Inotropes & Vasopressors

1. Applied Sciences Lecture Course Inotropes & Vasopressors Dr Cathy Armstrong SpR In Anaesthesia & Clinical Fellow in Undergraduate Medical Education Manchester Royal Infirmary March 2011

2. Objectives • Define the terms Inotrope & vasopressor • Discuss basic physiological principles • Discuss drug classification • Sympathomimetics • Other • Describe some clinical uses

3. Inotropes Vs. Vasopressors V

4. Inotropes • Drugs that affect the force of contraction of myocardial muscle • Positive or negative • Term “inotrope” generally used to describe positive effect

5. Vasopressor • Drugs that stimulates smooth muscle contraction of the capillaries & arteries • Cause vasoconstriction & a consequent rise in blood pressure

6. Which of these drugs does NOT cause a positive inotropic effect? • Adrenaline • Calcium • Digoxin • Enoximone • Nifedipine • Glucagon

7. Main Goal Tissue perfusion & oxygenation

8. ~ 1 r4 Physiological Principles MAP = CO x SVR CO = HR x SV Preload Contractility Afterload

9. Basic principles - Vasopressors MAP = CO x SVR CO = HR x SV Preload Contractility Afterload ~ 1 r4

10. Basic principles - Inotropes MAP = CO x SVR CO = HR x SV Preload Contractility Afterload

11. Mixed action drugs

12. Use of inotropes & vasopressors

13. Drug Classification • Sympathomimetics • Naturally occurring • Synthetic • Other inotropes • cAMP dependent • cAMP independent • Other vasopressors

14. Sympathomimetics • Sympathetic nervous system

15. Activation of intermediate messenger G - Protein Sympathomimetics • Drugs that stimulate adrenergic receptors • G-protein coupled receptors

16. Which adrenoceptor mediates cardiac muscle contraction? • 1 • 2 • 1 • 2

17. Which adrenoceptor mediates vascular smooth muscle contraction? • 1 • 2 • 1 • 2

18. Main classes of Adrenoceptor •  receptors • 1 • Located in vascular smooth muscle • Mediate vasoconstriction • 2 • Located throughout the CNS, platelets • Mediate sedation, analgesia & platelet aggregation

19. Main classes of Adrenoceptor •  receptors • 1 • Located in vascular smooth muscle • Mediate vasoconstriction • 2 • Located throughout the CNS, platelets • Mediate sedation, analgesia & platelet aggregation

20. Main classes of Adrenoceptor •  receptors • 1 • Located in the heart • Mediate increased contractility & HR • 2 • Located mainly in the smooth muscle of bronchi • Mediate bronchodilatation

21. Main classes of Adrenoceptor •  receptors • 1 • Located in the heart • Mediate increased contractility & HR • 2 • Located mainly in the smooth muscle of bronchi • Mediate bronchodilatation • Located in blood vessels • Dilatation of coronary vessels • Dilatation of arteries supplying skeletal muscle

22. β1 Adrenoceptor Adrenaline Adenyl cyclase G - Protein Increased heart muscle contractility cAMP ATP

23. Naturally occuring Epinephrine Norepinephrine Dopamine Synthetic Dobutamine Dopexamine Phenylephrine Metaraminol Ephedrine Sympathomimetics

24. Naturally occuring Epinephrine Norepinephrine Dopamine Synthetic Dobutamine Dopexamine Phenylephrine Metaraminol Ephedrine Sympathomimetics

25. Epinephrine • Stimulates  &  receptors • Predominantly  effects at low doses and  effects at high doses • Clinical uses • Cardiac arrest • Anaphylaxis • Low cardiac output states • Upper airway obstruction • Combination with local anaesthetics

26. Epinephrine • Side effects • Dysrhythmias • Increase in myocardial oxygen consumption

27. Cardiac arrest

28. What is the dose of epinephrine administered during cardiac arrest? • 100mcg • 1mg • 10mg • 100mg • 1g

29. Anaphylaxis

30. What is the IM dose of epinephrine in anaphylaxis • 100mcg • 1mg • 10mg • 100mg • 1g

31. 1mg of epinephrine • 1ml of 1:1000 • 10ml of 1:10,000

32. Norepinephrine • Predominantly stimulates 1 receptors • Most commonly used vasopressor in critical care • Very potent • Administered by infusion into a central vein • Uses • Hypotension due to vasodilatation • Septic shock

33. Dopamine • Effect dose dependent • Direct • Low dose - 1 • High dose - 1 • Indirect • Stimulates norepinephrine release • D1 receptors • Vasodilatation of mesenteric & renal circulation

34. Dobutamine • Synthetic • Predominantly 1 • Small effect at 2 • Uses • Low cardiac output states • Cardiogenic shock

35. Naturally occuring Epinephrine Norepinephrine Dopamine Synthetic Dobutamine Dopexamine Phenylephrine Metaraminol Ephedrine Sympathomimetics

36. Adrenoceptor dynamics • Desensitisation / down-regulation • Chronic heart failure • Prolonged use of inotrope / vasopressor • Sespis / acidosis

37. Other inotropes • cAMP dependent • Phosphodiesterase inhibitors • Glucagon • cAMP independent • Digoxin • Calcium • levosimendan

38. Phosphodiesterase inhibitors • Non-selective • Aminophylline • Selective • Phosphodiesterase 3 • Enoximone • milrinone

39. Phosphodiesterase inhibitors Adrenaline Adenyl cyclase G - Protein Increased heart muscle contractility cAMP ATP X PDE 3 AMP

40. Digoxin Inhibits (slows) NA/K ATPase K K Na NaK ATPase Na Na Reduced Na gradient slows Ca removal Na/Ca X-ch Ca

41. Other vasopressors • Vasopressin • Exogenous form of ADH • Acts on kidney to retain water & on peripheral blood vessels to cause intense vasoconstriction • V1 receptors • Used in severe shock • Used in cardiac arrest in USA

43. Summary Concept of inotropes & vasopressors Physiological principles Categories Sympathomimetics cAMP dependent / independent inotropes Vasopressin Discussed clinical uses All Figures were produced using Servier Medical Art - www.servier.com