Methacholine: What It Is, Characteristics, And How It Is Used In Asthma Testing
Asthma is a respiratory problem that is not always obvious. It can occur when there are particles and pollutants traveling in the air that activate the asthmatic response, and sometimes these particles are not so common.
However, given the severity 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 any case of asthma in the most precise way, 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 hidden disease. Let’s see below what the properties of this substance are and how the test that bears the same name is performed.
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 lung 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 acts by binding to and activating muscarinic acetylcholine receptors in the parasympathetic nervous system. Being very non-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 across the cell membrane. That is why It 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 very resistant to the action of the enzyme acetylcholinesterase.
It is hydrolyzed at a very slow rate, lower than that at which acetylcholine is hydrolyzed. This is why its action in the body is longer and it is almost completely resistant to hydrolysis by choline esterases or nonspecific butyrylcholinesterases.
Methacholine is used as the main test to confirm suspected asthma. The test in which methacholine is used is called nonspecific bronchial provocation test or methacholine test which, basically, serves to determine the existence of bronchial hyperreactivity, considered the main symptom of asthma.
This is abnormal sensitization of the airways, caused by an increase in airflow obstruction after being 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 the patient’s lung capacity and see how it affects the inhalation of methacholine at different doses. Methacholine is a drug with bronchoconstrictive action in people with asthma, that is, it narrows their bronchi when they inhale this substance, reducing their lung capacity for a limited time.
In the initial spirometry, the person’s baseline lung capacity is measured The patient takes a deep, maximum breath, filling his lungs with air as much as he can. Then, the mouthpiece is placed between the lips, exhaling, that is, blowing the contained air with all your 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% compared 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 necessary to decrease more than 20%, the greater the degree of bronchial reaction of the patient The diagnosis of asthma will be confirmed.
Very rarely, an asthmatic person will have a negative methacholine test result. Although in many cases asthma is evident, there are cases where it is not so obvious, which is why this test is so necessary, ensuring the diagnosis. There are people with asthma who may have had a very normal initial spirometry, without showing respiratory problems of any kind and with normal bronchodilation without the use of drugs.
This test is minimally invasive and is usually well tolerated by the patient , who will barely feel any discomfort. The only minimally important discomfort 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 attending the appointment with the pulmonologist. The patient must indicate if he or she has ever had asthmatic signs or a respiratory infection in the last 6 or 8 weeks , in addition to informing if in the last two months you have been immunized with vaccines. You should 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:
Contraindications, warnings and precautions
The main precaution that should be taken into account with the methacholine test is that it is performed 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 negatively affected by a cholinergic agent.
There are several medical conditions in which the use of methacholine, together with the rest of the muscarinic agonists, is contraindicated. Among them we find coronary insufficiency, peptic ulcers, myocardial infarction, uncontrolled high blood pressure , myasthenia gravis and urinary incontinence. This is because the similar action of this substance with that of the parasympathetic system can aggravate the symptoms of these medical problems.
Its use is also not recommended in cases of clinically apparent asthma or in cases in which hypersensitivity to other parasympathomimetic agents has been documented. It should not be used in treatments with beta-adrenergic blocking agents or 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 or very old patients, chronic lung diseases, allergic rhinitis without asthma, smokers or people who have been exposed to air pollutants. In these cases, in addition to there being 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 of childbearing age, it is necessary to find out if she is pregnant. No studies have been carried out on the teratogenic effects of methacholine in animal reproduction. It is unknown whether methacholine hydrochloride can cause harm to the fetus or affect the patient’s fertility. It should only be administered to pregnant women if its application is clearly necessary. It is not known whether methacholine, when inhaled, is excreted into breast milk.
Adverse reactions and interactions
Among the main adverse reactions of methacholine we can find headache, pharyngeal irritation, feeling of loss of consciousness and itching (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 due to its role as a cholinergic agonist. Methacholine reacts very toxically in combination with 0.5 to 1 mg of atropine sulfate intramuscularly or intravenously.
