07.02.4 Antimuscarinic Agents

The antimuscarinics agents can be used to reverse the effects of the parasympathetic nervous system. There are three groups of antimuscarinics agents. Firstly, the naturally occurring alkaloids such as atropine and hyoscine (which is also known as scopolamine) were the first antimuscarinics agents characterised. Secondly, there are the semi-synthetic derivatives such as Homatropine and ipratropium. Thirdly, there are synthetic congeners such as darifenacin.

Homatropine has a shorter duration of action than atropine, and is used when a short acting effect is required e.g. some eye applications. Ipratropium is quaternized and does not cross the blood brain barrier or readily cross membranes, and is used when systemic absorption is not required e.g. nasal spray for rhinorrhea, inhalation for bronchial effects.

Atropine is active after oral administration, does not select between M receptors, and has widespread effects, both beneficial and detrimental. Atropine is not commonly used clinically, as it will have many adverse effects. The exception is the use of atropine for its ability to reverses the effect of acetylcholine to slow heart rate. Thus, atropine is used to treat bradyarrhythmias (slow irregular heart rhythms), in the emergency situation, where it is administered intravenously.

Inhalation of ipratropium provides the reversal of bronchoconstriction (bronchodilation). Ipratropium is used in the treatment of allergic rhinitis (as a nasal spray), and in asthma, and Chronic Obstructive Pullmonary Disease (COPD) by inhalation. COPD is the combination of chronic bronchitis and emphysema, which is common in long term smokers. Antimuscarinics in combination with β₂-adrenoceptor agonists are also available for use in COPD e.g ipratropium with salbutamol. Improvement with ipratropium in COPD is relatively small, but it is used as there are no drugs that give major benefits in the treatment of COPD.

Acetylcholine increases gut motility. Antimuscarinic agents decrease gut motility. Hyoscine is occasionally used in the treatment of the diarrhea associated with irritable bowel syndrome, and as an aid to endoscopy.

Functional muscarinic M receptors on the urinary bladder are M₃, and this has prompted the search for M₃ selective antagonists to use in overactive bladder, as by selecting for M₃ receptor, many detrimental effects due to blocking the other M receptors would be avoided. Darifenacin shows some selectivity for M₃ receptors. As a consequence, darifenacin lower intravesicular (bladder) pressure, increase capacity, and reduces the frequency of contraction of the urinary bladder. Darifenacin is used in the treatment of overactive urinary bladder disease, and enuresis (bed wetting) in children. However, the selectivity for M₃ receptors with darifenacin is only partial, and the oral administration of these agents is still associated with dry mouth and dry eyes, which are side effects due to blocking M₂ receptors.

Atropine blocks the effects of acetylcholine on the eye to cause mydriasis (dilation of the pupil) and cycloplegia (paralysis of ciliary muscle, and loss of accommodation, and this is the basis for the ophthalmologic uses of antimuscarinics agents. The antimuscarinics are given as eye drops to promote mydriasis and cycloplegia. The mydriasis is required for the examination of retina and optic nerve. Cycloplegia is required to allow measurement of refractive errors. In ophthalmology, the shorter acting antimuscarinics such as homatropine are preferred, as they allow the subject to recover/see more quickly.