Tintinallis review Pharmacology of vasopressors and inotropes - PowerPoint Presentation

Slide1

Tintinallis reviewPharmacology of vasopressors and inotropes

Slide2

IntroductionVasopressor

Increase BP & MAP by vasoconstriction

Reserved for persist hypotension after volume resuscitation

Most have multiple actions on heart and vascular

Some are inotropes > improve cardiac output (LVHF or cardiogenic shock)

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Dopamine

Endogenous catecholamine

Metabolic precursor

of norepinephrine/epinephrine

Dopaminergic, α1, β1, and β2 receptors

Dose dependent

Intermediate (5-15 mcg/kg/min) > increase renal blood flow, heart rate, cardiac contractility and

outpur

High (>15 mcg/kg/min) > α-adrenergic effect > vasoconstriction

Low > no longer recommend

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Dopamine

Pharmacokinetics

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Dopamine

Indications

Hemodynamically hypotension by MI, trauma, heart and renal failure with unsuccessful fluid resuscitation

Unstable bradycardia unresponsive to atropine

Not recommend as first line vasopressor in septic shock

Dosing and

administration

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Dopamine

Adverse

effects

Chest pain, palpitation, ectopic beats and tachycardia

Hypotension (low doses)/Hypertension (higher doses)

Headache, N/V

Gangrene

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Epinephrine

Endogenous catecholamine

Nonselective

α-

and

β-

adrenergic agonist

Increases in SVR, heart rate, cardiac output, and BP

Bronchodilator in asthma

Treatment of anaphylactic reaction

Increases cerebral and coronary perfusion during resuscitation > ACLS

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Epinephrine

Pharmacokinetics

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Epinephrine

Indications

Anaphylaxis/hypersensitivity reaction and acute asthmatic attack

Cardiac arrest

Symptomatic bradycardia unresponsive to atropine or pacing

Severe sepsis and septic shock

Dosing and

administration

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Epinephrine

Adverse

effects

Angina, palpitations, arrhythmias, and tachycardia

Headache and N/V

Anxiety

Pulmonary edema

Tissue necrosis from extravasation (treat by local phentolamine)

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NorepinephrineEndogenous catecholamine

Stimulate

α-

,

β-

adrenergic receptors (

β1 > β2)

receptors

Peripheral vasoconstriction + increase BP (

α-

)

Inotropic effect + coronary artery dilate (

β-

)

Used in sepsis/septic shock and severe hypotension refractory to fluid resuscitation

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NorepinephrinePharmacokinetics

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NorepinephrineIndications

Acute and profound hypotension in post-arrest

Vasopressor of choice in severe sepsis/septic shock refractory to fluid resuscitation

Dosing and administration

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Norepinephrine

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NorepinephrineAdverse effects

Bradycardia, arrhythmia and cardiac arrest

Hypertension, N/V, and headache

Peripheral ischemia

Tissue necrosis

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PhenylephrineS

elective

α

1

-

adrenergic

agonist

Systemic arterial vasoconstriction > increase SVR

Dose-dependent elevation in SBP and DBP

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PhenylephrinePharmacokinetic

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PhenylephrineIndications

Hypotension and shock

Not recommend in septic/cardiogenic shock

Dosing and administration

Continuous IV infusion

50 – 150 mcg/min (0.02 – 0.2 mcg/kg/min)

IV bolus

100 – 500 mcg/dose IV every 10 – 15 min

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PhenylephrineAdverse effects

Hypertension

Decrease cardiac output

Reflex bradycardia and arrhythmias (rare)

Renal, mesenteric, myocardial, and extremities ischemia

Local necrosis

Caution in bradycardia, hyperthyroidism, heart block and coronary artery disease

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VasopressinE

ndogenous non-adrenergic vasopressor

Stimulates V1

receptors in vascular smooth

muscle, V2 receptors in kidneys

Peripheral vasoconstriction (V1)

Improve cerebral and cardiac perfusion (V1)

Antidiuretic effect (V2)

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VasopressinPharmacokinetics

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VasopressinIndications

Diabetes insipidus

Once used as

r

eplacement of 1

st

or 2

nd

dose of epinephrine in cardiac arrest (old)

Added to norepinephrine to lower dose in sepsis

Dosing and administration

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Vasopressin

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Vasopressin

Adverse effects

Diaphoresis, N/V, headache, and

urticaria

Bronchial constriction

Mesenteric ischemia

Arrhythmias, chest pain and myocardial infarction and cardiac

arrest

Gangrenous disorder

Venous thrombosis

Tissue necrosis

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Extravasation treatmentPhentolamine

Prevention

10 mg/L of solution containing vasopressors

Treatment

5 – 10 mg in 10 ml of NSS injected into the area of extravasation within 12 hours

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Inotropes

Dobutamine

Milrinone

“Prolonged

inotrope therapy has been associated

with increased mortality”

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Dobutamine

Synthetic dopamine analog

Potent inotropic and mild vasodilatory and chronotropic effects

Competitive α- and β-receptors (β

1

> β

2

> α) agonists

Increase contractility and heart rate (mostly neutral BP)

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DobutaminePharmacokinetics

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DobutamineIndications

S

hort-term management of acute

cardiac

decompensation > cardiogenic shock

Also used in septic shock with myocardial dysfunction/low cardiac output

Dosing and administration

Continuous infusion dose

of

2 - 40 mcg/kg/min

Maximum dose in septic shock 20 mcg/kg/min

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DobutamineAdverse effects

Hyper/hypotension

Tachycardia, arrhythmias, angina and myocardial ischemia

Hypokalemia

Phlebitis or local inflammation in extravasation (rarely necrosis)

Caution used in AF or post-MI

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MilrinoneI

notrope

with vasodilator

properties (“

Inodilator

”)

S

electively

inhibits the phosphodiesterase type III

enzyme > increase of

cAMP

in

myocardial and vascular smooth muscle

cells

Increased

cardiac contractility

with peripheral

arterial and venous vasodilation

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MilrinonePharmacokinetics

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MilrinoneIndications

Short-term

treatment

of acute

decompensated heart failure

Dosing and administration

IV loading dose

50 mcg/kg over 10 min

Continuous infusion

0.25 – 0.75 mcg/kg/min

Renal adjust in < 50 mL/min creatinine clearance

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MilrinoneAdverse effects

Ventricular

and supraventricular

arrhythmias

Hypotension

Angina

Headache

Not recommend in septic shock > hypotension and arrhythmia

“Fluid

resuscitation and electrolyte correction should

occur before

initiating

milrinone

”