Page 364 - Basic _ Clinical Pharmacology ( PDFDrive )

350 SECTION IV Drugs with Important Actions on Smooth Muscle

ATP

Bronchodilation AC + Beta agonists

+ cAMP

Bronchial tone
PDE – Theophylline
AMP
Acetylcholine + + Adenosine
Muscarinic – –
antagonists Theophylline
Bronchoconstriction

FIGURE 20–3 Bronchodilation is promoted by cAMP. Intracellular levels of cAMP can be increased by β-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.

slow inhalation of a nearly full breath and by 5 or more seconds adverse effects. Its current use is thus largely for treatment of the
of breath-holding at the end of inspiration. acute vasodilation and bronchospasm of anaphylaxis. Aerosol
Epinephrine is an effective, rapidly acting bronchodilator delivery of other, more β-selective agents has largely displaced its
when injected subcutaneously (0.4 mL of 1:1000 solution) or use in asthma (see below).
inhaled as a microaerosol from a pressurized canister (320 mcg per Ephedrine was used in China for more than 2000 years
puff). Maximal bronchodilation is achieved within 15 minutes before its introduction into Western medicine in 1924. Com-
after inhalation and lasts 60–90 minutes. Because epinephrine pared with epinephrine, ephedrine has a longer duration, oral
stimulates α and β as well as β receptors, tachycardia, arrhyth- activity, more pronounced central effects, and much lower
2
1
mias, and worsening of angina pectoris are potentially serious potency. Because of the development of more efficacious and

HO HO
CH 3 CH 3
HO CH CH 2 NH CH CH CH 2 NH C CH 3
OH CH 3 OH CH 3
HO
Isoproterenol Terbutaline

HO CH OH
2
CH 3 CH 3
CH CH 2 NH CH HO CH CH 2 NH C CH 3
OH CH 3 OH CH 3
HO
Metaproterenol Albuterol (salbutamol)

CH OH
2

HO CH CH 2 NH CH 2 (CH ) CH 2 O CH 2 (CH ) CH 2
2 2
2 4
OH
Salmeterol

FIGURE 20–4 Structures of isoproterenol and several β 2 -selective analogs.