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128 SECTION II Autonomic Drugs

10

Pupil
8
Accommodation (diopters) Pupil diameter (mm) 6

4

2 Accommodation

0
0 15 30 45 60 90 1 2 4 6 8 10
Time (minutes) (days)

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.

A 120 1.0 B
*
110 1.6 Effect
* 0
Heart rate (beats/min) 90 * * * 0.5 - * - M 2 -ChR occupancy (fraction) Salivary flow (g/min) 1.2 Receptor * *
100
Receptor occupancy

occupancy
80
0.8
70 Effect * 0.5 - * - M 2 -ChR occupancy (fraction)
* 0 0.4
60
*
50 0 1.0
0 0.1 1 10 100 0 0.1 1 10 100
Atropine dose (µg/kg) Atropine dose (µg/kg)

FIGURE 8–5 Effects of increasing doses of atropine on heart rate (A) and salivary flow (B) compared with muscarinic receptor occupancy
in humans. The parasympathomimetic effect of low-dose atropine is attributed to blockade of prejunctional muscarinic receptors that suppress
acetylcholine release. (Adapted, with permission, from Wellstein A, Pitschner HF: Complex dose-response curves of atropine in man explained by different functions of M 1
and M 2 cholinoceptors. Naunyn Schmiedebergs Arch Pharmacol 1988;338:19. Copyright © 1988 Springer-Verlag.)