Adrenaline

Uses

Adjunctive use in the management of cardiac arrest. It is used in cardiopulmonary resuscitation. Intracardiac puncture and intramyocardial injection of adrenaline may be effective when external cardiac compression and attempts to restore the circulation by electrical defibrillation or use of a pacemaker fail. Adrenaline is a drug that leads to increased blood pressure, increased heart rate, increased air entry, increased blood glucose, stimulates cardiac activity and reduces allergic reactions by reducing inflammatory response caused by histamine. Due to these properties, it is used for the treatment of allergic and anaphylactic reactions. Adrenaline is the favored treatment for anaphylactic shock and should be administered immediately if a person begins exhibiting severe allergic reactions. Adrenaline is also used in life threatening asthma when failing ventilation and continued deterioration despite nebulizer therapy.

Adrenaline is also used to associated treatment for these conditions: Anaphylaxis, Angioneurotic Edema, Bleeding, Bronchospasm, Complete Heart Block, Hypotension, Idiopathic Anaphylaxis, Laryngotracheobronchitis, Mild Intermittent Asthma, Nasal Congestion, Open Angle Glaucoma (OAG), Respiratory Distress, Severe Asthma, Syncope, Urticaria, Uterine Contractions, Ventricular Fibrillation, Resuscitation in cardiac arrest following anesthetic accidents, Serious allergic reactions, Severe hypersensitivity, Unresponsive Asystole, Unresponsive Bradycardia

How Adrenaline works

Adrenaline acts on alpha and beta-adrenergic receptors. Adrenaline acts on alpha and beta receptors and is the strongest alpha receptor activator . Through its action on alpha-adrenergic receptors, epinephrine minimizes the vasodilation and increased the vascular permeability that occurs during anaphylaxis, which can cause the loss of intravascular fluid volume as well as hypotension. Adrenaline relaxes the smooth muscle of the bronchi and iris and is a histamine antagonist, rendering it useful in treating the manifestations of allergic reactions and associated conditions . This drug also produces an increase in blood sugar and increases glycogenolysis in the liver . Through its action on beta-adrenergic receptors, epinephrine leads to bronchial smooth muscle relaxation that helps to relieve bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis .

Dosage

Adrenaline dosage

Cardiac arrest:

1. Intravenous injection: 1 mg injection repeated every 2-3 minutes as necessary.

2. Endotracheal: 2-3 mg via an endotracheal tube, repeated as necessary.

3. Intracardiac injection: 0.1 to 1 mg, direct into the atrium of the heart.

4. Intraspinal use: Usual dose is 0.2 to 0.4 mg added to anesthetic spinal fluid mixture (to prolong anesthetic action by limiting absorption).

Anaphylaxis, asthma or severe bronchospasm: Adult dose is 0.25 - 0.5 mg. It may be repeated at 5 minutes intervals until perfusion and respiratory status normalizes. In case of dose dilution: 1 mg of Adrenaline to be diluted in 9 ml Normal Saline.

Children: Intravenous injection: Initially 10 mcg/kg body weight, not to exceed 250 mcg. May be repeated every 3-5 minutes if necessary. Subsequent doses should be 100 mcg/kg.

Side Effects

Anxiety, restlessness, dizziness, headache, palpitations, rapid pulse, tremors, weakness and coldness of the extremities may be reported even with small doses and especially when given in conjunction with local anaesthetics.

Toxicity

Skin, LD₅₀ = 62 mg/kg (rat)

Pregnancy

Adrenaline is teratogenic in rats when given in doses about 25 times the human doses. It is unknown whether epinephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Adrenaline should be given to a pregnant woman only if clearly required in critical situations/emergencies .

Labor and Delivery Parenteral administration of epinephrine, if used as support for blood pressure during low or other spinal anesthesia for delivery, can lead to the acceleration of fetal heart rate and should not be used in obstetrics when maternal blood pressure is higher than 130/80. Adrenaline may delay the second stage of labour.

Common and generalized adverse effects: Transient and minor side effects of anxiety, headache, fear, and palpitations may occur with therapeutic doses of epinephrine, especially in hyperthyroid individuals. Repeated local injections may result in necrosis at sites of injection due to vascular constriction. Cerebral hemorrhage; hemiplegia; subarachnoid hemorrhage; anginal pain in patients with angina pectoris; anxiety; restlessness; throbbing headache; tremor; weakness; dizziness; pallor; respiratory difficulty; palpitation; apprehensiveness; sweating; nausea; vomiting .

Cardiovascular effects: Inadvertently induced high arterial blood pressure may result in angina pectoris (especially when coronary insufficiency is present), cardiac ischemia, or aortic rupture , . Adrenaline may cause serious cardiac arrhythmias in patients not suffering from heart disease and patients with organic heart disease receiving drugs that sensitize the cardiac muscle. With the injection of epinephrine 1:1,000, a paradoxical but transient lowering of blood pressure, bradycardia and apnea may occur immediately post-injection .

Cerebrovascular hemorrhage: Overdosage or accidental I.V. injection of epinephrine may lead to cerebrovascular hemorrhage resulting from the sharp rise in blood pressure .

Renal vasoconstriction: Parenterally administered epinephrine initially may produce constriction of renal blood vessels and decrease urine formation. High doses may cause complete renal shutdown .

Pulmonary edema: Fatality may also result from pulmonary edema due to the peripheral constriction and cardiac stimulation produced by epinephrine injection .

Digital vasoconstriction: Since epinephrine is a strong vasoconstrictor, accidental injection into the digits, hands or feet may lead to the loss of blood flow to the affected area. Treatment should be directed at vasodilation in addition to further treatment of anaphylaxis .

Precaution

The solution should not be used if it is pinkish or darker than slightly yellow or if it contains a precipitate. Adrenaline is readily destroyed by alkalies and oxidizing agents. In the latter category are Oxygen, Chlorine, Iodine, Permanganates, Chromates, Nitrites and salts of easily reducible metals, especially Iron. Adrenaline should not be mixed with Sodium bicarbonate; the solution is oxidised to adrenochrome and then forms polymers.

Special warnings and precautions for use

Administer slowly with caution to elderly patients and to patients with ischemic heart disease, hypertension, diabetes mellitus, hyperthyroidism or psychoneurosis. Use with extreme caution in patients with long-standing bronchial asthma and emphysema who have developed degenerative heart disease. Anginal pain may be induced when coronary insufficiency is present.

Interaction

Use of Adrenaline with excessive doses of digitalis, mercurial diuretics or other drugs that sensitize the heart to arrhythmias is not recommended. The adverse effects of Adrenaline may be potentiated by tricyclic antidepressants; certain antihistamines; e.g, Diphenhydramine, Tripelennamine, Chlorpheniramine and L-thyroxine Sodium.

Food Interaction

Adrenaline Drug Interaction

Moderate: albuterol, albuterolUnknown: diphenhydramine, diphenhydramine, fluticasone nasal, fluticasone nasal, montelukast, montelukast, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, ondansetron, ondansetron, cetirizine, cetirizine

Adrenaline Disease Interaction

Major: cardiovascular disease, dehydrationModerate: parkinson's disease, acidosis, diabetes

Elimination Route

Following I.V. (intravenous) injection, epinephrine disappears rapidly from the blood stream. Subcutaneously or I.M. (intramuscular) administered epinephrine has a rapid onset and short duration of action. Subcutaneous (SC) administration during asthmatic attacks may produce bronchodilation within 5 to 10 minutes, and maximal effects may occur within 20 minutes. The drug becomes fixed in the tissues rapidly , .

Half Life

The plasma half-life is approximately 2-3 minutes. However, when administered by subcutaneous or intramuscular injection, local vasoconstriction may delay absorption so that epinephrine's effects may last longer than the half-life suggests .

Clearance

Intravenous injection produces an immediate and intensified response. Following intravenous injection, epinephrine disappears rapidly from the blood stream .

Elimination Route

The majority of the dose of epinephrine is seen excreted in the urine , . About 40% of a parenteral dose of epinephrine is excreted in urine as metanephrine, 40% as VMA, 7% as 3-methoxy-4-hydroxyphenoglycol, 2% as 3,4-dihydroxymandelic acid, and the rest as acetylated derivatives. These metabolites are excreted mainly as the sulfate conjugates and, to a lesser extent, the glucuronide conjugates. Only small amounts of the drug are excreted completely unchanged .

Pregnancy & Breastfeeding use

Pregnancy Category C. It crosses the placenta and is excreted in breast milk. Adrenaline should only be used in pregnancy if the potential benefits outweigh the risks to the fetus.

Lactating mothers: It is excreted in breast milk and therefore Adrenaline is not recommended for use during lactation because of the risk of adverse effects of infants.

Contraindication

Hypertension, arteriosclerosis, coronary disease and hyperthyroidism. Not to be given to patients taking monoamine oxidase inhibitors.

Acute Overdose

Symptoms: Cardiac arrhythmia leading to ventricular fibrillation, severe hypertension leading to pulmonary edema and cerebral hemorrhage.

Treatment: Combined alpha and beta-adrenergic blocking agents such as Labetalol may counteract the effects of adrenaline, or a beta-blocking agent may be used to treat any supraventricular arrhythmias and Phentolamine to control the alpha-mediated effects on the peripheral circulation. Rapidly acting vasodilators such as nitrates and Sodium Nitroprusside may also be helpful. Immediate resuscitation support must be available.

Interaction with other Medicine

Use of Adrenaline with excessive doses of digitalis, mercurial diuretics or other drugs that sensitize the heart to arrhythmias is not recommended. The adverse effects of Adrenaline may be potentiated by tricyclic antidepressants; certain antihistamines; e.g, Diphenhydramine, Tripelennamine, Chlorpheniramine and L-thyroxine Sodium.

Storage Condition

Store below 25 °C. Protect from light.

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