Mood-Altering Drugs
Mood-altering drugs are the most frequently prescribed medications
in the United States. They include monoamine oxidase inhibitors (MAOIs), selective
serotonin reuptake inhibitors (SSRIs), phenothiazines, tricyclic antidepressant drugs,
other antidepressants that fail previous drug category
classification such as bupropion, and drugs of abuse such as cocaine. MAOIs, which
include isocarboxazid (Marplan), phenelzine (Nardil), pargyline (Eutonyl), tranylcypromine
(Parnate), and deprenyl, bind irreversibly to the enzyme MAO, thereby increasing
intraneuronal levels of amine neurotransmitters (serotonin, norepinephrine, dopamine,
epinephrine, octopamine). This increase is associated with an antidepressant effect,
an antihypertensive effect, an antinarcoleptic effect, elevation of liver enzymes,
and delayed onset of Parkinson's disease (deprenyl).[633]
Because two forms of the enzyme (MAO-A and MAO-B) are selective in vitro for substrate
(MAO-A is selective for serotonin, dopamine, and norepinephrine; MAO-B for tyramine
and phenylethylamine), presumably MAOIs selective for MAO-A or MAO-B would have different
effects.[969]
This is not known for certain inasmuch
as deprenyl (selegiline [Eldepryl]), an MAO-B-selective drug, improves a dopamine
deficiency state, parkinsonism.[633]
Interactions between MAOIs and a variety of foods and drugs containing
indirect-acting sympathomimetic substances such as ephedrine or tyramine (found especially
in aged cheeses) can occur for as long as 2 weeks after the last dose of MAOI is
given. The most serious effects of this interaction are convulsions and hyperpyrexic
coma (particularly after narcotics).
Anesthetic management of a patient given an MAOI can be chaotic;
for this reason it is widely accepted practice to discontinue MAOIs at least 2 to
3 weeks before any planned operation.[970]
[971]
[972]
[973]
[974]
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[978]
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An alternative point of view has been expressed regarding severely psychotic patients
or emergency surgery.[969]
[981]
[982]
[983]
Clearly,
the risk of discontinuing MAOIs must be weighed against the risk of suicidal tendencies
in some patients deprived of MAOIs. There are no reported experiences of interactions
between narcotics and deprenyl, so judgments about possible worsening of Parkinson's
disease and continuing MAOIs have no basis in data. It should be noted that severe
reactions have occurred when too short an interval existed between the administration
of MAOIs and tricyclic antidepressants.[849]
Emergency
surgery on patients given MAOIs can be punctuated by hemodynamic instability. A
regional block can be attempted as treatment of postoperative pain to avoid having
to give narcotics. Cases of hyperpyrexic coma after the administration of most narcotics
have been reported in humans, and animal studies document a 10% to 50% incidence
of hyperpyrexic coma in animals pretreated with MAOIs and then given a variety of
narcotics.[970]
[971]
[972]
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These reactions appear to be treated best by therapy supporting vital functions.
Alternative drugs for the treatment of severe depression include
the tricyclic antidepressant drugs: amitriptyline (Elavil, Endep), imipramine (Tofranil,
Presamine), desipramine (Norpramin), doxepin (Adapin, Sinequan), nortriptyline (Aventyl),
fluoxetine (Prozac), trazodone (Desyrel), and bupropion (Wellbutrin).[975]
Tricyclic antidepressant drugs also block the reuptake of neurotransmitters and
cause their acute release. Given chronically, these drugs decrease stores of noradrenergic
catecholamines. Tricyclic antidepressant drugs also produce side effects similar
to those of atropine (dry mouth, tachycardia, delirium, urinary retention) and can
cause changes on the ECG (changes in the T wave, prolongation of the QRS complex,
bundle branch block or other conduction abnormalities, or PVCs). Although arrhythmias
induced by tricyclic antidepressants have been treated successfully with physostigmine,
bradycardia has sometimes occurred.[975]
Drug interactions
with tricyclic antidepressants include those related to blockade of the reuptake
of norepinephrine (such as interference with the action of guanethidine) and fatal
arrhythmias after halothane and pancuronium.[984]
[985]
[986]
Such
interactions, though predictable for a population of patients, may not alter a patient's
threshold for arrhythmias. The newer antidepressants (the SSRIs) can also have serious
side effects. Fluoxetine, a tricyclic that also has an SSRI effect, causes nausea,
vomiting, headaches, nervousness, and possibly paranoia and ideas of suicide more
commonly than the other tricyclics do,[975]
but
it is less likely to cause anticholinergic effects or orthostatic hypotension. Bupropion
may cause nausea, vomiting, seizures, agitation, tremor, excitement, and increased
motor activity, but only rarely causes anticholinergic effects or orthostatic hypotension.
Switching between drugs for depression can cause hyperpyrexia and coma. Thus, switching
before surgery should not be requested casually.[975]
The effectiveness of phenothiazines and butyrophenones in schizophrenia
suggests a dopamine receptor blocking action. In addition, these drugs possess varying
degrees of parasympathetic stimulation and ability to block α-adrenergic receptors.
The phenothiazines include chlorpromazine (Thorazine, Chlor-PZ), promazine (Sparine),
triflupromazine (Vesprin), fluphenazine (Prolixin), trifluoperazine, prochlorperazine
(Compazine), and many others. The butyrophenones include droperidol and haloperidol
(Haldol). Both the phenothiazines and butyrophenones produce sedation, depression,
and antihistaminic, antiemetic, and hypothermic responses. They are also associated
with cholestatic jaundice, impotence, dystonia, and photosensitivity. Other side
effects associated with phenothiazines include orthostatic hypotension (partly as
a result of α-adrenergic blockade) and ECG abnormalities such as prolongation
of the QT or PR intervals, blunting of T waves, depression of the ST segment, and
on rare occasion, PVCs and torsades de pointes.[975]
[985]
[986]
Although
few data are available on the antidepressant drugs selective for serotonin (the SSRIs),
occasional case reports of severe hypotension and cardiac arrest with severe bradycardia
have been presented in abstract form.
Several important drug interactions are noteworthy for the phenothiazine
derivatives. The effects of CNS depressants (especially narcotics and barbiturates)
are enhanced by the concomitant administration of phenothiazines. In addition, the
CNS seizure threshold is lowered by the administration of phenothiazines, which should
be avoided in patients who are epileptic or withdrawing from any drug that depresses
the CNS. The antihypertensive effects of guanethidine and guanadrel are blocked
by tricyclic antidepressant drugs and the phenothiazines.[938]
Lithium carbonate is used to treat manic depression, but it is more effective in
preventing mania than relieving depression. In excitable cells, lithium mimics sodium
and decreases the release of neurotransmitters both centrally and peripherally.
Lithium prolongs neuromuscular blockade[987]
and
may decrease anesthetic requirements because
it blocks brainstem release of norepinephrine, epinephrine, and dopamine.
Psychoactive drugs such as amphetamines (including methamphetamines
and their smokable derivative in crystal form known as "ice") and cocaine acutely
release norepinephrine, epinephrine, and dopamine and block their reuptake. Taken
chronically, they deplete the nerve endings of these neurotransmitters.
Drugs that appear to increase central α-adrenergic release
increase anesthetic requirements, whereas drugs that appear to decrease central α-adrenergic
release decrease anesthetic requirements. (This may not be the mechanism by which
they alter anesthetic requirements, but it is a convenient way of remembering the
alteration.) Drugs that affect only the β-adrenergic receptors do not alter
anesthetic requirements.[227]
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