SEDIPROCT SUPPOSITORIES (20G)

Indications

• Adrenocortical insufficiency
• Inflammatory bowel disease
• Severe acute asthma
• Acute hypersensitivity reactions
• Congenital adrenal hyperplasia
• Replacement therapy in adrenal insufficiency

Dosage

Children: For children aged 1-5 months: Initially 25 mg 3 times a day, adjusted according to response. For children aged 6 months-5 years: Initially 50 mg 3 times a day, adjusted according to response. For children aged 6-11 years: Initially 100 mg 3 times a day, adjusted

Adults: 100-500 mg 3-4 times a day or when required. For replacement in adrenocortical insufficiency, 20-30 mg once daily, adjusted according to response.

Mechanism of action

Hydrocortisone binds to the glucocorticoid receptor, leading to decreased vasodilation and permeability of capillaries, inhibition of leukocyte migration to inflammation sites, and changes in gene expression that promote anti-inflammatory pathways. It inhibits phospholipase A2, NF-kappa B, and other inflammatory transcription factors, stabilizing leukocyte lysosomal membranes and reducing the release of destructive enzymes. High doses can raise sodium levels and decrease potassium levels through mineralocorticoid receptor activity.

Pharmacodynamics

Hydrocortisone's pharmacodynamic profile includes the inhibition of various inflammatory mediators and the promotion of anti-inflammatory cytokines. Its effects are dose-dependent, with lower doses providing anti-inflammatory benefits, while higher doses exhibit immunosuppressive effects. It has a wide therapeutic index and moderate duration of action.

Pharmacokinetics

Hydrocortisone is metabolized primarily in the liver, with its effects lasting for several hours to days. The onset of action varies with the route of administration, being more rapid when given intravenously. Its half-life is influenced by factors such as dose and administration route, and it is excreted through urine as metabolites.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to hydrocortisone or any excipients

Adverse effects

• Increased risk of infections
• Hyperglycemia
• Hypertension
• Fluid retention and edema
• Gastrointestinal disturbances
• Mood changes
• Osteoporosis
• Peptic ulcer disease
• Cushing's syndrome with long-term use

Interactions

• Mitotane: Moderate decrease in hydrocortisone exposure
• Rifampicin: Moderate decrease in hydrocortisone exposure
• Cobicistat: Unknown effect, potential increase in hydrocortisone exposure
• Idelalisib: Unknown effect, potential increase in hydrocortisone exposure
• Clarithromycin: Unknown effect, potential increase in hydrocortisone exposure

Precautions

• Use with caution in patients with diabetes
• Monitor for signs of infection during therapy
• Consider dose adjustment in patients with hepatic impairment
• Gradual withdrawal is recommended to avoid adrenal insufficiency after prolonged therapy

Pregnancy

Hydrocortisone is categorized as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Hydrocortisone is excreted in breast milk. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• Injectable form (sodium succinate)
• Modified-release tablets
• Immediate-release tablets

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

Indications

• Chronic venous insufficiency
• Varicose veins
• Hemorrhoids
• Edema associated with venous disorders

Dosage

Children: Refer to specific product guidelines and clinical studies for pediatric dosing recommendations, as safety and efficacy in children have not been well established.

Adults: Refer to specific product guidelines and clinical studies for dosing recommendations, as they may vary based on formulation and indication.

Mechanism of action

Esculosid exerts its effects through multiple mechanisms. It enhances venous tone and reduces capillary permeability, thereby decreasing edema. It also possesses anti-inflammatory properties by inhibiting the activity of pro-inflammatory mediators. Additionally, it may enhance the synthesis of prostaglandins, leading to improved vascular function and reduced symptoms associated with venous insufficiency.

Pharmacodynamics

The pharmacodynamics of esculosid include its ability to strengthen vascular walls and improve microcirculation. By reducing permeability of capillaries and enhancing venous return, it alleviates symptoms such as heaviness in the legs, swelling, and pain associated with venous disorders. The antioxidant properties of esculosid also contribute to its protective effects against oxidative stress in endothelial cells.

Pharmacokinetics

Esculosid is absorbed from the gastrointestinal tract following oral administration. It undergoes first-pass metabolism, which may affect its bioavailability. The elimination half-life and specific metabolic pathways are not extensively documented, but it is known to be metabolized in the liver. The excretion of its metabolites occurs primarily through the urine.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Headache

Precautions

• Use with caution in patients with known allergies to horse chestnut or related plants
• Monitor for potential bleeding in patients on anticoagulants

Pregnancy

There is insufficient data on the safety of esculosid during pregnancy; use only if clearly needed.

Breast-feeding

It is not known whether esculosid is excreted in human milk; use with caution.

Storage

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

Formulations

• Oral capsules
• Topical gel

Indications

• Bacterial conjunctivitis
• Other bacterial eye infections

Dosage

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

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Framycetine binds to specific 30S-subunit proteins and 16S rRNA within the bacterial ribosome. This binding interferes with the decoding site, resulting in misreading of mRNA and the incorporation of incorrect amino acids into polypeptides. This ultimately leads to the production of nonfunctional or toxic peptides and the disassembly of polysomes into inactive monosomes, contributing to its bactericidal effect.

Pharmacodynamics

Framycetine is particularly effective against aerobic bacteria, with its mechanism of action centered on the inhibition of bacterial protein synthesis. It is primarily used in ocular infections, where it exerts its effects locally. The bactericidal activity of framycetine results from its ability to disrupt the translational machinery necessary for protein production, thereby stopping bacterial growth and replication.

Pharmacokinetics

The pharmacokinetics of framycetine involve its topical application, particularly in ophthalmic formulations. Due to its local use, systemic absorption is minimal, and therefore, systemic pharmacokinetic data are less relevant. The duration of bactericidal activity has been shown to last from 48 to 72 hours following application. The drug is primarily eliminated through renal pathways.

Adverse effects

• Ocular irritation
• Hypersensitivity reactions
• Corneal damage
• Systemic absorption leading to nephrotoxicity or ototoxicity

Interactions

• May enhance the nephrotoxic effects of other aminoglycosides or nephrotoxic agents
• Potential interaction with neuromuscular blocking agents

Precautions

• Use with caution in patients with known sensitivity to aminoglycosides
• Monitor renal function in patients receiving prolonged therapy
• Avoid use in patients with myasthenia gravis due to potential neuromuscular blockade

Pregnancy

Framycetin should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. The safety of framycetin in pregnant women has not been established.

Breast-feeding

Framycetin is excreted in breast milk, caution is advised when used in nursing mothers.

Storage

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

Formulations

• Ophthalmic solution
• Ophthalmic ointment

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. Following topical application, corticosteroids produce anti-inflammatory, antipruritic, and vasoconstrictor actions. The activity of the drugs is thought to result at least in part from binding with a steroid receptor. Corticosteroids decrease inflammation by stabilizing leukocyte lysosomal membranes, preventing release of destructive acid hydrolases from leukocytes; inhibiting macrophage accumulation in inflamed areas; reducing leukocyte adhesion to capillary endothelium; reducing capillary wall permeability and edema formation; decreasing complement components; antagonizing histamine activity and release of kinin from substrates; reducing fibroblast proliferation, collagen deposition, and subsequent scar tissue formation; and possibly by other mechanisms as yet unknown. Corticosteroids, especially the fluorinated corticosteroids, have antimitotic activity on cutaneous fibroblasts and the epidermis. /Corticosteroids/ Reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFkappaB, known to modulate inflammatory responses including ROS generation. Plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels /were investigated/. p47(phox) subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47(phox) subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFkappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFkappaB and an increase in IL-10 may cause the inhibitory modulation on p47(phox) subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.

Pharmacodynamics

Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes. Hydrocortisone has a wide therapeutic index and a moderate duration of action. Patients should stop taking the medication if irritation or sensitization occurs.

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.

Mechanism of action

Framycetin binds to specific 30S-subunit proteins and 16S rRNA, four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes. Like other aminoglycoside antibiotic drugs, neomycin inhibits bacterial ribosomes by binding to the 30S ribosomal subunit of susceptible bacteria and disrupting the translational machinery of bacterial protein synthesis. Bacterial translation is normally initiated by the mRNA binding to the 30S ribosomal subunit and subsequent binding with 50S subunit for elongation. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ A class of angiogenesis inhibitor has emerged from our mechanistic study of the action of angiogenin, a potent angiogenic factor. Neomycin, an aminoglycoside antibiotic, inhibits nuclear translocation of human angiogenin in human endothelial cells, an essential step for angiogenin-induced angiogenesis. The phospholipase C-inhibiting activity of neomycin appears to be involved, because U-73122, another phospholipase C inhibitor, has a similar effect. In contrast, genistein, oxophenylarsine, and staurosporine, inhibitors of tyrosine kinase, phosphotyrosine phosphatase, and protein kinase C, respectively, do not inhibit nuclear translocation of angiogenin. Neomycin inhibits angiogenin-induced proliferation of human endothelial cells in a dose-dependent manner. At 50 microM, neomycin abolishes angiogenin-induced proliferation but does not affect the basal level of proliferation and cell viability. Other aminoglycoside antibiotics, including gentamicin, streptomycin, kanamycin, amikacin, and paromomycin, have no effect on angiogenin-induced cell proliferation. Most importantly, neomycin completely inhibits angiogenin-induced angiogenesis in the chicken chorioallantoic membrane at a dose as low as 20 ng per egg. These results suggest that neomycin and its analogs are a class of agents that may be developed for anti-angiogenin therapy. ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

Pharmacodynamics

Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. Neomycin mediates its bactericidal action by inhibiting bacterial protein synthesis, thereby suppressing the growth and survival of susceptible bacteria. Following oral administration, the duration of bactericidal activity of neomycin ranged from 48 to 72 hours. By decreasing colonic bacteria that produce ammonia, neomycin was shown to be effective as an adjunctive therapy in hepatic coma to improve neurologic symptoms. Neomycin is active against both gram positive and gram negative organisms, including the major _E. coli_ species resident in the colon as well as the enteropathogenic forms of _E. coli_. It is also active against _Klebsiella_-_Enterobacter_ group. Resistant strains of _E. coli_, _Klebsiella_ and _Proteus spp_. may emerge from neomycin therapy. Neomycin has no antifungal activity and has some activity against some protozoa.