Pharmacology for Anaesthesia and Intensive Care

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12 Sympathomimetics

Theophylline

Enoximone

Milrinone

O

N

S

O C N N N H

CN

O

O

N

N N

N

H

CH 3

CH 3

CH 3

CH 3

O

Figure 12.5.Structure of some phosphodiesterase inhibitors.

Mechanism of action

Aminophylline is a non-selective inhibitor of all five phosphodiesterase isoenzymes,

which hydrolyze cAMP and possibly cGMP, thereby increasing their intracellular

levels. It may also directly release noradrenaline from sympathetic neurones and

demonstrate synergy with catecholamines, which act via adrenoceptors to increase

intracellular cAMP. In addition it interferes with the translocation of Ca^2 +into smooth

muscle, inhibits the degranulation of mast cells by blocking their adenosine receptors

and potentiates prostaglandin synthetase activity.

Effects


Respiratory – aminophylline causes bronchodilation, improves the contractility

of the diaphragm and increases the sensitivity of the respiratory centre to carbon

dioxide. It works well in combination withβ 2 -agonists due to the different pathway

used to increase cAMP.