Autonomic pharmacology

Autonomic Pharmacology--Adrenergic Drugs

Page Back Page Forward

Return to Section Table of Contents

Return to Site Table of Contents

 

Table of Contents

 

 

 

Introduction

Adrenergic Agonists

Comparative Sympathomimetic Pharmacology

Drug

alpha

beta1

beta2

Mechanism of action

Peripheral resistance

Renal blood flow

Mean arterial pressure

CNS stimulation

Epinephrine

Direct

+/-

Yes

Norepinephrine (Levophed)

0

Direct

No

Dopamine (Intropin)

Direct

No

Isoproterenol (Isuprel)

0

Direct

+/-

Yes

Dobutamine (Dobutrex)

0

0

Direct

NC

 

Ephedrine

Direct+Indirect

Yes

Mephentermine (Wyamine)

Direct+Indirect

Yes

Amphetamines

Indirect

Yes

Metaraminol (Aramine)

Indirect+direct

No

Phenylephrine (Neo-Synephrine)

methoxamine (Vasoxyl)

0

0

Direct

No

--increased effect; --decreased effect

adapted from: Table 12-1 Stoelting, R.K., "Pharmacokinetics and Pharmacodynamics of Injected and Inhaled Drugs", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, p. 260

 

Categories of Action

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.199-242

Stoelting, R.K., "Sympathomimetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, p. 260

 

 

 

Epinephrine

 

Epinephrine

 Blood Pressure

  • A principal mechanism for arterial blood pressure control is the baroreceptor reflex.

  • The reflex is initiated by activation of stretch receptors located in the wall of most large arteries of the chest and neck.

  • A high density of baroreceptors is found in the wall of each internal carotid artery (just above the carotid bifurcation i.e. carotid sinus) and in the wall of the aortic arch.

As pressure rises and especially for rapid increases in pressure:

  • baroreceptor input to the tractus solitarius of the medulla results in inhibition of the vasoconstrictor center and excitation of the vagal (cholinergic) centers resulting in

  1. a vasodilatation of the veins and arterioles in the peripheral vascular beds.

  2. negative chronotropic and inotropic effects on the heart. (slower heart rate with reduced force of contraction)

 

 

Adrenergic

Cholinergic

Sino-atrial (SA) Node

beta1; beta2

increased rate

decreased rate (vagal)

Atrial muscle

beta1; beta 2

increased: contractility, conduction velocity

decreased: contractility, action potential duration

Atrio-ventricular (AV) node

beta1; beta 2

increased: automaticity, conduction velocity

decreased conduction velocity; AV block

His-Purkinje System

beta1; beta 2

increased: automaticity, conduction velocity

------

Ventricles

beta1; beta 2

increased: contractility, conduction velocity, automaticity, ectopic pacemaker

small decrease in contractility

Blood Pressure

Blood Pressure Effects

Epinephrine

Norepinephrine

Systolic

Mean Pressure

Diastolic

variable

Mean Pulmonary

0.1-0.4 ug/kg/min infusion rate

Adaptation of Table 10-2 from: Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.199-242

 Vascular Effects

Cardiac Effects

Smooth Muscle

 

Uterus

alpha1; beta2

Pregnant: contraction (alpha1); relaxation (beta2); Non-pregnant: relaxation (beta2)

variable

Pulmonary
 

Adrenergic 

Effects

Cholinergic
Tracheal and bronchial muscle beta 2 Relaxation contraction
Bronchial glands alpha1, beta2 decrease secretion; increased secretion stimulation

 

Metabolic Effects

Pancreas 
 

Adrenergic

Effects Cholinergic
Acini alpha decreased secretion secretion
Islets (beta cells) alpha2 decreased secretion ---------
Islets (beta cells) beta2 increased secretion ---------
Liver
 

Adrenergic 

Effects Cholinergic
Liver alpha1; beta2 glycogenolysis and gluconeogenesis -----------

Adipose Tissue

Adrenergic

Cholinergic

Fat Cells

alpha2; beta3  

lipolysis (thermogenesis)

---------

Electrolytes

 

Norepinephrine

 Blood Pressure Effects

Blood Pressure

Blood Pressure Effects

Epinephrine

Norepinephrine

Systolic

Mean Pressure

Diastolic

variable

Mean Pulmonary

Adaptation of Table 10-2 from: Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.199-242

 

                  Arterioles            
Coronary alpha1,2; beta 2 constriction;dilatation constriction

Skin/Mucosa

alpha1,2

constriction

dilatation

Skeletal Muscle

alpha; beta2

constriction,dilatation

dilatation

Cerebral

alpha

slight constriction

dilatation

Pulmonary

alpha1 , beta2

constriction; dilatation

dilatation

Abdominal viscera

alpha1, beta2

constriction; dilatation

-------

Salivary glands

alpha1,2

constriction

dilatation

Renal

alpha1,2;beta1,2

constriction;dilatation

---------

Based on Table 6-1: Lefkowitz, R.J, Hoffman, B.B and Taylor, P. Neurotransmission: The Autonomic and Somatic Motor Nervous Systems, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,( Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.110-111.

 

Vascular Effects


Peripheral Circulation

Peripheral Circulation

Epinephrine

Norepinephrine

Total Peripheral Resistance

Cerebral Blood Flow

no effect or decrease

Muscle Blood Flow

no effect or decrease

Cutaneous Blood Flow

Renal Blood Flow

Splanchnic Blood Flow

no effect or increase

increase, decrease

0.1-0.4 ug/kg/min IV infusion

Adaptation of Table 10-2 from: Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.199-242

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.204-213.

Page Back Page Forward

Return to Section Table of Contents

Return to Site Table of Contents

 

Dopamine

Dopamine

 

 

 

 

 

Isoproterenol (Isuprel)

Dobutamine (Dobutrex)

 

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.199-242

Page Back Page Forward

 

Return to Section Table of Contents

Return to Site Table of Contents

 

 

2 Selective Adrenergic Agonists

 

 

 Adverse Effects-Agonists

 

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.213-216.

 

 

 

Alpha1 Selective Adrenergic Agonists

Phenylephrine (Neo-Synephrine)

 

 

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.216-219.

 

alpha2 Selective Adrenergic Agonists and Miscellaneous Adrenergic Agonists

Introduction

Clonidine (Catapres)

Ephedrine

 

Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp.216-219

 

 

 

Amphetamine & related drugs

.

Drug Lists

Catecholamines

Drug

Receptors

Epinephrine

alpha1, alpha2 1, 2

Norepinephrine (Levophed)

alpha1, alpha2, 1

Isoproterenol (Isuprel)

1, 2

Dobutamine (Dobutrex)

1 (alpha1)

Dopamine (Intropin)

D-1 (alpha1 and 1 at high doses)

 

Direct adrenoceptor agonists

Drug

Receptor Selectivity

Phenylephrine (Neo-Synephrine)

alpha1

Methoxamine (Vasoxyl)

alpha1

Oxymetazoline (Afrin)

alpha1, alpha2

Clonidine (Catapres)

alpha2

Ritodrine (Yutopar)

2

Terbutaline (Brethine)

2

Albuterol (Ventolin,Proventil)

2

Salmeterol (Serevent)

2

 

 

Indirect sympathomimetics

  • Ephedrine, Pseudoephedrine

  • Cocaine

  • Tyramine

  • Amphetamine

  • Release & direct receptor activation

  • Uptake I inhibitor

  • Release

  • see ephedrine, but greater CNS actions

 

Alpha-Adrenoceptor antagonists

Drug

Receptor Selectivity (a1 vs. a2)

Prazosin (Minipress)

alpha1

Terazosin (Hytrin)

alpha1

Trimazosin

alpha1

Doxazosin (Cardura)

alpha1

Phentolamine (Regitine)

non-selective

Phenoxybenzamine (Dibenzyline)

only slightly selective for alpha1 (non-competitive)

Tolazoline (Priscoline)

non-selective

Labetalol (Trandate, Normodyne)

alpha1 (also non-selective beta-antagonist)

Yohimbine (Yocon)

alpha2

 

-Adrenoceptor antagonists

Drug

Receptor Selectivity (1 vs. 2)

Propranolol (Inderal)

non-selective

Metoprolol (Lopressor)

1

Esmolol (Brevibloc)

1

Atenolol (Tenormin)

1

Nadolol (Corgard)

non-selective

Timolol (Blocadren)

non-selective

Pindolol (Visken)

non-selective (partial agonist)

Labetalol (Trandate, Normodyne)

non-selective (selective a1-antagonist)

 

Adrenergic Neuron Blocking Drugs

Reserpine

Guanethidine (Ismelin)

  • non-selective blockade of vesicular uptake and storage of biogenic amines

  • similar to reserpine: Uptake I dependent

Page Back Page Forward

 

Return to Section Table of Contents

Return to Site Table of Contents

 

 

 

 

 

 

 
Google