PATIENTS GIVEN DRUG THERAPY FOR CHRONIC AND ACUTE
MEDICAL CONDITIONS
A steadily increasing number of potent drugs are being used to
treat disease, and the average hospitalized patient receives more than 10 drugs.
Many drugs have side effects that might make anesthesia more risky or patient management
more difficult. Knowing the pharmacologic properties and potential side effects
of commonly used drugs helps the anesthesiologist avoid pitfalls during anesthesia
and surgery.
The first step in avoiding these pitfalls is to obtain a drug
history from the patient, including vitamins, herbs, and supplements.[26]
[934]
Then, for every drug, medicine, and over-the-counter
preparation that the patient is using, the anesthesiologist should know the name,
classification of drug, diseases and conditions for which it is prescribed, and common
side effects. Having this knowledge before surgery helps the anesthesiologist avoid
making mistakes that might turn minor side effects into life-threatening situations.
If necessary, the anesthesiologist should return to the patient's bedside to search
for signs or symptoms of these effects. Unnecessary drugs should be discontinued
for at least three and preferably five half-lives of the drugs. This period should
be longer if metabolites of the drug have activity and longer half-lives. For essential
or beneficial drugs, the optimal dose should be determined in consultation with the
treating physician; the optimal dose is
that maximizing the ratio of therapeutic value to the risk of drug toxicity. Side
effects should be sought and either corrected preoperatively or at least planned
for in anesthetic management. For instance, if a patient is made hypokalemic with
diuretic drugs, hypokalemia might be corrected before surgery; an even better approach
would be to avoid hyperventilation during surgery (see the earlier section on hypokalemia).
This line of reasoning and planning is best done at least 1 week before surgery.
Ideally, the surgeon, internist, primary care practitioner, and anesthesiologist
should communicate regarding these topics well in advance of surgery. Understanding
the side effects of chronic drug therapy that affect the sympathetic nervous system
requires some knowledge of the basic pharmacologic characteristics of the sympathetic
nervous system.[811]
[812]
Pharmacologic Processes in the Sympathetic Nervous
System
The autonomic nervous system is discussed in detail in Chapter
16
. Although that review is comprehensive, it is important to remember
several points related to the pharmacology of the sympathetic nervous system when
considering chronic drug therapy.
Norepinephrine, dopamine, and epinephrine exert their physiologic
effect by interacting with an appropriate receptor at the target tissue. The primary
receptor acts through intermediary messenger systems (including cyclic 3',5'-adenosine
monophosphate [cAMP] or G-stimulatory or G-inhibitory proteins, or both) or can change
the conformation (and hence the affinity for ligands) of bordering or neighboring
receptors. These bordering or neighboring receptor effects may account for many
of the multitude of effects associated with catecholamines. The three major types
of catecholamine receptors are α-adrenergic, β-adrenergic, and dopaminergic.
These receptors are subdivided as follows:
- α1
-Receptor: Stimulation
constricts vascular smooth muscle and thus increases peripheral vascular resistance.
- α2
-Receptor: Stimulation
inhibits the release of norepinephrine itself (constituting negative feedback to
the sympathetic neuron). These receptors are largely presynaptic, although postsynaptic
vasoconstricting α2
-receptors exist on blood vessels.
- β1
-Receptor: Stimulation
increases the heart rate and the strength of cardiac contractions.
- β2
-Receptor: Stimulation
causes dilation of smooth muscles of the blood vessels and airway, relaxation of
uterine smooth muscle, and a variety of endocrine effects, including secretion of
renin.
- β3
-Receptor: Stimulation
results in greater release of norepinephrine from the sympathetic neuron (constituting
positive feedback to the sympathetic neuron).
- DA1
-receptor: Stimulation causes
dilation of vascular smooth muscle, notably in renal and mesenteric blood vessels.
- DA2
-receptor: Stimulation inhibits
the release of norepinephrine (presynaptic) and may also inhibit, through its ganglionic
actions, the release of acetylcholine. The class of dopamine receptors involved
in locomotion, inhibition of intestinal motility (antagonism of which accounts for
the increase in gastric emptying by metoclopramide), and vomiting is not known.
These different effects may be caused by slight differences in receptor conformations.
Figure 27-21
Antihypotensive drugs such as metaraminol (Aramine),
tyramine, and ephedrine create their effect by releasing catecholamines from the
granules of the nerve terminal. Therefore, when treatment with drugs such as methyldopa,
reserpine, or guanethidine depletes the store of norepinephrine (NE) in the granules,
little NE remains for release, and the antihypotensive drugs have been rendered ineffective.
The action of sympathomimetic substances is terminated through
an unusual process: the nerve ending uses an active reuptake system to recapture
most of the norepinephrine from the target tissue (see Chapter
16
). Obviously, blockage of this system permits more norepinephrine to
remain free to produce physiologic effects. In addition to this reuptake system,
two enzymes transform catecholamines metabolically: monoamine oxidase (MAO) and
catechol-O-methyltransferase (COMT) (see Chapter
16
).
