Clinical Use: Sympathomimetics

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Overview Shock aagonists ß- agonists dopamine and dobutamine Nitrates, Adrenergic Agonists, Amrinone and Milrinone Hypertension	Cardiac Arrhythmias Congestive Heart Failure Vascular Effects: a Adrenergic Agonists Nasal Decongestion Asthma Allergic Reactions

**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 Return to top menu

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)

**aagonists: 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 aagonists may be harmful by further compromising organ (e.g. renal) perfusion. Return to top menu

**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 (areceptor activation) may worsen myocardial performance Return to top menu

**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 aand ß receptors enhances contractility without substantially increasing either heart rate or peripheral resistance. Return to top menu

**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. Return to top menu

**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 a₂adrenergic receptors which then reduce sympathetic outflow. Return to top menu

**Cardiac Arrhythmias**
In cardiac arrest, epinephrine may be beneficial. Epinephrine may help initiate a rhythm by increasing myocardial automaticity. During external cardiac massage aagonists 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 aand ß adrenergic receptors increase diastolic pressures improving coronary perfusion. Termination of paroxysmal supraventricular tachycardia may be accomplished by increased vagal (cholinergic) reflex tone following aagonist administration. Other drugs (e.g. adenosine, Ca²⁺ channel blockers) are more commonly used. Return to top menu

**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. Return to top menu

**Vascular Effects: a Adrenergic Agonists**
Epinephrine: Vasoconstriction-reduced bleeding in surgical procedures nose and throat surgical procedures. a adrenergic agonists may be injected into the penis for treatment of priapism. Sinus surgery: local application of phenylephrine or oxymetazoline for vasoconstriction. Return to top menu

**Nasal Decongestion**
a 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 a₁ 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. a 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. Return to top menu

**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. Return to top menu

**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. Return to top menu