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Autonomic Nervous System--Adrenergic Pharmacology-Lecture I, slide 1

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Table of Contents

  • Introduction

  • Adrenergic Agonists

  • Comparative pharmacology

  • Categories of Actions

    • Smooth Muscle Effects

    • Cardiac Effects

    • Metabolic Effects

    • Endocrine

    • CNS Effects

    • Presynaptic Effects

  • Epinephrine

    • Blood Pressure

    • Vascular Effects

    • Cardiac Effects

    • Smooth Muscle

    • Metabolic

    • Electrolytes

    • Toxicities

    • Therapeutic Use

  • Norepinephrine  (Levophed)

    • Blood Pressure

    • Vascular Effects

    • Therapeutic Use

  • Dopamine  (Intropin)

    • Cardiovascular Effects

    • Therapeutic Use

  • Dopexamine dopexamine

  • Isoproterenol (Isuprel)

    • Adverse Effects

    • Therapeutic Use

  • Dobutamine  (Dobutrex)

    • Adverse Effects

    • Therapeutic Use

  • ß2 selective adrenergic agonists

    • Metaproterenol (Alupent)

    • Terbutaline  (Brethine)

    • Albuterol (Ventolin,Proventil)

    • Ritodrine  (Yutopar)

    • Adverse Effects

  • a-Selective Adrenergic Agonists

    • Methoxamine  (Vasoxyl)

    • Phenylephrine  (Neo-Synephrine)

  • a2 Selective Adrenergic Agonists

    • Introduction

    • Clonidine  (Catapres)

    • Guanfacine  (Tenex)

    • Guanabenz  (Wytensin)

    • a-methyl DOPA  (Aldomet)

    • Miscellaneous

      Amphetamine

      • Methylphenidate  (Ritalin)

      • Ephedrine

      • Vasoconstrictors

  • Clinical Use of Sympathomimetic Agents

 

  • Amphetamines

  • Adrenergic Neuronal Blocking Drugs

  • Classification of adrenoceptors ( a1, a21, ß2 and D1), molecular consequences of their activation, and their important locations.

    • ß  Receptors

    • a Receptors

    • "Desensitization" as it applies to adrenoceptor regulation

  • Catecholamine Metabolic Transformations

  • Pulmonary Uptake

  • Adrenergic and Cholinergic Effects on End Organs

  • Clinical Uses: Sympathomimetic Drugs: a/b Adrenergic Agonists

    • Overview

    • Shock

    • a agonists

    • Drugs Used in Treating Shock

    • Hypertension

    • Cardiac Arrhythmias

    • Congestive Heart Failure

    • Vascular Effects: a Adrenergic Agonists

    • Nasal Decongestion

    • Asthma

    • Allergic Reactions

  • Therapeutic Uses of Indirect-Acting Adrenergic Agonists

  • Adverse Effects: b Adrenergic Antagonists

  • a-Adrenergic Antagonists

    • Introduction

      • a1-adrenergic receptor antagonists

      • a2-adrenergic receptor antagonists

      • Phenoxybenzamine (Dibenzyline)

      • Phentolamine(Regitine) and tolazoline (Priscoline)

      • Prazosin  (Minipress) and Terazosin (Hytrin)

      • Others

  • b Adrenergic Antagonists

    • Introduction

    • ß receptor blockers: Effects on the heart

    • ß receptor blockers: Antihypertensive Effects

    • Pulmonary Effects

    • Metabolic Actions

    • Nonselective-ß adrenergic receptor antagonists

      • propranolol

      • nadolol

      • timolol

      • labetalol

    • Cardioselective ß1 adrenergic receptor antagonists

      • metoprolol

      • esmolol

      • atenolol

    • Adverse Effects of ß adrenergic receptor antagonists

    • Therapeutic Uses

 

 

 

 

Introduction

  • Distribution of adrenergic receptor subtypes and adrenergic receptor number are important factors in organ or cellular responses to adrenergic input.

    • Adrenergic receptor type in bronchiolar smooth muscle is principally ß2: epinephrine and isoproterenol might be expected to be effective bronchodilators because of their activity at ß2 receptors.

      • Norepinphrine is unlikely to have this same effect due to its relative lack of activity at ß2 sites.

    • Alpha receptor dominate in the cutaneous vascular beds.

      • Norepinephrine and epinephrine cause constriction.

      • Isoproterenol with limited activity at alpha receptors has little effect.

    • Both alpha and beta adrenergic receptor are present in skeletal muscle vascular beds.

      • Alpha receptor activation causes vasoconstriction.

      • Beta receptor activation promotes vasodilatation.

      • Since ß2 receptors are activated at lower, physiological concentrations, vasodilation results.

  • Physiological effects caused by sympathomimetcs are due not only to direct effects, but also to indirect or reflex effects.

    • Alpha receptor agonist causes an increase in blood pressure.

    • Carotid/aortic baroreceptors activations initiates a compensatory reflex.

    • Sympathetic tone is reduced (decreases heart rate)

    • Parasympathetic tone is increased (decreases heart rate)

    • Blood pressure tends to return to lower levels

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;

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

 

 

 

Categories of Action

 Smooth Muscle Effects

  • Smooth muscle activation, including activation of blood vessel vasculature (skin, kidney).

  • Activation of glands (salivary and sweat).

  • Smooth muscle inhibition, including inhibition of smooth muscle of the gut, bronchioles, and skeletal muscle vascular smooth muscle.

 

 Cardiac Effects

  • increased heart rate (positive chronotropic effect)

  • increased contractility (positive inotropic effect)

Metabolic Effects

  • increase in rate of muscle and liver glycogenolysis

  • increase in free-fatty acid release from fat

 

Endocrine

  • Regulation/modulation of insulin, pituitary, and renin secretion

 Central Nervous System Effects

  • Respiratory stimulation

  • CNS stimulation

  • Appetite attenuation

Presynaptic Effects

  • Presynaptic effects: modulation of  release of norepinephrine or acetylcholine

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

 

 

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