Adrenergic Drugs

Chapter 5 Adrenergic Drugs

I. Adrenoreceptor Agonists

1. Endogenous catecholamines (norepinephrine, epinephrine, and dopamine) are found in peripheral sympathetic nerve endings, the adrenal medulla, and the brain.

Endogenous catecholamines: norepinephrine, epinephrine, dopamine

2. Catecholamines affect blood pressure and heart rate.

a. Intravenous bolus injection (Fig. 5-1)

b. Intravenous infusion for 20 min (Fig. 5-2)

3. Some indirect agonists

a. Potentiate the effects of catecholamines by decreasing their disappearance from the synaptic cleft

(1) Monoamine oxidase (MAO) inhibitors

(2) Catechol-O-methyltransferase (COMT) inhibitors

5-1 Graphic representations of the effects of three catecholamines given by intravenous bolus injection on blood pressure and heart rate. Note that the pulse pressure is greatly increased with epinephrine and isoproterenol. Norepinephrine causes reflex bradycardia.

5-2 Comparison of the cardiovascular effects of four catecholamines when a low dose is given by intravenous infusion.

(From Brenner G and Stevens C: Pharmacology, 3rd ed. Philadelphia, Saunders, 2010, Figure 8-4.)

MAOI and COMT inhibitors block the metabolism of catecholamines.

(3) Tricyclic antidepressants (TCAs)

TCAs and cocaine block the reuptake of some catecholamines.

B. Physiological effects of selected agents (Table 5-1)

C. Selected catecholamines (Box 5-1)

1. Norepinephrine (NE)

a. Stimulates β₁– and α₁-adrenergic receptors causing increased contractility and heart rate as well as vasoconstriction

TABLE 5-1 Pharmacologic Effects and Clinical Uses of Adrenoreceptor Agonists

Drug
Direct-Acting Adrenoreceptor Agonists	Effect and Receptor Selectivity	Clinical Application
Catecholamines
Dobutamine	Cardiac stimulation (β₁) β₁ > β₂	Shock, heart failure
Dopamine	Renal vasodilation (D₁) Cardiac stimulation (β₁) Increased blood pressure (α₁) D₁ = D₂ > β₁ > α₁	Shock, heart failure
Epinephrine	Increased blood pressure (α₁) Cardiac stimulation (β₁) Bronchodilation (β₂) Vasodialtion (β₂) General agonist (α₁, α₂, β₁, β₂)	Anaphylaxis, open-angle glaucoma, asthma, hypotension, cardiac arrest, ventricular fibrillation, reduction in bleeding in surgery, prolongation of local anesthetic action
Isoproterenol	Cardiac stimulation (β₁) β₁ = β₂	Atrioventricular block, bradycardia
Norepinephrine	Increased blood pressure (α₁) α₁, α₂, β₁	Hypotension, shock

Noncatecholamines
Albuterol	Bronchodilation (β₂) β₂ > β₁	Asthma
Clonidine	Decreased sympathetic outflow (α₂)	Chronic hypertension
Oxymetazoline	Vasoconstriction (α₁)	Decongestant
Phenylephrine	Vasoconstriction, increased blood pressure, and mydriasis (α₁) α₁ > α₂	Pupil dilation, decongestion, mydriasis, neurogenic shock, blood pressure maintenance during surgery
Ritodrine	Bronchodilation and uterine relaxation (β₂)	Premature labor
Terbutaline	Bronchodilation and uterine relaxation (β₂) β₂ > β₁	Asthma, premature labor
Fenoldopam	Dilates renal and mesenteric vascular beds D₁-agonist	Hypertensive emergency

Indirect-Acting Adrenoreceptor Agonists
Amphetamine	Increased norepinephrine release General agonist (α₁, α₂, β₁, β₂)	Narcolepsy, obesity, attention deficit disorder
Cocaine	Inhibited norepinephrine reuptake General agonist (α₁, α₂, β₁, β₂)	Local anesthesia

Mixed-Acting Adrenoreceptor Agonists
Ephedrine	Vasoconstriction (α₁) General agonist (α₁, α₂, β₁, β₂)	Decongestant
Pseudoephedrine	Vasoconstriction (α₁)	Decongestant

α-Effect: vasoconstriction

β-Effect: inotropic, chronotropic

(1) Alpha effects (vasoconstriction) are greater than beta effects (inotropic and chronotropic effects)

(2) Often resulting in reflex bradycardia (see Figs. 5-1, 5-2)

• Occasionally to treat shock which persists after adequate fluid volume replacement

2. Epinephrine (EPI)

a. Pharmacokinetics

(1) Usually injected subcutaneously

(2) Given by intracardiac or intravenous route to treat cardiac arrest

(1) Treatment of asthma

(2) Treatment of anaphylactic shock or angioedema

EPI used to treat anaphylactic shock or angioedema

(3) Prolongation of action of local anesthetics, due to the vasoconstrictive properties of EPI

EPI used to prolong action of local anesthetics.

(4) Treatment of cardiac arrest, bradycardia, and complete heart block in emergencies

3. Dopamine (DA)

a. Mechanism of action

• Stimulates D₁ specific dopamine receptors on renal vasculature, and at higher doses it also stimulates β₁– and α₁-adrenergic receptors

(1) Low doses stimulate primarily renal dopamine receptors (0.5−2 µg/kg/min) causing vasodilation in the kidney.

(2) Moderate doses also stimulate β₁-adrenergic receptors (2−10 µg/kg/min) increasing cardiac contractility.

(3) High doses also stimulate α₁-adrenergic receptors (>10 µg/kg/min) causing vasoconstriction.

(1) Cardiogenic and noncardiogenic shock

(2) Dopamine increases blood flow through the kidneys

Dopamine increases renal blood flow; important in preventing ischemic kidney.

c. Adverse effects

(1) Premature ventricular tachycardia, sinus tachycardia

(2) Angina pectoris

4. Isoproterenol (ISO)

a. Mechanism of action is to stimulate

(1) β₁ receptors

(a) Heart to increase force of contraction and rate

(b) Kidney to facilitate renin secretion

(2) β₂ receptors

(a) Vasculature (vasodilation)

(b) Bronchioles (bronchodilation)

(3) β₃ receptors

Adipocytes to increase lipolysis

Potency of α₁-adrenoreceptor agonists: EPI > NE >> DA >>>> ISO

Potency of β₁-adrenoreceptor agonists: ISO >> EPI > NE = DA

Only gold members can continue reading. Log In or Register to continue

Related

Stay updated, free articles. Join our Telegram channel

Tags: Rapid Review Pharmacology

Apr 8, 2017 | Posted by admin in PHARMACY | Comments Off

Full access? Get Clinical Tree

Get Clinical Tree app for offline access

Get Clinical Tree app for offline access