Asthma anticholinergics

Keywords Anticholinergics asthma p-agonist corticosteroids drug response genetic association leukotriene polymorphisms. 

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). 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

Ipratropium is the most commonly used anticholinergic for treating bronchoconstriction in asthma. It is available as an MDI and solution for nebulization. Ipratropium has an onset of action of approximately 30 minutes and a duration of action of 4 to 8 hours. Care should be taken not to spray the metered-dose inhaler into or allow the nebulized solution to get in the patient s eyes, as it can cause mydriasis and blurred vision. 

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 is classified as an anticholinergic because it blocks acetylcholine release. It is indicated in asthma and chronic obstructive pulmonary disease and is available for inhalation. 

Anticholinergic effects Antihistamines have varying degrees of atropine-like actions use with caution in patients with a predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension. 

Use with caution in conditions which might be aggravated by anticholinergic therapy (eg, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, bladder neck obstruction, narrow angle glaucoma, bronchial asthma, cardiac arrhythmias). 

Uses Allergic Rxns itching Action Phenothiazine antihistamine serotonin antagonist Dose Adults. 4-20 mg PO qSh max 0.5 mg/kg/d Feds. 2-6 y 2 mg bid-tid (max 12 mg/24 h) 7-14 y 4 mg bid-tid in hepatic impair Caution [B, ] BPH Contra Neonates or <2 y NAG BOO acute asthma GI obst Disp Tabs, syrup SE Anticholinergic, drowsiness Interactions T Effects Wf CNS depressants, MAOIs, EtOH X effects OF epi, fluoxetine EMS Use other CNS depressants w/ caution concurrent EtOH use can T CNS depression higher epi doses may be needed if used OD May cause mood changes, Szs, CNS depression, or CNS stimulation symptomatic and supportive... 

Plotnick LH, Ducharme EM. Combined inhaled anticholinergics and beta2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev 2000. 

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. 

Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction. They may provide added bronchodi-lator effect in patients who are receiving beta -adrenergic agents for asthma. 

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