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The P-I-E-N-O Parkinsn's List Drug Database
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epinephrine / AdrenalinTM , BronchaidTM , EpifinTM , EpinalTM , EpipenTM , EpitrateTM , Eppy/NTM
BRONCHODILATOR:
Cardiac stimulant
Description: Epinephrine is an endogenous catecholamine that is used primarily as a cardiac stimulant and as a bronchodilator in cases of anaphylactic shock. Its use as a bronchodilator in the treatment of asthma has largely been superceded by nebulized albuterol. Endogenous epinephrine is produced primarily from norepinephrine in the adrenal medulla. The discovery of epinephrine's pharmacologic effects and synthesis date back to the late 1800s. Epinephrine can be administered by injection, inhalation, or administered topically to the eye; the effects of exogenous epinephrine are identical to those of the endogenous hormone. Epinephrine was approved by the FDA in 1939. Epinephrine administered by metered-dose inhaler is available without a prescription for treatment of asthma, however, in November 1994, the FDA expressed concern regarding OTC status for this dosage form.
Mechanism of Action: Epinephrine, a potent agonist at both ›-and œ-receptors throughout the body except for the sweat glands and facial arteries, has complex target organ effects. Epinephrine stimulates both ›-and œ-adrenergic receptors. Nonspecific œ-stimulation, combined with moderate › agonism, result in inotropic effects equal to those of dopamine and dobutamine but greater chronotropic effects than either agent. Subsequent to binding at the adrenergic receptor, the intracellular actions of epinephrine are mediated by cyclic adenosine monophosphate (cAMP). The production of cAMP is augmented by œ-stimulation and attenuated by ›-stimulation. There is some evidence that epinephrine's › properties make it more effective than pure œ-agonists for the treatment of some pulmonary conditions such as bronchiolitis in children.¥I
The major therapeutic effects of systemic epinephrine include: bronchial smooth muscle relaxation, cardiac stimulation, vasodilation in skeletal muscle, and stimulation of glycogenolysis in the liver and other calorigenic mechanisms. The effects of epinephrine on smooth muscle are varied and determined by relative receptor density and hormonal effects. When used topically in the eye in patients with open-angle glaucoma, epinephrine lowers intraocular pressure, produces a brief mydriasis, and may improve the coefficient of aqueous outflow. When used topically on the skin or mucosal surfaces, epinephrine constricts arterioles, thus producing local vasoconstriction and hemostasis in small blood vessels.
Epinephrine primarily exerts its relaxant effect on bronchial smooth muscle via stimulation of œA-receptors. œA-stimulation also prevents mast cell secretion of histamine and other autocoids, thus antagonizing its effect on end organs and reversing bronchoconstriction and edema. Furthermore, ›-stimulation may decrease secretions from the bronchial mucosa, attenuating the development of edema.
The potent cardiac effects of epinephrine are primarily mediated via stimulation of œA-receptors on the myocardium and conducting system of the heart. The stimulation of these receptors results in both increased inotropic and chronotropic effects. Systolic blood pressure is usually elevated as a result of increased inotropy, although diastolic blood pressure is decreased secondary to epinephrine-induced vasodilation. As a result, pulse pressure is increased. Epinephrine indirectly causes coronary artery vasodilation, particularly during cardiac arrest. Epinephrine can simultaneously increase myocardial oxygen supply (secondary to coronary vasodilation) and increase oxygen demand (secondary to a positive inotropic and chronotropic effect on the heart). Increased myocardial excitability and automaticity markedly increase the potential for developing dysrhythmias.
Blood flow to skeletal muscles is augmented by epinephrine via œA-stimulation, resulting in vasodilation. At normal therapeutic doses, this effect is only mildly countered by the vasoconstriction caused by ›-stimulation. At higher doses, however, vasoconstriction and elevation of both peripheral vascular resistance and blood pressure can occur.
The metabolic effects of epinephrine relate primarily to the regulatory processes that control glucose concentration in the plasma. œA-stimulation of the skeletal muscle and liver increases glycogenolysis. ›-stimulation of the liver increases gluconeogenesis and inhibits insulin release by the pancreatic islet cells. Furthermore, in adipose cells, œ-stimulation will induce the catabolism of triglycerides, therefore increasing plasma free fatty acids. Serum potassium concentrations fluctuate after administration of epinephrine. Initially, hyperkalemia occurs secondary to release of potassium ions from hepatocytes. Hypokalemia quickly follows as potassium ions are taken up by the skeletal muscle.
Pharmacokinetics: Epinephrine is administered either by injection, by inhalation, or topically to the eye. The oral bioavailability of epinephrine is poor, owing to its rapid and extensive metabolism in the gut and liver; as a result, epinephrine is not administered orally. Epinephrine is, however, well absorbed systemically when administered by intramuscular (IM) or subcutaneous (SQ) routes. Subcutaneous administration is favored over intramuscular. Onset of action after subcutaneous administration is 5-15 minutes, and the duration of action is 1-4 hours. The onset of action after IM administration is variable, and the duration of action is 1-4 hours. Absorption of an IM dose may be increased both quantitatively and qualitatively by massaging the area of injection, which increases local blood flow. After inhalation of a normal dose, the drug is only slightly absorbed systemically, and its effects are limited primarily to the respiratory tract. The onset of action after an inhaled dose is 1-5 minutes, and the duration of action is 1-3 hours. The onset of action of various effects of an intraocular dose range from minutes to 1 hour, and the duration of these actions are from less than 1 hour to 24 hours. Epinephrine is distributed throughout the body. Epinephrine crosses the placenta but does not penetrate the blood-brain barrier to a great extent. Epinephrine will distribute into breast milk.
The pharmacologic activity of epinephrine is rapidly terminated by uptake and metabolism in the synaptic cleft. Circulating drug is metabolized by the enzymes catechol-o-methyltransferase and monoamine oxidase in the liver and in other tissues. These inactive metabolites are then conjugated to either sulfates or glucuronides and renally excreted. Minimal amounts of the drug are excreted unchanged in the urine.
CONTRAINDICATIONS/PRECAUTIONS: Epinephrine, particularly when administered intravenously, is absolutely contraindicated in shock secondary to causes other than anaphylactic shock. Cardiovascular conditions where epinephrine should be avoided include hemorrhagic shock, severe organic cardiac disease with coronary insufficiency, cardiac dilatation, and cardiac arrhythmias other than the treatment of ventricular fibrillation. The cardiovascular effects of epinephrine (i.e., increased myocardial oxygen demand, chronotropy, proarrhythmic potential, and vasoactivity) may be detrimental in these conditions.
Epinephrine is absolutely contraindicated in patients with sulfite hypersensitivity unless the patient is being treated for an emergent condition such as anaphylaxis or cardiac arrest.
Although indicated for open-angled glaucoma, epinephrine is absolutely contraindicated in closed-angle glaucoma because it can exacerbate this condition.
Epinephrine injection should never be injected into extremities such as fingers, toes, nose, and genitalia because it can cause severe tissue necrosis due to vasoconstriction of small blood vessels. Injection of epinephrine-containing local anesthetics into these areas should also be avoided.
Epinephrine is classified as a pregnancy category C drug. Epinephrine is absolutely contraindicated during active labor since, as a œA-receptor agonist, it can delay progression to the second stage.
Epinephrine is absolutely contraindicated during general anesthesia with cyclopropane, chloroform, or trichloroethylene and is relatively contraindicated with other halogenated hydrocarbon anesthetics (e.g., cyclopropane) since increased cardiac irritability via myocardial sensitization to catecholamines can occur (see Drug Interactions).
Epinephrine is relatively contraindicated in cerebrovascular disease such as cerebral arteriosclerosis or organic brain syndrome because of the sympathomimetic (presumably ›) effects in the cerebrovascular system and the potential for cerebrovascular hemorrhage with IV use.
Epinephrine is relatively contraindicated in hypertension because of the risk of worsening this condition.
Epinephrine is relatively contraindicated in hyperthyroidism because patients with this condition may be more sensitive to catecholamines and thus thyrotoxic or cardiotoxic symptoms can occur.
Epinephrine is relatively contraindicated in diabetes mellitus because the drug can cause hyperglycemia due to increased glycogenolysis in the liver, decreased tissue uptake of glucose, and decreased insulin release from the pancreas.
DRUG INTERACTIONS: Systemic administration of epinephrine with other sympathomimetics may produce additive pharmacodynamic effects that increase the risk of developing adverse effects.
Epinephrine and ›-blockers are pharmacological opposites. Antagonists at ›-adrenergic receptors can block the vasopressor response to epinephrine. Some ergot alkaloids, such as ergonovine, are ›-receptor agonists and theoretically will antagonize the ›-adrenergic vasopressor response to epinephrine. Phenothiazines also block ›-receptors. Epinephrine is ineffective as a vasopressor for phenothiazine-induced hypotension and may worsen this condition. Epinephrine should not be used as a vasopressor for phenothiazine overdose.
Epinephrine and œ-blockers are pharmacologic opposites. œ-blockers oppose the actions of epinephrine. œ-blockers can antagonize the cardiostimulatory and bronchodilatory effects of epinephrine. Halothane, cyclopropane, and other general anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine.
Cardiac glycosides can sensitize the myocardium to the actions of epinephrine. Systemic administration of epinephrine to patients receiving cardiac glycosides may induce proarrythmias.
Tricyclic antidepressants (TCAs); HA-blockers (particularly diphenhydramine, tripelennamine, and chlorpheniramine); thyroid hormones; and reserpine can inhibit tissue uptake of epinephrine and/or can increase receptor sensitivity to epinephrine, thereby potentiating its effects.
Simultaneous use of epinephrine with oxytocics can cause severe, prolonged hypertension. In addition, epinephrine, secondary to œA-receptor agonism, can interfere with oxytocic action.
ADVERSE REACTIONS: Systemic administration of epinephrine may lead to generalized CNS stimulation manifested as fear, anxiety, nervousness, sleeplessness, excitability, psychomotor agitation, impaired memory, headache, and disorientation. These reactions can occur with therapeutic doses of systemic epinephrine. In patients with underlying psychiatric disturbances, epinephrine can induce more pronounced CNS effects including panic, hallucinations, aggressive behavior, and expression of suicidal or homicidal tendencies.
Adrenergically modulated vasoactive and smooth muscle responses to epinephrine can result in nausea/vomiting, diaphoresis, pallor, respiratory distress, respiratory weakness, or apnea.
Cardiac arrhythmias, including premature ventricular contractions (PVCs), sinus tachycardia, hypertension, palpitations, and severe ventricular arrhythmias, are well described potential adverse effects of epinephrine due to œ-stimulation of the myocardium and conduction system. ECG changes, including a decrease in ST-T wave changes, can occur with or without cardiovascular symptomatology. Angina, dyspnea, pulmonary edema, and ischemia result from the increased workload and subsequent oxygen demands of the adrenergically stimulated heart.
Extravasation of epinephrine, especially with repeated injections or high infusion rates, can result in severe tissue damage and necrosis. Caution should be observed to avoid extravasation of epinephrine, since it can cause tissue necrosis and/or gangrene or other injection site reaction in the surrounding areaShould extravasation occur, the affected area should be generously infiltrated with 5-10 mg of phentolamine using a very small gauge needle to reduce and/or prevent devastating tissue sloughing and necrosis.
Metabolic acidosis secondary to accumulation of lactic acid has been associated with long-term administration or overdose of epinephrine.
Pulmonary reactions, primarily upper respiratory irritation and pharyngeal dryness, can result from inhalation of epinephrine solution or aerosols.
Medication errors associated with epinephrine can be fatal, so care must be exercised to ensure that the appropriate preparation, concentration, dose, and route of administration are used for the appropriate indication. Not all parenteral forms of epinephrine can be administered IV.
PATIENT INFORMATION:
What does epinephrine inhalation aerosol do?
Epinephrine (Medihaler-EpiTM , BronkaidTM Mist) can help to open up air passages and make breathing easier for people with various lung problems such as severe asthma. Some generic epinephrine inhaltion aerosols are available.
What should my doctor, dentist, or pharmacist know before I use epinephrine?
They need to know if you have any of the following conditions:
How should I use this medicine?
Epinephrine aerosol is for inhalation through the mouth. Shake the canister well. Tilt your head back slightly. Breathe out fully, emptying as much air as possible from your lungs. Keep the canister upright. Keep the inhaler about 1 inch from your open mouth (or place the mouthpiece loosely between your open lips). Press down on the inhaler (one puff) while breathing in deeply and slowly. Hold your breath for at least 10 seconds and then exhale (breathe out). Wait for at least 1 to 2 minutes between puffs. Do not use more often than directed.
What if I miss a dose?
If you miss a dose, use it as soon as you can. If it is almost time for your next dose, use only that dose. Do not use double or extra doses.
What other medicines can interact with epinephrine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before starting or stopping any of your medicines.
What side effects may I notice from using epinephrine?
Serious side effects with epinephrine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with epinephrine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I use epinephrine?
Check with your doctor if your symptoms do not improve within 20 minutes of epinephrine inhalation, or if they get worse.
Make sure you are using your inhaler properly. Do not use extra or more frequent inhalations; they will not improve your condition.
To stop your mouth getting dry after inhaling epinephrine, rinse out your mouth with water.
Do not get the aerosol spray in your eyes.
Do not use epinephrine products if you are pregnant, especially during labor as epinephrine may delay contractions.
If you also use ipratropium (AtroventTM ) or an inhaled steroid (such as beclomethasone or triamcinolone) use the epinephrine first. Wait at least 5 minutes before using the other inhaler.
If you are diabetic epinephrine may increase your blood sugar. Check your blood or urine sugar often and contact your doctor if you have any problems.
If you are going to have surgery tell your doctor or dentist that you are using epinephrine.
Do not treat yourself for coughs, colds or allergies without checking with your pharmacist or doctor. Non-prescription medicines may contain ingredients that will increase the effects of your medicine.
Where can I keep my medicine?
Keep out of the reach of children.
Store at room temperature between 15 and 30C (59 and 86F) unless otherwise indicated by the manufacturer. Do not freeze. Protect from light. Throw away any unused medicine after the expiration date.
The P-I-E-N-O Parkinsn's List Drug Database Index
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