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Nursing Pharmacology Chapter 5:  Autonomic Pharmacology--Adrenergic Drugs

Table of Contents

 

Overview--Clinical Uses

  • Positive inotropic agent

    • increase myocardial contractility

  • Vasopressors

    • increase systemic blood-pressure after sympathetic nervous system blockade following regional anesthetia

    • maintenance of systemic blood-pressure during:

      • during elimination of excess inhaled anesthetic

      • during restoration of intravascular fluid volume

      • prolonged sympathomimetic administration to support blood-pressure is not recommended

      • Disadvantages associated with using sympathomimetics without significant ß1 -- adrenergic effects:

        • intense vasoconstriction

        • hypertensive responses promoting reflex-mediated bradycardia

  • Treatment of bronchospasm impatient with asthma

  • Addition to local anesthetic solutions -- reducing systemic local anesthetic absorption

  • Management of severe allergic (hypersensitivity) reactions

 

Shock: Inadequate Tissue Perfusion

  • Hypovolemic shock: Dehydration or Blood Loss

    • Treatment includes fluid infusion to obtain adequate cardiac preload (filling pressure) without precipitating pulmonary congestion and compromising oxygenation.

  • Cardiac Failure (Cardiogenic Shock (pump failure) due to excessive myocardial tissue loss or arrhythmia

  • Cardiac Output obstruction (pulmonary embolism, aortic dissection, pericardial tamponade)

  • Loss of peripheral vascular tone (Septic Shock or anaphylaxis)

 

Drugs Used in Treating Shock

α agonists: increase peripheral vascular resistance

  • Norepinephrine, phenylephrine, metaraminol, mephenteramine and methoxamine may be used to maintain blood pressure in severe hypotension.

  • The objective is to ensure adequate CNS perfusion.

  • The use of these agents may be indicated if the hypotensive state is due to sympathetic failure, such as possibly occurring following spinal anesthesia or injury.

  •  In shock due to other causes, reflex vasoconstriction is typically intense; adding a agonists may be harmful by further compromising organ (e.g. renal) perfusion.
 

ß- agonists: increase heart rate and contractility

  •  Increasing heart rate and contractility by isoproterenol, epinephrine or norepinephrine may adversely affect cardiac performance in damaged myocardium.

  • These agents increase myocardial oxygen requirements and may induce arrhythmias.

  • Norepinephrine by increasing afterload (α receptor activation) may worsen myocardial performance
 

Dopamine and Dobutamine

  • Dopamine, (Intropin), at low concentrations, acts at D1 receptors and improve myocardial contractility (positive inotropism).

  • Dopamine (Intropin) produces less of an increase in heart rate compared to isoproterenol and dopamine dilates renal arteries, promoting better kidney perfusion.

  • Dobutamine (Dobutrex), through complex actions mediated by a and ß receptors enhances contractility without substantially increasing either heart rate or peripheral resistance.
 

Drugs in Cardiogenic Shock: Nitrates, Adrenergic Agonists, Amrinone (Inocor) and Milrinone (Primacor)

  • In cardiogenic shock precipitated by acute myocardial infarction, salvage of reversibly damaged myocardial may be accomplished by:

    • supplemental oxygen

    • i.v. nitroglycerin (decreasing preload)

    • intra-aortic balloon pump (reducing afterload)

    • surgery to repair valve pathologies or to revascularize

  • Cardiogenic Shock may be caused myocardial stunning due to prolonged cardiopulmonary bypass.

    • Dopamine (Intropin) and Dobutamine (Dobutrex) may be useful as positive inotropic agents

      • Dobutamine (Dobutrex) may be preferable because of a decreased likelihood of increasing heart rate and peripheral resistance (increasing afterload increases myocardial work).

    • Amrinone (Inocor) and milrinone (Primacor) (phosphodiesterase inhibitors) have positive inotropic effects that may be useful if other agents are ineffective.
 

Antihypertensive Effects

  • Centrally-acting sympathomimetics, such as clonidine (Catapres) or methyldopa (Aldomet), are effective antihypertensive drugs.

  • For clonidine (Catapres), the mechanism of action is activation of α2 adrenergic receptors which then reduce sympathetic outflow.
 

Cardiac Arrhythmias

  • In cardiac arrest, epinephrine may be beneficial.

    • Epinephrine may help initiate a rhythm by increasing myocardial automaticity.

  • During external cardiac massage a agonists may improve cerebral perfusion by shunting blood to the brain (since cerebral vessels are thought to be relatively insensitive to vasoconstricting effects of these drugs).

  • Epinephrine by activating both a and ß adrenergic receptors increase diastolic pressures improving coronary perfusion.

  • Termination of paroxysmal supraventricular tachycardia may be accomplished by increased vagal (cholinergic) reflex tone following a agonist administration. Other drugs (e.g. adenosine, Ca2+ channel blockers) are more commonly used.
 

Congestive Heart Failure

  • ß adrenergic receptor agonists have had limited use in chronic management of congestive heart failure.

  • In congestive failure, a significant loss of ß1 receptors (50%) occurs. Loss of receptor number and desensitization limit ß adrenergic receptor agonist efficacy.
 

Vascular Effects: α-Adrenergic Agonists

  • Epinephrine: Vasoconstriction-reduced bleeding in surgical procedures nose and throat surgical procedures.

  • α adrenergic agonists may be injected into the penis for treatment of priapism.

  • Sinus surgery: local application of phenylephrine or oxymetazoline for vasoconstriction.
 

Nasal Decongestion

  • α-adrenergic agonists are effective decongestants. (allergic, acute or chronic rhinitis).

  • These agents increase airflow by decreasing nasal mucosal volume.

  • Nasal mucosal volume is decreased by α1 adrenergic receptor constricting effects on nasal venous capacitance vessels.

  • Chronic use or upon discontinuation, a "rebound" hyperemia worsens congestion. This rebound effect and loss of efficacy with chronic use limits clinical efficacy.

  • alpha-adrenergic agonists, such as phenylephrine, should be used with caution in hypertensive patients or those using a monoamine oxidase inhibitor (MAO).

  • Preparations are available for both oral and topical use. Oral use is associated with increased systemic effects.
 

Asthma

  • ß adrenergic receptor agonists have a prominent role in chronic and acute management of asthma.

  • ß2 selective adrenergic receptor agonists, mediating bronchodilation, are preferable.

  • Clinical management of asthma is discussed in more detail elsewhere.
 

Allergic Reactions

  • Epinephrine is the agent of choice in emergency management of acute hypersensitivity reactions (reaction to food, insect bites, drug allergy)

  • Subcutaneous epinephrine administration alleviate symptoms rapidly and may be lifesaving when airway is compromised or in hypotensive shock.

  • Mechanism: ß adrenergic receptor activation may suppress mast release of histamine and leukotriene mediators.

  • Glucocorticoids and antihistamines are also used in management of severe hypersensitivity reactions.

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