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
Objectives
 Understand the vasopressor and inotropic agent
receptor physiology
 Understand appropriate clinical applicat...
Background
 Vasopressors are class of drugs that elevate Mean
Arterial Pressure (MAP) by inducing vasoconstriction.
 Ino...
Receptor Physiology
 Main categories of adrenergic receptors relevant
to vasopressor activity:
 Alpha-1adrenergic recept...
Receptor
Physiology
Receptor Location Effect
Alpha-1 Adrenergic
Vascular
wall Vasoconstriction
Heart
Increase duration of
...
PHARMACOLOGICAL ACTIONS
Cardiac effects
 Positive chronotropic effect
 An action that increases heart rate
 Positive dr...
Cardiac effects of epinephrine
Cardiac output is determined by heart rate and stroke
volume
Epi→ β1receptors at SA node→↑H...
vascular smooth muscle
 In blood vessels
supplying skin,
mucous membranes,
viscera and kidneys,
vascular smooth
muscle ha...
α1+β1 effect
β2 effect (at low
doses) Mainly α -
action
β Blocker
β2 effect
α
Blocker
EE
(A)
(B)
Biphasic
Response
vascular smooth muscle
 In blood vessels supplying skeletal muscle,
vascular smooth muscle has both alpha1 and
beta2 adre...
Effects of epinephrine on blood vessel
caliber
 Blood vessels to
skin, mucous
membranes, viscera
and kidneys
 Stimulatio...
Effects of epinephrine on blood vessel caliber: skeletal
muscle
 At low plasma concentrations of Epi, β2 effect
predomina...
Effects of Epi on arterial blood pressure
Arterial BP = CO x PVR
Epinephrine:
↑ CO
Low doses ↓ PVR (arteriolar dilation ...
Effects of epinephrine on airways
 Epi→β2-adrenergic
receptors on airway
smooth muscle→
rapid, powerful
relaxation→
bronc...
Effects of epinephrine in the eye
 Epi at α1-
adrenergic
receptors on
radial
smooth
muscle →
contraction→
mydriasis
 Epi...
OTHER SYSTEMS
 GIT: Peristalsis is reduced, sphincters are contracted.
 Bladder : Detrusors relaxed, trigone contracted
...
Mnemonic for therapeutic uses of adrenaline
ABCDEG
A- Anaphylactic shock
B- Bronchial asthma
C- Cardiac arrest
D- Delay ab...
Epinephrine (contd..)
Adverse effects of epinephrine
Hypertensive crisis
Dysrhythmias
Angina pectoris
Necrosis follow...
Dose(ng/kg/min Receptor SVR
10-30 Beta May decrease
30-50 Beta,alpha variable
>150 Alpha and beta increased
NE
 Primary physiological postganglionicsympathetic
 Actions alpha 1&2 adrenergic action and beta agonist
HR Variable
Contractility Increased
CO Increasde or decreased
BP increased
SVR Increased
PVR increased
advantage
 Redistibutiob of blood
 Direct adrenergic agonist
 Elicit intense alpha one and two adrenergic agonism
disadvantage
 Reduce organ perfusion
 MI
 Pulmonary vasoconstriction
 Arrhythmias
 Skin necrosis
 Septic shock
 Vasoplegia after CPB
 Condition in which SVR rise needed with cardiac
stimulation
 Use through central line only
 Dose 15-30ng/kg/min iv
 30-300ng/kg/min
 Minimize duration of use
 Watch for oliguria and metabolic acidosis
 Can u...
Dopamine (DA)
 Dopaminergic neurons in brain, enteric nervous
system and kidney
 Dopaminergic receptors in brain, mesent...
Dopamine
 Moderate doses DA:
Stimulate DA receptors in mesenteric and
renal vascular beds → vasodilation
Stimulate β1 r...
Receptor activation
1-3 mcg/kg/min DA Increaesed renal and
mesentric blood flow
3-10mcg/kg/min beta1+beta 2+dopa Increases...
advantages
 At low dose renal blood flow increases
 BP response easy to titrate
disadvantage
 Indirect action get deminished
 Skin necrosis
 Pulmonary vasoconstriction
 Tachycardia and arrythmia
 M...
Therapeutic uses
 Shock (moderate doses)
↑ blood flow to kidney and mesentery
↑ cardiac output
 Refractory congestive ...
administration
 Cental line only
 Correct hypovolemia before use
 At 5-10mcg/kg/min the response is not adequate add
ep...
Synthetic Catecholamines: Dobutamine
 It’s a derivative of DA but not a D1 or D2 receptor
agonist
 Stimulates β1- and β2...
Heart rate Increased
Contractility Increased
CO Increased
BP Increased
SVR Decresed
LVEDP Decreased
PVR Decreased
LAP Decr...
advantages
 After load reduction—improve LV &RV fn
 Renal blood flow may increase
disavantages
 Tachycardia and arrhythmias
 Tachyphylaxis more than 72hrs
 Coronary steal
 Nonselective vasodilator
 ...
Dobutamine: Therapeutic uses
 Cardiogenic Shock
 MI
 Cardiac surgery
 Refractory congestive heart failure
 Administration…through i/v central line only
Clinical uses
 Dose…2-20mcg/kg/min
 Increases CO with lesser increment in MVO2 and
higher coronary blood flow
 Beta blo...
Major toxic effects of catecholamines
 All are potentially arrhythmogenic
 Epi and isoproterenol more arrhythmogenic tha...
Adverse effects
 CNS:
Restlessness
Palpitation
Anxiety, tremors
 CVS:
Increase BP….cerebral haemmorrhage
Ventricula...
Non-catecholamine direct-acting adrenergic
agonists
Ephedrine
Stimulates α1-, β1 and β2-adrenergic receptors and ↑
NE rel...
 Plant dervived
 Sympathomimetic
EFFECTS
Heart rate Increased
Contractility Increased
CO Increased
BP Increased
SVR Slighltly incresed
Pre load increased
advantages
 Easily titrated
 Short duration(i/m can prolong )
 Tachyphylaxis
 Safe in pregnancy
 Ideal to correct sym...
Dis advantage
 Effect is decreased with NE stores get depleted
 Malignant hypertion with MAO inhibiors
routes
 i/v ,,,i/m,,,oral,,,s/c
 Dose5-10mg i/v bolus,25-50mg i/m
phenylephrine
 Synthetic
 Acts on pre synaptic alpha 1
 Vasoconstriction…mainly arteriolar
Minimal venous
Mbmainly by ...
effects
Heart rate Decreased
Contractility --
CO Nad or decreased
BP Increased
SVR Incresed
Pre load Minimal change
advantages
 Short
 Increses perf press with low SVR
 With hypotension increses CPP
 Useful in fixed out put lesions,CA...
disadvantages
 Inceases PVR
 Decreases SV secon to decrese in after load
 Rarely may induce coronary artery spasm or in...
indication
 Hypotension due to pheripheral vasodilatation
 Temporay therapy
 R-L shunt
 SVT
dose
 0.5-10mcg/kg/min
 i/v bolus1-10mcg/kg bolus
 For TOF5-50mcg/kg
vasopressin
 Endogenous ADH
 Pheripheral vasoconstriction(v1)
 No action on beta
 More constriction on skin,adipose,in...
advantage
 Acts independently of adrenergic
 When phenylephrine or NE ineffetive
 Without producingSE increases coronar...
disadvantage
 Decreses splanchnic circulation
 Adverse effects of severe constriction
 Decreased platelet roduction
 L...
uses
 Alternative to epinephrine…>in countershock –
refractory arrhythmias dose(40units i/v)
 Septic shock
 Vasoplegia ...
milrinone
 Powerful ionotrope,vasodilatory property
 Increses
cAMPionotrophy,lusitrophy,chronotropy,dromotr
opy,increas...
HR No change or slight increase
CO Increased
BP Variable
SVR & PVR Decreased
Preload Decreased
MVO2 Unchnaged or incresed
advantage
 Favourable effect on myocardial oxygen supply and
demand balance
 No tachyphylaxis
 No tachycardia or minimal
disadvantage
 Arrhythmia
use
 25-75 mcg/kg/min over 1-10 min
 Maintanance0.5mcg/kg/min
 Administer before changing the patient from pump
use
 Low CO
 Increased LVEDP
 Pulmonary hypotension
 RV failure
 Use as a bridge in cadiac transplatation to
supplime...
Clinical
Application
1st Line Agent
2nd Line
Agent
Septic Shock Norepinephrine (Levophed) Vasopressin
Phenylephrine
(Neosy...
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Ionotropes and vasopressors

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Ionotropes and vasopressors

  1. 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. 2. Objectives  Understand the vasopressor and inotropic agent receptor physiology  Understand appropriate clinical application of vasopressors and inotropic agents
  3. 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. 4. Receptor Physiology  Main categories of adrenergic receptors relevant to vasopressor activity:  Alpha-1adrenergic receptor  Beta-1, Beta-2 adrenergic receptors  Dopamine receptors
  5. 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. 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. 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. 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. 9. α1+β1 effect β2 effect (at low doses) Mainly α - action β Blocker β2 effect α Blocker EE (A) (B) Biphasic Response
  10. 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. 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. 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. 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. 14. Effects of epinephrine on airways  Epi→β2-adrenergic receptors on airway smooth muscle→ rapid, powerful relaxation→ bronchodilation
  15. 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. 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. 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. 18. Epinephrine (contd..) Adverse effects of epinephrine Hypertensive crisis Dysrhythmias Angina pectoris Necrosis following extravasation Hyperglycemia
  19. 19. Dose(ng/kg/min Receptor SVR 10-30 Beta May decrease 30-50 Beta,alpha variable >150 Alpha and beta increased
  20. 20. NE  Primary physiological postganglionicsympathetic  Actions alpha 1&2 adrenergic action and beta agonist
  21. 21. HR Variable Contractility Increased CO Increasde or decreased BP increased SVR Increased PVR increased
  22. 22. advantage  Redistibutiob of blood  Direct adrenergic agonist  Elicit intense alpha one and two adrenergic agonism
  23. 23. disadvantage  Reduce organ perfusion  MI  Pulmonary vasoconstriction  Arrhythmias  Skin necrosis
  24. 24.  Septic shock  Vasoplegia after CPB  Condition in which SVR rise needed with cardiac stimulation
  25. 25.  Use through central line only
  26. 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. 27. Dopamine (DA)  Dopaminergic neurons in brain, enteric nervous system and kidney  Dopaminergic receptors in brain, mesenteric and renal vascular beds
  28. 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. 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. 30. advantages  At low dose renal blood flow increases  BP response easy to titrate
  31. 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. 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. 33. administration  Cental line only  Correct hypovolemia before use  At 5-10mcg/kg/min the response is not adequate add epinephrine or milrinone
  34. 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. 35. Heart rate Increased Contractility Increased CO Increased BP Increased SVR Decresed LVEDP Decreased PVR Decreased LAP Decreased
  36. 36. advantages  After load reduction—improve LV &RV fn  Renal blood flow may increase
  37. 37. disavantages  Tachycardia and arrhythmias  Tachyphylaxis more than 72hrs  Coronary steal  Nonselective vasodilator  Mild hypokalemia 
  38. 38. Dobutamine: Therapeutic uses  Cardiogenic Shock  MI  Cardiac surgery  Refractory congestive heart failure
  39. 39.  Administration…through i/v central line only
  40. 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. 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. 42. Adverse effects  CNS: Restlessness Palpitation Anxiety, tremors  CVS: Increase BP….cerebral haemmorrhage Ventricular tachycardia, fibrillation May precipitate angina or AMI
  43. 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. 44.  Plant dervived  Sympathomimetic
  45. 45. EFFECTS Heart rate Increased Contractility Increased CO Increased BP Increased SVR Slighltly incresed Pre load increased
  46. 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. 47. Dis advantage  Effect is decreased with NE stores get depleted  Malignant hypertion with MAO inhibiors
  48. 48. routes  i/v ,,,i/m,,,oral,,,s/c  Dose5-10mg i/v bolus,25-50mg i/m
  49. 49. phenylephrine  Synthetic  Acts on pre synaptic alpha 1  Vasoconstriction…mainly arteriolar Minimal venous Mbmainly by MAO
  50. 50. effects Heart rate Decreased Contractility -- CO Nad or decreased BP Increased SVR Incresed Pre load Minimal change
  51. 51. advantages  Short  Increses perf press with low SVR  With hypotension increses CPP  Useful in fixed out put lesions,CAD,TOF
  52. 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. 53. indication  Hypotension due to pheripheral vasodilatation  Temporay therapy  R-L shunt  SVT
  54. 54. dose  0.5-10mcg/kg/min  i/v bolus1-10mcg/kg bolus  For TOF5-50mcg/kg
  55. 55. vasopressin  Endogenous ADH  Pheripheral vasoconstriction(v1)  No action on beta  More constriction on skin,adipose,intestine etc
  56. 56. advantage  Acts independently of adrenergic  When phenylephrine or NE ineffetive  Without producingSE increases coronary perfussion after arrest
  57. 57. disadvantage  Decreses splanchnic circulation  Adverse effects of severe constriction  Decreased platelet roduction  Lactic acidosis is common
  58. 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. 59. milrinone  Powerful ionotrope,vasodilatory property  Increses cAMPionotrophy,lusitrophy,chronotropy,dromotr opy,increases automaticity
  60. 60. HR No change or slight increase CO Increased BP Variable SVR & PVR Decreased Preload Decreased MVO2 Unchnaged or incresed
  61. 61. advantage  Favourable effect on myocardial oxygen supply and demand balance  No tachyphylaxis  No tachycardia or minimal
  62. 62. disadvantage  Arrhythmia
  63. 63. use  25-75 mcg/kg/min over 1-10 min  Maintanance0.5mcg/kg/min  Administer before changing the patient from pump
  64. 64. use  Low CO  Increased LVEDP  Pulmonary hypotension  RV failure  Use as a bridge in cadiac transplatation to suppliment /potentiate beta receptors
  65. 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
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