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Goldfrank's Manual of Toxicologic Emergencies

Goldfrank's Manual of Toxicologic Emergencies

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Published by Kang Kyu Choi
Goldfrank's Manual of Toxicologic Emergencies
Goldfrank's Manual of Toxicologic Emergencies

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EPIDEMIOLOGY

Hallucinogens are a diverse group of naturally occurring and synthetic drugs
that alter and distort perception, thought, and mood without clouding the sen-
sorium. Natural compounds have been used for thousands of years by many
different cultures, largely during religious ceremonies. Synthetic hallucino-
gen use began with the discovery of lysergic acid diethylamide (LSD). The
use of contemporary hallucinogens has grown in venues like all-night dance
clubs and “rave parties.”

SPECIFIC HALLUCINOGENS

The term hallucinationmay be defined as false perception that has no basis in
the external environment. Hallucinations are distinct from illusions, which
are misinterpretations of an actual experience. Hallucinogenic substances
may also have illusogenic effects. Although the term psychedelichas been
used for years, other terms, like entheogen and entactogen, frequently appear.
Entheogens are “substances which generate the god or spirit within,” whereas
entactogens create an awareness of “the touch within.”
The major structural classes of hallucinogens include the lysergamides, in-
dolealkylamines (tryptamines), phenylethylamines (amphetamines), arylhexam-
ines, cannabinoids, harmine alkaloids, and the tropane alkaloids. In addition,
there are several unique hallucinogens, such as salvinorin A. This chapter focuses
on lysergamides, tryptamines, phenylethylamines, and salvinorin A. Further dis-
cussion on the other classes of hallucinogens can be found in Chaps. 73, 81, 83,
and 113.

Lysergamides

Lysergamides are derivatives of lysergic acid. Naturally occurring lysergamides
are found in several species of morning glory (Rivea corymbosa,Ipomoea viola-

cea) and Hawaiian baby wood rose (Argyreia nervosa). The synthetic lyserga-
mide, LSD, is derived from an ergot alkaloid of the fungus, Claviceps purpurea.
It is a water-soluble, colorless, tasteless, and odorless powder. LSD is typically
sold as liquid-impregnated blotter paper, microdots, tiny tablets, “window pane”
gelatin squares, liquid, powder, or tablets. The minimum effective oral dose is 25
µg, and typical street doses range from 20–80 µg. The onset of effects may oc-
cur 30–60 minutes after exposure, with a duration of effect of 10–12 hours. LSD
users typically experience heightened awareness of auditory and visual stimuli
with size, shape, and color distortions. The classic finding is a synesthesia,
which is best described as a confusion of the senses. Users may describe “hear-
ing colors” or “seeing sounds.” Depersonalization and a sensation of enhanced
insight or awareness can occur.

Indolealkylamines (Tryptamines)

Indolealkylamines, or tryptamines, represent a class of natural and synthetic
compounds that structurally share a substituted monoamine group. Endogenous

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672

PART C THE CLINICAL BASIS OF MEDICAL TOXICOLOGY

tryptamines include serotonin and melatonin. Naturally occurring exogenous
tryptamines include psilocybin, bufotenine, and dimethyltryptamine (DMT).
Psilocybin is found in 3 major genera of mushrooms: Psilocybe, Panaelous,
andConocybe (Chap. 113). The effects of psilocin are similar to LSD, but with
a shorter duration of action of about 4 hours. DMT is a potent short-acting hal-
lucinogen and is used as an hallucinogenic “snuff.” DMT is also a component
of the hallucinogenic tea, Ayahuasca. In Ayahuasca, dimethyltryptamine-con-
taining plants (eg, Psychotria viridis) are combined with plants containing
harmine alkaloids (eg,Banisteriopsis caapi) that inhibit monoamine oxidases
to increase the oral bioavailability of DMT. DMT is typically smoked, snorted,
or injected. By this route, its hallucinogenic effects peak in 5–20 minutes, with
a duration of 30–60 minutes. Certain species of the toad genus Bufoproduce
bufotenine, a tryptamine, and 5-methoxydimethyl tryptamine (or 5-Meo-
DMT), as part of a complex defensive venom. The toad venom glands also pro-
duce cardioactive steroids, and death has resulted from overdose (Chap. 62).
Two of the more important synthetic tryptamines include N,N-diisopropyl-5-
methoxytryptamine (5-Meo-DiPT, Foxy Methoxy), and α-methyltryptamine
(AMT, IT-290). 5-Meo-DiPT is most commonly ingested, but may be smoked
or insufflated. Effects begin 20–30 minutes after ingestion. The hallucinogenic
effects are reported to last from 3–6 hours. AMT is a monoamine oxidase in-
hibitor that was initially marketed as an antidepressant in the former Soviet
Union. Despite its chemical similarity to DMT, the effects of AMT can last
from 12–16 hours.

Phenylethylamines (Amphetamines)

Endogenous phenylethylamines include dopamine, norepinephrine, and ty-
rosine. Exogenous phenylethylamines are known for their ability to stimu-
late catecholamine release and cause a variety of physiologic and psychiat-
ric effects, including hallucinations. Methylenedioxymethamphetamine
(MDMA), amphetamine, and methamphetamine are well-known members
of this family and are discussed in detail in Chap. 73. The best recognized
of the naturally occurring phenylethylamines is mescaline. Mescaline is
found in peyote (Lophophora williamsii), a small, blue-green spineless cac-
tus that grows in dry and rocky slopes throughout the southwestern United
States and northern Mexico. Nausea, vomiting, and diaphoresis often pre-
cede the onset of hallucinations.

Salvia divinorum

Salvia divinorum is a perennial herb classified as a member of the mint fam-
ily or Labiatae. Although there are more than 500 species of Salvia, only S.

divinorumis recognized for its hallucinogenic properties. The plant may be
chewed, smoked, or ingested as tea. Hallucinations occur nearly immediately
after exposure and last only 1–2 hours. Synesthesias are reported.

PHARMACOKINETICS

LSD is the most studied hallucinogen, and there is extensive information about
its pharmacokinetics. Plasma protein binding is more than 80% and volume of
distribution is 0.28 L/kg. LSD has an elimination half-life of about 2.5 hours.
Only small amounts are eliminated unchanged in the urine. Tolerance to the
psychological effects of LSD occurs within 2 or 3 days following daily dosing,

80HALLUCINOGENS

673

but rapidly dissipates if the drug is withheld for 2 days. Psychological cross-tol-
erance among mescaline, psilocybin, and LSD is reported in humans. There is
no evidence for physiologic tolerance, physiologic dependence, or a with-
drawal syndrome with LSD. Limited tolerance is demonstrated between psilo-
cybin and cannabinoids such as marijuana.

PHARMACOLOGY

Although the lysergamide, indolealkylamine, and phenylethylamine halluci-
nogens are structurally distinct, studies support a common site of action on
central serotonin (5-HT) receptors. The 5-HT

2Areceptor is the most likely
common site of hallucinogen action. The lysergamide, indolealkylamine, and
phenylethylamine hallucinogens all bind to the 5-HT

2class of receptors.
There is a good correlation between the affinity of both indolealkylamine and
phenylethylamine hallucinogens for 5-HT

2receptors in vitro and hallucino-

genic potency in humans in vivo.

CLINICAL EFFECTS

Physiologic changes accompany and often precede the perceptual changes in-
duced by hallucinogens. The physical effects may be caused by direct drug
effect or by a response to the disturbing or enjoyable hallucinogenic experi-
ence. Sympathetic effects are variable and include mydriasis, tachycardia,
hypertension, tachypnea, hyperthermia, and diaphoresis. Other reported clin-
ical findings include piloerection, dizziness, hyperactivity, muscle weakness,
ataxia, altered mental status, coma, and hippus, a rhythmic dilation and con-
striction of the pupils. Nausea and vomiting often precede the psychedelic ef-
fects produced by psilocybin and mescaline.
Potentially life-threatening complications, such as hyperthermia, coma, res-
piratory arrest, hypertension, tachycardia, and coagulopathy, can occur follow-
ing a massiveLSD overdose. The vast majority of morbidity from hallucinogen
use is associated with trauma.
The psychological effects of hallucinogens are dose related and affect
changes in arousal, emotion, perception, thought process, and self-image.
The response to the drug is related to the user’s mindset, emotions, or expec-
tations at the time of exposure, and can be altered by the group or setting.
Perceptual distortions are common, typically involving distortion of body im-
age and alteration in visual perceptions. Acute adverse psychiatric effects of
hallucinogens include panic reactions, true hallucinations, psychosis, and
major depressive dysphoric reactions. Acute panic reaction, the most com-
mon adverse effect, presents with frightening illusions, tremendous anxiety,
apprehension, and a terrifying sense of loss of self-control.

LABORATORY

Routine drug-of-abuse screens do not detect LSD or other hallucinogens. Al-
though LSD exposure can be detected by more sophisticated testing, these tests
are not valuable in the clinical setting. Depending on their structure, phenyleth-
ylamines may cause positive qualitative urine testing for amphetamines.

TREATMENT

Most hallucinogen users do not seek medical attention because they experi-
ence only the desired effect of the drug. For any hallucinogen user who does

674

PART C THE CLINICAL BASIS OF MEDICAL TOXICOLOGY

present to the emergency department, initial treatment must begin with atten-
tion to airway, breathing, circulation, level of consciousness, and abnormal
vital signs. Even when hallucinogen exposure is suspected, the basic ap-
proach to altered mental status should include consideration of dextrose, thia-
mine, naloxone, and oxygen therapy as indicated, along with a vigorous
search for other etiologies.
Hallucinogens rarely produce life-threatening toxicity. Sedation with benzodi-
azepines is usually sufficient to treat hypertension, tachycardia, and hyperther-
mia. Benzodiazepines remain the cornerstone of therapy, as the sedating effect
can diminish both endogenous and exogenous sympathetic effects. Hyperthermia
requires urgent sedation with benzodiazepines and rapid cooling.
Gastrointestinal decontamination with activated charcoal may be consid-
ered for asymptomatic patients with recent ingestions, but is probably not
helpful after clinical symptoms appear, and attempts to use it may lead to fur-
ther agitation. Excessive physical restraint should be avoided out of concern
for hyperthermia and rhabdomyolysis.
Serotonin syndrome can occur after hallucinogen use, and has been de-
scribed after LSD, tryptamine, and phenylethylamine use. Specific therapy
with cyproheptadine may be warranted (Chap. 70).

LONG-TERM EFFECTS

Long-term consequences of LSD use include prolonged psychotic reactions, se-
vere depression, and exacerbation of preexisting psychiatric illness. Flashbacks
have been reported in 15–80% of LSD users. Anesthesia, alcohol intake, and
medications can precipitate flashbacks. These abnormal perceptions can be trig-
gered during times of stress, illness, and exercise, and are often a virtual recur-
rence of the initial hallucinations. Hallucinogen-persisting perception disorder
(HPPD) is a chronic problem associated with LSD abuse. According to the Di-

agnostic and Statistical Manual of Mental Disorders,4th Edition (DSM-IV), the
diagnosis of HPPD requires the recurrence of perceptual symptoms that were
experienced while intoxicated with the hallucinogen that causes functional im-
pairment and is not a result of a medical condition. Symptoms are primarily vi-
sual, and reality testing is typically intact in HPPD. One finding described after
LSD use is palinopsia, or “trailing,” which refers to the continued visual percep-
tion of an object after it has left the field of vision.
Although many drugs have been tried to treat patients with HPPD, most
have not proven beneficial. Clonazepam reportedly improves, and haloperi-
dol and risperidone exacerbate, panic and visual symptoms.

675

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