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1. D R R I Y A S A
D R S M C S I , K A R A K O N A M
Vasopressors and Inotropic
Agents

2. Objectives
 Understand the vasopressor and inotropic agent
receptor physiology
 Understand appropriate clinical application of
vasopressors and inotropic agents

3. Background
 Vasopressors are class of drugs that elevate Mean
Arterial Pressure (MAP) by inducing vasoconstriction.
 Inotropes increase cardiac contractility.
 Many drugs have both vasopressor and inotropic
effects.
 Vasopressors are indicated for a decrease of >30
mmHg from baseline systolic blood pressure or MAP
<60 mmHg, when either condition results in end-
organ dysfunction secondary to hypoperfusion.

4. Receptor Physiology
 Main categories of adrenergic receptors relevant
to vasopressor activity:
 Alpha-1adrenergic receptor
 Beta-1, Beta-2 adrenergic receptors
 Dopamine receptors

5. Receptor
Physiology
Receptor Location Effect
Alpha-1 Adrenergic
Vascular
wall Vasoconstriction
Heart
Increase duration of
contraction without
increased chronotropy
Beta Adrenergic Beta-1 Heart
↑Inotropy and
chronotropy
Beta-2
Blood
vessels Vasodilation
Dopamine Renal Vasodilation
Splanchnic
(mesenteric
)
Coronary
Cerebral

6. PHARMACOLOGICAL ACTIONS
Cardiac effects
 Positive chronotropic effect
 An action that increases heart rate
 Positive dromotropic effect
 An action that speeds conduction of electrical impulses (↑
conduction velocity through AV node)
 Positive inotropic effect
 An action that increases the force of contraction of cardiac
muscle

7. Cardiac effects of epinephrine
Cardiac output is determined by heart rate and stroke
volume
Epi→ β1receptors at SA node→↑HR
Epi→ β1receptors on ventricular myocytes→
↑ force of contraction
CO = HR x SV

8. vascular smooth muscle
 In blood vessels
supplying skin,
mucous membranes,
viscera and kidneys,
vascular smooth
muscle has almost
exclusively alpha1-
adrenergic receptors
 Also biphasic
response
α1

9. α1+β1 effect
β2 effect (at low
doses) Mainly α -
action
β Blocker
β2 effect
α
Blocker
EE
(A)
(B)
Biphasic
Response

10. vascular smooth muscle
 In blood vessels supplying skeletal muscle,
vascular smooth muscle has both alpha1 and
beta2 adrenergic receptors
α1
β2
α1 stimulation β2 stimulation

11. Effects of epinephrine on blood vessel
caliber
 Blood vessels to
skin, mucous
membranes, viscera
and kidneys
 Stimulation of α1-
adrenergic receptors
causes constriction
of vascular smooth
muscle
α1

12. Effects of epinephrine on blood vessel caliber: skeletal
muscle
 At low plasma concentrations of Epi, β2 effect
predominates→ vasodilation
 At high plasma concentrations of Epi, α1 effect
predominates→ vasoconstriction
α1
β2

13. Effects of Epi on arterial blood pressure
Arterial BP = CO x PVR
Epinephrine:
↑ CO
Low doses ↓ PVR (arteriolar dilation in
skeletal muscle)
High doses ↑PVR

14. Effects of epinephrine on airways
 Epi→β2-adrenergic
receptors on airway
smooth muscle→
rapid, powerful
relaxation→
bronchodilation

15. Effects of epinephrine in the eye
 Epi at α1-
adrenergic
receptors on
radial
smooth
muscle →
contraction→
mydriasis
 Epi at B2-
adrenergic
receptors→
relaxation of
ciliary muscle
α1
β2

16. OTHER SYSTEMS
 GIT: Peristalsis is reduced, sphincters are contracted.
 Bladder : Detrusors relaxed, trigone contracted
 Splenic capsule : Contracts (alpha action), RBCs are poure
 Skeletal muscle : Neuromuscular transmission is facilitated
(Tremors due to beta 2 actions)
 CNS: Restlessness , tremors , fall in BP and bradycardia
 Metabolic : Hyperglycemia, lipolysis

17. Mnemonic for therapeutic uses of adrenaline
ABCDEG
A- Anaphylactic shock
B- Bronchial asthma
C- Cardiac arrest
D- Delay absorption of local anesthetics
E- Epistaxis, Elevate BP
G- Glaucoma
Others : Reduce nasal congestion, Induces mydriasis

18. Epinephrine (contd..)
Adverse effects of epinephrine
Hypertensive crisis
Dysrhythmias
Angina pectoris
Necrosis following extravasation
Hyperglycemia

19. Dose(ng/kg/min Receptor SVR
10-30 Beta May decrease
30-50 Beta,alpha variable
>150 Alpha and beta increased

20. NE
 Primary physiological postganglionicsympathetic
 Actions alpha 1&2 adrenergic action and beta agonist

21. HR Variable
Contractility Increased
CO Increasde or decreased
BP increased
SVR Increased
PVR increased

22. advantage
 Redistibutiob of blood
 Direct adrenergic agonist
 Elicit intense alpha one and two adrenergic agonism

23. disadvantage
 Reduce organ perfusion
 MI
 Pulmonary vasoconstriction
 Arrhythmias
 Skin necrosis

24.  Septic shock
 Vasoplegia after CPB
 Condition in which SVR rise needed with cardiac
stimulation

25.  Use through central line only

26.  Dose 15-30ng/kg/min iv
 30-300ng/kg/min
 Minimize duration of use
 Watch for oliguria and metabolic acidosis
 Can use along with vasodilators to counter act alpha
stimulation
 RVF—FOR stimulatinf Left atriumplus inhaled
nitric oxide

27. Dopamine (DA)
 Dopaminergic neurons in brain, enteric nervous
system and kidney
 Dopaminergic receptors in brain, mesenteric and
renal vascular beds

28. Dopamine
 Moderate doses DA:
Stimulate DA receptors in mesenteric and
renal vascular beds → vasodilation
Stimulate β1 receptors in heart → ↑HR
and ↑force of contraction
 High doses DA:
Stimulate α1 receptors → vasoconstriction

29. Receptor activation
1-3 mcg/kg/min DA Increaesed renal and
mesentric blood flow
3-10mcg/kg/min beta1+beta 2+dopa Increases
HR,CO,contractility
Decreses SVR
>10 alpha Increases SVR,decreases
renal blood flow,increases
HR,

30. advantages
 At low dose renal blood flow increases
 BP response easy to titrate

31. disadvantage
 Indirect action get deminished
 Skin necrosis
 Pulmonary vasoconstriction
 Tachycardia and arrythmia
 MVO2 increases ,MI can occur if coronory flow
doesn’t increase

32. Therapeutic uses
 Shock (moderate doses)
↑ blood flow to kidney and mesentery
↑ cardiac output
 Refractory congestive heart failure
Moderate doses ↑ cardiac output without
↑PVR

33. administration
 Cental line only
 Correct hypovolemia before use
 At 5-10mcg/kg/min the response is not adequate add
epinephrine or milrinone

34. Synthetic Catecholamines: Dobutamine
 It’s a derivative of DA but not a D1 or D2 receptor
agonist
 Stimulates β1- and β2-adrenergic receptors, but at
therapeutic doses, β1-effects predominate
 Increases force of contraction more than increases
heart rate
↑CO = ↑HR x ↑ ↑ SV

35. Heart rate Increased
Contractility Increased
CO Increased
BP Increased
SVR Decresed
LVEDP Decreased
PVR Decreased
LAP Decreased

36. advantages
 After load reduction—improve LV &RV fn
 Renal blood flow may increase

37. disavantages
 Tachycardia and arrhythmias
 Tachyphylaxis more than 72hrs
 Coronary steal
 Nonselective vasodilator
 Mild hypokalemia


38. Dobutamine: Therapeutic uses
 Cardiogenic Shock
 MI
 Cardiac surgery
 Refractory congestive heart failure

39.  Administration…through i/v central line only

40. Clinical uses
 Dose…2-20mcg/kg/min
 Increases CO with lesser increment in MVO2 and
higher coronary blood flow
 Beta blocked patients SVR may incease

41. Major toxic effects of catecholamines
 All are potentially arrhythmogenic
 Epi and isoproterenol more arrhythmogenic than dopamine
and dobutamine
 Some can cause hypertension
 Epinephrine, in particular, can cause CNS effects –
fear, anxiety, restlessness
 Dobutamine can cause vomiting and seizures in
cats – must be used at very low doses

42. Adverse effects
 CNS:
Restlessness
Palpitation
Anxiety, tremors
 CVS:
Increase BP….cerebral haemmorrhage
Ventricular tachycardia, fibrillation
May precipitate angina or AMI

43. Non-catecholamine direct-acting adrenergic
agonists
Ephedrine
Stimulates α1-, β1 and β2-adrenergic receptors and ↑
NE release from noradrenergic fibers
Repeated injections produce tachyphylaxis
It is resistant MAO, orally
Longer acting (4-6), cross BBB

44.  Plant dervived
 Sympathomimetic

45. EFFECTS
Heart rate Increased
Contractility Increased
CO Increased
BP Increased
SVR Slighltly incresed
Pre load increased

46. advantages
 Easily titrated
 Short duration(i/m can prolong )
 Tachyphylaxis
 Safe in pregnancy
 Ideal to correct sympathectomy induced relative
hypovolemia
 After spinal or epidural

47. Dis advantage
 Effect is decreased with NE stores get depleted
 Malignant hypertion with MAO inhibiors

48. routes
 i/v ,,,i/m,,,oral,,,s/c
 Dose5-10mg i/v bolus,25-50mg i/m

49. phenylephrine
 Synthetic
 Acts on pre synaptic alpha 1
 Vasoconstriction…mainly arteriolar
Minimal venous
Mbmainly by MAO

50. effects
Heart rate Decreased
Contractility --
CO Nad or decreased
BP Increased
SVR Incresed
Pre load Minimal change

51. advantages
 Short
 Increses perf press with low SVR
 With hypotension increses CPP
 Useful in fixed out put lesions,CAD,TOF

52. disadvantages
 Inceases PVR
 Decreases SV secon to decrese in after load
 Rarely may induce coronary artery spasm or internal
mammary,radial or gastro epiploiec

53. indication
 Hypotension due to pheripheral vasodilatation
 Temporay therapy
 R-L shunt
 SVT

54. dose
 0.5-10mcg/kg/min
 i/v bolus1-10mcg/kg bolus
 For TOF5-50mcg/kg

55. vasopressin
 Endogenous ADH
 Pheripheral vasoconstriction(v1)
 No action on beta
 More constriction on skin,adipose,intestine etc

56. advantage
 Acts independently of adrenergic
 When phenylephrine or NE ineffetive
 Without producingSE increases coronary perfussion
after arrest

57. disadvantage
 Decreses splanchnic circulation
 Adverse effects of severe constriction
 Decreased platelet roduction
 Lactic acidosis is common

58. uses
 Alternative to epinephrine…>in countershock –
refractory arrhythmias dose(40units i/v)
 Septic shock
 Vasoplegia after bypass
 In drug interaction related hypotension such as ACE
or GA

59. milrinone
 Powerful ionotrope,vasodilatory property
 Increses
cAMPionotrophy,lusitrophy,chronotropy,dromotr
opy,increases automaticity

60. HR No change or slight increase
CO Increased
BP Variable
SVR & PVR Decreased
Preload Decreased
MVO2 Unchnaged or incresed

61. advantage
 Favourable effect on myocardial oxygen supply and
demand balance
 No tachyphylaxis
 No tachycardia or minimal

62. disadvantage
 Arrhythmia

63. use
 25-75 mcg/kg/min over 1-10 min
 Maintanance0.5mcg/kg/min
 Administer before changing the patient from pump

64. use
 Low CO
 Increased LVEDP
 Pulmonary hypotension
 RV failure
 Use as a bridge in cadiac transplatation to
suppliment /potentiate beta receptors

65. Clinical
Application
1st Line Agent
2nd Line
Agent
Septic Shock Norepinephrine (Levophed) Vasopressin
Phenylephrine
(Neosynephrine)
Epinephrine
(Adrenalin)
Heart Failure Dopamine Milrinone
Dobutamine
Cardiogenic
Shock Norepinephrine (Levophed)
Dobutamine
Anaphylactic
Shock Epinephrine (Adrenalin) Vasopressin
Neurogenic
Shock
Phenylephrine
(Neosynephrine)
Hypotension
Anesthesi
a-
induced
Phenylephrine
(Neosynephrine) vasopressin