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

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autonomic nervous system exercises dominant control of various
organs (Table 11–5). For example, blockade of sympathetic ganglia
interrupts adrenergic control of arterioles and results in vasodilation,
improved peripheral blood flow in some vascular beds, and a fall in
blood pressure. Generalized ganglionic blockade also may result in
atony of the bladder and GI tract, cycloplegia, xerostomia, diminished
perspiration, and by abolishing circulatory reflex pathways,
NH
Figure 11–7. Ganglionic blocking agents.
postural hypotension. These changes represent the generally undesirable
features of ganglionic blockade that severely limit the therapeutic
efficacy of ganglionic blocking agents.
Cardiovascular System. Existing sympathetic tone is critical in
determining the degree to which blood pressure is lowered by ganglionic
blockade; thus, blood pressure may be decreased only minimally
in recumbent normotensive subjects but may fall markedly
in sitting or standing subjects. Postural hypotension was a major limitation
in ambulatory patients receiving ganglionic blocking drugs.
Changes in heart rate following ganglionic blockade depend
largely on existing vagal tone. In humans, mild tachycardia usually
accompanies the hypotension, a sign that indicates fairly complete
ganglionic blockade. However, a decrease may occur if the heart rate
is high initially.
Cardiac output often is reduced by ganglionic blocking drugs
in patients with normal cardiac function, as a consequence of diminished
venous return resulting from venous dilation and peripheral
pooling of blood. In patients with cardiac failure, ganglionic blockade
frequently results in increased cardiac output owing to a reduction
in peripheral resistance. In hypertensive subjects, cardiac output,
stroke volume, and left ventricular work are diminished.
Although total systemic vascular resistance is decreased in
patients who receive ganglionic blocking agents, changes in blood
flow and vascular resistance of individual vascular beds are variable.
Reduction of cerebral blood flow is small unless mean systemic blood
pressure falls below 50-60 mm Hg. Skeletal muscle blood flow is
unaltered, but splanchnic and renal blood flow decrease following the
administration of a ganglionic blocking agent.
Absorption, Distribution, and Elimination. The absorption of quaternary
ammonium and sulfonium compounds from the enteric tract
is incomplete and unpredictable. This is due both to the limited ability
of these ionized substances to penetrate cell membranes and to
the depression of propulsive movements of the small intestine and
Table 11–5
Usual Predominance of Sympathetic or Parasympathetic Tone at Various Effector Sites, and Consequences
of Autonomic Ganglionic Blockade
SITE PREDOMINANT TONE EFFECT OF GANGLIONIC BLOCKADE
Arterioles Sympathetic (adrenergic) Vasodilation; increased peripheral blood
flow; hypotension
Veins Sympathetic (adrenergic) Dilation: peripheral pooling of blood; decreased
venous return; decreased cardiac output
Heart Parasympathetic (cholinergic) Tachycardia
Iris Parasympathetic (cholinergic) Mydriasis
Ciliary muscle Parasympathetic (cholinergic) Cycloplegia—focus to far vision
Gastrointestinal tract Parasympathetic (cholinergic) Reduced tone and motility; constipation;
decreased gastric and pancreatic secretions
Urinary bladder Parasympathetic (cholinergic) Urinary retention
Salivary glands Parasympathetic (cholinergic) Xerostomia
Sweat glands Sympathetic (cholinergic) Anhidrosis
Genital tract Sympathetic and parasympathetic Decreased stimulation