How Do Ipratropium and Albuterol Inhalers Work?

This product is a compound preparation, and its components are: each vial (2.5 ml) for inhalation solution contains ipratropium bromide 0.500 mg (equivalent to ipratropium bromide 0.522 mg) and salbutamol sulfate 3.000 mg (equivalent to Salbutamol base 2.5 mg).
Ipratropium Bromide Salbutamol

Citalite® (compound ipratropium bromide solution for inhalation), this product is suitable for patients who need a combination of bronchodilators for the treatment of reversible bronchospasm related to airway obstructive diseases.

Drug Name: Compound ipratropium bromide solution for inhalation

Hanyu Pinyin: Xi Ru Yong Fu Fang Yi Bing Tuo Xiu An Rong Ye
Drug type: Occupational injury medical insurance

Cobbit ingredients

Necessary characteristics

Colorless or almost colorless clear liquid.

Cobbit indications

This product is suitable for patients who need a variety of bronchodilators in combination to treat reversible bronchospasm related to airway obstructive diseases.

Cobbit Specifications

2.5 ml: 0.500 mg of ipratropium bromide (equivalent to 0.522 mg of ipratropium bromide monohydrate) and 3.000 mg of salbutamol sulfate (equivalent to 2.5 mg of salbutamol base).

Cobbit dosage

This product can be administered through a suitable nebulizer or intermittent positive pressure ventilator.

The following recommended dosages are for adults (including the elderly) and adolescents over 12 years:

Acute episode:

In most cases, a single vial or therapeutic dose can relieve symptoms. For severe cases, when one vial of the treatment dose does not relieve the symptoms, two vials of medicine can be used for treatment, but the patient must see a doctor or go to the nearest hospital as soon as possible.

Maintenance treatment period:

Use one vial 3 to 4 times a day.

Instructions for use:

This product can only be inhaled through a suitable nebulizing device and cannot be administered orally or by other routes.

1. Prepare the nebulizer as required by the manufacturer or under the guidance of a doctor to add the nebulizer.
2. Remove a vial from the drug strip.

3 Twist the top firmly and open the vial.

4 Squeeze the vial into the nebulizer dish.

5. Install the nebulizer and use the medicine according to the instructions.
6. After using the nebulizer, you should discard the remaining liquid in the nebulizer medicine dish and clean the nebulizer in accordance with the manufacturer's instructions for the next use.

Since this product does not contain preservatives, in order to prevent the drug from being contaminated by bacteria, it should be used immediately after the medicine bottle is opened. It is very important to use a new small medicine bottle for each inhalation treatment. Bottles that have been opened or damaged should be discarded and should not be used.

Users should be reminded in particular: Do not mix this product with other drugs in the same nebulizer!

Cobbit adverse reactions

As with other beta agonist drugs, common adverse effects of this product include headaches, dizziness, anxiety, tachycardia, skeletal muscle tremor and palpitations, especially for susceptible patients.

The use of ₂ receptor agonists can lead to potentially severe hypokalemia.

Like other inhalation treatments, cough, local irritation may occur, and inhaled trachea is rare.

Like other beta drugs, nausea, vomiting, sweating, muscle weakness, and myalgia / muscle spasm can occur after administration. In rare cases, diastolic blood pressure has decreased, systolic blood pressure has increased, and arrhythmias have occurred, especially with larger doses. Rear.

Very few cases have skin or allergic reactions, especially in hypersensitivity patients.

Few reports have reported psychological changes following inhaled treatment with pseudo-beta drugs.

The most common non-respiratory adverse reactions associated with anticholinergics are dry mouth and dysphonia.

There are reports of ocular complications (such as dilated pupils, increased intraocular pressure, and angle-closure glaucoma) when nebulized solution enters the eye when ipratropium bromide is used alone or concurrently with adrenergic ₂ receptor agonists ,eye pain).

Ocular side effects, gastrointestinal dysfunction, and urinary retention have occurred in only a few cases and can fully return to normal (see [Cautions] ).

Cobbit Taboo

Hypertrophic obstructive cardiomyopathy, tachycardia. Those who are allergic to any component of this product or to atropine and its derivatives are contraindicated.

Cobbit notes

Very few cases have reported that allergic reactions such as urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema may occur quickly after using this product.

Eye complications

When aerosolized ipratropium bromide enters the eye alone or in combination with an epinephrine beta ₂ receptor agonist, ocular complications such as dilated pupils, increased intraocular pressure, and angle-closure are reported. Glaucoma, eye pain).

Eye pain or discomfort, blurred vision, redness caused by conjunctival congestion, and corneal edema, but halo or colored imaging of the vision may be signs of acute angle-closure glaucoma. If you experience some of these symptoms, you should first use a miotic and consult your doctor immediately.

Patients should use this product properly under guidance. Care should be taken to avoid contact with liquids or aerosols . Patients are advised to inhale the nebulizing solution through the mouthpiece. If the device is not available, a suitable nebulizing mask can be used. Patients with glaucoma tend to be reminded to protect their eyes.

With the following diseases, especially when the dosage exceeds the recommended dosage, this product should be used with caution after weighing the risks / benefits: diabetes that has not been effectively controlled, recent myocardial infarction, severe organic cardiovascular disease, hyperthyroidism, chromaffin cells Tumors, high-risk individuals with angle-closure glaucoma, enlarged prostate, or obstructed neck in bladder cancer.

The use of beta ₂ stimulants can lead to potentially severe hypokalemia. In addition, hypoxia can aggravate the effect of hypokalemia on heart rhythm.

Patients with cystic fibrosis are more likely to develop gastrointestinal motility disorders.

When severely exacerbated dyspnea occurs, ask a doctor for treatment in time.

If it is necessary to use more than the recommended dosage to control the symptoms, the patient's treatment plan should be determined by the doctor.

Medications for pregnant women and lactating women

The safety of this product in human pregnancy has not been determined, and the drug should be used with caution in pregnancy, especially in the first three months.

The inhibitory effect of this product on uterine contraction should be considered.

Salbutamol sulfate and ipratropium bromide can be excreted from breast milk, and it is unknown how it affects the newborn. Although non-fat-soluble tetravalent alkali can enter milk, it is unlikely that ipratropium bromide will enter the baby to a greater extent. Especially when inhaled. However, since many drugs are excreted from breast milk, they should be used with caution in lactating women.

Cobbit medication for children

There is no clinical experience in using this product in children under 12 years of age.

Copiter Geriatrics

No special notice.

Cobine Drug Interactions

Concomitant use of xanthine derivatives, beta-adrenergics, and anticholinergics can increase side effects.

Xanthine derivatives, corticosteroids and diuretics can enhance hypokalemia caused by beta receptor agonists. Special attention should be paid to patients with severe airway obstruction.

Hypokalemia may increase the risk of arrhythmia in patients taking digoxin. It is recommended to monitor blood potassium levels in such cases.

Concurrent application of beta-blockers can significantly reduce bronchodilator effect.

-adrenergic agonists should be used with caution in patients who are receiving monoamine oxidase inhibitors or tricyclic antidepressants, because -adrenergic agonists can be enhanced.

Inhalation of halogenated hydroxyl anesthetics such as halothane, trichloroethylene, and enflurane can increase the susceptibility of beta receptor agonists to cardiovascular effects.

Cobiter overdose

symptom:

Side effects in excess are mainly caused by salbutamol.

Symptoms of overdose are caused by -adrenergic overstimulation, the most obvious manifestations of which are tachycardia, palpitations, tremor, hypertension, hypotension, widened pulse pressure, sore throat, arrhythmia, and flushing.

In view of prolonged treatment and topical application, the symptoms of ipratropium bromide overdose (such as dry mouth and visual disturbances) are actually mild and transient.

treatment:

In severe cases, sedatives and tranquilizers can be used.

-blockers, especially selective ₁ -blockers are suitable specific antidote, but it must be considered that the use of such drugs may increase bronchial obstruction, and patients with bronchial asthma should carefully adjust the dose.

Cobite Pharmacology and Toxicology

Ipratropium bromide is a tetravalent ammonium compound with anticholinergic (parasympathetic) properties. Preclinical trials have shown that it inhibits the reflex of the vagus nerve by antagonizing the transmitter acetylcholine released by the vagus nerve. Anticholinergic drugs can prevent the increase of intracellular monocyclic guanosine monophosphate caused by the interaction between acetylcholine and muscarinic receptors on bronchial smooth muscle.

After inhalation of ipratropium bromide, the effect is limited to the lungs and dilates the bronchi. It does not affect the whole body.

Salbutamol is a beta ₂ adrenergic receptor agonist, which acts to relax the smooth muscles of the airways. It acts on all smooth muscles from the main trachea to the terminal alveoli and antagonizes bronchoconstriction.

In this product, ipratropium bromide and salbutamol superimpose on muscarinic and 2 adrenergic receptors in the lungs to produce bronchiectasis, and the effect is better than single administration.

Controlled trials of patients with moderate to severe chronic obstructive pulmonary disease have shown that the bronchodilator effect of this product is superior to the use of its single component and has no potential side effects.

Acute toxicity tests have been performed on rats and dogs. The ratio of ipratropium bromide / salbutamol is the highest technically measurable dose, that is, 887/5397 g / kg body weight in rats and 165/862 g / kg body weight in dogs without signs of systemic toxicity. The compound is locally resistant Accepts well. According to the tested species (mouse, rat, and dog), the calculated LD50 of intravenous administration of ipratropium bromide is about 12-20 mg / kg body weight, and the salbutamol is 60-70 mg / kg body weight.

Rats and dogs were divided into two groups to conduct a 13-week inhalation toxicity test with ipratropium bromide and salbutamol. In this test, the heart was proven to be the target organ. Ipratropium bromide / salbutamol was used in rats at doses of 31.3 / 183.4 to 375.5 / 2188.4 g / kg body weight / day, and a dose-independent increase in cardiac weight was observed without any detectable histopathological changes. For dogs at a dose of 32.3 / 197.6 to 129.2 / 790.4 g / kg body weight / day, ipratropium bromide / salbutamol may slightly increase heart rate, and at higher doses, histopathological scarring of the left ventricular papillary muscle and / Or fibrosis, sometimes accompanied by mineralization.

The results obtained in the above tests are the results of a commonly known action of salbutamol -adrenaline.

The toxicological properties of the other ingredient, ipratropium bromide, have been known for many years. It has typical anticholinergic effects, such as dry head mucous membranes, dilated pupils, and only occurs in dogs with dry keratoconjunctivitis. (Dry eye) and tone decreased in rats, and gastrointestinal motility was suppressed.

There have been experimental studies on the reproductive toxicity of the two components of this product. Higher doses of salbutamol can cause palate in mice. This phenomenon is known and can occur when other beta-adrenergic drugs are used. It is currently speculated that this response is due to an increase in maternal corticosteroid levels and is considered to be a stress result unrelated to other species. In addition, the potential for teratogenic potential of salbutamol shown in preclinical data has been considered and has been restricted to women. In addition to these findings, tests with salbutamol and ipratropium bromide have shown only minor effects on embryos, fetuses, and young animals, all of which are within the maternal toxicity range.

Both albuterol and ipratropium bromide have been tested in vitro and in vivo, and neither has a mutagenic effect.

Several in vivo carcinogenicity tests were performed on salbutamol and ipratropium bromide to study their tumor characteristics.

After oral administration of salbutamol in mice, the incidence of ovarian mesangial leiomyomas increased 100 times higher than the human inhaled therapeutic dose, which was not found in rats and dogs. Simultaneously taking beta-blockers can prevent the occurrence of leiomyoma. These results are speculated to be species-specific and have no clinical relevance, so there is no need to limit clinical use.

Ipratropium bromide was not carcinogenic in mice and rats.

There are no reports of immunotoxicity caused by this product or its active ingredients.

Pharmacokinetics

Ipratropium bromide can be absorbed quickly after inhalation, and it is estimated that the systemic bioavailability after inhalation is less than 10% of the dose. The renal excretion of ipratropium bromide after intravenous administration is 46%, and the half-life of the terminal elimination phase of intravenous administration is about 1.6 hours. The half-life of scavengers and metabolites determined by radiolabeling is 3.6 hours. Ipratropium bromide does not cross the blood-brain barrier.

By oral inhalation or oral gastrointestinal tract, salbutamol is quickly and completely absorbed in the body. The highest plasma concentration was reached within 3 hours. After 24 hours, the urine was excreted. The elimination half-life is 4 hours. Salbutamol can cross the blood-brain barrier, and its concentration is about 5% of the plasma concentration.

It has been shown that ipratropium bromide and salbutamol do not increase systemic absorption when used in combination with either drug alone. The enhanced efficacy of this product is due to the combined effect of being restricted to the lungs after inhalation.

Cobbit storage

Store below 25 ° C in the dark.

Keep out of reach of children!

Cobbit packaging

Low density polyethylene, 2.5 ml / piece, 10 pieces / box.

Cobbit validity

24 months

Cobbit standards

Import Drug Registration Standard JX20100077

Cobbit approval number

Import Drug Registration Certificate No. H20100608

Cobbit Manufacturing

Boehringer Ingelheim International (UK)

Cobbit approval date

October 27, 2006

Cobbit Revision Date

August 06, 2010 ^[1]