Anticholinergic bronchodilators

Therapeutic Function Anticholinergic bronchodilator Chemical Name (-)-N-Ethylnorscopolamine methobromide... 

Hansel TT, Barnes PJ, Tiotropium bromide A novel once-daily anticholinergic bronchodilator for the treatment of COPD, Drugs Today (Bare) 38 585-600, 2002. 

Atrovent 2.7 (0.1) An anticholinergic bronchodilator that inhibits smooth muscle in the bronchial. 

Saberi F, O Donnell DE. The role of tiotropium bromide, a long-acting anticholinergic bronchodilator, in the management of COPD. Treat Respir Med. 2005 4 275-281. 

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. 

Tiotropium (Spiriva) was also developed as an anticholinergic bronchodilator that is similar to ipratropium, but with longer lasting effects.88 Tiotropium only needs to be inhaled once each day, whereas ipratropium is often inhaled 3 or 4 times each day.8,98 It appears that tiotropium may also be superior to ipratropium in improving pulmonary function and reducing the frequency and severity of exacerbations in people with COPD.41,51 Future studies will continue to clarify how tiotropium and other anticholinergics can be used to provide optimal treatment of COPD.7... 

Andionisen NR, Connett JE, Kiley JP, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on die rate of decline of FEVi The Lung Health Study. JAMA 1994 272 1497-1505. 

The modern usage of P2" go Asts for the treatment of asthma dates to 1903 when the effect of injected epinephrine [51-43-4] (adrenaline) C2H23NO2, (1 R = CH3) was investigated (see Epinephrine and norepinephrine) (33). As in some other modem treatments, eg, xanthines and anticholinergics, the roots of P2" go Ast therapy for asthma can be found in historical records which document the use of herbal extracts containing ephedrine [299-42-3] C qH NO, (2) as bronchodilators. Epinephrine and ephedrine are stmcturaHy related to the catecholamine norepinephrine [51-41-2] CgH NO, (1, R = H), a neurotransmitter of the adrenergic nervous system (see Neuroregulators). 

At this writing anticholinergic agents are not widely used for the symptomatic treatment of asthma, although compounds such as atropine [51 -55-8] C17H23NO3, (18) have been used for centuries (111). Inhalation of the smoke produced by burning herbal mixtures, such as Datura Stramonium provided bronchodilation and rehef from some of the symptoms of asthma. The major active component in these preparations was atropine or other closely related alkaloids (qv). 

The two major types of bronchodilators are the sym-padiomimetics and die xantiiine derivatives. The anticholinergic drug ipratropium bromide (Atrovent) is used for bronchospasm associated witii COPD, chronic bronchitis, and emphysema. Ipratropium is included in die Summary Drug Table Bronchodilators. Chapter 25... 

As greater control of the disease state is achieved with aerosol therapy, manufacturers are considering combining some of their most successful products to achieve bronchodilation and anti-inflammatory effect in a single dose. These combinations may increase interest in the use of anticholinergics in addition to fl2-adrenergic agonists. 

Ipratropium bromide and tiotropium bromide are competitive inhibitors of muscarinic receptors they produce bronchodilation only in cholinergic-mediated bronchoconstriction. Anticholinergics are effective bronchodila-tors but are not as potent as /J2-agonists. They attenuate, but do not block, allergen- or exercise-induced asthma in a dose-dependent fashion. 

Ipratropium bromide has a slower onset of action than short-acting /J2-agonists (15 to 20 minutes vs. 5 minutes for albuterol). For this reason, it may be less suitable for as-needed use, but it is often prescribed in this manner. Ipratropium has a more prolonged bronchodilator effect than short-acting /l2-agonists. Its peak effect occurs in 1.5 to 2 hours and its duration is 4 to 6 hours. The recommended dose via MDI is two puffs four times a day with upward titration often to 24 puffs/day. It is also available as a solution for nebulization. The most frequent patient complaints are dry mouth, nausea, and, occasionally, metallic taste. Because it is poorly absorbed systemically, anticholinergic side effects are uncommon (e.g., blurred vision, urinary retention, nausea, and tachycardia). 

Methylxanthines are no longer considered first-line therapy for COPD. Inhaled bronchodilator therapy is preferred over theophylline for COPD because of theophylline s risk for drug interactions and the interpatient variability in dosage requirements. Theophylline may be considered in patients who are intolerant or unable to use an inhaled bronchodilator. A methylxanthine may also be added to the regimen of patients who have not achieved an optimal clinical response to an inhaled anticholinergic and [i2-agonist. 

The dose and frequency of bronchodilators are increased during acute exacerbations to provide symptomatic relief. Short-acting / -agonists are preferred because of their rapid onset of action. Anticholinergic agents may be added if symptoms persist despite increased doses of /T-agonisls. 

Pharmacology Ipratropium for oral inhalation is an anticholinergic (parasympatholytic) agent that appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine. The bronchodilation following inhalation is primarily a local, site-specific effect, not a systemic one. 

Albuterol Ipratropium (Combivent, DuoNeb) [Bronchodilator/Adrenergic, Anticholinergic] Uses coPD ... 

Action Combo of P-adrenergic bronchodilator quaternary anticholinogic Dose 2 inhal qid neb 3 mL q6h Caution [C, +] Contra Peanut/soybean allergy Disp Met-dose inhaler soln for neb (DuoNeb) SE Palpitations, tach, nervousness, GI upset, dizziness, blurred vision Interactions T Effects Wf anticholinergics, including ophthalmic meds effects W/ herb jaborandi tree, pill-bearing spurge EMS See Albuterol may cause transient blurred vision/irritation... 

Although atropine and related compounds possess bronchodilator activity, their use is associated with the typical spectrum of anticholinergic side effects (see Chapter 13), and they are no longer used in the treatment of asthma. To improve the clinical utility of anticholinergics, quaternary amine derivatives of atropine were developed. By virtue of their positive charge, these drugs are absorbed poorly across mucosal surfaces and thus produce fewer side effects than atropine, especially when given by inhalation. 

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