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Methamphetamine intoxication
Methamphetamine Intoxication A Speedy New Treatment
NANCY E. GARY, M.D. PARVIN SAIDI, M.D. Piscafaway, New Jersey
This communication describes the use of droperidol in methamphetamine poisoning. Droperldol antagonizes the central stimulatory effects of amphetamines producing a person who is indifferent to environmental stimuli, calm and cooperative. Coupled with an acid diuresis, causing a fivefold increase in the urinary concentration of methamphetamine and recovery of 66 per cent of the ingested drug, a seriously intoxicated patient showed rapid improvement. Amphetamine and methamphetamine remain common causes of poisoning despite inclusion of these drugs in “The Comprehensive Drug Abuse Prevention Act of 1970” [I]. Little has been added to the management of amphetamine intoxication since Espelin and Done [2] advocated chlorpromazine as an effective antagonist of the central stimulatory effects of the amphetamines. Droperidol is similar to chlorpromazine in this action, but it has the added advantage of producing, without sedation, a general quiescence and a sense of detachment from external stimuli [3]. Forced acid diuresis has been a recommended treatment procedure based on experimental data; however, actual removal of amphetamine by this technic in the patient made severely ill by amphetamine poisoning has not been documented previously [4-61. The effect of this combination of therapeutic modalities and the gradual recovery from early hemostatic derangement seen in a seriously intoxicated patient are discussed. CASE REPORT
From the Nephrology and Hematology Sections, Department of Medicine, College of Medicine and Dentistry of New, Jersey, Rutgers Medical School, Piscataway, New Jersey. Requests for reprints should be addressed to Dr. Nancy E. Gary, CMDNJ-Rutgers Medical School, Raritan Valley Hospital, 275 Greenbrook Road, Green Brook, New Jersey 08812. Manuscript accepted March 17, 1977.
A 27 year old man who habitually ingested about 20 mg of methamphetamine daily was hospitalized 1 hour after eating 1,400 mg of “street” methamphetamine (18 bags each containing approximately 80 mg of undetermined purity).* On admission to St. Vincent’s Hospital and Medical Center of New York, the patient was agitated, combative and hallucinating. His blood pressure was 180/100 mg Hg, pulse rate 146/min, respirations 28/min and oral temperature 37OC. His pupils were widely dilated and reactive to light. The remainder of his physical examination was noncontributory. On admission, the urinary concentration of methamphetamine was 2.7 mg/dl. Other laboratory studies included a direct bilirubin 0.3 mg/dl, total bilirubin 1.2 mg/dl, blood urea nitrogen 12 mg/dl, lactic dehydrogenase (LDH) 2,780 Wordlesky-Ladue units, serum glutamic oxaloacetic transaminase (SGOT) 1,205 Karmen units and creatinine phosphokinase (CPK) 3,278 Siegel-Cohan units. Plasma haptoglobin was 350 mg/dl and plasma hematin 0. Arterial blood gases on room air revealed a pH of 7.43, carbon dioxide Two packets of methamphetamine were obtained from the patient’s usual “dealer” and submitted for analysis. A reliable purity assay could not be done because of an interfering reaction between the foil wrapper and the contents of the packets. l
March1978
The American Journal of Medicine
Volume 64
537
METHAMPHETAMINE
INTOXICATION-GARY,
SAIDI
tension 26 mm Hg, bicarbonate 16 meq/liter and oxygen tension 71 mm Hg. Urinalysis showed a pH of 6.0, 1-F protein and 1-t blood (Ames Reagent stix). Microscopic examination revealed 5 to 6 red blood cells, sheets and casts of renal tubular epithelial cells and 3 to 5 hyaline casts/lpf. Serial hematologic and hemostatic parameters are presented in Table I. In the emergency room, the patient was given 120 mg of phenobarbital intramuscularly. Ninety minutes later, on admission to the intensive care unit, the blood pressure was 180/100 mm Hg, pulse rate 168/min, respirations 40/min and temperature 42% rectally. The intravenous administration of droperidol at the rate of 2.5 mg/min was begun. Within 15 minutes of the start of droperidol administration (total dose 13 mg), the patient had become subdued and calm with a blood pressure of 112/70 mm Hg, a pulse rate of 1 lG/min and a respiratory rate of 26/min. His temperature was reduced with the application of a hypothermia blanket to 39.4OC rectally in 1 hour. Two hours after admission intravenous mannitol (12.5 g) was given to initiate a diuresis. Acid diuresis was begun 3 l/2 hours later by using 500 ml each of the following solutions in rotation at a rate to match the patient’s urinary output of 200 to 600 ml/hour: 5 per cent dextrose and water to which 1.5 g of ammonium chloride was added, 5 per cent dextrose and water, and normal saline solution. The acid infusion was terminated after 16 hours at which time the patient was entirely asymptomatic and had stable vital signs with a blood pressure of 1 lo/70 mm Hg, a pulse rate of 96/min, respirations of 18/min and an oral temperature of 37%. Arterial blood gases were frequently measured during acid diuresis; the lowest arterial pH was 7.38, carbon dioxide tension 31 mm Hg and bicarbonate 17 meq/liter.
COMMENTS Illegally synthesized black market “speed” (methamphetamine) is used intravenously to produce a “speed binge” or “flash.” Repeated use may induce a state of paranoid thought [7], manifested in our patient by fear of a raid by the police which led him to dispose of all the methamphetamine in his possession by ingesting it. TABLE I
Hematologlc and Coagulation Parameters Day 1 A.M. P.M.
Hemoglobin (g/dl) Hematocrit vol (%) White blood cells (per mm3) Retlculocyte (%) Platelets (per mm3)
Day 2
Day 3
Day 6
15.6 12.9 13.6 47 38 43 13,800 13,600 15,800
15 46 8,400
15 46 9,500
3 2;;, 000 25112
Prothrombin time/ control (set) Partial thromboplastin 91136 time/control (set) Fibrinogen (mg/dl) <75
538
March 1978
:::
.
.
... .
.
:::
.
. .
Il.4112 32136
340
The American Journal of Medicine
The usual clinical picture seen foltowing intoxication with substantial quantities of “speed” is one of euphoria, hallucinations, assaultiveness, mydriasis and sweating. Hypertension, cardiac arrhythmias and hyperpyrexia have also been documented [2]. In fatal cases of poisoning the panic state is followed by convulsions, coma and death from intracranial hemorrhages or cardiac arrhythmias [ 11. More recently, attention has been called to acute renal failure and a coagulopathy consistent with a fibrinolytic state [8]. Heat injury, secondary to the hyperpyrexia of amphetamine intoxication, has been proposed as the basic mechanism of the acute renal failure as well as the coagulopathy. The data in our patient do not allow a clear-cut differential between primary fibrinolysis and fibrinoiysis secondary to disseminated intravascular coagulation (DIG). However, his normal platelet count and the normal morphology of his red cells on peripheral smear suggest the former diagnosis. Substantial quantities of amphetamine and its metabolites are excreted in urine. Since the dissociation constant of amphetamine is 9.93 (methamphetamine 10.1 l), the percentage of nonionized amphetamine increases in alkaline urine, thus facilitating renal tubular absorption of the drug. With acidification of urine, the relative amount of ionized amphetamine increases, reducing its reabsorption, thus increasing the excretion in the urine [ 41. Beckett and co-workers [!?I] demonstrated in volunteer subjects undergoing acid or alkaline loading that from 57 to 66 per cent of the administered amphetamine was recovered unchanged in a period of 6 hours in urines with pH ranging between 4.8 and 5.15; but less than 5 per cent of the drug was recovered when the urine was alkalinized to a pH of 7.6 to 8.3. During mannitol diuresis the methamphetamine concentration in our patient’s urine (pH > 6.0) was 2.7 mg/dl. Urinary methamphetamine levels were determined by gas chromatography [9]. With mannitol alone, 5.0 mg of the drug was recovered in the urine over 2 l/2 hours. After ammonium chloride administration, 952 mg was excreted in 16 hours. The total recovery of methamphetamine in urine was 957 mg, representing about 66 per cent of that ingested (Figure 1). Plasma methamphetamine levels measured fiuorometrically [lo] varied in our patient from 1.O to 3.9 kg/ml indicating that less than 1 per cent of the ingested dose was circulating in the plasma. This low plasma concentration suggests either rapid metabolism, impaired absorption of the drug or sequestration in tissues. The prompt onset of symptoms favors rapid absorption. The distribution space calculated by dividing the total dose ingested by the first serum level gives a value of several hundred liters. Neutral amphetamine has low
Volume 64
METHAMPHETAMINE
aqueous solubility but is extracted by organic solvents and, therefore, may be concentrated in body fat. The neuroleptic butyrophenones, droperidol and haloperidol, are pharmacologically similar to chlorpromazine and are potent antagonists of the central effects of amphetamines. Haloperidol has been shown to have an antiamphetamine potency 15 to 20 times greater than chlorpromazine and to reduce lethality in rats when given 15 minutes after a dose of d-amphetamine which produced a 70 per cent to 80 per cent mortality [ 111. Within 10 minutes of the intravenous administration of droperidol, the patient experiences general quiescence and a sense of detachment and indifference to environmental stimuli but with minimal hypnotic effect [3]. Mild hypotension and reflex tachycardia may occur after the intravenous administration of both droperidol [ 121 and chlorpromazine [ 131. These abnormalities are generally more sustained and may be associated with respiratory depression with the latter drug [ 131. Because of these unique properties, butyrophenones may be superior amphetamine antagonists. Since the amphetamine-intoxicated patient is usually hyperreactive to external stimuli, droperidol’s effect of environmental disconnection coupled with mild somnolence is ideal in this setting. Droperidol is reasonably free from serious toxicity or adverse side effects. When equipotent doses were tested in animals, the LDso of droperidol was 30 times less lethal than haloperidol and 300 times less than chlorpromazine [ 141. Droperidol was chosen over haloperidol in our patient because of its lower LDsO,and the ease with which it may be gradually administered intravenously. Although the usual recommended dose of droperidol is 0.1 mg/kg of body weight, the amount given to an amphetamine-intoxicated patient may be titrated as it was in our patient against the desired response by slow intravenous administration. Droperidol should be administered by a physician experienced with its use and in a setting in which treatment is available should sudden hypotension or ventilatory depression occur. Contraindications to
12.5gn
INTOXICATION-GARY,
SAID1
Monnitol 3gm
0
Ammonium
Chloride
1
’
1
2
4
6
8
IO
12
14
16
I8
2’3
Figure 1. Effect of urinary pH on methamphatamine cretion and serum concentration during diuresis.
ex-
forced acid diuresis include renal failure, oliguria and myoglobinuria. It is concluded that the central stimulatory effects resulting from acute methamphetamine poisoning may safely be controlled with the intravenous administration of droperidol, whereas the urinary excretion of the drug is rapidly facilitated with forced acid diuresis. Coupled with external measures to reduce body temperature, this treatment program facilitated prompt recovery of a seriously poisoned patient. ACKNOWLEDGMENT
We are indebted to toxicologists: J. l-l. Bidanset, Ph.D., Stephen Cohen and Joseph Balkon of the Office of the Medical Examiner, County of Nassau, East Meadow, New York, for all the methamphetamine analyses.
REFERENCES 1. 2. 3.
4.
Kalant H, Kalant (XI: Death in Amphetamine Users: causes and rates. Can Med Assoc J 112: 299, 1975. Espelin DE, Done AK: Amphetamine Poisoning. N Engl J Med 278: 1361. 1968. Ferrari HA, Stephen CR: Neuroleptanalgesia pharmacology and clinical experiences with droperidol and fentanyl. South Med J 59: 815, 1966. lnnes IR, Nickerson M: Norepinephrine, epinephrine and the sympathomimetic amines. The Pharmacological Basis of Therapeutics, 5th ed. (Goodman LS, Gilman A, eds), New
5. 6.
7.
8.
March 1978
York, Macmillan Publishing Co., Inc., 1975. p 496. Beckett AH, Rowland M: Urinary excretion kinetics of amphetamine in man. J Pharm Pharmacol 17: 628, 1965. anggard E, Gunne LM, Jiinsson LE, et al.: Pharmacokinetic and clinical studies on amphetamine dependent subjects. Eur J Clin Pharmacol 3: 3, 1970. Smith DE: An analysis of 310 cases of acute high-dose methamphetamine toxicity in Haight Ashbury. Clin Toxicol 3: 117. 1970. Glnsberg MD, Hertzman M. Schmidt-Norwara WW: Amphet-
The American Journal of Medlclne
Volume 64
539
METHAMPHETAMINE
INTOXICATION-GARY,
SAIDI
amine intoxication with coagulopathy, hyperthermia and reversible renal failure. Ann Intern Med 73: 81, 1970. 9.
12.
Lebish P, Finkle BS, Brackett JW Jr: Determination of amphetamine, m&harnphetamine and related amines in blood and urine by gas chromatography with hydrogen-flame ionization detector. Clin Chem 16: 195. 1970.
13.
10.
Monforte J, Bath RJ, Sunshine I: Fluorometric determination of primary and secondary amines in blood and urine after thin layer chromatography. Clin Chem 18: 1329. 1972.
14.
11.
Davis WM, Logston DG, Hickenbottom
540
March 1979
JP: Antagonism
The American Journal of Medlclne
of
Volume 84
acute amphetamine intoxication by haloperidol and propranolol. Toxicol Appl Pharmacol 29: 397, 1974. Yelnosky J, Kafz R, Dietrich EV: A study of some of the pharmacologic actions of droperidol. Toxicol Appl Pharmacol 8: 37, 1964. Byck R: Drugs and the treatment of psychiatric disorders, The Pharmacological Basis of Therapeutics, 5th ed. (Goodman LS, Gilman A, eds), New York, Macmillan Publishing Co., Inc., 1975, p 162. Morrison JD: Drugs used in neuroleptanalgesia. Int Anesthesiol Clin 7: 141, 1969.
NANCY E. GARY, M.D. PARVIN SAIDI, M.D. Piscafaway, New Jersey
This communication describes the use of droperidol in methamphetamine poisoning. Droperldol antagonizes the central stimulatory effects of amphetamines producing a person who is indifferent to environmental stimuli, calm and cooperative. Coupled with an acid diuresis, causing a fivefold increase in the urinary concentration of methamphetamine and recovery of 66 per cent of the ingested drug, a seriously intoxicated patient showed rapid improvement. Amphetamine and methamphetamine remain common causes of poisoning despite inclusion of these drugs in “The Comprehensive Drug Abuse Prevention Act of 1970” [I]. Little has been added to the management of amphetamine intoxication since Espelin and Done [2] advocated chlorpromazine as an effective antagonist of the central stimulatory effects of the amphetamines. Droperidol is similar to chlorpromazine in this action, but it has the added advantage of producing, without sedation, a general quiescence and a sense of detachment from external stimuli [3]. Forced acid diuresis has been a recommended treatment procedure based on experimental data; however, actual removal of amphetamine by this technic in the patient made severely ill by amphetamine poisoning has not been documented previously [4-61. The effect of this combination of therapeutic modalities and the gradual recovery from early hemostatic derangement seen in a seriously intoxicated patient are discussed. CASE REPORT
From the Nephrology and Hematology Sections, Department of Medicine, College of Medicine and Dentistry of New, Jersey, Rutgers Medical School, Piscataway, New Jersey. Requests for reprints should be addressed to Dr. Nancy E. Gary, CMDNJ-Rutgers Medical School, Raritan Valley Hospital, 275 Greenbrook Road, Green Brook, New Jersey 08812. Manuscript accepted March 17, 1977.
A 27 year old man who habitually ingested about 20 mg of methamphetamine daily was hospitalized 1 hour after eating 1,400 mg of “street” methamphetamine (18 bags each containing approximately 80 mg of undetermined purity).* On admission to St. Vincent’s Hospital and Medical Center of New York, the patient was agitated, combative and hallucinating. His blood pressure was 180/100 mg Hg, pulse rate 146/min, respirations 28/min and oral temperature 37OC. His pupils were widely dilated and reactive to light. The remainder of his physical examination was noncontributory. On admission, the urinary concentration of methamphetamine was 2.7 mg/dl. Other laboratory studies included a direct bilirubin 0.3 mg/dl, total bilirubin 1.2 mg/dl, blood urea nitrogen 12 mg/dl, lactic dehydrogenase (LDH) 2,780 Wordlesky-Ladue units, serum glutamic oxaloacetic transaminase (SGOT) 1,205 Karmen units and creatinine phosphokinase (CPK) 3,278 Siegel-Cohan units. Plasma haptoglobin was 350 mg/dl and plasma hematin 0. Arterial blood gases on room air revealed a pH of 7.43, carbon dioxide Two packets of methamphetamine were obtained from the patient’s usual “dealer” and submitted for analysis. A reliable purity assay could not be done because of an interfering reaction between the foil wrapper and the contents of the packets. l
March1978
The American Journal of Medicine
Volume 64
537
METHAMPHETAMINE
INTOXICATION-GARY,
SAIDI
tension 26 mm Hg, bicarbonate 16 meq/liter and oxygen tension 71 mm Hg. Urinalysis showed a pH of 6.0, 1-F protein and 1-t blood (Ames Reagent stix). Microscopic examination revealed 5 to 6 red blood cells, sheets and casts of renal tubular epithelial cells and 3 to 5 hyaline casts/lpf. Serial hematologic and hemostatic parameters are presented in Table I. In the emergency room, the patient was given 120 mg of phenobarbital intramuscularly. Ninety minutes later, on admission to the intensive care unit, the blood pressure was 180/100 mm Hg, pulse rate 168/min, respirations 40/min and temperature 42% rectally. The intravenous administration of droperidol at the rate of 2.5 mg/min was begun. Within 15 minutes of the start of droperidol administration (total dose 13 mg), the patient had become subdued and calm with a blood pressure of 112/70 mm Hg, a pulse rate of 1 lG/min and a respiratory rate of 26/min. His temperature was reduced with the application of a hypothermia blanket to 39.4OC rectally in 1 hour. Two hours after admission intravenous mannitol (12.5 g) was given to initiate a diuresis. Acid diuresis was begun 3 l/2 hours later by using 500 ml each of the following solutions in rotation at a rate to match the patient’s urinary output of 200 to 600 ml/hour: 5 per cent dextrose and water to which 1.5 g of ammonium chloride was added, 5 per cent dextrose and water, and normal saline solution. The acid infusion was terminated after 16 hours at which time the patient was entirely asymptomatic and had stable vital signs with a blood pressure of 1 lo/70 mm Hg, a pulse rate of 96/min, respirations of 18/min and an oral temperature of 37%. Arterial blood gases were frequently measured during acid diuresis; the lowest arterial pH was 7.38, carbon dioxide tension 31 mm Hg and bicarbonate 17 meq/liter.
COMMENTS Illegally synthesized black market “speed” (methamphetamine) is used intravenously to produce a “speed binge” or “flash.” Repeated use may induce a state of paranoid thought [7], manifested in our patient by fear of a raid by the police which led him to dispose of all the methamphetamine in his possession by ingesting it. TABLE I
Hematologlc and Coagulation Parameters Day 1 A.M. P.M.
Hemoglobin (g/dl) Hematocrit vol (%) White blood cells (per mm3) Retlculocyte (%) Platelets (per mm3)
Day 2
Day 3
Day 6
15.6 12.9 13.6 47 38 43 13,800 13,600 15,800
15 46 8,400
15 46 9,500
3 2;;, 000 25112
Prothrombin time/ control (set) Partial thromboplastin 91136 time/control (set) Fibrinogen (mg/dl) <75
538
March 1978
:::
.
.
... .
.
:::
.
. .
Il.4112 32136
340
The American Journal of Medicine
The usual clinical picture seen foltowing intoxication with substantial quantities of “speed” is one of euphoria, hallucinations, assaultiveness, mydriasis and sweating. Hypertension, cardiac arrhythmias and hyperpyrexia have also been documented [2]. In fatal cases of poisoning the panic state is followed by convulsions, coma and death from intracranial hemorrhages or cardiac arrhythmias [ 11. More recently, attention has been called to acute renal failure and a coagulopathy consistent with a fibrinolytic state [8]. Heat injury, secondary to the hyperpyrexia of amphetamine intoxication, has been proposed as the basic mechanism of the acute renal failure as well as the coagulopathy. The data in our patient do not allow a clear-cut differential between primary fibrinolysis and fibrinoiysis secondary to disseminated intravascular coagulation (DIG). However, his normal platelet count and the normal morphology of his red cells on peripheral smear suggest the former diagnosis. Substantial quantities of amphetamine and its metabolites are excreted in urine. Since the dissociation constant of amphetamine is 9.93 (methamphetamine 10.1 l), the percentage of nonionized amphetamine increases in alkaline urine, thus facilitating renal tubular absorption of the drug. With acidification of urine, the relative amount of ionized amphetamine increases, reducing its reabsorption, thus increasing the excretion in the urine [ 41. Beckett and co-workers [!?I] demonstrated in volunteer subjects undergoing acid or alkaline loading that from 57 to 66 per cent of the administered amphetamine was recovered unchanged in a period of 6 hours in urines with pH ranging between 4.8 and 5.15; but less than 5 per cent of the drug was recovered when the urine was alkalinized to a pH of 7.6 to 8.3. During mannitol diuresis the methamphetamine concentration in our patient’s urine (pH > 6.0) was 2.7 mg/dl. Urinary methamphetamine levels were determined by gas chromatography [9]. With mannitol alone, 5.0 mg of the drug was recovered in the urine over 2 l/2 hours. After ammonium chloride administration, 952 mg was excreted in 16 hours. The total recovery of methamphetamine in urine was 957 mg, representing about 66 per cent of that ingested (Figure 1). Plasma methamphetamine levels measured fiuorometrically [lo] varied in our patient from 1.O to 3.9 kg/ml indicating that less than 1 per cent of the ingested dose was circulating in the plasma. This low plasma concentration suggests either rapid metabolism, impaired absorption of the drug or sequestration in tissues. The prompt onset of symptoms favors rapid absorption. The distribution space calculated by dividing the total dose ingested by the first serum level gives a value of several hundred liters. Neutral amphetamine has low
Volume 64
METHAMPHETAMINE
aqueous solubility but is extracted by organic solvents and, therefore, may be concentrated in body fat. The neuroleptic butyrophenones, droperidol and haloperidol, are pharmacologically similar to chlorpromazine and are potent antagonists of the central effects of amphetamines. Haloperidol has been shown to have an antiamphetamine potency 15 to 20 times greater than chlorpromazine and to reduce lethality in rats when given 15 minutes after a dose of d-amphetamine which produced a 70 per cent to 80 per cent mortality [ 111. Within 10 minutes of the intravenous administration of droperidol, the patient experiences general quiescence and a sense of detachment and indifference to environmental stimuli but with minimal hypnotic effect [3]. Mild hypotension and reflex tachycardia may occur after the intravenous administration of both droperidol [ 121 and chlorpromazine [ 131. These abnormalities are generally more sustained and may be associated with respiratory depression with the latter drug [ 131. Because of these unique properties, butyrophenones may be superior amphetamine antagonists. Since the amphetamine-intoxicated patient is usually hyperreactive to external stimuli, droperidol’s effect of environmental disconnection coupled with mild somnolence is ideal in this setting. Droperidol is reasonably free from serious toxicity or adverse side effects. When equipotent doses were tested in animals, the LDso of droperidol was 30 times less lethal than haloperidol and 300 times less than chlorpromazine [ 141. Droperidol was chosen over haloperidol in our patient because of its lower LDsO,and the ease with which it may be gradually administered intravenously. Although the usual recommended dose of droperidol is 0.1 mg/kg of body weight, the amount given to an amphetamine-intoxicated patient may be titrated as it was in our patient against the desired response by slow intravenous administration. Droperidol should be administered by a physician experienced with its use and in a setting in which treatment is available should sudden hypotension or ventilatory depression occur. Contraindications to
12.5gn
INTOXICATION-GARY,
SAID1
Monnitol 3gm
0
Ammonium
Chloride
1
’
1
2
4
6
8
IO
12
14
16
I8
2’3
Figure 1. Effect of urinary pH on methamphatamine cretion and serum concentration during diuresis.
ex-
forced acid diuresis include renal failure, oliguria and myoglobinuria. It is concluded that the central stimulatory effects resulting from acute methamphetamine poisoning may safely be controlled with the intravenous administration of droperidol, whereas the urinary excretion of the drug is rapidly facilitated with forced acid diuresis. Coupled with external measures to reduce body temperature, this treatment program facilitated prompt recovery of a seriously poisoned patient. ACKNOWLEDGMENT
We are indebted to toxicologists: J. l-l. Bidanset, Ph.D., Stephen Cohen and Joseph Balkon of the Office of the Medical Examiner, County of Nassau, East Meadow, New York, for all the methamphetamine analyses.
REFERENCES 1. 2. 3.
4.
Kalant H, Kalant (XI: Death in Amphetamine Users: causes and rates. Can Med Assoc J 112: 299, 1975. Espelin DE, Done AK: Amphetamine Poisoning. N Engl J Med 278: 1361. 1968. Ferrari HA, Stephen CR: Neuroleptanalgesia pharmacology and clinical experiences with droperidol and fentanyl. South Med J 59: 815, 1966. lnnes IR, Nickerson M: Norepinephrine, epinephrine and the sympathomimetic amines. The Pharmacological Basis of Therapeutics, 5th ed. (Goodman LS, Gilman A, eds), New
5. 6.
7.
8.
March 1978
York, Macmillan Publishing Co., Inc., 1975. p 496. Beckett AH, Rowland M: Urinary excretion kinetics of amphetamine in man. J Pharm Pharmacol 17: 628, 1965. anggard E, Gunne LM, Jiinsson LE, et al.: Pharmacokinetic and clinical studies on amphetamine dependent subjects. Eur J Clin Pharmacol 3: 3, 1970. Smith DE: An analysis of 310 cases of acute high-dose methamphetamine toxicity in Haight Ashbury. Clin Toxicol 3: 117. 1970. Glnsberg MD, Hertzman M. Schmidt-Norwara WW: Amphet-
The American Journal of Medlclne
Volume 64
539
METHAMPHETAMINE
INTOXICATION-GARY,
SAIDI
amine intoxication with coagulopathy, hyperthermia and reversible renal failure. Ann Intern Med 73: 81, 1970. 9.
12.
Lebish P, Finkle BS, Brackett JW Jr: Determination of amphetamine, m&harnphetamine and related amines in blood and urine by gas chromatography with hydrogen-flame ionization detector. Clin Chem 16: 195. 1970.
13.
10.
Monforte J, Bath RJ, Sunshine I: Fluorometric determination of primary and secondary amines in blood and urine after thin layer chromatography. Clin Chem 18: 1329. 1972.
14.
11.
Davis WM, Logston DG, Hickenbottom
540
March 1979
JP: Antagonism
The American Journal of Medlclne
of
Volume 84
acute amphetamine intoxication by haloperidol and propranolol. Toxicol Appl Pharmacol 29: 397, 1974. Yelnosky J, Kafz R, Dietrich EV: A study of some of the pharmacologic actions of droperidol. Toxicol Appl Pharmacol 8: 37, 1964. Byck R: Drugs and the treatment of psychiatric disorders, The Pharmacological Basis of Therapeutics, 5th ed. (Goodman LS, Gilman A, eds), New York, Macmillan Publishing Co., Inc., 1975, p 162. Morrison JD: Drugs used in neuroleptanalgesia. Int Anesthesiol Clin 7: 141, 1969.