Proctoheal New Ointment

Indications

• Ventricular arrhythmias, especially after myocardial infarction
• Local anesthesia for minor surgical procedures
• Pain relief in conditions such as oral ulceration and inflammation

Dosage

Children: Refer to the BNF for Children

Adults: For ventricular arrhythmias, an initial intravenous bolus of 100 mg is given over a few minutes, followed by a continuous infusion of 4 mg/minute for 30 minutes, then reduced to 2 mg/minute for 2 hours, and finally to 1 mg/minute. The total dose should not exceed 3 mg/kg.

Mechanism of action

Lidocaine hydrochloride exerts its effects by blocking voltage-gated sodium channels in neurons, which inhibits the influx of sodium ions during depolarization. This action prevents the generation and conduction of nerve impulses, resulting in local anesthesia. The drug also stabilizes neuronal membranes and decreases the excitability of both peripheral and central nerves.

Pharmacodynamics

The onset of action for lidocaine is rapid, typically occurring within minutes of administration, with a duration of action that can vary based on the route of administration and the presence of additives such as epinephrine. Lidocaine can be used to manage ventricular arrhythmias by decreasing myocardial excitability and conduction velocity, thus stabilizing the cardiac rhythm.

Pharmacokinetics

Lidocaine is well-absorbed when administered intravenously, with peak plasma concentrations occurring shortly after infusion. It is extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP1A2 and CYP3A4, producing active metabolites. The elimination half-life of lidocaine ranges from 1.5 to 2 hours, and it is excreted mainly in urine. Caution is advised in cases of hepatic impairment, as the metabolism of lidocaine may be significantly reduced, leading to increased plasma levels.

Contra-indications

• All grades of atrioventricular block
• Severe myocardial depression
• Sino-atrial disorders

Adverse effects

• Anxiety
• Arrhythmias
• Cardiac arrest
• Circulatory collapse
• Confusion
• Dizziness
• Drowsiness
• Euphoric mood
• Headache
• Hypotension (may lead to cardiac arrest)
• Loss of consciousness
• Methaemoglobinaemia
• Muscle twitching
• Nausea
• Neurological disorders
• Tinnitus
• Tremor
• Blurred vision
• Vomiting

Interactions

• Antiarrhythmics

Precautions

• Acute porphyrias (consider infusion of glucose for its anti-porphyrinogenic effects)
• Congestive cardiac failure (consider lower dose)
• Post cardiac surgery (consider lower dose)
• Monitor serum potassium
• Caution in hepatic impairment (risk of increased exposure)
• Caution in renal impairment (possible accumulation of lidocaine and active metabolites)

Pregnancy

Crosses the placenta but not known to be harmful in animal studies-use if benefit outweighs risk.

Breast-feeding

Present in milk but amount too small to be harmful.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Lidocaine hydrochloride 5 mg per 1 ml solution for injection
• Lidocaine hydrochloride 10 mg per 1 ml solution for injection
• Lidocaine hydrochloride 10% solution for oral use

Indications

• Eczema
• Psoriasis
• Contact dermatitis
• Allergic dermatitis
• Seborrheic dermatitis

Dosage

Children: Refer to specific product information or clinical guidelines for appropriate dosing in children, as it varies by formulation and condition treated.

Adults: Refer to specific product information or clinical guidelines for appropriate dosing, as it varies by formulation and condition treated.

Mechanism of action

Acetonide exerts its effects by binding to glucocorticoid receptors in the cytoplasm of target cells, leading to the translocation of the receptor-ligand complex into the nucleus. This complex then influences the expression of specific genes, resulting in decreased production of pro-inflammatory cytokines and increased production of anti-inflammatory proteins. This modulation of gene expression contributes to its anti-inflammatory and immunosuppressive effects.

Pharmacodynamics

The pharmacodynamics of acetonide involve its ability to inhibit the migration of leukocytes to sites of inflammation, reduce the production of inflammatory mediators such as prostaglandins and leukotrienes, and suppress the immune response. The potency and duration of action can vary based on the specific formulation and concentration used.

Pharmacokinetics

Acetonide is absorbed through the skin when applied topically, with systemic absorption depending on the formulation, application area, and duration of use. It undergoes hepatic metabolism, and its metabolites are excreted primarily through the urine. The half-life and clearance rates can vary based on individual patient factors and specific formulations.

Contra-indications

• Hypersensitivity to acetonide or any component of the formulation.
• Active or untreated infections at the site of application.

Adverse effects

• Local irritation or burning sensation at the application site.
• Skin thinning or atrophy with prolonged use.
• Systemic effects such as adrenal suppression with high doses or prolonged therapy.

Interactions

• Increased risk of systemic effects when used with other corticosteroids.
• Potentially altered metabolism when administered with CYP3A4 inhibitors or inducers.

Precautions

• Use with caution in patients with a history of tuberculosis or other infections.
• Monitor for signs of adrenal insufficiency in patients on high doses.
• Avoid application to large areas of the body or under occlusive dressings.

Pregnancy

Acetonide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare professional before use.

Breast-feeding

Limited data available. Use with caution as it may be excreted in breast milk. Consult with a healthcare professional before use.

Storage

Store at room temperature, away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• Topical cream
• Topical ointment
• Topical solution

Indications

• Atopic dermatitis
• Psoriasis
• Contact dermatitis
• Seborrheic dermatitis
• Allergic rhinitis
• Asthma
• Eczema

Dosage

Children: Refer to the BNF for Children for appropriate dosing recommendations for pediatric patients.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated and the formulation used.

Mechanism of action

Flucinolone exerts its effects by binding to glucocorticoid receptors in the cytoplasm of target cells. This receptor-ligand complex translocates to the nucleus, where it regulates the expression of genes involved in inflammation and immune response. The anti-inflammatory action is primarily due to the inhibition of pro-inflammatory cytokines, suppression of leukocyte infiltration, and stabilization of lysosomal membranes.

Pharmacodynamics

The pharmacodynamics of flucinolone involve its ability to modulate the immune response and decrease inflammation. It reduces the production of inflammatory mediators such as prostaglandins and leukotrienes, leading to decreased redness, swelling, and pain associated with inflammatory conditions. Additionally, flucinolone has an impact on metabolism, influencing glucose levels and protein synthesis in target tissues.

Pharmacokinetics

Flucinolone is typically well-absorbed when applied topically, with systemic absorption varying based on the formulation and the site of application. It is metabolized predominantly in the liver, and the metabolites are excreted primarily via the kidneys. The half-life of flucinolone can be influenced by factors such as the route of administration and individual patient characteristics.

Contra-indications

• Hypersensitivity to flucinolone or any component of the formulation
• Active infections (viral, bacterial, or fungal) in the area to be treated
• Rosacea or perioral dermatitis

Adverse effects

• Skin thinning or atrophy
• Telangiectasia
• Striae
• Burning or itching at the site of application
• Systemic absorption leading to adrenal suppression (with prolonged use)

Interactions

• May enhance the effects of other topical corticosteroids
• Caution with concurrent use of other immunosuppressive agents

Precautions

• Use with caution in patients with a history of hormonal disorders
• Monitor for signs of local or systemic infection
• Avoid prolonged use on large surface areas or under occlusive dressings

Pregnancy

Flucinolone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Systemic absorption may occur, which poses risks.

Breast-feeding

Caution is advised when using flucinolone while breastfeeding. It is recommended to avoid application on the breast unless necessary.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Topical cream
• Topical ointment
• Topical solution
• Topical lotion

Indications

• Local anesthesia for surgical and diagnostic procedures
• Management of certain types of arrhythmias
• Topical anesthesia for mucosal surfaces

Dosage

Children: Refer to the BNF for Children for specific pediatric dosing information.

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Lidocaine acts by diffusing through neural sheaths into the axoplasm, where it is ionized and binds reversibly to sodium ion channels on nerve cell membranes. This binding keeps the channels in an open state, preventing nerve depolarization and thus blocking action potential transmission. This mechanism facilitates its anesthetic effects by aborting pain signal generation and preventing their transmission to the brain.

Pharmacodynamics

Excessive blood levels of lidocaine may lead to changes in cardiac output, total peripheral resistance, and mean arterial pressure. The block of autonomic fibers and the direct depressant effect on the cardiovascular system can cause hypotension when recommended dosages are exceeded. Lidocaine's action on sodium channels affects cardiac myocytes, potentially leading to hypotension, bradycardia, myocardial depression, arrhythmias, or even cardiac arrest.

Pharmacokinetics

Lidocaine is absorbed rapidly and widely distributed throughout the body. It undergoes extensive hepatic metabolism, primarily by cytochrome P450 enzymes, leading to various metabolites. Its elimination half-life is approximately 1.5 to 2 hours, but this can vary based on factors such as hepatic blood flow and enzyme activity.

Contra-indications

• Hypersensitivity to lidocaine or any amide local anesthetics
• Severe degree of heart block
• A history of malignant hyperthermia

Adverse effects

• Hypotension
• Bradycardia
• Myocardial depression
• Cardiac arrhythmias
• CNS stimulation followed by depression
• Dizziness
• Nausea
• Vomiting
• Tinnitus

Interactions

• cimetidine+lidocaine: Moderate (increases exposure)
• cobicistat+lidocaine: Unknown (increases concentration)
• lidocaine+suxamethonium: Unknown (increases effects)
• ciprofloxacin+lidocaine: Unknown (increases exposure)

Precautions

• Use with caution in patients with hepatic impairment
• Use with caution in patients with cardiac conditions
• Monitor for signs of systemic toxicity, especially after high doses or rapid administration

Pregnancy

Lidocaine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as FDA pregnancy category B.

Breast-feeding

Lidocaine is excreted in breast milk, but at therapeutic doses, it is not expected to cause adverse effects in nursing infants. Monitor infants for any signs of sedation.

Storage

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

Formulations

• Lidocaine injection solution
• Lidocaine cream
• Lidocaine gel
• Lidocaine patch

Mechanism of action

Lidocaine is a local anesthetic of the amide type. It is used to provide local anesthesia by nerve blockade at various sites in the body. It does so by stabilizing the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. In particular, the lidocaine agent acts on sodium ion channels located on the internal surface of nerve cell membranes. At these channels, neutral uncharged lidocaine molecules diffuse through neural sheaths into the axoplasm where they are subsequently ionized by joining with hydrogen ions. The resultant lidocaine cations are then capable of reversibly binding the sodium channels from the inside, keeping them locked in an open state that prevents nerve depolarization. As a result, with sufficient blockage, the membrane of the postsynaptic neuron will ultimately not depolarize and will thus fail to transmit an action potential. This facilitates an anesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their generation in the first place. In addition to blocking conduction in nerve axons in the peripheral nervous system, lidocaine has important effects on the central nervous system and cardiovascular system. After absorption, lidocaine may cause stimulation of the CNS followed by depression and in the cardiovascular system, it acts primarily on the myocardium where it may produce decreases in electrical excitability, conduction rate, and force of contraction. Abnormal, repetitive impulse firing arising from incomplete inactivation of Na+ channels may be involved in several diseases of muscle and nerve, including familial myotonias and neuropathic pain syndromes. Systemic local anesthetics have been shown to have clinical efficacy against myotonias and some forms of neuropathic pain, so we sought to develop an in vitro model to examine the cellular basis for these drugs' effects. In frog sciatic nerves, studied in vitro by the sucrose-gap method, peptide alpha-toxins from sea anemone (ATXII) or scorpion (LQIIa) venom, which inhibit Na+ channel inactivation, induced repetitively firing compound action potentials (CAPs) superimposed on a plateau depolarization lasting several seconds. The initial spike of the CAP was unaffected, but the plateau and repetitive firing were strongly suppressed by 5-30 uM lidocaine. Lidocaine caused a rapid, concentration-dependent decay of the plateau, quantitatively consistent with blockade of open Na(+) channels. Early and late repetitive firing were equally suppressed by lidocaine with IC50 = 10 uM. After washout of lidocaine and LQIIa, the plateau and repetitive firing remained for > 1 hr, showing that lidocaine had not caused dissociation of channel-bound alpha-toxin. These findings indicate that therapeutic concentrations of lidocaine can reverse the "abnormal" features of action potentials caused by non-inactivating Na+ channels without affecting the normal spike component. Lidocaine controls ventricular arrhythmias by suppressing automaticity in the His-Purkinje system and by suppressing spontaneous depolarization of the ventricles during diastole. These effects occur at lidocaine concentrations that do not suppress automaticity of the sinoatrial (SA) node. At therapeutic plasma concentrations, lidocaine has little effect on atrioventricular (AV) node conduction and His-Purkinje conduction in the normal heart. Specialized conducting tissues of the atria are less sensitive to the effects of lidocaine than are those of ventricular tissues. Lidocaine has a variable effect on the effective refractory period (ERP) of the AV node; the drug shortens the ERP and the action potential duration of the His-Purkinje system. Lidocaine does not appear to affect excitability of normal cardiac tissue. Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydroly

Pharmacodynamics

Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded. In particular, such cardiac effects are likely associated with the principal effect that lidocaine elicits when it binds and blocks sodium channels, inhibiting the ionic fluxes required for the initiation and conduction of electrical action potential impulses necessary to facilitate muscle contraction. Subsequently, in cardiac myocytes, lidocaine can potentially block or otherwise slow the rise of cardiac action potentials and their associated cardiac myocyte contractions, resulting in possible effects like hypotension, bradycardia, myocardial depression, cardiac arrhythmias, and perhaps cardiac arrest or circulatory collapse. Moreover, lidocaine possesses a dissociation constant (pKa) of 7.7 and is considered a weak base. As a result, about 25% of lidocaine molecules will be un-ionized and available at the physiological pH of 7.4 to translocate inside nerve cells, which means lidocaine elicits an onset of action more rapidly than other local anesthetics that have higher pKa values. This rapid onset of action is demonstrated in about one minute following intravenous injection and fifteen minutes following intramuscular injection. The administered lidocaine subsequently spreads rapidly through the surrounding tissues and the anesthetic effect lasts approximately ten to twenty minutes when given intravenously and about sixty to ninety minutes after intramuscular injection. Nevertheless, it appears that the efficacy of lidocaine may be minimized in the presence of inflammation. This effect could be due to acidosis decreasing the amount of un-ionized lidocaine molecules, a more rapid reduction in lidocaine concentration as a result of increased blood flow, or potentially also because of increased production of inflammatory mediators like peroxynitrite that elicit direct actions on sodium channels.