Amphetamine intoxication

Definisi

Eiology

Marked tolerance develops after amphetamine use and leads to rapid escalation of drug doses.
Increasing the dose produces increasing toxicity and complications in patients with acute and
chronic amphetamine use.

epidemiologi

Frequency
United States

Accurate estimation of illicit amphetamine use is difficult. An estimated 13 million Americans use these
compounds without medical supervision. Random toxicologic screens performed in the ED indicate
amphetamine presence in about 2% of patients. Self-reporting among college students indicates an
approximate 4% prevalence. An aged-matched survey of fourth-year medical students revealed that about
1.2% use amphetamines.

Sulit memperkirakan penggunaan obat terlarang amfetamin secara akurat. Diperkirakan 13 juta orang
Amerika menggunakan komponen ini tanpa pengawasan medis. Toxicologic screens acak yang diakukan
di UGD menunjukkan adanya amfetamin sekitar 2% dari pasien. Pelaporan diri di kalangan mahasiswa
menunjukkan kurang lebih 4% kejadian. Survei an aged-matched dari mahasiswa kedokteran tahun
keempat mengungkapkan bahwa 1,2% menggunakan amfetamin.

Locations of amphetamine drug factories may establish the regional nature of amphetamine use. [12] Use of
these drugs in the United States mostly occurs in the large cities of the southwest. Of all amphetamine drug
factory busts, 75% have occurred in California, Texas, and Oregon. At UC Davis's ED in the late 1980s, the
prevalence of amphetamine toxicity was found to be 0.69%.

Lokasi pabrik obat amfetamin dapat membentuk daerah penggunaan amfetamin. Pengunaan obat ini di
Amerika Serikat sebagian besar terjadi di kota-kota besar barat daya. Dari semua pabrik obat amfetamin,
75% berada di California, Texas, dan Oregon. At UC Davis's ED in the late 1980s, kejadian toksisitas
amfetamin ditemukan 0,69%.

Despite the large focus of use in the western United States during the 1980s, many episodes of
methamphetamine complications occurred in Minneapolis and Philadelphia. Importation of amphetamines
from the Far East fuels Hawaiian drug use. As of August 1999, amphetamine-producing laboratories have
sprung up in Mexico; border city narcotics officers blame the more lucrative street valuation of
methamphetamine in the United States compared with cocaine. Amphetamines then are imported through
cities along the US-Mexico border for sale at prices up to $26,000 per kilogram (cocaine is approximately
$14,000 per kilogram).

Meskipun penggunaan di Amerika Serikat bagian barat selama tahun 1980 menjadi fokus besar, banyak
bagian kompllikasi methampheamin terjadi di Minneapolis dan Philadelphia. impor penggunaan obat
amfetamin dari the Far East fuels Hawaiian. Pada bulan Agustus 1999, laboratorium produksi amfetamin
bermunculan di Meksiko; petugas narkotika perbatasan kota menyalahkan proses valuasi yang lebih
menguntungkan dari methamphetamin di Amerika Serikat dibandingkan dengan kokain. amfetamin
kemudian diimpor melalui kota sepanjang perbatasan US-Meksiko untuk dijual dengan harga hingga $
26.000 per kilogram (kokain adalah sekitar $ 14.000 per kilogram).

International

Amphetamine use has been found to be increasing in Europe. In 1993, in the Frankfurt area, 9% of
reckless driving arrests were associated with amphetamine use. [13] A study among adolescents in Taiwan
found a prevalence of 2.7% and an estimated lifetime amphetamine use of about 4%. [14] In the United
 Kingdom, the number of amphetamine confiscations by law enforcement is only exceeded by that of
cannabis.

Penggunaan amfetamin telah ditemukan meningkat di Eropa. Pada tahun 1993, di daerah Frankfurt, 9%
dari penangkapan pengemudi sembrono dikaitkan dengan penggunaan amfetamin. Sebuah studi
dikalangan remaja di Taiwan menemukan prevalensi 2,7% dan diperkirakan penggunaan amfetamin
seumur hidup sekitar 4%. Di UK, jumlah penyitaan amfetamin oleh penegak hukum hanya exceeded by
that of cannabis.

Ring methoxylated amphetamine compounds have been found in a number of autopsies performed in
Europe. Whether these are contaminants or byproducts in the production of
methylenedioxymethamphetamine (MDMA) preparations, also known as Ecstasy, is unclear. Neither
amphetamine nor methamphetamine was found in the blood of these individuals, suggesting that
amphetamines were not deliberately added in the compounding of these Ecstasy tablets.

Senyawa amfetamin cincin methoxylated telah ditemukan di sejumlah otopsi yang dilakukan di Eropa.
Apakah ini persiapan kontaminan atau produk sampingan dalam produksi
methylenedioxymethamphetamine (MDMA), juga dikenal sebagai ekstasi, tidak jelas. Baik amphetamine
atau sabu ditemukan di dalam darah orang ini, menunjukkan bahwa amfetamin tidak sengaja ditambahkan
dalam peracikan tablet ekstasi tersebut.

The United Nations' 2012 World Drug Report estimated a worldwide prevalence of illicit use of
amphetamine type stimulants to be 0.3-1.2%.[15]

2012 World Report Obat PBB memperkirakan prevalensi di seluruh dunia penggunaan terlarang jenis
amphetamine stimulan untuk menjadi 0,3-1,2%

Mortality/Morbidity
Acute overdose of amphetamines produces seizures, hypertension, tachycardia, hyperthermia, psychosis,
hallucinosis, stroke, and fatality.

Overdosis akut amfetamin menghasilkan kejang, hipertensi, takikardia, hipertermia, psikosis, halusinasi,
stroke, dan kematian

One study at San Francisco General Hospital from 1975-1987 determined that approximately 25%
of seizures were secondary to amphetamine use. [16]
In a few patients, amphetamine use produces long-term paranoid schizophrenia; whether this
results from unmasking underlying disease is unclear. Severe psychological depression and prolonged
sleep follow chronic use and binges.
Habitual amphetamine use produces toxic psychosis resembling paranoid schizophrenia.
Hallucinations, delusions, and bizarre violent behavior are common.
Amphetamine use was associated with an increased risk of myocardial infarctions in 15-45 year
olds in Texas. [17]
Satu studi di Rumah Sakit Umum San Francisco dari 1975-1987 menetapkan bahwa sekitar 25% dari
kejang yang sekunder untuk penggunaan amfetamin.
Pada beberapa pasien, penggunaan amfetamin menghasilkan jangka panjang skizofrenia paranoid;
apakah ini hasil dari penyakit yang mendasari unmasking jelas. Depresi psikologis yang parah dan tidur
berkepanjangan mengikuti penggunaan kronis dan binges.
penggunaan amfetamin Kebiasaan menghasilkan psikosis beracun menyerupai skizofrenia paranoid.
Halusinasi, delusi, dan perilaku kekerasan aneh yang umum.
Penggunaan Amphetamine dikaitkan dengan peningkatan risiko infark miokard pada usia 15-45 tahun
di Texas.

Race
In the United States, amphetamine use characteristically occurs among single white men. Data from rural
populations reveal that Caucasians use amphetamines significantly more than African Americans. [18]

Di Amerika Serikat, penggunaan amfetamin khas terjadi di antara orang kulit putih tunggal. Data dari
penduduk pedesaan mengungkapkan bahwa Kaukasia menggunakan amfetamin secara signifikan lebih
dari Amerika Afrika.

Sex
 Amphetamine use characteristically occurs among single white men aged 20-35 years who are typically
unemployed.[19] However, amphetamine use is becoming more common among women and other ethnic
groups.

Penggunaan amfetamin khas terjadi di antara orang kulit putih tunggal berusia 20-35 tahun yang biasanya
menganggur. Namun, penggunaan amfetamin menjadi lebih umum di kalangan perempuan dan kelompok
etnis lainnya.

A recent study suggests that the action of estrogen within the CNS might explain why fewer women than
men use amphetamines. Women in their late follicular phase (when estrogen levels are high and
progesterone levels are low) were more likely to report "unpleasant stimulation" when exposed to
amphetamine. This effect was not observed in the early follicular phase, when both hormone levels are low.
[20]

Sebuah studi terbaru menunjukkan bahwa aksi estrogen dalam SSP mungkin menjelaskan mengapa
perempuan lebih sedikit daripada pria menggunakan amfetamin. Wanita pada akhir fase folikuler mereka
(ketika tingkat estrogen yang tinggi dan tingkat progesteron rendah) lebih mungkin untuk melaporkan
"stimulasi menyenangkan" bila terkena amfetamin. Efek ini tidak diamati dalam fase folikuler awal, ketika
kedua tingkat hormon yang rendah.

Clinical manifestation

Patients with amphetamine intoxication often are identified by a change of mental status alone or
associated with another injury and/or illness.

Central nervous system manifestations are as follows:

Change of mental status, disorientation, and headache

Dyskinesias
Agitation
Formication
Symptoms of stroke
Cardiovascular manifestations are as follows:

Chest pain
Palpitations
Gastrointestinal manifestations are as follows:

Dry mouth
Nausea and vomiting
Diarrhea
Skin/cutaneous manifestations are as follows:

Diaphoresis
Erythematous painful rashes, needle marks
Infected deep ulcerations (ecthyma)
Genitourinary (GU) manifestations include difficult micturition. Ocular manifestations include mydriasis.

Pasien dengan amfetamin keracunan sering diidentifikasi oleh perubahan status mental sendiri atau
berhubungan dengan cedera lain dan / atau penyakit.
Central manifestasi sistem saraf adalah sebagai berikut:
Perubahan status mental, disorientasi, dan sakit kepala
Diskinesia
Agitasi
Formication
Gejala stroke
Manifestasi kardiovaskular adalah sebagai berikut:
Sakit dada
Palpitasi
Manifestasi gastrointestinal adalah sebagai berikut:
Mulut kering
Mual dan muntah
Diare
 Kulit / manifestasi kulit adalah sebagai berikut:
Diaphoresis
eritematosa ruam menyakitkan, tanda jarum
ulserasi dalam Terinfeksi (ecthyma)
Genitourinari (GU) Manifestasi termasuk berkemih sulit. Manifestasi okular termasuk midriasis.

Amfetamin mempengaruhi otak dan membuat rasa nikmat, meningkatkan

energi, dan meningkatkan mood (Kemenkes, 2010). Kondisi intoksikasi stimulan
akan menimbulkan beberapa gejala psikotik, beberapa hari sampai beberapa
minggu (Kemenkes, 2010). Gejala psikologik penggunaan amfetamin menurut
Kemenkes (2010), Hawari (2006) dan Japardi (2002), yaitu agitasi psikomotor,
rasa gembira (elation), harga diri meningkat (grandiosity), bayak bicara
(melantur), kewaspadaan meningkat (paranoid), halusinasi penglihatan (melihat
bayangan/sesuatu yang sebenarnya tidak ada), mudah tersinggung. Gejala fisik
yang ditimbulkan menurut Hawari (2006) dan Japardi (2002), yaitu jantung
berdebar (palpitasi), pupil melebar (dilatasi pupil), tekanan darah naik, keringat
berlebihan, mual dan muntah, tingkah laku maladaptif, sulit tidur gangguan
dilusi (waham) dan menurut Mitra bintibmas (2010) semua aktivitas tubuh
dipercepat.

Diagnosis

Physical
Physical examination findings may demonstrate the strong central nervous system and peripheral nervous
system stimulation produced by amphetamine compounds. Modification of the basic amphetamine
molecule produces compounds with variable effects on target organs. Methamphetamine produces
prominent central nervous system effects with minimal cardiovascular stimulation.

Individuals who chronically use amphetamines intravenously are at risk of infection and vascular injury.

General findings are as follows:

Weight loss
Hyperactivity, confusion, and agitation (may combine to produce severe hyperthermia, which can
be worse in physically restrained individuals)
Diaphoresis
Mydriasis
Anorexia

Cardiovascular findings are as follows:

Alpha- and beta-adrenergic stimulation can lead to systolic and diastolic blood pressure increases
Heart rate may be unchanged or slow in response to hypertension
Increasing doses produce tachycardia and other dysrhythmias, including ventricular tachycardia
and fibrillation
Hypertensive crisis or vasospasm may lead to stroke

Central nervous system findings are as follows:

Increased alertness
Euphoria
Confusion or agitation
 Bruxism
Stroke caused by acute amphetamine toxicity

Cutaneous findings are as follows:

Skin flushing
Infected deep ulcerations (ecthyma) in patients with formication
Skin track marks, cellulitis, abscesses, phlebitis, or vasculitis with intravenous use

Other organ system findings are as follows:

Respiratory distress secondary to acute lung injury (ALI), in patients who smoke amphetamines
Gastrointestinal - Nausea or vomiting
Dental - "Meth mouth," a condition of eroded teeth

Laboratory Studies
Patients with amphetamine intoxication who present with no life-threatening signs or symptoms may be
treated with sedation and observation and may require no laboratory workup.

Patients who are experiencing seizures or prolonged mental status changes require rapid serum glucose
determination (eg, fingerstick) and electrolyte testing.

Patients with suicidal ideations should have serum acetaminophen level checked.

Evaluate renal and hepatic function of patients who are demonstrating significant or prolonged
hyperthermia and search for infectious causes.

When appropriate, evaluation may include urinalysis, urine culture, blood culture, spinal fluid analysis and
staining, and culture of material from cutaneous sources.

Because hyperthermia may induce disseminated intravascular coagulation (DIC), monitor for DIC and treat
appropriately if it occurs.

Obtain urine and serum creatinine kinase levels to monitor for rhabdomyolysis. If the dipstick result is
positive for blood but shows few or no red blood cells on microscopic examination, rhabdomyolysis may be
present.

Urine specimens for drug and toxicologic screens may be collected after Foley catheter placement if the
physician believes that these tests will help guide therapy.

Usually, the presence of pure sympathomimetic toxidrome precludes the need for drug screening.
However, with methamphetamine and other designer amphetamines, peripheral effects may not be
observed.

Imaging Studies
Patients who are demonstrating only mild symptoms from amphetamine intoxication often respond to
sedation and recover rapidly under observation. Such patients require no imaging studies unless trauma is
suspected.
Obtain a chest radiograph for patients complaining of chest pain or respiratory distress. Obtain a CT scan
of the head for patients with recurrent seizures or prolonged mental status changes if no metabolic cause
can be quickly found and corrected.

Look for infectious causes in patients who are demonstrating significant or prolonged hyperthermia; this
may include chest radiography, echocardiography, CT of the head and abdomen, and extremity
ultrasonography of suspected abscesses.

Other Tests
Perform electrocardiographic testing and monitor patients complaining of chest pain. Obtain appropriate
cardiac enzyme testing if pain is prolonged or cardiac injury is suspected.

treatment
Prehospital Care
Prehospital care of patients with amphetamine intoxication often requires physical and chemical restraint of
the patient and treatment of complications of intoxication, including seizures, loss of competent airway,
cardiac dysrhythmias, and trauma.

Emergency Department Care

Patients with amphetamine intoxication who present with no life-threatening signs or symptoms may be
treated with sedation and observation.

Complications may require the physician to perform procedures to establish airway management or fluid
resuscitation or to initiate vigorous cooling measures.

In patients with acute oral ingestion, GI decontamination is performed by the administration of activated
charcoal. Orogastric lavage often is not necessary but may be performed when the patient presents with
immediately life-threatening intoxication shortly after ingestion. Whole-bowel irrigation may be indicated in
suspected cases of body stuffing or body packing (large quantities of drugs in wrapping for international
transport or drug hiding, respectively).

Foley catheter placement may be useful to monitor urine output, particularly in situations in which diuretics
are administered to manage pulmonary edema. Patients often have decreased urination due to the effects
on bladder sphincter muscles to prevent passing urine. Other individuals may be dehydrated after
recreational use in raves and club events. Quick assessment of bladder fullness can be performed with
bedside ultrasonography or bladder palpation.

Agitation or persisting seizures in patients with amphetamine toxicity requires generous titration of
benzodiazepines and a calm soothing environment. Avoid physical restraints, if possible.

Significant cardiac dysrhythmias may require cardioversion, defibrillation, and antidysrhythmics. Prolonged
hypertension may present a cardiovascular risk. Use benzodiazepine sedation (nonspecific sympatholysis)
to initially manage hypertension, if present. Refractory cases or cases associated with significant end-organ
toxicity (eg, cardiovascular accident [CVA], myocardial ischemia) can be managed with intravenous
phentolamine, nitroprusside, or nitroglycerin.

Avoid use of beta-blockers in order to prevent unopposed alpha effect (vasoconstriction). Note that
combination alpha-adrenergic and beta-adrenergic antagonists may play a valuable role in managing
tachycardias; this recommendation is based on class IIb evidence in the revision of unstable angina/non-
ST segment elevation myocardial infarction guidelines by the American Heart Association (based on
similarities of amphetamine and cocaine toxicities).[22]

Cardiogenic pulmonary edema can be managed with nitroglycerin and diuretics.

Aggressively cool hyperthermic patients with evaporative cooling, ice packs to the groin and axilla, and use
of "ice-bath" (total body immersion in ice). Patients with severe hyperthermia (temperature >104F)
associated with psychomotor agitation may require immediate neuromuscular paralysis to rapidly decrease
temperature. Temperature control should be achieved within 15-20 minutes upon presentation in order to
prevent multiorgan failure and death.

Haloperidol is controversial[23] in the treatment of agitation in any patient with the potential to seize or
develop hyperthermia because of associations with lowering the seizure threshold and altering
thermoregulation.

Of all neuroleptic drugs, however, haloperidol rarely is associated with seizures (minimal effects on seizure
threshold). In addition, animal studies suggest that haloperidol can antagonize amphetamine-induced
hyperthermia. Haloperidol can be considered as an adjunct to benzodiazepines for afebrile patients with
normal vital signs and psychomotor agitation that requires chemical restraint.

Look for and treat traumatic injuries in patients with amphetamine intoxication.

Medication Summary
Medications available for amphetamine toxicity include gastric decontaminants (charcoal with or without
sorbitol), sedatives to control CNS stimulation caused by amphetamines (benzodiazepines, antipsychotics),
muscle relaxants (benzodiazepines, dantrolene), and several drugs to control possible hemodynamic
cardiovascular disturbances (alpha-adrenergic blockers, nitrates, diuretics).

Further Outpatient Care

Patients may need referral for outpatient detoxification centers or for management of addictive behaviors.