User:Benadryl Submarine/Budesonide

Budesonide, sold under the brand name Pulmicort among others, is a steroid medication. It is available as an inhaler, nebulization solution', pill', nasal spray, and rectal forms. The inhaled form is used in the long-term management of asthma and chronic obstructive pulmonary disease (COPD). The nasal spray is used for allergic rhinitis and nasal polyps. Modified-release pills or capsules and rectal forms may be used for inflammatory bowel disease including Crohn's disease, ulcerative colitis, and microscopic colitis.

Contraindications
Budesonide is contraindicated in people with:


 * Known hypersensitivity to budesonide or any component of the formulation. 
 * Status asthmaticus or other acute episodes of asthma which would require intensive, immediate measures. 

In Canada, there are additional contraindications labeled for Budesonide for people with:


 * Systemic or local bacterial, fungal and viral infections. 
 * Active or quiescent pulmonary tuberculosis. 

Side effects
Nasal budesonide inhalers have been associated with a number of side effects. These include nose irritation or burning, bleeding or sores in the nose, lightheadedness, upset stomach, cough, hoarseness, dry mouth, rash, sore throat, bad taste in mouth, change in mucus, and blurred vision. Other symptoms which should be reported immediately include difficulty in breathing, swelling of the face, white patches in the throat, mouth, or nose, irregular menstrual periods, severe acne, and on rare occasions, behavioral changes (mostly affecting children).

Overdose
Acute toxicity from an overdose of Budesonide is significantly more rare than an overdosing of budesonide over a prolonged period of therapy, however both can can cause systemic toxicity that manifests as hypercortisolism. Symptoms of an overdose include more specific symptoms such as darkening and thinning of the skin, changes in body fat around the face, neck, back, and waist, increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex, as well as some less specific symptoms such as diarrhea, dizziness, loss of appetite, mental depression, nausea, skin rash, unusual tiredness or weakness, or vomiting.

Interactions
'''Budesonide is mainly metabolized in the liver by the enzyme CYP34A. Drugs that are CYP3A4 inhibitors such as ketoconazole, clarithromycin, ritonavir, and nefazodone, among many others, may inhibit the metabolism of Budesonide, prolonging its elimination and leading to possible increased rates of corticosteroid adverse effects due to unwanted drug accumulation. Grapefruit is also a potent inhibitor of CYP3A4, and its consumption is not recommended while on budesonide treatment .'''

___an aside___

''' * removing high-fat meal delays absorption from interactions. Slowing gastric emptying and therefore delaying absorption without impeding overall absorption is not an interaction specific to Budesonide nor irregular. However I'll add this part to the pharmacokinetics section.'''

''' * removing information regarding echinacea. Theoretically, it is thought to have immunostimulant properties that may antagonize the pharmacologic effects of immunosuppressants. However, I could not find any solid clinical cases of drug interactions that have been reported for Budesonide or corticosteroids, and Lexi-comp shows no interactions. Interactions Between Herbal Medicines and Prescribed Drugs states "the currently available evidence suggests that echinacea is unlikely to pose serious health threats for patients combining it with conventional drugs". Most information advocating for the possible interaction stem around 1990-2000 and state their recommendation is theoretical and not based on clinical cases. Drugs.com doesn't include the interaction either.'''

Brand names
Budesonide is a drug that is marketed under various brand and generic names internationally, some notable examples for each formulation are listed here;

Inhalation: Pulmicort; Pulmicort Flexhaler, Pulmicort Nebuamp, Pulmicort Turbuhaler, TARO-Budesonide, TEVA-Budesonide, Novolizer budesonid meda, Budenova.

'''Systemic (oral pills): Tarpeyo, Uceris, Eohilia, Cortiment, Entocort Jorveza. '''

'''Nasal: MYLAN-Budesonide AQ, Rhinocort Aqua, Formancis. '''

'''Topical: Entocort, Uceris, Budenofalk. '''

Economics
In 2019, generic budesonide was listed as being involved in Teva's price fixing scheme in the United States.

Legal status
In May 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Kinpeygo, intended for the treatment of primary immunoglobulin A nephropathy. The applicant for this medicinal product is Calliditas Therapeutics AB. Kinpeygo is a hybrid medicine of Entocort which has been authorised in the EU since 2 April 1992. Kinpeygo contains the same active substance as Entocort but has a different formulation and a different indication. Kinpeygo was approved for medical use in the European Union in July 2022.

Mechanism of action
'''Budesonide is an agonist of glucocorticoid receptors. Among its effects are:'''


 * Controls the rate of protein synthesis. 
 * Depresses the migration of polymorphonuclear leukocytes and fibroblasts. 
 * Reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.
 * Has a potent glucocorticoid activity and weak mineralocorticoid activity.

Pharmacokinetics
Different pharmacokinetic proprieties can be seen in the absorption of budesonide depending on how it is formulated. When taken as an extended-release oral capsule, budesonide has an oral bioavailability of 9–21% and reaches peak plasma concentrations (Cmax) within 2–8 hours. A high fat meal when taken with the capsule can lengthen the time it takes to reach Cmax by another 2.3 hours, but will not have any other affects on the the pharmacokinetics properties of budesonide. When inhaled through an metered dose inhaler,  34% of budesonide is deposited in the lung with a bioavailability of 39% and reaches Cmax within 10 minutes.  When nebulized, budesonide has an bioavailability of 6% and reaches Cmax  within 1–3 hours.  When formulated as a rectal foam, budesonide has an bioavailability of 3% to 27% and reaches Cmax  around 1.5 hours.

The plasma protein binding of budesonide is around 85-90%, with an apparent volume of distribution of 2.2-3.9L/kg. '''Budesonide is 80-90% metabolized at first pass in the liver by the hepatocytic cytochrome P450 isoenzyme 3A4 (CYP3A4) into two metabolites: 16 alpha-hydroxyprednisolone and 6 beta-hydroxybudesonide. Both of these metabolites have a negligible glucocorticoid activity of less than 1% compared to the parent compound budesonide. 60% of budesonide is excreted is through the urine as its metabolites, no unchanged budesonide is detectable in urine. The average elimination half-life in plasma is between 2-3.6 hours.'''