Asthma antimuscarinic agents

Ipratropium bromide is an antimuscarinic agent indicated in asthma and in chronic obstructive pulmonary disease but it is more effective in the latter. The drug is available only for inhalation because of the potential side-effects if given orally. 

Observation of the use of leaves from Datura stramonium for asthma treatment in India led to the discovery of atropine, a potent competitive inhibitor of acetylcholine at postganglionic muscarinic receptors, as a bronchodilator. Interest in the potential value of antimuscarinic agents increased with demonstration of the importance of the vagus nerves in bronchospastic responses of laboratory animals and by the development of a potent atropine analog that is poorly absorbed after aerosol administration and that is therefore relatively free of systemic atropine-like effects. 

Nevertheless, antimuscarinic agents are valuable in some patients with asthma or COPD. 

List one antimuscarinic agent promoted for each of the following uses to produce mydriasis and cycloplegia to treat parkin.sonism, peptic ulcer, and asthma. 

A. Prototypes and Pharmacokinetics Atropine and other naturally occurring belladonna alkaloids were used for many years in the treatment of asthma with only modest benefits. A quaternary antimuscarinic agent designed for aerosol use, ipratropium, has achieved much greater success. This drug is dehvered to the airways by pressurized tierosol. When absorbed, ipratropium is rapidly metabolized and has little systemic action. 

D. Clinical Use Asthma. Muscarinic blockers are useful in one-third to two-thirds of asthmatic patients agonists are effective in almost all. For acute bronchospasm, therefore, the beta agonists are usually preferred. However, in chronic obstructive pulmonary disease (which is often associated with acute episodes of bronchospasm), the antimuscarinic agents may be more effective and less toxic than beta agonists. 

Ipratropium Antimuscarinic agent aerosol for asthma, chronic obstructive pulmonary dis-... 

Bronchodilation is another property of belladonna alkaloids of potential usefulness. Due to relaxation of the smooth musculature of bronchial passageways, this effect has found applications in asthma and other pulmonary obstructive conditions. At one time the smoking of cigarettes made of stramonium leaves was popular. More recently, atropine, quater-nized with isopropyl bromide (Ipratropium, Fig. 8-13) has been introduced as an aerosol for inhalation. This renewed interest in antimuscarinics resulted in part from clarifications of the role of the parasympathetic system in bronchial obstructions. The availability of a potent agent such as atropine in a poorly absorbed form (i.e., quatemized) would minimize systemic effects following inhalation. Ipratropium bromide does not cross the BBB. It is longer acting and more bronchoselective than atropine methylbromide and exhibits no CNS effects. 

---