SCHERIPROCT

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

• Local anesthesia for dental procedures
• Pain relief for minor surgical interventions
• Management of anal fissures and hemorrhoids

Dosage

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

Adults: Refer to established guidelines for local anesthetic administration. Dosage varies based on the procedure and formulation used.

Mechanism of action

Cinchocain exerts its anesthetic effect by blocking voltage-gated sodium channels in the neuronal cell membrane. This inhibition prevents the influx of sodium ions during the depolarization phase of action potentials, thereby reducing neuronal excitability and conduction of nerve impulses. As a result, the transmission of pain signals to the central nervous system is interrupted.

Pharmacodynamics

The pharmacodynamic properties of cinchocain involve its potency as a local anesthetic, which is determined by its chemical structure and affinity for sodium channels. The onset of action is relatively rapid, and the duration of anesthetic effect can vary based on the formulation and site of administration. The drug is effective in providing short-term analgesia and is often used in combination with other agents to enhance anesthetic efficacy.

Pharmacokinetics

Cinchocain is absorbed at the site of administration, with the rate of absorption influenced by factors such as the formulation and local blood flow. It undergoes hydrolysis primarily in the liver, where it is metabolized to inactive metabolites. The elimination half-life can vary, but the drug is generally excreted in urine. Due to its potential for systemic absorption, careful consideration of dosing and administration technique is necessary to minimize the risk of systemic toxicity.

Contra-indications

• Hypersensitivity to cinchocain or any of its components
• Severe liver disease
• Severe heart block
• Myasthenia gravis

Adverse effects

• Local skin reactions
• Systemic allergic reactions
• Cardiovascular effects such as arrhythmias
• CNS effects including dizziness, tremors, and seizures
• Hypotension

Interactions

• Other local anesthetics may increase the risk of toxicity
• Beta-blockers may enhance the cardiovascular effects
• Drugs that affect liver enzymes may alter cinchocain metabolism

Precautions

• Use with caution in patients with cardiac conditions
• Monitor for signs of systemic toxicity
• Avoid use in areas with compromised blood supply
• Caution in patients with renal impairment

Pregnancy

Use only if the potential benefit justifies the potential risk to the fetus. Limited data available.

Breast-feeding

Cinchocain should be used with caution during breastfeeding due to limited data on excretion in breast milk.

Storage

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

Formulations

• Topical cream
• Injection solution

Indications

• Cannabinoid biosynthesis
• Potential therapeutic effects in metabolic disorders
• Influence on lipid metabolism

Dosage

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

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

Mechanism of action

Hexanoate may participate in cannabinoid biosynthesis pathways, influencing the production of endocannabinoids that play roles in various physiological processes, including pain modulation, appetite regulation, and inflammation. The precise mechanisms through which hexanoate exerts its effects are still under investigation, but it is thought to affect metabolic pathways linked to lipid metabolism and endocannabinoid signaling.

Pharmacodynamics

Hexanoate is involved in energy metabolism and can influence lipid metabolism. It may also modulate the endocannabinoid system, which is crucial for maintaining homeostasis in the body. The pharmacodynamic effects of hexanoate include potential impacts on appetite, pain perception, and inflammatory responses.

Pharmacokinetics

The pharmacokinetics of hexanoate include metabolism primarily in the liver, where it can be converted into various metabolites. It may be absorbed through the gastrointestinal tract when consumed and can be incorporated into cellular membranes or utilized for energy production. The exact absorption rates, distribution, and elimination half-life of hexanoate require further investigation.

Pregnancy

There is insufficient data on the safety of hexanoate in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is limited information available on the excretion of hexanoate in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

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.