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
Phenylephrine Epinephrine Norepinephrine Isoproterenol Dobutamine Dopamine Digoxin Atropine Calcium Calcium Channel Blockers Amiodarone
Beta Blockers Nitroglycerin Ketamine Fentanyl Morphine Propofol Midazolam Morphine Nitroglycerin Norepinephrine Phenyleprhine Propofol Midazolam

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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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 minutes.

30. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Dihydropyridone-
Nifedipine Arterial V/D
Non-Dihydropyridone
(Benzothiazepine)
Diltiazem Arterial V/D
No venous V/D
(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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Dihydropyridone-
Nifedipine Arterial V/D
Non-Dihydropyridone
(Benzothiazepine)
Diltiazem Arterial V/D
No venous V/D
(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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Beta Blockers _
_ _
-SA/AV -

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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Nitroglycerine
Low dose ven V/D
High dose art 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 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
ACE Inhibitors - +

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

45. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Mg Sulfate +

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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Phentolamine

48. Phentolamine Use in extravasation injuries from vasopressors
(ie norepi, 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. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Ketamine _ +
  +

51. Ketamine Interacts with at least 10 different receptors.
One of these are the opioid receptors
Negative inotrope but due to secondary CNS simulation causes increase in pulmonary BP, heart rate, cardiac output and myocardial O2 demand.
Usually there will be no change in systemic vascular resistance.
Possesses bronchodilator activity (used in asthma intubations)
Does not increase ICP. (NeuroCritCare Aug 2014)

52. Ketamine Dosing Analgesic dosing (sub dissociative) – 0.1 - 0.2 mg/kg
Procedural sedation (sub dissociative) – 0.25 – 0.5 mg/kg. Can be associated with ‘nightmare’ like haze.
Dissociative dose (intubation) 1 – 2 mg/kg
Withdrawal agitation associated more with younger age, co-morbidity and dose. (~ %)

53. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Ketamine _ +
  +
Fentanyl

54. Fentanyl
Usually has minimal or no effect on BP, LV Pressure and cardiac output. Initial large boluses can decrease MAP. May have some negative Chronotropy (decrease HR) that can be treated with atropine. Addition of benzodiazepines can cause CV depression

55. Alfentanil
Opioid analgesic 1/4 - 1/10 as potent as Fentanyl. Can be used in sublingual form for pain control Single injection can last up to 30 minutes, S.L minutes. Usual dose is mcg/kg IV, 0.56 mg SL Onset of action IV is 4 times faster than Fentanyl Very few CV effects other than bradycardia Side effects can be respiratory depression, muscle rigidity

56. Remifentanil
Opioid analgesic Approximately twice as potent as Fentanyl. Usually used as an infusion. Very short half life ~ 4 minutes (1 – 11 minutes) Causes decrease HR, BP, RR, tidal volume. Side effects can be muscle rigidity (dose and speed related), pruritus

57. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Ketamine _ +
  +
Fentanyl
Morphine ++

58. Morphine
Lowers BP via decreasing alpha adrenergic tone mediated through the CNS.

59. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Ketamine _ +
  +
Fentanyl
Morphine ++
Propofol

60. Propofol
Can cause large reduction in MAP via venous and arterial vasodilation. It also blocks normal baroreceptor mediated tachycardia which would normally counteract these changes.

61. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Ketamine _ +
  +
Fentanyl
Morphine ++
Propofol
Midazolam

62. Midazolam
Has minimal CV effects. ie ‘a clean drug’. Since Fentanyl also has minimal CV effects, these two drugs have been used a lot together over the years.

63. b1 b1 b1 Drug a1 Inotr Chron Dromo b2 V/C V/D
Ketamine _ +
  +
Fentanyl
Morphine ++
Propofol
Midazolam
Etomidate _ _ _ _ _

64. Etomidate
Ultra short acting non nonbarbiturate general anesthetic Onset of action – 30 – 60 seconds. Duration 2 – 3 minutes. Has minimal CV effects. Dosage: RSI 0.3 mg/kg IV push over seconds Procedural sedation: Initial: 0.1 to 0.2 mg/kg IV, followed by 0.05 mg/kg every 3 to 5 minutes prn.

65. Questions ?

66. Mixing Phenylephrine and Epinephrine
Phenylephrine: With a 5 ml syringe, draw 1 ml of 50mg/ml (1 vial) Phenylephrine. Mix it in 100 cc minibag of normal saline Draw out 3 – 5 cc of solution. This is now Phenylephrine 100 mcg/ml Put labels on both the minibag and the syringe Dose is 50 – 100 mcg/min ie give 0.5 – 1 ml q2-5 minutes. Action is within 1 minutes and lasts for min.

67. Mixing Phenylephrine and Epinephrine
Epinephrine: Take a 10 cc N/S syringe. Discard 1 cc. Take a preloaded syringe of Epi 1:10,000 from the cardiac drawer. Take the bottom stopper off the syringe. With the 9 cc Saline syringe, draw out 1 cc Epi (1:10,000) You now have 10 mls of Epinephrine 10 mcg/ml Dose is 0.5 – 2 ml (5-20 mcg) q 2-5 min Onset 1 minute, duration 2-5 minutes.