Chemistry - An endogenous catecholamine, epinephrine occurs as white to nearly white, microcrystalline powder or granules. It is only very slightly soluble in water, but it readily forms water soluble salts (e.g., HCl) when combined with acids. Both the commercial products and endogenous epinephrine are in the levo form, which is about 15 times more active than the dextro-isomer. The pH of commercial injections are from 2.5 - 5. Epinephrine is sometimes known as Adrenalin .
Storage/Stability/Compatibility - Epinephrine HCl for injection should be stored in tight containers and protected from light. Epinephrine will darken (oxidation) upon exposure to light and air. Do not use the injection if it is pink, brown or contains a precipitate. The stability of the injection is dependent on the form and the preservatives present, and may vary from one manufacturer to another. Epinephrine is rapidly destroyed by alkalies, or oxidizing agents.
Epinephrine HCl is reported to be compatible with the following intravenous solutions: Dextran 6% in dextrose 5%, Dextran 6% in normal saline, dextrose-Ringer’s combinations, dextrose-lactated Ringer’s combinations, dextrose-saline combinations, dextrose 2.5%, dextrose 5% (becomes unstable at a pH > 5.5), dextrose 10%, Ringer’s injection, lactated Ringer’s injection, normal saline, and sodium lactate 1/6 M. Epinephrine HCl is reportedly compatible with the following drugs: amikacin sulfate, cimetidine HCl, dobutamine HCl, metaraminol bitartrate, and verapamil HCl.
Epinephrine HCl is reported to be incompatible with the following intravenous solutions: Ionosol-D-CM, Ionosol-PSL (Darrow’s), Ionosol-T w/ dextrose 5% (Note: other Ionosol product are compatible), sodium chloride 5%, and sodium bicarbonate 5%. Epinephrine HCl is reportedly incompatible with the following drugs: aminophylline, cephapirin sodium, hyaluronidase, mephentermine sulfate, sodium bicarbonate, and warfarin sodium. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.
Pharmacology - Epinephrine is an endogenous adrenergic agent that has both alpha and beta activity. It relaxes smooth muscle in the bronchi and the iris, antagonizes the effects of histamine, increases glycogenolysis, and raises blood sugar. If given by rapid IV injection it causes direct stimulation of the heart (increased heart rate and contractility), and increases systolic blood pressure. If given slowly IV, it usually produces a modest rise in systolic pressure and a decrease in diastolic blood pressure. Total peripheral resistance is decreased because of beta effects.
Uses/Indications - Epinephrine is employed primarily in veterinary medicine as a treatment for anaphylaxis and in cardiac resuscitation. Because of its vasocontrictive properties, epinephrine is also added to local anesthetics to retard systemic absorption and prolong effect.
Pharmacokinetics - Epinephrine is well absorbed following IM or SQ administration. IM injections are slightly faster absorbed than SQ administration; absorption can be expedited by massaging the injection site. Epinephrine is rapidly metabolized in the GI tract and liver after oral administration and is not effective via this route. Following SQ injection, the onset of action is generally within 5-10 minutes. The onset of action following IV administration is immediate and intensified.
Epinephrine does not cross the blood-brain barrier, but does cross the placenta and is distributed into milk.
Epinephrine’s actions are ended primarily by the uptake and metabolism of the drug into sympathetic nerve endings. Metabolism takes place in both the liver and other tissues by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) to inactive metabolites.
Contraindications/Precautions - Epinephrine is contraindicated in patients with narrow-angle glaucoma, hypersensitivity to epinephrine, shock due to non-anaphylactoid causes, during general anesthesia with halogenated hydrocarbons or cyclopropane, during labor (may delay the second stage) and in cardiac dilatation or coronary insufficiency. Epinephrine should also not be used in cases where vasopressor drugs are contraindicated (e.g., thyrotoxicosis, diabetes, hypertension, toxemia of pregnancy). It should not be injected with local anesthetics into small appendages of the body (e.g., toes, ears, etc.) because of the chance of necrosis and sloughing.
Use epinephrine with caution in cases of hypovolemia; it is not a substitute for adequate fluid replacement therapy. It should be used with extreme caution in patients with a prefibrillatory cardiac rhythm, because of its excitatory effects on the heart. While epinephrine’s usefulness in asystole is well documented, it also can cause ventricular fibrillation; use cautiously in cases of ventricular fibrillation.
Adverse Effects/Warnings - Epinephrine can induce a feeling of fear or anxiety, tremor, excitability, vomiting, hypertension (overdosage), arrhythmias (especially if patient has organic heart disease or has received another drug that sensitizes the heart to arrhythmias), hyperuricemia, and lactic acidosis (prolonged use or overdosage). Repeated injections can cause necrosis at the injection site.
Overdosage - Symptoms seen with overdosage or inadvertent IV administration of SQ or IM dosages can include: sharp rises in systolic, diastolic, and venous blood pressures, cardiac arrhythmias, pulmonary edema and dyspnea, vomiting, headache, and chest pain. Cerebral hemorrhages may result because of the increased blood pressures. Renal failure, metabolic acidosis and cold skin may also result.
Because epinephrine has a relatively short duration of effect, treatment is mainly supportive. If necessary, the use an alpha-adrenergic blocker (e.g., phentolamine) or a beta-adrenergic blocker (e.g., propranolol) can be considered to treat severe hypertension and cardiac arrhythmias. Prolonged periods of hypotension may follow, which may require treatment with norepinephrine.
Drug Interactions - Do not use with other sympathomimetic amines (e.g., isoproterenol) because of additive effects and toxicity. Certain antihistamines (diphenhydramine, chlorpheniramine, etc.) and l-thyroxine may potentiate the effects of epinephrine.
Propranolol (or other beta-blockers) may potentiate hypertension, and antagonize epinephrine’s cardiac and bronchodilating effects by blocking the beta effects of epinephrine.
Nitrates, alpha-blocking agents, or diuretics may negate or diminish the pressor effects of epinephrine. When epinephrine is used with drugs that sensitize the myocardium (halothane, high doses of digoxin) monitor for signs of arrhythmias. Hypertension may result if epinephrine is used with oxytocic agents.
Note: Be certain when preparing injection that you do not confuse 1:1000 (1 mg/ml) with 1:10,000 (0.1 mg/ml) concentrations. To convert a 1:1000 solution to a 1:10,000 solution for IV or intra-tracheal use, dilute each ml with 9 ml of normal saline for injection. Epinephrine is only one aspect of treating cardiac arrest, refer to specialized references or protocols for more information.
a) 3 - 5 ml of 1:1,000 per 450 kg of body weight either IM or SQ. For foal resuscitation: 0.1 ml/kg of 1:1,000 IV (preferably diluted with saline) (Robinson 1987)
a) For emergency treatment of a newborn calf, calculate the dose at 0.1 ml/kg of a 1:1000 solution. Have prepared and labeled in a syringe. Give inter-cardiac, intra-tracheal, or IV if there is no heart beat:
200 lb (90 kg) calf = 9 ml
250 lb (113 kg) calf = 11.3 ml
300 lb (136 kg ) calf = 13.6 ml (Schmitt, 2001).
a) Schmitt,D.L. 2001. Riddle’s Elephant and Wildlife Sanctuary Elephant Birth Protocol. www.elephantcare.org/protodoc_files/birthpro.pdf
Monitoring Parameters -
1) Cardiac rate/rhythm
2) Respiratory rate/auscultation during anaphylaxis
3) Urine flow if possible
4) Blood pressure, and blood gases if indicated and if possible
Client Information - Pre-loaded syringes containing an appropriate amount of epinephrine may be dispensed to clients for treatment of anaphylaxis in animals with known hypersensitivity. Anaphylactic symptoms (depending on species) should be discussed. Clients should be instructed in proper injection technique (IM or SQ) and storage conditions for epinephrine. Do not use epinephrine if it is outdated , discolored or contains a precipitate.
Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved and Human-Approved Products: Epinephrine is approved for use in dogs, cats, horses, cattle, sheep, and swine.
Epinephrine HCl for Injection 0.1 mg/ml (1:10,000) in 10 ml syringes (human-label); (Rx)
Epinephrine HCl for Injection 1 mg/ml (1:1,000) in 1 ml amps & syringes and 10 ml, 30 ml and 100 ml vials; Adrenalin Chloride® (P-D); Veterinary-labeled generic; (Rx)
It is also available in products labeled for human use as a powder form (aerosol) for inhalation, and a sterile suspension for injection. Epinephrine bitartrate is available as a powder form (aerosol) for inhalation. Epinephrine HCl is also available as a solution for nebulization and in automatically injecting syringes for treatment of hypersensitivity reactions.
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