OLCORT OINT

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

Dosage

Children: Refer to specific drug information for detailed dosage recommendations.

Adults: Refer to specific drug information for detailed dosage recommendations.

Mechanism of action

The mechanism of action varies depending on the specific drug that 'contains' certain active ingredients. Each compound will have its own unique pharmacological pathway and target within the body, which can include receptor modulation, enzyme inhibition, or other biochemical interactions.

Pharmacodynamics

Pharmacodynamics will depend on the active ingredients in the formulation. It generally encompasses the biochemical and physiological effects of the drug and its mechanisms of action, including the relationship between drug concentration and effect.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of the specific active ingredients within the formulation. This can vary significantly based on the drug's chemical properties, route of administration, and individual patient factors.

Pregnancy

Consult with a healthcare provider before use, as safety during pregnancy has not been established.

Breast-feeding

Consult with a healthcare provider before use, as it is not known if this drug is excreted in human milk.

Storage

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

Indications

• Severe infections caused by gram-negative bacteria
• Complicated urinary tract infections
• Bacterial sepsis
• Endocarditis caused by susceptible organisms

Dosage

Children: Dosing in children is also weight-based and varies by indication. Refer to the BNF for Children for specific dosing recommendations.

Adults: Dosage varies significantly based on the infection severity and type, renal function, and the specific bacterial susceptibility. Refer to clinical guidelines or the BNF for precise dosing.

Mechanism of action

Gram works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit of the bacteria, causing misreading of the mRNA and ultimately preventing the synthesis of essential proteins necessary for bacterial growth and replication.

Pharmacodynamics

The pharmacodynamics of Gram include its bactericidal activity against susceptible bacteria. The drug shows concentration-dependent killing, meaning that higher drug concentrations correlate with greater bactericidal effects. The post-antibiotic effect is noted, where bacterial growth is inhibited even after the drug concentration falls below the minimum inhibitory concentration (MIC).

Pharmacokinetics

Gram is usually administered parenterally (intravenously or intramuscularly), and its absorption can vary based on the route of administration. It is distributed widely in body fluids and tissues, although it does not penetrate well into the central nervous system. The drug is primarily eliminated through the kidneys, and its half-life may be prolonged in patients with renal impairment. Monitoring of drug levels may be necessary to avoid toxicity.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Allergic reactions
• Rash
• Renal dysfunction

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function during therapy
• Assess for potential allergic reactions

Pregnancy

Use only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Use with caution, as it may be excreted in breast milk. Consult with a healthcare provider.

Storage

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