Articaine Hydrochloride + Epinephrine

Uses

Articaine and Epinephrine is an amide local anesthetic containing a vasoconstrictor used for local, infiltrative, or conductive anesthesia in both simple and complex dental procedures.

Articaine Hydrochloride + Epinephrine 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 Articaine Hydrochloride + Epinephrine works

Epinephrine acts on alpha and beta-adrenergic receptors. Epinephrine 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. Epinephrine 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

Articaine Hydrochloride + Epinephrine dosage

Below are the recommended volumes and concentrations of articaine-epinephrine for various types of anesthetic procedures. The dosages suggested below are for normal healthy adults, administered by submucosal infiltration and/or nerve block.

Infiltration: 0.5 mL to 2.5 mL or 20 mg to 100 mg of articaine

Nerve block: 0.5 mL to 3.4 mL or 20 mg to 136 mg of articaine

Oral surgery: 1.0 mL to 5.1 mL or 40 mg to 204 mg of articaine.

For normal healthy adults, the maximum dose of articaine administered by submucosal infiltration and/or nerve block should not exceed 7 mg/kg of body weight.

Side Effects

Common side effects include Pain, headache, facial edema, gingivitis, paresthesia, infection. Other side effects include pain, headache, positive blood aspiration into syringe, swelling, face edema, infection, neck pain, abdominal pain, ear pain, taste perversion, and accidental injury have been reported

Gastrointestinal side effects including nausea and emesis, gingivitis, constipation, diarrhea, dyspepsia, glossitis, gum hemorrhage, mouth ulceration, nausea, stomatitis, tongue edema, tooth disorder, and vomiting have been reported.

Musculoskeletal side effects including trismus, arthralgia, myalgia, back pain, and osteomyelitis have been reported.

General side effects including sleepiness, malaise, and asthenia have been reported.

Nervous system side effects including paresthesia, numbness and tingling, dizziness, dry mouth, facial paralysis, hyperesthesia, increased salivation, nervousness, neuropathy, paresthesia, somnolence, and exacerbation of Kearns-Sayre syndrome have been reported.

Cardiovascular side effects including palpitation, hemorrhage, migraine, syncope, tachycardia, and elevated blood pressure have been reported.

Respiratory side effects including pharyngitis, rhinitis, sinus pain, and sinus congestion have been reported.

Toxicity

Skin, LD₅₀ = 62 mg/kg (rat)

Pregnancy

Epinephrine 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. Epinephrine 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. Epinephrine 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 , . Epinephrine 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

The administration of local anesthetic solutions containing epinephrine to patients receiving monoamine oxidase inhibitors, nonselective beta-adrenergic antagonists or tricyclic antidepressants may produce severe, prolonged hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.

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. There are no adequate and well-controlled studies in pregnant women with articaine with epinephrine. This should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether Articaine and Epinephrine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this combination is administered to a nursing woman.

Contraindication

Articaine HCl and Epinephrine is contraindicated in patients who are hypersensitive to products containing sulfites. Products containing sulfites may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Special Warning

Pediatric Use: Safety of doses greater than 7 mg/kg of articaine in pediatric patients has not been established. Dosages in pediatric patients should be reduced, commensurate with age, body weight, and physical condition.

Renal or Hepatic Insufficiency: No studies have been performed with articaine and epinephrine in renal and hepatic impaired patient.

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.

Storage Condition

Store below 25 °C. Protect from light.

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