Explain the need for antimuscarinics used in conjunction with acetylcholinesterase inhibitors

Explain the need for antimuscarinics used in conjunc-tion with acetylcholinesterase inhibitors.

Inhibitors of acetylcholinesterase cause a dramatic increase in the concentration of acetylcholine at all effector organs. While this improves neuromuscular transmission by acting on the nicotinic receptor of the neuromuscular junction, increased acetylcholine concentration has many undesirable effects on visceral end-organs. These effects are mediated by the muscarinic subset of acetylcholine recep-tors. Atropine and glycopyrrolate are used to prevent these muscarinic effects (Table 25.1).

The most dramatic and feared muscarinic effect is that on the heart. Acetylcholinesterase inhibitors may cause profound bradycardia, nodal or ventricular escape beats, or even asystole. Increased gastrointestinal motility with excess salivation and diarrhea are other undesirable effects.

The pulmonary system is profoundly affected as well, with increased airway secretions and bronchospasm causing wheezing and difficulty in ventilation.

To prevent these undesirable side-effects, acetyl-cholinesterase inhibitors are given with an antimuscarinic agent, either atropine or glycopyrrolate. Administration of these agents together with acetylcholinesterase inhibitors prevents life-threatening bradydysrhythmias and limits airway secretions, avoiding ventilatory problems.

Because the onset time of atropine is more rapid than that of glycopyrrolate, it is frequently used in combination with edrophonium. Atropine 0.01 mg/kg should precede the administration of edrophonium. Once a tachycardia occurs, appropriate doses of edrophonium may be given. This ensures that atropine’s vagolytic effects precede the vagotonic (bradycardic) effects of edrophonium. Atropine, 0.02 mg/kg, may be combined with or precede the admin-istration of neostigmine. This may result in tachycardia, however, because atropine has a more rapid onset than neostigmine. Glycopyrrolate, with a slower onset than atropine, is usually administered together with neostigmine, providing offsetting chronotropic stability. Neostigmine and glycopyrrolate may be given separately or combined in a single syringe. The latter approach, while generally safe, should not be used in patients with conduction defects or sick sinus syndrome, because life-threatening bradycardia may result. Occasionally, patients who do not demonstrate a tachycardic response to antimuscarinics are encountered. These patients should not receive acetylcholinesterase inhibitors unless a functioning pacemaker is available. Alternatively, neuromuscular muscle relaxants may be allowed to wear off spontaneously.