ER Drugs and their cardiovascular effects

1. ER Drugs and their cardiovascular effects Prepared by Shane Barclay MD

2. Objectives Review some of the common drugs used in the ER and review their cardiovascular effects.

3. Why these drugs and why the CV effects? Think of these drugs as your ‘menu’ that you are going to be able to ‘offer’ patients for various conditions. Of all their potential side effects it is the cardiovascular ones that are most important for working in the ER. Obviously this is not an exhaustive list of ER drugs, but the ones with CV effects.

4. The List of drugs PhenylephrineEpinephrine NorepinephrineIsoproterenolDobutamine DopamineDigoxinAtropine Calcium Calcium Channel BlockersAmiodarone Beta BlockersNitroglycerinKetamine Fentanyl MorphinePropofol MidazolamMorphineNitroglycerinNorepinephrinePhenyleprhinePropofolMidazolam

5. Remember pharmacology from med school ! • Alpha 1 – Agonists cause peripheral vasoconstriction. Antagonists cause vasodilation. • Alpha 2 – CNS mediated, agonists cause hypotension, sedation… • Beta 1 – Heart effects: agonists positive, antagonists negative – inotropic (strength of contraction), chronotropic (heart rate), dromotropic (‘conduction’) • Beta 2 – Lung effects: Agonists cause bronchodilation. Antagonists cause bronchoconstriction.

6. Remember pharmacology from med school ! ER drug ‘pharmacology’ is mainly about alpha and beta activity. Half lives, volume of distribution etc are also important but will not be covered here.

7. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phenylephrine +++

8. Phenylnephrine • Uses: cardiogenic shock, decompensated atrial fib, diastolic heart failure.. • Can be used as a bolus or infusion, although usually it is used in small boluses.

9. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++

10. Epinephrine Unlike phenylephrine Epi has both alpha and beta activity. Uses: - ACLS – V. Fib/V-Tach, asystole (1:10,000 solution IV) Anaphylaxis – (1:1,000 solution S.C. ) Peri intubation, septic shock while getting norepi, etc As a pressor can be given as an IV bolus or infusion.

11. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++ Norepinephrine +++ ++ ++ ++ +

12. Norepinephrine Has more alpha adrenergic properties than epinephrine, but less positive inotropic effect. Is used in a variety of conditions where you need both ‘pressor’ and ‘inotropic’ support. ie – sepsis, cardiovascular collapse, CHF, etc Can be given through a peripheral line, but better if via a central line.

13. Norepinephrine Dosage “Up to Date” Dosages Hypotension/Shock Start 0.1 mcg/kg/min – (range 0.1-1.5 mcg/kg/min) Sepsis Start 0.01 mcg/kg/min (range 0.01 – 3 mcg/kg/min)

14. Norepinephrine Dosage “One starting dose” 0.1 mcg/kg/min then titrate.

15. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++ Norepinephrine +++ ++ ++ ++ + Isoproterenol ++ ++ ++ +

16. Isoproterenol Non selective beta 1 , beta 2 agonist Structurally related to epinephrine. Uses: Bradycardia Torsades - to shorten the QT interval by increasing rate Dose: 0.4 mg IV then 2 – 20 mcg/min

17. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phenylephrine +++ Epinephrine ++ +++ ++ ++ ++ Norepinephrine +++ ++ ++ ++ + Isoproterenol ++ ++ ++ Dobutamine ++ ++ +

18. Dobutamine The “cardiac squeeze” drug Main use is in Cardiogenic Shock Start 2 mcg/kg/min

19. b1b1b1Drug a1InotrChronDromob2 V/C V/D Dopamine Dopaminergic: 0.5-2 mcg/kg/min Renal V/D Beta 1 effects: 2-10 mcg/kg/min + + Alpha effects: > 10mcg/kg/min +

20. Dopamine Although a very commonly used drug in the past, the issue of ‘dose’ effect has relegated dopamine to a ‘rarely’ used pressor now.

21. b1b1b1Drug a1InotrChronDromob2 V/C V/D Digoxin + -

22. Digoxin Like Dopamine, digoxin has been used less and less in recent years. However given its primarily inotropic effect is can be of benefit for some patients in chronic congestive heart failure.

23. b1b1b1Drug a1InotrChronDromob2 V/C V/D Digoxin + - Atropine + +SA/+AV

24. Atropine Anticholinergic antimuscarinic In addition to increasing heart rate can cause dry mouth, urinary retention, blurred vision, mydriasis, reduce bowel spasm, agitation, confusion, drowsiness and amnesia. Use prior to intubation? Especially if using Ketamine for induction agent to decrease salivation.

25. b1b1b1Drug a1InotrChronDromob2 V/C V/D Digoxin + - Atropine + +SA/+AV Calcium +

26. Calcium - indications • Hypocalcemia • Calcium channel blocker overdose • Shock – positive inotrope • Hyperkalemia • Hypermagnesemia

27. Calcium – 2 Forms Calcium Chloride Quickly cleaved in the plasma to free Calcium and Chloride Usual dose is 1-2 gm (but can be as much as 4-5 gm) Is usually recommended to be given via a central line or a very good antecubital vein. Injection into tissue/interstitial can cause necrosis and sloughing.

28. Calcium – 2 Forms Calcium Gluconate Metabolized in the liver to free calcium Usual dose is 3 times that of CaCl (ie 3 -6 gm) Can be given through a peripheral IV line.

29. Calcium – Administration Calcium Chrolide Comes in 1 gm/10 ml vial Give maximum 1 ml/minute – i.e. 10 minutes Calcium Gluconate Give 3 gm over 15-20 minutes.

30. b1b1b1Drug a1InotrChronDromob2 V/C V/D Dihydropyridone- Nifedipine - - - Arterial V/D Non-Dihydropyridone (Benzothiazepine) Diltiazem - - - Arterial V/D No venous V/D Non-Dihydropyridone (Phenylakytlamine) Verapamil - - - - Min. Art V/D

31. Calcium Channel Blockers Nifedipine and Diltiazem have negative inotropic and chronotropic effects, and block the AV node to treat arrhythmias. Both cause arterial vasodilation. Verapamil has weak arterial vasodilation properties compared to other CCB, but is a potent AV node blocking agent.

32. b1b1b1Drug a1InotrChronDromob2 V/C V/D Dihydropyridone- Nifedipine - - - Arterial V/D Non-Dihydropyridone (Benzothiazepine) Diltiazem - - - Arterial V/D No venous V/D Non-Dihydropyridone (Phenylakytlamine) Verapamil - - - - Min. Art V/D Amiodarone + -

33. Amiodarone Nifedipine and Diltiazem have negative inotropic and chronotropic effects, and block the AV node to treat arrhythmias. Both cause arterial vasodilation. Verapamil has weak arterial vasodilation properties compared to other CCB, but is a potent AV node blocking agent. Amiodarone has positive inotropic effects along with negative dromotropic effects on both the SA and AV node.

34. Amiodarone The drug that “never met an arrhythmia it didn’t like” can be used for VT, VF, Wide Comples Tachy, A Fib, SVT Amiodarone has positive inotropic effects along with negative dromotropic effects on both the SA and AV node, which is its main mechanism of action. (it prolongs the action potential, thus refractory period, of all cardiac fibers)

35. b1b1b1Drug a1InotrChronDromob2 V/C V/D

36. Beta Blockers As the name suggests, beta blockers block all Beta adrenergic receptors – beta 1 and beta 2 ‘Selective’ beta blockers don’t block Beta 2 receptors. All Beta blockers affect heart rate (Chromotropic) as well as block the SA and AV node.

37. b1b1b1Drug a1InotrChronDromob2 V/C V/D Beta Blocker - - - - -SA/AV - Epinephrine ++ +++ ++ +SA/AV ++

38. Beta Blockers and Epinephrine As the previous slide shows, beta blockers and epinephrine have virtually opposite effects. Clinically this is why patients on beta blockers who are having an anaphylactic reaction can be very difficult to treat with epinephrine.

39. Glucagon Promotes gluconeogenesis Promotes production of cAMP (including in the myocardium) Therefore can ‘get around’ beta blockade. Used for impacted food bolus in the esophagus, hypoglycemia, blocker overdose or in patients on beta blockers having anaphylactic reactions Dose: 1 – 2 mg Glucagon IV

40. b1b1b1Drug a1InotrChronDromob2 V/C V/D

41. Nitroglycerin • Predominately a venodilator, but at high doses is also an arteriodilator. • Reduces preload and afterload. • Preload reduction (venous V/D) decreases myocardial O2 demand. • Afterload reduction increases stroke volume and ejection fraction • Active metabolite is Nitric Oxide (not nitrous oxide!)

42. Nitroglycerin – bioavailability • Oral table Nitro - < 1% bioavailable due to liver metabolism. • SL nitro – onset 1-2 minutes and ~ 30-40% bioavailable. • So a 400 mcg spray dose has about 100 + mcg plasma level for 4-5 minutes • Nitro patch – takes 15 minutes before any plasma level is detectable and peaks by 3-4 hours. Is about 60-70% bioavailable. • So a 400 mcg patch will have about 250 mcg plasma level but will take up to 2 hours to attain that level.

43. b1b1b1Drug a1InotrChronDromob2 V/C V/D

44. ACE Inhibitors Reduce afterload and preload via vasodilation (inhibiting angiotension II) which in turn improve oxygen to tissue.

45. b1b1b1Drug a1InotrChronDromob2 V/C V/D

46. Magnesium Sulfate Has Beta 2 agonist properties which is why it can be used in asthmatics. It also lowers systolic blood pressure without affecting diastolic blood pressure, thus its use in eclampsia. Slows SA /AV node recovery time and slows antegrade and retrograde conduction over accessory pathways. Thus its use in WPW, AVNRT, MAT, polymorphic VT, VF

47. b1b1b1Drug a1InotrChronDromob2 V/C V/D Phentolamine ++

48. Phentolamine Use in extravasation injuries from vasopressors (ienorepi, vasopressin, epinephrine..) Prevention of extravasation injuries: • Avoid hand and wrist IVs for pressors • Avoid lousy IV’s generally for pressors • Can add 10 mg Phentolamine to each liter of IV solution containing norepinephrine. • Did I mention avoiding crappy peripheral IVs?

49. Phentolamine Treatment Steps: • Stop the IV but don’t remove it. • Start the vasopressor in another line. • Suck out as much as you can from the blown IV. • Comes in 5 mg per 1 ml vial. Place in 9 ml of N/S • Administer up to 0.2 mg/kg into the catheter and S.C. around the site • Watch for systemic hypotension (should be on a pressor) • Call plastics.

50. b1b1b1Drug a1InotrChronDromob2 V/C V/D