2312 Nonselective 3adrenergic agonists

Non-selective ^-adrenergic agonists are not recommended for asthma treatment. Some of ihesc drugs are used in oral OTC drugs for the common cold. These combinations do not follow good therapeutic practices, and arc not recommended during pregnancy.

Hexoprenaline, isoprenaline, and orciprenaline

Pharmacology and toxicology

Hexoprenaline, isoprenaline (isoproterenol), and orciprenaline have a stimulating effect on .Vrcceptors. They are non-selective .^-adrenergic agents that act on both and fij-receptors, and therefore have unwanted side effects on cardiac and metabolic functions, central nervous system, and motility of the gastrointestinal tract.

There is no experience in the use of orciprenaline and hexoprenaline during pregnancy. Limited experience with isoprenaline does not show adverse effects on embryonal and fetal development.

Recommendation. Hexoprenaline, isoprenaline, and orciprenaline should not be given to pregnant women. Only specific .^-adrenergic drugs are recommended during pregnancy. Inadvertent use is not an indication for the termination of pregnancy.

Adrenalin (epinephrine)

Pharmacology and toxicology

Adrenalin (epinephrine) is a catecholamine, which is normally present in the body. It has both a- and .-¡-adrenergic properties, and causes a slight vasoconstriction in the bronchi. Adverse effects on the cardiovascular system are so severe that it is not indicated for the treatment of bronchial asthma, ¡^-adrenergic agents are preferred. In the case of acute spastic airway obstruction, adrenalin may be effective when given subcutaneously or as an aerosol. Due to a-adrenergic effects, systemic application can impair uterine blood flow resulting in fetal hypoxia. Catecholamines cross the placenta where they arc inactivated. There is no clear evidence of an increased risk of congenital malformations when using adrenalin in human pregnancy (Heinonen 1977).

Adrenalin is also available in combination with local anesthetics. Adverse effects during pregnancy have not been reported following the use of such preparations.

Recommendation. The systemic use of adrenaline during pregnancy is restricted to emergency cases. Inadvertent use is not an indication for the termination of pregnancy. Local anesthetics with adrenaline may be used during pregnancy.

Ephedrine and other sympathomimetics

Pharmacology and toxicology

Ephedrine, pseudoephedrine, phenylephrine, and related coin-pounds are u-adrenergic receptor agonists, which cause bloodvessel constriction. It has been demonstrated that (»-adrenergic receptor agonists slow uterine blood flow, but their effects have not been sufficiently studied in relation to most reproductive outcomes in animals or humans. Ephedrine is one of the first drugs that was used for the treatment of asthma. It causes an increased release of catecholamines, and has both a- and ^-adrenergic properties. It has a short duration of action. Ephedrine is no longer in use for the treatment of asthma because of the unwanted side effects, especially on the cardiovascular system. Pseudoephedrine, phenylephrine, and phenylpropanolamine are sometimes used in combination with dextromethorphan, doxylamine, etc., for treating the common cold.

Pseudoephedrine is often used to reduce airflow resistance in the nasal cavity. Ephedrine, and phenylephrine, have been associated with hemorrhages and cardiovascular and limb malformations in animal models. Risk of ventricular septal defects was associated with decongestant use in pregnant women in one recent study (review in Werler 2006). The vasoconstrictive cffects of these drugs raise the hypothesis that their use in early prcgnancy might increase the risk of vascular disruption defects. Decongestant use in the first trimester has been discussed in association with small increases in risks of gastroschisis, small intestinal atresia, and hemifacial microsomia (review in Werler 2006). The majority of decon gestant use is in oral form, and the question of whether intranasal formulations carry risk has not been adequately addressed.

Recommendation. The systemic use of ephedrlne and other sympathomimetics should be avoided during pregnancy. Inadvertent use is not an indication for the termination of pregnancy.

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