2. Eye—The pupillary constrictor muscle (see Figure 6–9) depends on muscarinic cholinoceptor activation. This activation is blocked by topical atropine and other tertiary antimuscarinic drugs and results in unopposed sympathetic dilator activity and mydriasis (Figure 8–4). Dilated pupils were considered cosmetically desirable during the Renaissance and account for the name belladonna (Italian, “beautiful lady”) applied to the plant and its active extract because of the use of the extract as eye drops during that time.
The second important ocular effect of antimuscarinic drugs is to weaken contraction of the ciliary muscle, or cycloplegia. Cycloplegia results in loss of the ability to accommodate; the fully atropinized eye cannot focus for near vision (Figure 8–4).
Both mydriasis and cycloplegia are useful in ophthalmology. They are also potentially hazardous, since acute glaucoma may be induced in patients with a narrow anterior chamber angle.
A third ocular effect of antimuscarinic drugs is to reduce lacrimal secretion. Patients occasionally complain of dry or “sandy” eyes when receiving large doses of antimuscarinic drugs.
3. Cardiovascular system—The sinoatrial node is very sensitive to muscarinic receptor blockade. Moderate to high therapeutic doses of atropine cause tachycardia in the innervated and spontaneously beating heart by blockade of vagal slowing. However, lower doses often result in initial bradycardia before the effects of peripheral vagal block become manifest (Figure 8–5). This slowing may be due to block of prejunctional M1 receptors (autoreceptors, see Figures 6–3 and 7–4A) on vagal postganglionic fibers that normally limit acetylcholine release in the sinus node and other tissues. The same mechanisms operate in the atrioventricular node; in the presence of high vagal tone, atropine can significantly reduce the PR interval of the electrocardiogram by blocking muscarinic receptors in the atrioventricular node. Muscarinic effects on atrial muscle are similarly blocked, but these
FIGURE 8–4 Effects of topical scopolamine drops on pupil diameter (mm) and accommodation (diopters) in the normal human eye. One drop of 0.5% solution of drug was applied at zero time, and a second drop was administered at 30 minutes (arrows). The responses of 42 eyes were averaged. Note the extremely slow recovery. (Reproduced, with permission, from Marron J: Cycloplegia and mydriasis by use of atropine, scopolamine, and homatropine-paredrine. Arch Ophthalmol 1940;23:340. Copyright © 1940 American Medical Association. All rights reserved.) effects are of no clinical significance except in atrial flutter and arteries, and sympathetic cholinergic nerves cause vasodilation in fibrillation. The ventricles are less affected by antimuscarinic drugs the skeletal muscle vascular bed (see Chapter 6). Atropine can at therapeutic levels because of a lesser degree of vagal control. In block this vasodilation. Furthermore, almost all vessels contain toxic concentrations, the drugs can cause intraventricular conduc-endothelial muscarinic receptors that mediate vasodilation (see tion block that has been attributed to a local anesthetic action. Chapter 7). These receptors are readily blocked by antimuscarinic
Most blood vessels, except those in thoracic and abdominal vis-drugs. At toxic doses, and in some individuals at normal doses, cera, receive no direct innervation from the parasympathetic sys-antimuscarinic agents cause cutaneous vasodilation, especially in tem. However, parasympathetic nerve stimulation dilates coronary the upper portion of the body. The mechanism is unknown.