SCHERIPROCT OINTMENT

Indications

• Corticosteroid-responsive conditions
• Autoimmune diseases
• Inflammatory eye conditions
• Certain malignancies
• Chronic inflammatory disorders

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing recommendations based on age and weight.

Adults: Refer to the BNF for specific adult dosing guidelines based on the condition being treated. Doses may vary depending on the severity of the condition and the clinical response.

Mechanism of action

Prednisolone binds to the glucocorticoid receptor, resulting in altered gene expression that decreases vasodilation, capillary permeability, and leukocyte migration to sites of inflammation. It inhibits phospholipase A2, reducing the production of arachidonic acid derivatives, and suppresses pro-inflammatory transcription factors such as NF-Kappa B. This results in an anti-inflammatory effect at lower doses and immunosuppressive effects at higher doses.

Pharmacodynamics

Corticosteroids like prednisolone exert their effects by inhibiting pro-inflammatory signals and promoting anti-inflammatory signals through their action on the glucocorticoid receptor. Prednisolone has a relatively short half-life of 2.1 to 3.5 hours, and while it has a wide therapeutic window, long-term use can lead to hypothalamic-pituitary-adrenal axis suppression and increased infection risk.

Pharmacokinetics

Prednisolone is rapidly absorbed and has a short duration of action. Its pharmacokinetics involve extensive metabolism in the liver, primarily through hepatic enzymes, leading to various metabolites. The elimination half-life is approximately 2.1 to 3.5 hours, and it is primarily excreted in the urine. Chronic use can affect circadian rhythms and homeostasis.

Contra-indications

• Known allergy to prednisolone or any of its components
• Systemic fungal infections
• Active tuberculosis
• Untreated bacterial infections

Adverse effects

• Increased susceptibility to infections
• Gastrointestinal disturbances
• Fluid retention
• Hypertension
• Cushing's syndrome
• Osteoporosis
• Mood changes
• Hyperglycemia

Interactions

• Mitotane (Moderate - decreases exposure)
• Rifampicin (Moderate - decreases exposure)
• Cobicistat (Unknown - increases exposure)
• Idelalisib (Unknown - increases exposure)
• Clarithromycin (Unknown - increases exposure)

Precautions

• Monitor for signs of infection during therapy
• Use with caution in patients with a history of gastrointestinal ulcers
• Tapering of dosage may be necessary to avoid withdrawal symptoms
• Consider potential effects on growth in pediatric patients

Pregnancy

Prednisolone is classified as a Category C drug. It should only be used if the potential benefits justify the potential risk to the fetus.

Breast-feeding

Prednisolone is excreted in breast milk. Caution should be exercised when administered to nursing mothers.

Storage

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

Formulations

• Tablets: 2 mg, 4 mg, 16 mg, 100 mg
• Suspension for injection
• Powder and solvent for solution for injection

Indications

• Metabolic disorders
• Food additive
• Potential role in cannabinoid synthesis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to specific clinical guidelines or consult the BNF for appropriate dosing information.

Mechanism of action

Caproate acts as a precursor in the cannabinoid biosynthesis pathway. It influences lipid metabolism and may modulate various physiological processes through its interaction with fatty acid receptors, although specific receptor interactions and downstream effects require further elucidation.

Pharmacodynamics

Caproate is associated with lipid metabolism and may have roles in energy production and cellular signaling. Its effects can vary based on concentration and biological context, contributing to metabolic processes and potentially impacting appetite regulation and energy homeostasis.

Pharmacokinetics

Caproate is absorbed through the gastrointestinal tract and metabolized in the liver. It undergoes β-oxidation to produce energy and can be incorporated into various lipid structures. The pharmacokinetic profile, including absorption, distribution, metabolism, and excretion, can be influenced by factors such as diet and individual metabolic rates.

Pregnancy

There is limited data on the use of caproate in pregnancy. Caution is advised.

Breast-feeding

Caution is advised as the effects on the nursing infant are not well studied.

Storage

Store in a well-closed container at room temperature, away from light.

Indications

• Local anesthesia for minor surgical procedures
• Topical anesthetic for skin and mucous membrane procedures
• Dental anesthesia

Dosage

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

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Cinchocaine functions by blocking both the initiation and conduction of nerve impulses. It decreases the permeability of the neuronal membrane to sodium ions through inhibition of sodium channels. This stabilizes the membrane and inhibits depolarization, leading to the failure of propagated action potentials and subsequent conduction blockade. The anesthetic action progressively develops in a nerve, increasing the threshold for electrical excitability, slowing impulse conduction, and decreasing the probability of propagation of the action potential.

Pharmacodynamics

As an amide-type local anesthetic, cinchocaine shares pharmacodynamic properties with other agents in its class, such as lidocaine. It provides a reversible blockade of nerve conduction, effectively numbing the area to which it is applied. Its onset and duration of action may vary based on concentration and the specific formulation used.

Pharmacokinetics

Cinchocaine is absorbed through mucous membranes and the skin, with its onset of action typically occurring within minutes. The duration of action can vary, often lasting for several hours. It is metabolized primarily in the liver and excreted through the kidneys. The pharmacokinetic profile may be influenced by factors such as the route of administration and individual patient characteristics.

Adverse effects

• Local irritation
• Allergic reactions
• Systemic toxicity (e.g., seizures, cardiac arrest)

Precautions

• Use with caution in patients with a history of hypersensitivity to local anesthetics
• Caution in patients with severe hepatic impairment

Pregnancy

Cinchocaine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as a category B drug.

Breast-feeding

Cinchocaine is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Topical cream
• Gels
• Ointments

Mechanism of action

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels. Although altered homeostatic regulation, including disturbance of 24-h rhythms, is often observed in the patients undergoing glucocorticoid therapy, the mechanisms underlying the disturbance remains poorly understood. We report here that chronic treatment with a synthetic glucocorticoid, prednisolone, can cause alteration of circadian clock function at molecular level. Treatment of cultured hepatic cells (HepG2) with prednisolone induced expression of Period1 (Per1), and the prednisolone treatment also attenuated the serum-induced oscillations in the expression of Period2 (Per2), Rev-erbalpha, and Bmal1 mRNA in HepG2 cells. Because the attenuation of clock gene oscillations was blocked by pretreating the cells with a Per1 antisense phosphothioate oligodeoxynucleotide, the extensive expression of Per1 induced by prednisolone may have resulted in the reduced amplitude of other clock gene oscillations. Continuous administration of prednisolone into mice constitutively increased the Per1 mRNA levels in liver and skeletal muscle, which seems to attenuate the oscillation in the expressions of Per2, Rev-erbalpha, and Bmal1. However, a single daily administration of prednisolone at the time of day corresponding to acrophase of endogenous glucocorticoid levels had little effect on the rhythmic expression of clock genes. These results suggest a possible pharmacological action by prednisolone on the core circadian oscillation mechanism and indicate the possibility that the alteration of clock function induced by prednisolone can be avoided by optimizing the dosing schedule. Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Prednisolone has a short duration of action as the half life is 2.1-3.5 hours. Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Mechanism of action

Local anesthetics block both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions through sodium channel inhibition. This reversibly stabilizes the membrane and inhibits depolarization, resulting in the failure of a propagated action potential and subsequent conduction blockade. ... PREVENT THE GENERATION & THE CONDUCTION OF THE NERVE IMPULSE. THEIR PRIMARY SITE OF ACTION IS THE CELL MEMBRANE. ... BLOCK CONDUCTION BY DECREASING OR PREVENTING THE TRANSIENT INCREASE IN THE PERMEABILITY OF EXCITABLE MEMBRANES TO NA IONS THAT IS NORMALLY PRODUCED BY A SLIGHT DEPOLARIZATION ... /LOCAL ANESTHETICS/ AS ANESTHETIC ACTION PROGRESSIVELY DEVELOPS IN A NERVE, THE THRESHOLD FOR ELECTRICAL EXCITABILITY GRADUALLY INCREASES, THE RATE OF RISE OF THE ACTION POTENTIAL DECLINES, IMPULSE CONDUCTION SLOWS, & THE SAFETY FACTOR FOR CONDUCTION DECREASES; THESE FACTORS DECREASE PROBABILITY OF PROPAGATION OF THE ACTION POTENTIAL, AND NERVE CONDUCTION FAILS. /LOCAL ANESTHETICS/ ... CAN BLOCK K ION CHANNELS. ... BLOCKADE OF CONDUCTION IS NOT ACCOMPANIED BY ANY LARGE OR CONSISTENT CHANGE IN RESTING MEMBRANE DUE TO BLOCK OF K ION CHANNELS. /LOCAL ANESTHETICS/ ... SITE AT WHICH LOCAL ANESTHETICS ACT, AT LEAST IN THEIR CHARGED FORM, IS ACCESSIBLE ONLY FROM THE INNER SURFACE OF THE MEMBRANE. ... LOCAL ANESTHETICS APPLIED EXTERNALLY FIRST MUST CROSS THE MEMBRANE BEFORE THEY CAN EXERT A BLOCKING ACTION. /LOCAL ANESTHETICS/ ... ACT ON ANY PART OF NERVOUS SYSTEM & ON EVERY TYPE OF NERVE FIBER. /LOCAL ANESTHETICS/

Pharmacodynamics

Dibucaine is an amide-type local anesthetic, similar to lidocaine.