Catecholamines, Adrenergic Agonists and AntagonistsD

Adrenergic Receptor Type

G protein-coupled

The 2 Alpha-Adrenergic Receptors

alpha-1 and alpha-2

Gq Protein

coupled to alpha-1 receptor

Gi (inhibitory) Protein

coupled to alpha-2 receptor

The 2 Beta Adrenergic Receptors

beta-1 and beta-2

Alpha-Adrenergic Effect

blood vessel vasoconstriction

Beta-1 Effect

heart muscle contraction

Beta-2 Effect

smooth muscle relaxation

Gs Protein

coupled to beta receptors

IP3 Pathway

route of alpha-1 receptors

Inhibitory cAMP-Dependent Pathway

route of alpha-2 receptors

Stimulatory cAMP-Dependent Pathway

route of beta-1 and beta-2 receptors

IP3 Pathway Mech

PLC activated —> cleaves PIP2 to DAG & IP3 —> IP3 receptor/channel on SR activates —> Ca influx and muscle contracts

Inhibitory cAMP-Dependent Pathway Mech

adenylyl cyclase inactivated —> less cAMP —> less PKA —> MLCK not inhibited —> vasoconstriciton

Beta-1 Stimulatory cAMP-Dependent Pathway Mech

adenylyl cyclase activated —> more cAMP —> more PKA —> calcium channel promotion —> troponin interaction —> inc heart rate, CO, contractility

cAMP Activation Target

PKA (target)

MLCK Inhibitor

PKA (inhib)

MLCK Role

activate actin/smooth muscle contraction

Beta-2 Stimulatory cAMP-Dependent Pathway Mech

adenylyl cyclase activation —> more cAMP —> more PKA —> MLCK inhibition —> vasodilation

3 Classes of Adrenergic Agonist Drugs

vasopressors, positive inotropes, mixed

Adrenergic Agonist Basic Properties

mimic function of sympathetic nervous system

Positive Inotrope Effect

increase in heart rate, contractility and cardiac output

Phenylephrine Class

vasopressor

Vasopressor Effect

vasoconstriction

Phenylephrine Selectivity

alpha-1

Phenylephrine Action

vasocontrict, increase BP

Phenylephrine Indications

acute hypotension due to septic shock, chronic postural/orthostatic hypotension

Dobutamine Class

Positive Inotrope

Dobutamine Selectivity

beta-1

Dobutamine Action

increase heart rate etc.

Dobutamine Indications

heart failure and cardiogenic shock

Dobutamine Contraindications

hypertrophic cardiomyopathy

Isoproterenol Class

Positive Inotrope

Isoproterenol Selectivity

beta-1 > > beta-2

Isoproterenol Action

increase heart rate etc

Isoproterenol Indications

Refractory Bradycardia

Norepinephrine Class

vasopressor and positive inotrope

Common Norepinephrine Use

medical emergency

Norepinephrine Selectivity

selective for alpha-1 and beta-1

Norepinephrine Action

vasoconstriction and increase cardiac output

Norepinephrine Indications

acute hypotension and shock

Epinephrine Class

vasopressor and positive inotrope

Epinephrine Selectivity

both alphas and both betas

Low Dose Epinephrine Action

beta stim, positive inotrope actions

High Dose Epinephrine Action

alpha stim, vasoconstriction

Epinephrine Indications

cardiac arrest, bradycardia and anaphylactic shock

Dopamine Class

vasopressor and inotrope properties

Dopamine Selectivity

D1 > beta-1 > alpha-1

Low Dose Dopamine Action

increase renal and mesenteric blood flow

Intermediate Dose Dopamine Action

positive inotrope acions

High Dose Dopamine Action

vasoconstriction

Dopamine Indications

Shock and 2nd line to Bradycardia after NE

Dopamine Contraindications

tachycardia

Adrenergic Antagonist Basic Properties

reduce catecholamine action; decrease BP, heart rate and vascular resistance

Phenoxybenzamine Class

alpha blocker

Phenoxybenzamine Selectivity

nonselective (alpha-1 > alpha-2)

Phenoxybenzamine Indications

hypertension from pheochromocytomas

Phenoxybenzamine Adverse Effects

HTF (hypotension, tachycardia, fatigue)

Phentolamine Class

alpha-blocker

Phentolamine Selectivity

nonselective fr

Phentolamine Reversibility

reversible

Phentolamine Indications

hypertension and cardiac stimulation

Phentolamine Adverse Effects

AA’s (arrhythmias and angina)

Phenoxybenzamine Reversibility

Irreversible

-zosin Class

alpha blocker

-zosin Selectivity

alpha-1 > > > > alpha-2

-zosin Reversibility

reversible

-zosin Indications

chronic hypertension and urinary retention

-zosin Adverse Effects

very few, bc selective!

Beta Blocker suffix

-olol

L C T P N -olol Class

beta-blocker

L C T P N -olol Selectivity

nonselective

L C T P N -olol Action

slow heart rate and reduce contractility

L C T P N -olol Indication

arrhythmias, hypertension, chronic heart failure, myocardial ischemia

L C T P N -olol Adverse Effects

bradycardia and bronchospasm

L and C Beta Blockers are Safe For…

pregnancy

Nadolol is Different because…

longer half-life

A M B -olol Class

beta-blocker

A M B -olol Selectivity

beta-1 > > > > > beta-2

A M B -olol Action

reduces contractility and slows heart rate

A M B -olol Indication

chronic heart failure, hypertension, preferred in asthmatics