatment of Angina

45. 1- Long Acting Nitrates : Oral S.R., Trans-dermal patch or Ointment. And / or 2- Calcium Channel Blocker And / or 3-  -Blocker And / or 4- Nicorandil B) Long Term Prophylaxis : II-Treatment of Angina C) Anti-Platelet Drugs: 1- Aspirin : 75 – 150 mg / day orally 2- Dipyridamol : 75 mg tds orally

46. 2- Nitroglycerine S.L., Spray, I.V. then Oral & Transdermal. 3- Nifedipine 4- Cardio-selective  1-Blocker with out I.S.A. e.g. Atenolol. 5- Anti-Thrombotics  Aspirin & Heparin 6- Coronary Artery Reperfusion Surgery . B) Variant Angina  Treatment of Acute tacks & Prophylaxis : 1- Nitrates and / or Calcium Channel Blocker. 2- Avoid Non-selective  -Blockers C) Unstable Angina 1- Hospitalization.

47. B-blockers Propranolol Others Nitrates Glyceryl trinitrate Isosorbide dinitrate Isosorbide mononitrate C.C.B. Nifedipine Diltiazem verapamil

48. Ranolazine: mechanism of action not known, decreases sodium calcium exchanger leads to decrease in intra cellular calcium concentration resulting in reduced cardiac contractility used for symptomatic treatment of stable angina pectoris

49. Trimetazidine: metabolic modulator partially inhibits fatty acid oxidation pathway in cardiac cells, used as a add-on therapy for anginapectoris.

50. Acute myocardial infarction therapy: Antiplatelet drugs Analgesics ACE inhibitors Anticoagulants Beta blockers Nitrates Oxygen therapy Thrombolytic therapy and Others like hypolipidemic agents and correction of acidosis - sodium bicarbonate