259 Atropine and other anticholinergic spasmolytics
Pharmacology and toxicology
Atropine, a belladonna-alkaloid, is a classic parasympatholytic, which inhibits the action of acetylcholine by competitively blocking muscarine rcccptors. With local application (in the eye), systemic availability is negligible when applied properly. I-Atropinc is the biologically active enantiomer, and is sometimes encountered under the name hyoscyarnine.
Atropine reaches concentrations in the fetus equivalent to those in the mother within a few minutes. Although atropine may alter fetal heart rate or inhibit fetal breathing after systemic application, exposure to this drug during pregnancy has not been associated with adverse developmental effects or significant fctotoxicity at recommended therapeutic dosages.
Atropine-like belladonna-alkaloids and their derivatives arc parasympatholytic agents, used in the relief of visceral spasms of the gastrointestinal tract and of colic of the biliary and genitourinary systems; some of these agents are used in the treatment of peptic ulcer. Mydriasis (for diagnostical purpose), respiratory tract disorders, urinary incontinence and Parkinsonism are other indications.
Atropine-like belladonna alkaloids such as scopolamine and homatropine, and the tertiary amine derivatives of these belladonna alkaloids such as flavoxate, oxybutynin, tolterodine, cyclopentolate, and tropicamide, have central (CNS) and peripheral effects similar to those of atropine. With systemic use, effects similar to those of atropine cannot be ruled out. Scopolamine has an hypnotic action.
It is also available as a mydriatic, and as a patch for prevention of motion sickness (see Chapter 2.4). Ilomatropine, cyclopentolate, and tropicamide are available as a mydriatic.
Flavoxate, oxybutynin, and tolterodine are smooth-muscle relaxants for the urinary tract or bladder.
The quaternary ammonium derivatives of atropine-like belladonna alkaloids have peripheral effects similar to those of atropine; central (CNS) effects are negligible. With systemic application, peripheral effects similar to those of atropine cannot be ruled out. The quaternary ammonium derivatives arc mostly used as spasmolytics and for gastrointestinal disorders. Among them, butylscopolamine is the most widely used spasmolytic. Butylscopolamine is poorly absorbed after oral administration. Two cases of eclamptic seizures after the intravenous administration of butylscopolamine in patients with severe pre-eclampsia were reported (Kobayashi 2002).
Others are clidinium, glycopyrronium, methantheline, methylscopo-lamirte, pipenzolate, pipoxolan, propantheline, and trospium chloride.
There are no detailed studies in humans concerning the use of these anticholinergic drugs during pregnancy. The same applies to the antispasmodics denaverin, hymecromon, mebeverine, papaverine, phenamazide, pinaverium, and tiropramide.
Specific embryotoxic effects in humans have not thus far been observed with the use of the belladonna alkaloids and derivatives mentioned, but documented experience is very limited.
Diclofenac, a nonsteroidal anti-inflammatory drug (NSAÏD), and as such a prostaglandin synthetase inhibitor, is used as a spasmolytic in the relief of kidney and biliary colic (sec Chapter 2.1 ).
Recommendation. Anticholinergics, including atropine, can be used throughout pregnancy when strongly indicated. Functional effects, i.e. on the fetal heart rate, must be considered with systemic use. Butylscopolamine is the spasmolytic of choice in this group of medications. Diagnostic application of anticholinergics in the eye can be undertaken during pregnancy. Diarrhea should not be treated routinely with anticholinergics.
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