Oxybutynin

Pharmacological properties

Oxybutynin has a direct antispasmodic effect on detrusor smooth muscle fibers, as well as an anticholinergic effect, blocking the effect of acetylcholine on smooth muscle m-cholinergic receptors. these properties cause relaxation of the bladder detrusor. in patients with unstable bladder, driptan increases the volume of the bladder and reduces the frequency of spontaneous detrusor contractions.

Pharmacokinetics According to pharmacokinetic reports, after oral administration, oxybutynin is rapidly absorbed in the digestive tract, C_max in blood plasma is achieved in less than 1 h, and then decreases biexponentially with T_½ from 2 to 3 hours. The maximum effect is observed within 3-4 hours, the residual effect may occur even after the 10th hour.

Equilibrium concentration is reached after 8 days of oral administration of the drug. In elderly people leading an active lifestyle, oxybutynin does not show the ability to accumulate, and its pharmacokinetics does not differ from that in other adult patients. However, in debilitated elderly patients, C values_max and AUC increase significantly. Oxybutynin is extensively metabolized in the liver, primarily with the help of enzymes of the cytochrome P450 system, in particular CYP 3A4, which is found mainly in the liver and intestinal walls; its metabolites also have an M-anticholinergic effect. The main route of excretion are the kidneys; only 0.3–0.4% of the unchanged active ingredient is determined in the urine of rats after 24 hours and 1% in the urine of dogs after 48 hours. Thus, in rats and dogs, oxybutynin is almost completely metabolized.

Indications

Urinary incontinence, peremptory urination or rapid urination with instability of the bladder due to neurogenic dysfunction of the bladder (detrusor hyperreflexia), which is noted in diseases such as multiple sclerosis and spina bifida, or due to idiopathic instability of the detrusor function (motor urgent). also used to control overactive bladder that occurs after surgery on the bladder or prostate gland, or with concomitant cystitis.

Use in children

Oxybutynin hydrochloride is indicated for use in children with:

• urinary incontinence, peremptory urination or rapid urination with instability of the bladder function due to idiopathic overactive bladder or neurogenic bladder dysfunction (detrusor hyperactivity);
• nocturnal enuresis associated with hyperactivity of the detrusor, in combination with non-drug treatment in case of failure of another therapy.

Application

The drug is administered orally. the tablet can be divided into two equal doses.

Adults The usual dose is 5 mg 2-3 times a day. The dose can be increased to a maximum - 5 mg 4 times a day - to obtain a clinical effect, subject to tolerability of side effects.

Elderly patients. In elderly patients, T_½ the drug is increased, so it is recommended to use a dose of 2.5 mg 2 times a day, in particular for debilitated patients. The dose can be increased to 5 mg 2 times a day to obtain a clinical effect, provided that the side effects are well tolerated.

Children from the age of 5 years. Neurogenic instability of the bladder, nocturnal enuresis: the usual dose is 2.5 mg 2 times a day. The dose can be increased to 5 mg 2-3 times a day to obtain a clinical effect, provided that the side effects are well tolerated. With nocturnal enuresis, the last dose should be taken before bedtime.

Children. For children under 5 years of age, the use of the drug is not recommended due to insufficient data on safety and effectiveness.There is limited evidence of the possibility of using oxybutynin in children with monosymptomatic nocturnal enuresis (unrelated to detrusor hyperactivity). In children over the age of 5 years, the drug should be used with caution, since they may be more sensitive to the effects of oxybutynin, in particular regarding the manifestations of adverse reactions from the central nervous system and psyche.

Contraindications

Hypersensitivity to the active substance or to any other component of the drug; myasthenia gravis; narrow-angle glaucoma or small anterior chamber of the eye; patients with fever or conditions of elevated ambient temperature due to the risk of provoking hyperpyrexia; children under 5 years old; esophageal dysfunction, including hiatal hernia; functional or organic gastrointestinal obstruction, including pyloric stenosis, paralytic bowel obstruction, intestinal atony; patients with ileostomy, colostomy, toxic megacolon; severe ulcerative colitis; patients with obstruction of the urinary tract, when urinary retention may worsen, for example, with prostatic hypertrophy.

Side effects

From the gastrointestinal tract: nausea, constipation, dry mouth, discomfort in the abdomen, diarrhea, vomiting and gastroesophageal reflux.

From the side of metabolism and nutrition: loss of appetite.

From the side of the central nervous system: headache, dizziness, drowsiness, cramps.

From the psyche: agitation, hallucinations, nightmares, cognitive impairment (confusion, disorientation, anxiety, delirium, paranoia).

From the side of the heart: tachycardia and cardiac arrhythmias.

From the eyes: blurred vision, dilated pupils, increased intraocular pressure, angle-closure glaucoma and dry conjunctiva.

From the kidneys and urinary tract: dysuria and urinary retention.

From the side of the vessels: hot flashes (more pronounced in children than in adults).

On the part of the skin and subcutaneous tissues: dry skin, allergic reactions, including skin rashes, urticaria, angioedema and photosensitivity.

special instructions

The drug should be used with caution in elderly patients, who may be more sensitive to the effects of oxybutynin and may need a dose reduction (see application). the drug should also be used with caution in patients with autonomic neuropathy, gastrointestinal diseases, including severe gastrointestinal motility disorders, in patients with impaired liver or kidney function or cerebrovascular insufficiency.

After taking Driptan, it is possible to increase the clinical manifestations of hyperthyroidism, IHD, chronic heart failure, hypertension, prostatic hyperplasia, cardiac arrhythmias, and tachycardia.

It is believed that oxybutynin is not safe for patients with porphyria, since it showed porphyrinogenicity in experiments on animals and in vitro.

Long-term use of the drug Driptan can lead to the development of dental caries due to a decrease or cessation of salivation. In this regard, it is recommended to regularly check the condition of the teeth with prolonged use of the drug.

In case of urinary tract infection, antibiotic therapy should be prescribed.

Patients with rare inherited forms of galactose intolerance, lactase deficiency, or glucose and galactose malabsorption syndrome should not take Driptan because of the lactose content.

Use during pregnancy or lactation. The safety of oxybutynin during pregnancy has not been established. Animal studies have revealed the occurrence of reproductive toxicity when using doses that are toxic to mothers, so oxybutynin should be avoided during pregnancy, unless there are safer alternatives.

In animals, oxybutynin penetrates into the mother’s milk, therefore, Driptan should not be prescribed to women during lactation.

The ability to influence the reaction rate when driving vehicles or other mechanisms. The drug may cause decreased visual acuity or drowsiness.Patients should not drive a car or work with other mechanisms, except when it has been previously established that the drug does not impair the patients ability to physical or mental activity.

Interactions

With simultaneous use with lizuride, there is a risk of impaired consciousness, therefore, regular clinical supervision of patients is necessary.

With caution, Driptan should be used with other anticholinergics because of the potential potentiation of the anticholinergic effect.

Isolated cases of interaction between anticholinergics and phenothiazines, amantidine, butyrophenones, levodopa, digitalis preparations, and tricyclic antidepressants were noted. Caution should be exercised if oxybutynin is used concomitantly with these drugs.

Due to decreased gastric motility, oxybutynin may impair the absorption of other drugs.

Overdose

Symptoms symptoms of an overdose of driptan develop in order from an increase in the usual side effects from the central nervous system (from anxiety and agitation to psychotic behavior) to circulatory disorders (hot flashes, decreased hell, circulatory failure, etc.), respiratory failure, paralysis and coma.

Treatment. In case of an overdose, mainly symptomatic treatment is used: immediate gastric lavage; with severe life-threatening anticholinergic syndrome, the use of neostigmine (or physostigmine) is possible; elimination of a fever.

With severe anxiety or excitement, IV diazepam should be administered.

With iv tachycardia, propranolol is administered.

With urinary retention, bladder catheterization is indicated.

In case of paralysis of the respiratory muscles, perform mechanical ventilation.

Storage conditions

Out of the reach of children at a temperature not exceeding 30 ° c.

Conditions of dispensing from pharmacies: by prescription.