Methacholine: what it is, characteristics, and how it is used in the asthma test

Asthma is a breathing problem that is not always obvious. It can occur when there are particles and pollutants traveling in the air environment that activate the asthmatic response, and sometimes these particles are not so common.

However, given the seriousness of this condition, if it appears, the person may have a serious problem. For this reason it has become necessary to create specific tests to confirm in the most precise way any case of asthma, and the methacholine test is one of them.

Methacholine is a bronchoconstrictor agent. ideal for generating an asthmatic response in those who suffer from the most masked disease. Let's see below what are the properties of this substance and how the test that bears the same name is performed.

• Related article: "Types of drugs (according to their use and side effects)"

What is methacholine?

Methacholine is a bronchoconstrictor agent that is used in the diagnosis of asthma, specifically the main symptom of this medical condition: bronchial hyperreactivity. It has its own test, called the methacholine test, and is indicated when other pulmonary function tests, such as generic spirometry, do not suggest a definitive diagnosis. This substance, once aspirated, produces miosis.

It is a non-selective synthetic cholinergic, choline ester type.. It works by binding to and activating muscarinic receptors for acetylcholine in the parasympathetic nervous system. Being very low selective, this substance is highly activating of all muscarinic receptors and has a very limited effect on nicotinic receptors.

pharmacokinetics

Methacholine is a quaternary amine that is insoluble through the cell membrane. That is why cannot cross the blood-brain barrier nor can it be absorbed from the gastrointestinal tract. Once inside the body, this substance is metabolized slowly, since it is highly resistant to the action of the enzyme acetylcholinesterase.

It hydrolyzes at a very slow rate, less than that at which acetylcholine hydrolyzes. This is why its action in the body is longer and it is almost completely resistant to hydrolysis by choline esterases or non-specific butyrylcholinesterases.

Applications

Methacholine is used as the main test to confirm suspicions of asthma. The test in which methacholine is used is called a nonspecific bronchial challenge test or methacholine test. which basically serves to determine the existence of bronchial hyperreactivity, considered the main symptom of asthma.

It is the abnormal sensitization of the airways, caused by an increase in airflow obstruction after having been in contact with specific stimuli.

What is the methacholine test to detect asthma?

The methacholine test consists of doing, first, an initial spirometry that will be accompanied by other spirometry, in order to check what is the lung capacity of the patient and see how it affects methacholine inhalation at different doses. Methacholine is a drug with bronchoconstrictive action in people with asthma, that is, close their bronchi when they inhale this substance, reducing their lung capacity for a while limited.

In the initial spirometry, the person's baseline lung capacity is measured.. The patient takes a deep and maximum inspiration, filling his lungs with air as much as possible. Then, the mouthpiece is placed between his lips, exhaling, that is, blowing out the contained air with all his might for at least six seconds. This process will be repeated a minimum of three times.

When you have a clear idea of ​​the patient's lung capacity, methacholine will be administered. in increasing doses, and after each dose a new spirometry will be done.

If the patient is showing a decrease in lung capacity greater than 20% with respect to the initial spirometry, the methacholine test will be considered positive. That is, it will mean that the patient is reacting to this substance, showing bronchoconstriction and briefly losing lung capacity. The lower the dose required to decrease more than 20%, the greater the degree of bronchial reaction of the patient.. The diagnosis of asthma will be confirmed.

On very rare occasions, a person with asthma will have a negative methacholine test. Although in many cases asthma is evident, there are some that are not so, for this reason this test is so necessary, ensuring the diagnosis. There are people with asthma who may have had very normal initial spirometry, showing no respiratory problems of any kind, and normal non-drug bronchodilation.

This test is minimally invasive and is usually well tolerated by the patient., who will hardly feel any discomfort. The only minor inconvenience is the time it takes to perform the test, and the need to perform several spirometry tests that require a little lung effort.

Requirements to be able to apply the test

In order to apply this test, it is necessary for the patient to meet a series of requirements and guidelines before going to the appointment with the pulmonologist. The patient must indicate if they have ever had asthmatic signs or a respiratory infection in the last 6 to 8 weeks, in addition to informing if in the last two months he has been immunized with vaccines. You must report possible pregnancy, heart disease or if you have recently had hives.

The patient must have avoided the consumption of the following substances for the following periods of time:

• Caffeinated drinks (coffee and tea): last 6 hours.
• Tobacco: do not smoke the day before the test.
• Inhaled bronchodilators: past 12 hours.
• Parenteral bronchodilators: last 12 hours.
• Short-acting oral bronchodilators: last 18 hours.
• Long-acting oral bronchodilators: last 48 hours.

Contraindications, Warnings and Precautions

The main precaution to be taken with the methacholine test is that it be done under the supervision of a specialized doctor, have emergency equipment and medication to avoid any unforeseen event. The risks and benefits of applying the test should be assessed in cases of epilepsy, cardiovascular disease with bradycardia, vagotonia, peptic ulcer, urinary tract obstruction, or other conditions that may be adversely affected by an agent cholinergic

There are several medical conditions in which the use of methacholine, together with the rest of muscarinic agonists, is contraindicated. Among them we find coronary insufficiency, peptic ulcers, myocardial infarction, uncontrolled arterial hypertension, myasthenia gravis and urinary incontinence. This is because the similar action of this substance with that of the parasympathetic system can aggravate the symptoms in these medical problems.

Its use is also not recommended in cases of clinically apparent asthma or in cases where hypersensitivity to other parasympathomimetic agents has been documented. It should not be used in treatments with beta-adrenergic blocking agents or with cholinesterase inhibitors. Treatment for asthma and hay fever inhibit the airway response to the test.

The application of this test can give false positives in diseases such as influenza, respiratory tract infections, very young patients or very old people, chronic lung diseases, allergic rhinitis without asthma, smokers or people who have been exposed to pollutants aerial. In these cases, in addition to being able to have a false positive for asthma, there is a risk of severe bronchoconstriction and a highly dangerous reduction in respiratory function.

If the patient is a woman and is of childbearing age, it is necessary to find out if she is pregnant. Studies on the teratogenic effects of methacholine in animal reproduction have not been performed. It is not known whether methacholine hydrochloride can harm the fetus or affect fertility in the patient. It should only be administered to pregnant women if its application is clearly necessary. It is not known whether methacholine, when inhaled, is excreted in breast milk.

Adverse reactions and interactions

Among the main adverse reactions of methacholine we can find headache, pharynx irritation, sensation of loss of consciousness and pruritus (tingling sensation on the skin). The therapeutic use of this drug is limited due to its adverse cardiac effects, such as bradycardia and hypotension, which are doubled by its role as a cholinergic agonist. Methacholine reacts very toxically in combination with 0.5 to 1 mg atropine sulfate intramuscularly or intravenously.

Bibliographic references:

• Katzung, Bertram G. (2004). Basic and Clinical Pharmacology (9th edition). ISBN 0-07-141092-9.
• Lotvall J, Inman M, O'Byrne P (1998). Measurement of airway hyperresponsiveness: new considerations. Thorax 53: 419-424. PMID 9708238.
• R. Asero, E. Madonini. (2006) Bronchial hyperresponsiveness is a common feature in patients with chronic urticaria. J Investig Allergol Clin Immunol; Vol. 16(1): 19-23.