MEDICAINE 2%

Indications

• Local anesthesia for minor surgical procedures
• Anaesthesia before venepuncture
• Anaesthesia for skin lesions
• Regional anesthesia techniques (e.g., for cervical curettage or debridement of leg ulcers)

Dosage

Children: Neonate: Apply up to 1 g for a maximum of 1 hour before procedure, under occlusive dressing. For children 1-2 months, the same dosage applies. Consult BNF for Children for further dosing information.

Adults: Apply up to 10 g under occlusive dressing for 30–60 minutes before the procedure. Specific dosage may vary based on the procedure and patient condition; consult BNF for detailed guidelines.

Mechanism of action

Mepivacaine exerts its effects by binding to voltage-gated sodium channels on the neuronal cell membrane, inhibiting sodium influx, which is essential for the generation and conduction of action potentials in nerve fibers. This leads to a reversible loss of sensation in the targeted area.

Pharmacodynamics

Mepivacaine provides rapid onset of anesthesia, with effects typically lasting between 1 to 3 hours depending on the mode of administration and concentration used. It is favored for its lower potential for vasodilation compared to other local anesthetics, thus providing a more prolonged effect in certain settings.

Pharmacokinetics

Mepivacaine is rapidly absorbed into the bloodstream when administered parenterally. It is metabolized primarily in the liver and excreted in the urine, with a half-life of approximately 1.5 to 2.5 hours in healthy adults. The drug's pharmacokinetics can be altered in patients with hepatic impairment, necessitating caution in such populations.

Contra-indications

• Avoid injection into infected tissues
• Avoid injection into inflamed tissues
• Severe atrio-ventricular conduction disorders not controlled by a pacemaker
• Hypersensitivity to mepivacaine or other amide local anesthetics

Adverse effects

• Arrhythmia
• Dizziness
• Hypertension
• Hypotension
• Nausea
• Paraesthesia
• Vomiting
• Neurotoxicity
• Sexual dysfunction (in adults)
• Methaemoglobinaemia
• Fever (in adults)
• Headache (in adults)
• Skin reactions

Interactions

• Antiarrhythmics
• Other local anesthetics

Precautions

• Consider dose reduction in elderly and debilitated patients
• Caution in patients with cardiovascular disease, epilepsy, hypovolaemia, impaired cardiac conduction, impaired respiratory function, and myasthenia gravis
• Increased risk of toxic plasma concentrations in patients with hepatic impairment

Pregnancy

Use with caution in early pregnancy.

Breast-feeding

Use with caution.

Storage

Store below 25°C, protect from light.

Formulations

• Mepivacaine hydrochloride cream 5% (Denela, Emla, Nulbia), containing 25 mg of lidocaine and 25 mg of prilocaine per gram

Indications

• Anaphylaxis
• Cardiac arrest
• Severe asthma exacerbations
• Shock (including septic shock)
• Vasopressor support in critical care

Dosage

Children: For an

Adults: For anaphylaxis, 0.3 to 0.5 mg (0.3 to 0.5 mL of a 1:1000 solution) intramuscularly. For cardiac arrest, 1 mg (10 mL of a 1:10,000 solution) intravenously every 3 to 5 minutes during resuscitation.

Mechanism of action

Adrenalinated exerts its effects primarily through the activation of adrenergic receptors, specifically the alpha and beta receptors. It stimulates alpha-1 adrenergic receptors which leads to vasoconstriction, increasing peripheral resistance and blood pressure. Activation of beta-1 adrenergic receptors enhances cardiac output by increasing heart rate and contractility. Stimulation of beta-2 adrenergic receptors causes bronchodilation, improving airflow in patients with bronchospasm.

Pharmacodynamics

The pharmacodynamic effects of adrenalinated include increased heart rate, increased myocardial contractility, vasodilation in skeletal muscle, and bronchodilation. The onset of action is rapid, with effects typically observed within minutes of administration. The duration of action is variable but generally lasts from 5 to 15 minutes, depending on the route of administration.

Pharmacokinetics

Adrenalinated is rapidly absorbed when administered via intravenous or intramuscular routes. It is metabolized primarily by the liver and other tissues through the action of catechol-O-methyltransferase and monoamine oxidase, leading to the formation of inactive metabolites. The half-life is very short, approximately 2 to 3 minutes, necessitating repeated dosing or continuous infusion in critical care settings. Excretion occurs primarily through the urine as metabolites.

Contra-indications

• Hypersensitivity to adrenaline or any component of the formulation
• Caution in patients with cardiovascular disease, hyperthyroidism, or diabetes mellitus

Adverse effects

• Tachycardia
• Hypertension
• Anxiety
• Tremors
• Palpitations
• Nausea
• Vomiting
• Headache
• Dizziness
• Sweating
• Pallor

Interactions

• Non-selective beta-blockers may antagonize the effects of adrenaline
• Monoamine oxidase inhibitors (MAOIs) can potentiate the effects of adrenaline
• Tricyclic antidepressants may enhance the cardiovascular effects of adrenaline
• Other sympathomimetics may increase the risk of cardiovascular effects

Precautions

• Use with caution in patients with a history of seizures
• Monitor patients with pre-existing cardiovascular disease closely
• Use in an appropriate environment due to potential for rapid physiological changes

Pregnancy

Adrenaline should only be used during pregnancy if clearly needed, as it may affect uterine contraction.

Breast-feeding

Adrenaline is considered to be safe during breastfeeding, but caution is advised due to potential effects on the infant.

Storage

Store at room temperature, away from light. Do not freeze.

Formulations

• Injection solution (e.g., adrenaline hydrochloride)
• Inhalation solution
• Topical preparations

Indications

• Anaphylaxis
• Cardiac arrest
• Severe asthma exacerbations
• Croup
• Vasodilatory shock

Dosage

Adults: For anaphylaxis, 0.5 mg (0.5 mL of 1:1000 solution) intramuscularly may be administered. In cardiac arrest, 1

Mechanism of action

Epinephrine acts on alpha and beta-adrenergic receptors. It minimizes vasodilation and increases vascular permeability during anaphylaxis, counteracting hypotension. Additionally, it relaxes bronchial smooth muscle, alleviating bronchospasm and wheezing. Its positive inotropic and chronotropic effects increase myocardial contractility and heart rate, respectively. The drug also raises blood sugar levels through glycogenolysis in the liver and acts as a histamine antagonist, beneficial in allergic reactions.

Pharmacodynamics

Epinephrine mimics sympathetic nervous system actions, increasing heart rate, myocardial contractility, and renin release via beta-1 receptors. Its beta-2 effects produce bronchodilation, aiding in asthma treatment. In croup, nebulized epinephrine results in significant symptom reduction. It also alleviates pruritus, urticaria, and angioedema, and relaxes smooth muscle in the gastrointestinal and genitourinary tracts, enhancing its efficacy in anaphylaxis.

Pharmacokinetics

Epinephrine is rapidly absorbed and has a short duration of action. It is metabolized mainly by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) in the liver and other tissues. The onset of action occurs within minutes when administered parenterally, while the effects may last for several minutes, depending on the route of administration. The drug is excreted mainly in the urine as metabolites.

Contra-indications

• Hypersensitivity to adrenaline or any of its components
• In patients with narrow-angle glaucoma
• During general anaesthesia with halogenated hydrocarbons
• In cases of cardiomyopathy or ventricular tachyarrhythmias

Adverse effects

• Tachycardia
• Hypertension
• Anxiety
• Tremors
• Headache
• Nausea
• Vomiting
• Palpitations

Interactions

• Betablockers, selective: Increases risk of hypertension and bradycardia
• Entacapone: Increases risk of cardiovascular adverse effects
• Opicapone: Increases risk of cardiovascular adverse effects
• Tolcapone: Increases effects

Precautions

• Caution in patients with cardiovascular disease
• Caution in patients with hyperthyroidism
• Caution in patients with diabetes mellitus due to glycemic effects
• Monitor patients for potential adverse cardiovascular effects

Pregnancy

Epinephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It crosses the placenta.

Breast-feeding

Epinephrine is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store at room temperature, protected from light. Do not freeze.

Formulations

• Injection solution (1:1000, 1:10,000)
• Inhalation solution
• Auto-injector device

Indications

• Used as a stabilizing agent in pharmaceuticals
• Used in food products as a preservative or acidity regulator

Dosage

Children: Refer to specific product information for dosing recommendations in children, as pediatric dosing guidelines will depend on the formulation and indication.

Adults: Refer to specific product information for detailed dosing recommendations, as the dosage of bitartrate can vary based on its use in different formulations.

Mechanism of action

Bitartrate acts primarily as a buffering agent, helping to maintain pH balance in formulations. It may enhance the solubility of specific active ingredients, thereby facilitating their absorption and efficacy. The precise mechanisms may vary depending on the specific bitartrate compound and its application.

Pharmacodynamics

The pharmacodynamics of bitartrate compounds are largely dependent on their specific use. Generally, bitartrate can influence the pharmacokinetics of co-administered drugs by altering their solubility and stability. This can lead to increased absorption and improved therapeutic outcomes. The effects on the central nervous system or other systems are not well characterized, as bitartrate is primarily used for its physicochemical properties rather than direct pharmacological effects.

Pharmacokinetics

The pharmacokinetics of bitartrate compounds largely depend on the specific formulation and the active ingredients involved. Generally, bitartrate salts are expected to dissociate in the gastrointestinal tract, contributing to the systemic availability of the active drug. The absorption, distribution, metabolism, and excretion profiles will vary based on the formulation and route of administration.

Pregnancy

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

Breast-feeding

Bitartrate is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• Local infiltration anesthesia
• Regional anesthesia
• Dental procedures
• Minor surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. The order of loss of nerve function typically follows pain, temperature, touch, proprioception, and skeletal muscle tone.

Pharmacodynamics

Mepivicaine is an amide local anesthetic characterized by a reasonably rapid onset and medium duration of action. Systemic absorption can lead to minimal effects on the cardiovascular and central nervous systems, with limited changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance at therapeutic doses.

Pharmacokinetics

Mepivacaine is absorbed systemically when used in local anesthesia, leading to effects on the cardiovascular and central nervous systems. Its pharmacokinetics involve metabolism primarily in the liver, with renal excretion of metabolites. The specific half-life and distribution can vary based on the route of administration and patient factors.

Contra-indications

• Hypersensitivity to mepivacaine or other amide local anesthetics
• Severe heart block
• Hypovolemia
• Infection at the injection site

Adverse effects

• Dizziness
• Tinnitus
• Nausea
• Vomiting
• Headache
• Allergic reactions
• Cardiovascular effects such as hypotension or arrhythmias

Interactions

• Other local anesthetics can increase the risk of toxicity
• Certain antiarrhythmics may have additive effects on cardiac conduction
• Monoamine oxidase inhibitors (MAOIs) may enhance the effects of local anesthetics

Precautions

• Use with caution in patients with hepatic impairment
• Caution in patients with cardiovascular disease
• Monitor for signs of systemic toxicity during administration
• Use with caution in pregnant patients

Pregnancy

Mepivacaine should only be used during pregnancy if the benefits outweigh the risks. Limited data is available on its safety in pregnant women.

Breast-feeding

Mepivacaine is excreted in breast milk. Caution is advised if the mother is breastfeeding.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Injection solution (e.g., 1%, 2% concentrations)

Mechanism of action

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. The mechanism of rise in blood pressure ... is threefold: a direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action), an increased heart rate (positive chronotropic action), vasoconstriction in many vascular beds, especially in precapillary resistance vessels of skin, mucosa, and kidney, along with marked constriction of veins. ... Epinephrine affects respiration primarily by relaxing bronchial muscle. It has a powerful bronchodilator action, most evident when bronchial muscle is contracted because of disease, as in bronchial asthma, or in response to drugs or various autacoids. In such situations, epinephrine has a striking therapeutic effect as a physiological antagonist to substances that cause bronchoconstriction. The beneficial effects of epinephrine in asthma also may arise from inhibition of antigen-induced release of inflammatory mediators from mast cells, and to a lesser extent from diminution of bronchial secretions and congestion within the mucosa. Inhibition of mast cell secretion is mediated by beta2 receptors, while the effects on the mucosa are mediated by alpha receptors The electrophysiologic effects of circulating epinephrine in humans were examined in four study groups of 10 subjects each. In 10 subjects without structural heart disease (Group 1) and in 10 patients with coronary disease or dilated cardiomyopathy (Group 2) epinephrine infusion at 25 and 50 ng/kg body weight per min for 14 min resulted in an elevation of the plasma epinephrine concentration in the physiologic range. In both groups it produced a dose-dependent decrease in the effective refractory period of the atrium, atrioventricular node and ventricle and improvement in atrioventricular node conduction. Epinephrine facilitated the induction of sustained ventricular tachycardia in 3 of the 20 subjects. In Group 3, a beta-adrenergic blocking dose of propranolol was added to the infusion of 50 ng/kg per min of epinephrine. Propranolol not only reversed the effects of epinephrine, but also lengthened these variables compared with baseline values. In group 4, propranolol was administered first, followed by 50 ng/kg per min of epinephrine. Propranolol alone slowed atrioventricular node conduction and mildly prolonged the refractory periods. In the presence of beta-blockade, epinephrine had no effect on atrioventricular node properties but resulted in a lengthening of the atrial and ventricular effective refractory periods. In conclusion, epinephrine in physioloic doses shortens the effective refractory period of the atrium, atrioventricular node and ventricle, improves atrioventricular node conduction and may facilitate the induction of sustained ventricular tachycardia. The overall electrophysiologic effects of epinephrine result from stimulation of beta-receptors. Stimulation of alpha-receptors by epinephrine has no effect on the atrioventricular node but prolongs the effective refractory period of the atrium and ventricle, partially offsetting the shortening of refractory periods mediated by beta-receptor stimulation. Epinephrine

Pharmacodynamics

Epinephrine is a sympathomimetic drug. It causes an adrenergic receptive mechanism on effector cells and mimics all actions of the sympathetic nervous system except those on the facial arteries and sweat glands. Important effects of epinephrine include increased heart rate, myocardial contractility, and renin release via beta-1 receptors. Beta-2 effects produce bronchodilation which may be useful as an adjunct treatment of asthma exacerbations as well as vasodilation, tocolysis, and increased aqueous humor production. In croup, nebulized epinephrine is associated with both clinically and statistically significant transient reduction of croup symptoms 30 minutes post-treatment. Epinephrine also alleviates pruritus, urticaria, and angioedema and may be helpful in relieving gastrointestinal and genitourinary symptoms associated with anaphylaxis because of its relaxing effects on the smooth muscle of the stomach, intestine, uterus, and urinary bladder.

Mechanism of action

Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.

Pharmacodynamics

Mepivicaine is an amide local anesthetic. Mepivicaine as a reasonably rapid onset and medium duration and is known by the proprietary names as Carbocaine and Polocaine. Mepivicaine is used in local infiltration and regional anesthesia. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal.