BUNASE 200MCG

Indications

• Chronic bowel disorders
• Crohn's disease affecting the ileum or ascending colon
• Ulcerative colitis
• Asthma management

Dosage

Children: For children 1-17 years: 3 mg three times a day for up to 8 weeks for Crohn's disease; 1 enema daily for 4 weeks for ulcerative colitis in children 12-17 years.

Adults: For Crohn's disease: 9 mg once daily for up to 8 weeks; for ulcerative colitis: 1 enema daily for 4 weeks. Dosage may vary, so refer to specific guidelines.

Mechanism of action

Budesonide exerts its effects by binding to corticosteroid receptors, modulating the expression of genes involved in inflammatory processes. This action leads to a significant reduction in inflammation and immune response.

Pharmacodynamics

As a potent anti-inflammatory agent, budesonide reduces the activity of inflammatory mediators and inhibits the recruitment of inflammatory cells to sites of inflammation, thus alleviating symptoms associated with conditions like asthma and inflammatory bowel disease.

Pharmacokinetics

Budesonide is rapidly absorbed after administration, with a significant first-pass metabolism resulting in a lower systemic exposure. It has a half-life of approximately 2-3 hours, and its effects can be prolonged due to its local action in the gut when used for bowel disorders.

Adverse effects

• Insomnia
• Stomatitis
• Taste disorders
• Diarrhoea
• Muscle twitching
• Oedema
• Anaemia
• Decreased appetite
• Ataxia
• Lymphadenopathy
• Macrocytosis
• Aseptic meningitis
• Severe cutaneous adverse reactions (SCARs)
• Parotitis
• Nephrotic syndrome
• Pseudomembranous enterocolitis
• Blood disorders

Interactions

• Grapefruit juice (severe - increases exposure)
• Cenobamate (moderate - decreases exposure)
• Mitotane (moderate - decreases exposure)
• Rifampicin (moderate - decreases exposure)
• Cobicistat (unknown - increases exposure)
• Idelalisib (unknown - increases exposure)
• Clarithromycin (unknown - increases exposure)

Precautions

• Caution in hepatic impairment
• Caution in renal impairment
• Monitor blood counts and liver function tests

Pregnancy

Theoretical risk of neonatal haemolysis; adequate folate supplements advised.

Breast-feeding

Small amounts may appear in milk; theoretical risk of neonatal haemolysis, especially in G6PD-deficient infants.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Budenofalk® Capsules
• Entocort® Capsules
• Entocort® Enema
• Oral suspension

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Other respiratory conditions requiring aerosolized delivery

Dosage

Children: Refer to specific inhalation product guidelines; dosing varies based on the medication being delivered.

Adults: Refer to specific inhalation product guidelines; dosing varies based on the medication being delivered.

Mechanism of action

Propellants function by creating a pressurized environment within an aerosol canister. When the valve is opened, the pressure difference allows the propellant to expand rapidly, forming a mist or spray of the active drug for inhalation. This mechanism ensures the drug is delivered efficiently and uniformly.

Pharmacodynamics

The pharmacodynamics of propellants is primarily related to their ability to deliver medications effectively. By creating an aerosolized form, they enhance the surface area of the drug, leading to improved absorption in the respiratory tract. The choice of propellant can also influence the stability and effectiveness of the drug being delivered.

Pharmacokinetics

The pharmacokinetics of propellants involve their behavior in the body after delivery. Generally, propellants are not intended to have therapeutic effects themselves, and thus their absorption, distribution, metabolism, and excretion are not typically a focus. However, the inhaled medication's pharmacokinetics will depend on the propellant used, including factors like solubility and particle size which affect the drug's deposition in the lungs.

Pregnancy

Limited data are available on the safety of propellants during pregnancy. It is advisable to avoid exposure unless absolutely necessary and to consult with a healthcare provider.

Breast-feeding

Caution is advised as the effects of propellants during breastfeeding are not well studied. Consultation with a healthcare provider is recommended.

Storage

Store in a cool, dry place away from direct sunlight and heat sources. Ensure that containers are kept tightly closed and 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. To investigate the roles of signal transduction and activator of transcription 6 (STAT6) and orosomucoid 1-like 3 (ORMDL3) in airway remodeling among asthmatic mice and to observe the effects of budesonide (BUD) on their expression, thirty mice were randomly divided into control, asthma, and BUD intervention group. The mice were sensitized and challenged with ovalbumin (OVA) to establish a mouse model of asthma. The BUD intervention group received aerosol inhalation of BUD dissolved in normal saline 30 minutes before each OVA challenge, while normal saline was used instead of OVA solution in the control group. The pathological changes in the airway were observed by hematoxylin-eosin staining and Masson staining. The interleukin-13 (IL-13) level in lung homogenate was measured by enzyme-linked immunosorbent assay. The mRNA expression of STAT6 and ORMDL3 was measured by RT-PCR. The asthma group showed more pathological changes in the airway than the control and BUD intervention groups, and the BUD intervention group had reduced pathological changes in the airway compared with the asthma group. The asthma and BUD intervention groups had significantly higher IL-13 levels and mRNA expression of STAT6 and ORMDL3 than the control group (P<0.05), and these indices were significantly higher in the asthma group than in the BUD intervention group (P<0.05). The Pearson correlation analysis showed that STAT6 mRNA expression was positively correlated with ORMDL3 mRNA expression (r=0.676, P=0.032). STAT6 and ORMDL3 may be involved in the airway remodeling of mice, and BUD can reduce airway remodeling in asthmatic mice, possibly by down-regulating mRNA expression of STAT6 and ORMDL3. Mucus hypersecretion from airway epithelium is a characteristic feature of severe asthma. Glucocorticoids (GCs) may suppress mucus production and diminish the harmful airway obstruction. We investigated the ability of GCs to suppress mRNA expression and protein synthesis of a gene encoding mucin, MUC5AC, induced by transforming growth factor (TGF)-alpha in human mucoepidermoid carcinoma (NCI-H292) cells and the molecular mechanisms underlying the suppression. We determined if GCs such as dexamethasone (DEX), budesonide (BUD), and fluticasone (FP) could suppress MUC5AC production induced by a combination of TGF-alpha and double-strand RNA, polyinosinic-polycytidylic acid (polyI:C). MUC5AC mRNA expression and MUC5AC protein production were evaluated. The signaling pathways activated by TGF-alpha and their inhibition by GCs were tested using a phosphoprotein assay and MUC5AC promoter assay. DEX significantly suppressed the expression of MUC5AC mRNA and MUC5AC protein induced by TGF-alpha. The activation of the MUC5AC promoter by TGF-alpha was significantly inhibited by DEX. DEX did not affect activation of downstream pathways of the EGF receptor or mRNA stability of MUC5AC transcripts. DEX, BUD, and FP suppressed MUC5AC protein expression induced by a combination of TGF-alpha and polyI:C in a dose-dependent manner. GCs inhibited MUC5AC production induced by TGF-alpha alone or a combination of TGF-alpha and polyI

Pharmacodynamics

Budesonide is a glucocorticoid used to treat respiratory and digestive conditions by reducing inflammation. It has a wide therapeutic index, as dosing varies highly from patient to patient. Patients should be counselled regarding the risk of hypercorticism and adrenal axis suppression.