Bronchodilators muscarinic antagonists

Muscarinic antagonists inhibit secretions and relax smooth muscle in the respiratory system. The parasympathetic innervation of respiratory smooth muscle is most abundant in large airways, where it exerts a dominant constrictor action. In agreement with this innervation pattern, muscarinic antagonists produce their greatest bronchodilator effect at large-caliber airways. 

Bronchodilation is promoted by cAMP. Intracellular levels of cAMP can be increased by 13-adrenoceptor agonists, which increase the rate of its synthesis by adenylyl cyclase (AC) or by phosphodiesterase (PDE) inhibitors such as theophylline, which slow the rate of its degradation. Bronchoconstriction can be inhibited by muscarinic antagonists and possibly by adenosine antagonists. 

The anticholinergic bronchodilators include ipratropium and tiotropium, which are muscarinic receptor blockers that are similar in structure and function to atropine. Although atropine is the prototypical muscarinic antagonist, its use in respiratory conditions is usually limited because it is readily absorbed into the systemic circulation and tends to produce many side effects even when administered by inhalation. Alternatively, ipratropium (Atrovent) is an anticholinergic agent that is poorly absorbed into the systemic circulation and can be administered by an aerosol inhaler.110 Thus, inhaled ipratropium is associated with substantially fewer systemic side effects. 

Bronchodilators include sympathomimetics, especially selective agonists, muscarinic antagonists, methylxanthines, and leukotriene receptor blockers. 

Norepinephrine opens the pupil of the eye acetylcholine narrows it. Note that an antagonist of acetylcholine at the muscarinic receptor, atropine, has the same outcome as norepinephrine (see above). Norepinephrine is a bronchodilator in contrast, acetylcholine is a bronchoconstrictor. Norepinephrine increases the heart rate, chronotropy, whereas acetylcholine slows the heart rate, bradycardy. Norepinephrine decreases the rate of intestinal movements, whereas acetylcholine increases them. In all these cases, the effects of these neurotransmitters are opposed. 

Q10 Other bronchodilator agents include nebulized ipratropium. Ipratropium is a muscarinic receptor antagonist that helps to relax bronchial smooth muscle which has contracted via parasympathetic stimulation. The xanthines theophylline and aminophylline (theophylline ethylenediamine) are alternative bronchodilator agents. These agents may act as phosphodiesterase inhibitors and, although they have been used as bronchodilators for many years, adverse CNS, GI and cardiovascular effects may limit their usefulness. 

Isopto Atropine atropine, isoprenaline [ban. inn] (Isopropylnorepinephrine isoproterenol hydrochloride [usan] Isuprel etc. isoproterenol sulfate [usan] Aludrin Medihaler-lso ) is a P-adrenoceptor AGONIST which therapeutically can be used as a bronchodilator in antiasthmatic treatment. The (f )-form is levisoprenaline [inn]. isopropamide iodide [ban. inn] is a quaternary ammonium MUSCARINIC CHOUNOCEPTOR ANTAGONIST, which can be used as a visceral ANTISPASMODIC and as an adjunct in treating peptic ulcers. 

In an attempt to reduce the occurrence of side effects associated with absorption into the systemic circulation, quaternary ammonium compounds have been developed as muscarinic cholinoceptor antagonists, for example, ipratropium bromide, glycopyrrolate methylbromide. As a result of their polar nature, these compounds are poorly absorbed across lipid membranes and, therefore, do not easily enter the systemic circulation or the central nervous system (to produce undesirable side effects), but they do induce bronchodilation of long duration [34,35]. The only significant side effect of the quaternary ammonium compounds is dry mouth, an effect perhaps to be expected for a muscarinic cholinoceptor antagonist administered as an aerosol via the mouth. 

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