Cardiovascular Drugs

1. Cardiovascular Drugs Chris G. Wherrett, MD, FRCPC Department of Anesthesiology Ottawa Hospital General Campus October 11, 2012

2. Objectives • To highlight clinically relevant features of basic clinical pharmacology of cardiovascular drugs used in anesthesia and critical care • To highlight clinically irrelevant features of these drugs that find their way into exams • To stimulate some interest in a topic that can be overwhelming

3. References • 1) Stoelting, 4th Edition (2006) • Chapters 12-16 2) TOH Parenteral Drug Manual Infonet > Pharmacy Dept.

4. Q & A Format • Not real exam questions • Anything goes • Previous sessions “format confusing” • I’ve simplified some questions • Please ask for clarification • Intended to challenge in a different way • I’ve addressed all comments in feedback that I could understand • Some of you may not agree with this format

5. 1) Greatest incidence of CNS effects of beta blockers 2) Half life after IV administration 3-4 hr 3) Depression of myocardial contractility and reduction in heart rate occur at similar serum levels 4) Maximum IV dose 0.2 mg/kg 5) Has ISA and MSA 6) Increases SVR Re: Propranolol

6. 1) Greatest incidence of CNS effects of beta blockers 2) Half life after IV administration 3-4 hr 3) Depression of myocardial contractility and reduction in heart rate occur at similar serum levels 4) Maximum IV dose 0.2 mg/kg 5) Has ISA and MSA 6) Increases SVR Re: Propranolol (2)

7. 1) Atropine 2) Dopamine 3) Isoproterenol 4) Dobutamine 5) Glucagon 6) Ca++ Metoprolol overdose should be treated with:

8. 1) Decrease myocardial ischemia through effects on myocardial oxygen consumption, diastolic perfusion period and collateral flow 2) Decrease infarct size in AMI 3) Decrease morbidity and mortality in AMI 4) CXD in hypertrophic cardiomyopathies 5) Improve EF in patients with CHF 6) Reduce mortality in noncardiac surgery Beta blockers, actions:

9. 1) Nonselective Beta antagonist 2) Indicated for supraventricular dysrhythmias and life- threatening ventricular tachydysrhythmias 3) Effect due to blockade of cardiac beta receptors to SNS 4) Safety profile similar to other Beta blockers 5) Less effect on contractility than other Beta blockers Sotalol:

10. 1) Useful to treat glaucoma because it decreases production of aqueous humour 2) Deleted 3) When administered topically, systemic effects are rare 4) Has less Beta-2 effect than Betaxolol Timolol:

11. 1) SNP 2) NTG 3) Hydralazine 4) Enalaprilat 5) Trimethaphan 6) Labetalol, Esmolol 7) Diltiazem, Nifedipine, Nimodipine 8) Phenoxybenzamine Which antihypertensive drugs cause cerebral vasodilation?

12. 1) Nifedipine 2) Propranolol 3) NTG 4) Ephedrine 5) Dobutamine Contra-Indicated in hypertrophic cardiomyopathy:

13. 1) Negative inotropes 2) Negative chronotropes 3) Diltiazem has least negative inotropy 4) Verapamil can significantly decrease myocardial function 5) Diltiazem is the most potent coronary vasodilator CEBs, hemodynamic effects:

14. 1) Negative inotropes (all) 2) Nifedipine increases CO, HR, contractility 3) Diltiazem has least negative inotropy 4) Verapamil can significantly decrease myocardial function 5) Diltiazem is the most potent coronary vasodilator CEBs, hemodynamic effects: (2)

15. 1) Is contraindicated in hypertensive emergencies 2) Is useful for treatment of hypertension in the PACU 3) Indications Nifedipine:

16. 1) Half-life 9 min 2) Prolonged duration with atypical plasma cholinesterase 3) Beta-1 selective 4) Causes more hypotension than propranolol 5) Safe in bronchospastic disease 6) Prolongs duration of succinylcholine 7) Useful to convert acute Atrial Flutter to sinus Esmolol:

17. Labetalol Propranolol Nadolol Metoprolol Atenolol Acebutolol Bisoprolol Which Beta Blocker has longest duration of action?

18. 1) Is a pro-drug of enalapril, given intravenously 2) Is contraindicated in renovascular hypertension 3) IV dose is 0.625 - 1.25 mg q6h 4) Postinduction hypotension is more common if ACEIs taken on the morning of surgery 5) Hypotension can be treated with crystalloid, phenylephrine, and vasopressin Enalaprilat:

19. 1) Act independently of ACE 2) Antagonize Angiotensin I at AT1 receptors 3) Losartan is the prototype 4) Side effects profile is similar to ACEI’s Angiotensin Receptor Blockers:

20. 1) Is a sympathomimetic, a synthetic, and a catecholamine 2) Has both direct and indirect actions at adrenergic nerve endings 3) May produce arrhythmias 4) Hemodynamic profile is the same as Epinephrine 5) Is limited by tachyphylaxis 6) Comes from a Chinese plant "Ma Huang" 7) Can be given IV, IM, PO Ephedrine:

21. 1) Is a sympathomimetic, a synthetic, and a catecholamine 2) Has both direct and indirect actions at adrenergic nerve endings 3) May produce arrhythmias 4) Hemodynamic profile is the same as Epinephrine 5) Is limited by tachyphylaxis 6) Comes from a Chinese plant "Ma Huang" 7) Can be given IV, IM, PO 8) Associated with lower umbilical Artery pH than Phenylephrine Ephedrine: (2)

22. 1) Is a nonselective alpha antagonist 2) Requires up to 2 weeks to control BP in pheochromocytoma 3) Causes orthostatic hypotension, miosis, nasal stuffiness, tachycardia, impotence 4) Uses include: Preop control with pheo Excessive vasoconstriction e.g. Raynaud’s Acute hypertensive emergencies 5) Should be given prior to beta blockade Phenoxybenzamine:

23. 1) What are indications? 2) What is unique about PK 3) What is IV dosing: Amiodarone:

24. 1) Thyroid hyperfunction 2) Thyroid hypofunction 3) Bradycardia 4) Pulmonary fibrosis 5) Facial discolouration Side effects of amiodarone:

25. 1) Indicated with pre-existing metabolic acidosis, hyperkalemia, TCA overdose 2) Prolongs survival in animal models 3) May precipitate with catecholamines 4) Improves ability to defibrillate NaHCO3 in cardiac arrest:

26. 1) Beta blockers 2) Nitroprusside 3) Both of above 4) Hydralazine 5) CEBs Useful drugs in aortic dissection:

27. 1) Theoretical detrimental effects in cardiac arrest 2) Can precipitate dig toxicity 3) Serum ionised Ca++ does not decrease when citrated blood given < 100mL / 70kg / min 4) CaCl2 contains 3x as much Ca++ as gluconate but is irritating to veins 5) List 4 indications Calcium:

28. 1) Diltiazem 2) Beta blockers 3) Clonidine 4) Methyldopa 5) Reserpine 6) ACEIs 7) CEBs Withdrawal syndromes may occur with (1):

29. 1) Diltiazem 2) Beta blockers 3) Clonidine 4) Methyldopa 5) Reserpine 6) ACEIs 7) CEBs Withdrawal syndromes may occur with: (2)

30. 1) More effective than digoxin in controlling HR in AF 2) Ineffective in converting AF to NSR 3) CXD in VT 4) CXD in SVT with Aberrancy due to WPW 5) CXD in narrow complex SVT 6) CXD in AF with WPW Verapamil

31. The patient is on Nifedipine for HTN She is being treated with Vancomycin for CAPD catheter-related peritonitis Why is “40 of Roc” asking for trouble? A 50 kg patient is having a CAPD catheter removed

32. 1) A nonspecific phosphodiesterase inhibitor 2) Increases cAMP which increases intracellular Ca++ 3) Increases HR 4) Increases MVO2 5) Has T/2 3.5 hr 6) Effective in presence of Beta- blockade Amrinone:

33. 1) A second generation PDE-5 inhibitor 2) More potent than Amrinone 3) Side effects include thrombocytopenia 4) Improves diastolic relaxation 5) Decreases pulmonary vascular resistance 6) Causes hypotension 7) Rapid onset inotropic effect Milrinone

34. 1) Has effects similar to Norepinephrine 2) Decreases coronary perfusion 3) Causes miosis 4) Can decrease CO 5) Overdose should be treated with Beta-blockers Phenylephrine:

35. 1) List some drugs causing skin necrosis 2) Tx 3) Other effects of extravasation Extravasation of vasopressors

36. 1) Diminished response in CHF 2) Skin necrosis with extravasation 3) Renal vasoconstriction 4) Increased MVO2 5) Shifts blood flow away from skeletal muscle 6) Causes hypoglycemia 7) May impair functional myocardial recovery following ischemic injury Effects of Dopamine

37. 1) Diminished response in CHF 2) Skin necrosis with extravasation 3) Renal vasoconstriction 4) Increased MVO2 5) Shifts blood flow away from skeletal muscle 6) Causes hypoglycemia 7) May impair functional myocardial recovery following ischemic injury Effects of Dopamine (2)

38. 1) Decreases incidence of ARF in surgical patients at risk 2) Improve creatinine clearance after a renal insult 3) Is antagonized by Droperidol and Metoclopramide 4) Improves Na+ and H2O excretion 5) Can cause intrapulmonary shunting and mesenteric ischemia 6) “bad medicine” Renal Dose Dopamine

39. 1) Is a pure Beta-1 agonist 2) Produces vasoconstrictive effects through stimulation of alpha receptors 3) Produces vasodilatory effects through stimulation of Beta-2 receptors 4) Produces inotropic effects through myocardial alpha-1 receptors 5) May produce vasoconstriction in beta-blocked patients Dobutamine receptor effects:

40. 1) Is a pure Beta-1 agonist 2) Produces vasoconstrictive effects through stimulation of alpha receptors 3) Produces vasodilatory effects through stimulation of Beta-2 receptors 4) Produces inotropic effects through myocardial alpha-1 receptors 5) May produce vasoconstriction in beta-blocked patients Dobutamine receptor effects (2):

41. 1) Increased SV 2) Decreased SVR, PVR 3) No effect on RBF 4) Improves coronary supply:demand ratio 5) BP increases, decreases, or remains same 6) Has minimal effect on HR Dobutamine, hemodynamic effects:

42. 1) 3rd Degree heart block 2) Post cardiac transplant 3) Countereffect profound Beta blockade 4) Post CABG surgery low output syndrome 6) Asthma 7) Torsade de Pointes Isoproterenol, indications:

43. 1) Coronary vasodilation 2) Decreased LVEDP 3) Decreased afterload 4) Redistribution of flow to ischemic areas 5) Vasodilation of pulmonary arteries and veins NTG, most important mechanism in myocardial ischemia

44. 1) Approved 2) Off Label 3) Other NTG, list clinical indications

45. 1) Acts independently of Beta receptors and Phosphodiesterase 2) Increases myocardial contractility and HR 3) Stimulates release of catecholamines 4) Metabolic effects include hypokalemia, hypoglycemia 5) Used to diagnose pheochromocytoma 6) Inhibits gastric motility Glucagon:

46. 1) Prolongation of AV node conduction 2) Enhanced parasympathetic nervous system activity 3) Dose-related increase in myocardial contractility 4) Reduced sympathetic tone What are mechanisms for the decrease in HR with digoxin therapy in CHF?

47. 1) Hypokalemia, hypomagnesemia, hypercalcemia 2) Hypertrophic cardiomyopathies 3) WPW 4) Pt requiring cardioversion 5) Impaired renal function 6) SA node dysfunction Digoxin, List Some Precautions/Contraindications:

48. Answers: Atrial tachycardia with block Commonest Junctional tachycardias, escape rhythms Bigeminy, PVCs, VT VF Commonest cause of death Worsening CHF List common cardiac manifestations of digoxin toxicity

49. 1) Dobutamine 2) Isoproterenol 3) Propranolol Diastolic perfusion time is increased by:

50. 1) Decreases RBF 2) Alpha effect in skeletal muscle 3) Beta effect in skin, mucosa 4) Drug of choice for ____ shock 5) May decrease cardiac output 6) Overdose best treated with Propranolol Epinephrine