Both salmeterol and formoterol (7) agonists are structurally related to salbutamol, in that they have an aromatic moiety replacing the catechol group but that is resistant to metabolism by catechol-O-methyl transferase. However, in place of the N-isopropyl group, these compounds bear a large lipophilic N-substituent that appears to be responsible for the high affinity in lung and prolonged duration of action of these drugs [40]. Whether this is due to improved receptor-binding characteristics or is the result of a selective uptake mechanism by lung tissue is open to question. This issue is dealt with in detail in the section on structural factors. The drug formoterol, when given by inhalation, is 10 times more potent than salbutamol and produces clinically significant bronchodilation for 8 hours when administered at a dose of 6 mg [41]. In an attempt to obtain optimal control of asthma, a combination therapy of an inhaled long-acting b2-agonist and an inhaled corticosteroid (i.e., salmeterol/fluticasone and formoterol/budesonide) has been utilized, where the corticosteroids suppresses chronic inflammation of asthma while the b2-agonist induces bronchodilation and inhibits mast cell mediator release. Furthermore, it has been found that there are more positive interactions between both drug types. Corticosteroids increase the expression of b2-receptors by increasing gene transcription, while b2-agonists may potentiate the molecular mechanism associated with corticosteroid action, leading to an additive or sometimes synergistic suppression of inflammatory mediator release [42].

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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