DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

228 parasympathetic postganglionic nerve terminals in the
SA node, which normally inhibit ACh release
(Wellstein and Pitschner, 1988).
Larger doses of atropine cause progressive tachycardia
by blocking M 2
receptors on the SA nodal pacemaker
cells, thereby antagonizing parasympathetic
(vagal) tone to the heart. The resting heart rate is
increased by ~35-40 beats per minute in young men
given 2 mg of atropine intramuscularly. The maximal
heart rate (e.g., in response to exercise) is not altered
by atropine. The influence of atropine is most noticeable
in healthy young adults, in whom vagal tone is
considerable. In infancy and old age, even large doses
of atropine may fail to accelerate the heart. Atropine
often produces cardiac arrhythmias, but without significant
cardiovascular symptoms.
SECTION II
NEUROPHARMACOLOGY
Atropine can abolish many types of reflex vagal cardiac slowing
or asystole, such as from inhalation of irritant vapors, stimulation
of the carotid sinus, pressure on the eyeballs, peritoneal stimulation,
or injection of contrast dye during cardiac catheterization. Atropine
also prevents or abruptly abolishes bradycardia or asystole caused by
choline esters, acetylcholinesterase inhibitors, or other parasympathomimetic
drugs, as well as cardiac arrest from electrical stimulation
of the vagus.
The removal of vagal tone to the heart by atropine also may
facilitate AV conduction. Atropine shortens the functional refractory
period of the AV node and can increase ventricular rate in patients
who have atrial fibrillation or flutter. In certain cases of seconddegree
AV block (e.g., Wenckebach AV block), in which vagal
activity is an etiological factor (as with digitalis toxicity), atropine
may lessen the degree of block. In some patients with complete AV
block, the idioventricular rate may be accelerated by atropine; in others
it is stabilized. Atropine may improve the clinical condition of
patients with inferior or posterior wall myocardial infarction by
relieving severe sinus or nodal bradycardia or AV block.
Circulation. Atropine, in clinical doses, completely
counteracts the peripheral vasodilation and sharp fall in
blood pressure caused by choline esters. In contrast,
when given alone, its effect on blood vessels and blood
pressure is neither striking nor constant. This result is
expected because most vascular beds lack significant
cholinergic innervation. In toxic and occasionally in
therapeutic doses, atropine can dilate cutaneous blood
vessels, especially those in the blush area (atropine
flush). This may be a compensatory reaction permitting
the radiation of heat to offset the atropine-induced rise
in temperature that can accompany inhibition of
sweating.
Respiratory System. Although atropine can cause some
bronchodilation and decrease in tracheobronchial
secretion in normal individuals by blocking parasympathetic
(vagal) tone to the lungs, its effects on the
respiratory system are most significant in patients with
respiratory disease. Atropine can inhibit the bronchoconstriction
caused by histamine, bradykinin, and
the eicosanoids, which presumably reflects the participation
of reflex parasympathetic (vagal) activity in the
bronchoconstriction elicited by these agents. The ability
to block the indirect bronchoconstrictive effects of these
mediators forms the basis for the use of muscarinic
receptor antagonists, along with β adrenergic receptor
agonists, in the treatment of asthma (Chapter 36).
Muscarinic antagonists also have an important role in
the treatment of chronic obstructive pulmonary disease
(Chapter 36).
Atropine inhibits the secretions of the nose, mouth, pharynx,
and bronchi, and thus dries the mucous membranes of the respiratory
tract. This action is especially marked if secretion is excessive and
formed the basis for the use of atropine and other muscarinic antagonists
to prevent irritating inhalational anesthetics such as diethyl
ether from increasing bronchial secretion. While the newer inhalational
anesthetics are less irritating, muscarinic antagonists are similarly
used to decrease the rhinorrhea associated with the common
cold or with allergic and nonallergic rhinitis. Reduction of mucous
secretion and mucociliary clearance can, however, result in mucus
plugs, a potentially undesirable side effect of muscarinic antagonists
in patients with airway disease.
Eye. Muscarinic receptor antagonists block the cholinergic
responses of the pupillary sphincter muscle of the
iris and the ciliary muscle controlling lens curvature
(Chapter 64). Thus, they dilate the pupil (mydriasis)
and paralyze accommodation (cycloplegia). The wide
pupillary dilation results in photophobia; the lens is
fixed for far vision, near objects are blurred, and objects
may appear smaller than they are. The normal pupillary
reflex constriction to light or upon convergence of the
eyes is abolished. These effects can occur after either
local or systemic administration of the alkaloids.
However, conventional systemic doses of atropine (0.6 mg)
have little ocular effect, in contrast to equal doses of scopolamine,
which cause evident mydriasis and loss of accommodation. Locally
applied atropine produces ocular effects of considerable duration;
accommodation and pupillary reflexes may not fully recover for
7-12 days. Other muscarinic receptor antagonists with shorter durations
of action are therefore preferred as mydriatics in ophthalmologic
practice (Chapter 64). Pilocarpine and choline esters (e.g.,
carbachol) in sufficient concentrations can reverse the ocular effects
of atropine.
Muscarinic receptor antagonists administered systemically
have little effect on intraocular pressure except in patients predisposed
to angle-closure glaucoma, in whom the pressure may occasionally
rise dangerously. The rise in pressure occurs when the
anterior chamber is narrow and the iris obstructs outflow of aqueous