asthma
Parallel to the increasing rate of environmental pollution, the asmatiform forms are constantly increasing. Asthmatic people become hypersensitive to stimuli of different nature (chemical, physical, thermal, allergenic), which are the triggering cause of the asthmatic crisis.
Asthma is a chronic inflammation of the respiratory tract in which the bronchi are restricted due to the presence of edema and, occasionally, due to spasmogenic substances released by local cells or cells that infiltrate at a bronchial level through the circulatory stream.
These substances, called spasmogens, are the mediators of bronchoconstriction and can cause an immediate or late asthmatic attack.
The main mediators of bronchoconstriction are histamine, prostanoids (thromboxanes and some prostaglandins), some leukotrienes (in particular cysteinyl leukotrienes), platelet activating factor (PAF) and some neuropeptides (some neurokinins).
Asthma medications
Any drug that can reduce inflammation at the bronchial level or antagonize the effects of the reactions triggered by spasmogens is potentially an asthma remedy.
Anti-asthmatic drugs are divided into several categories:
- Glucocorticoids
- Beta-2 Agonists
- Xanthine derivatives
- Benzopiranoni
- antimuscarinics
- leukotriene
Glucocorticoids
Glucocorticoids act indirectly by inhibiting the enzyme phospholipase A2 and, consequently, the formation of arachidonic acid and its subsequent conversion into leukotrienes and prostaglandins (substances with inflammatory activity).
They are also known as corticosteroids because they are normally produced by the adrenal cortex from cholesterol. The main hormone of the group is cortisol (or hydrocortisone).
Glucocorticoids are therefore able to reduce edema and the number of asthmatic attacks. The best known are flunisolide, administered by inhalation using self-dosed dispensers (250 µg per spray) and beclomethasone ( Clenil ®) with a similar route of administration (100, 200, 400 µg by spray) or by aerosol.
Aerosol drugs are often associated with a beta-2 agonist to achieve a greater bronchodilatory effect and are preferred by asthmatics when they have difficulty in inhaling the drug orally or nasally.
The use of oral glucocorticoids (capsules, tablets) should only be done when results are not obtained by inhalation and for short periods of time, due to the rather obvious side effects (greater susceptibility to infections, especially if they originate viral, diffuse edema, therefore swelling, hypertension and bone demineralization).
Beta2-agonists
The beta2-agonist drugs are derivatives of norepinephrine, a hormone that acts on the adrenergic receptors above all of the alpha and beta1 type, but little on the B2 that are important for asthma, because, if stimulated, they cause a relaxation of the bronchial smooth muscle, with consequent airway dilation. It follows that any drug capable of enhancing the activity of these receptors, hence the name Beta2-agonists, is useful as an asthma.
The best known and used is salbutamol ( Ventolin ®) which, by inhalation (0.2 mg per spray) produces a rapid action that lasts for about three hours. Salbutamol is also used to prevent asthma attacks in view of physical exertion, even if we remember being banned from healthy athletes (it is considered doping).
Salbutamol can also be used as an aerosol, systemically (cpr 2-4 mg; cos 4-6 mg) or parenterally (0.5 mg vials). Systemic administration is used only when asthmatic seizures are too frequent because, although it is quite selective for B2 receptors, it also maintains activity against B1 which, concentrated at cardiac level, when stimulated lead to an increase in heart rate (tachycardia). ) becoming dangerous, especially for heart patients (see: clenbuterol).
Next to salbutamol, there are other B2-agonist drugs with a longer duration of action and therefore used in maintenance therapy and not in seizures (which require a medicine with a fast pharmacological activity). These include salmeterol ( Aliflus ®, Serevent ®, Seretide ®) in doses of 0.25 mg per spray (to be inhaled once or twice in 24 h, only one evening inhalation may be sufficient).
Xanthine derivatives
The xanthine derivatives originate from theophylline or 1, 3 dimethylxanthine, an analogue of caffeine present in tea and endowed with a discrete bronchodilator activity. At therapeutic doses it is able to inhibit phosphodiesterases, enzymes that hydrolyze cyclic nucleotides. In doing so, theophylline increases the bioavailability of the cyclic AMP which is a mediator of the relaxation of the bronchial musculature.
At therapeutic doses, theophylline is not very soluble and for this reason salts are made using the acid characteristics of the nitrogen present in position 7. Salt is obtained by combining two theophylline molecules with an ethylenediamine molecule, obtaining aminophylline (in vials or in tablets, for a total of 200-300 mg / day and never at doses higher than 400 mg / day).
Aminophylline is a second or third choice antiasthmatic that is used only when the other drugs are not effective. At high doses it can induce vomiting, agitation, tachycardia, arrhythmia and become lethal.
Benzopiranoni
Among the benzopyranones we remind the cromoglicico acid, an antiallergic drug, usable also in the form of sodium salt. This medicine is used in some mild forms of allergies that can affect the eye, nasal mucosa (rhinitis) or bronchi; is a first choice drug that is used at the first appearance of allergic symptoms, exclusively by inhalation, in the prevention of attacks (aerosol for children or spray inhalers for children and adults). Among the anti-asthmatics is the drug that gives the absolute fewest side effects, but it has a limited percentage effectiveness (only 30-35% of patients find benefit from the use of this drug). The mechanism of action seems to be due to its ability to inhibit the release of spasmogens from the cells residing in the bronchi and also to those that come through the blood (prevents the release of histamine).
antimuscarinics
Antimuscarinics act by inhibiting the muscarinic M3 receptors for acetylcholine present at the bronchial level. This substance is in fact a neurotransmitter of the parasympathetic system which, by stimulating its muscarinic and nicotinic receptors, induces the contraction of the skeletal and bronchial muscles. For this reason, going to block the muscarinic acetylcholine receptors at the bronchial level we obtain a bronchodilation useful for asthmatics. Atropine, the active principle derived from Atropa belladonna, preferentially blocks the M1 and M2 receptors but little M3. Despite this, however, it has a slight bronchodilator activity, but it is little used because it leads to the functionality of the epithelial cilia of the airways (with consequent stagnation of mucus which in the asthmatic is already produced in abundance in itself); the therapeutic effect is therefore scarcely evident.
The ipratropium bromide ( ATEM ®, BREVA ®) is instead an M2 and M3 antagonist, capable of giving bronchodilation without interfering with the activity of the cilia (in doses of 20 µg per spray). It is widely used in the presence of chronic obstructive pulmonary disease (COPD) - a disease characterized by chronic asthma, bronchitis and pulmonary emphysema -. Side effects are mostly limited to the appearance of dryness in the mouth and mucous membranes.
leukotriene
Antileukotrienes block the CYS and LT1 receptors present at the bronchial and pulmonary levels. Their excessive stimulation by cistenilleucotrieni leads to marked bronchospasm and inflammation of the bronchial mucosa. By blocking these receptors we will therefore obtain a beneficial action for asthmatic patients.
Among the most popular antileucotriene drugs we mention montelukast ( SINGULAIR ®), very important because it is able to reduce the number of asthmatic attacks and, gradually, bronchial edema. Its anti-inflammatory activity is however lower than that of corticosteroids, although it does not give particularly serious side effects. Antileucotrienes, very useful in persistent therapy, are not suitable in the asthmatic crisis.
