Unit-IV; Professional Sales Representative (PSR).pptx
Ionotropes and vasopressors
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
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
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
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 atriumplus 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
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
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
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
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
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
63. use
25-75 mcg/kg/min over 1-10 min
Maintanance0.5mcg/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