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Acute, transient urinary retention from combined ecstasy and methamphetamine use
The Journal of Emergency Medicine, Vol. 26, No. 2, pp. 173–175, 2004 Copyright © 2004 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/04 $–see front matter
doi:10.1016/j.jemermed.2003.05.007
Selected Topics: Toxicology
ACUTE, TRANSIENT URINARY RETENTION FROM COMBINED ECSTASY AND METHAMPHETAMINE USE Joa˜o H. Delgado,
MD,*,†
Michael J. Caruso, MD,* Javier C. Waksman, MD,‡ and Dan Stillman, MD‡
MD,†,‡,§
Benjamin Honigman,
*Denver Health Medical Center, Denver, Colorado, †Rocky Mountain Poison and Drug Center, Denver, Colorado, ‡University of Colorado Health Sciences Center, Denver, Colorado, and §Toxicology Associates, Denver, Colorado Reprint Address: Joa˜o H. Delgado, MD, Rocky Mountain Poison and Drug Center, 1001 Yosemite St., Suite 200, Denver, CO 80230
e Abstract—Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) are synthetic amphetamine analogs that have become increasingly popular, particularly among adolescents and young adults. Many deleterious physiologic effects arising from the use of these agents have been well documented in the medical literature. Urinary retention, however, has rarely been reported as an effect of MDMA or methamphetamine use and is thought to occur as a result of alpha-adrenoceptor stimulation of the bladder neck. We report a case of acute, transient urinary retention due to combined MDMA and methamphetamine use with laboratory confirmation. © 2004 Elsevier Inc.
of acute, transient urinary retention associated with methamphetamine and MDMA with laboratory confirmation of their use.
CASE REPORT An 18-year-old man presented to the ED for evaluation of acute-onset urinary retention. According to the patient, he had attended a party the previous evening, where he consumed large amounts of alcohol. When he awoke the following morning he developed lower abdominal pain and the inability to void. On presentation, he was in mild distress and complained of suprapubic pain and a feeling of bladder fullness. His temperature was 38.3°C, heart rate 144 beats/min, blood pressure 145/93 mm Hg, and respiratory rate 18 breaths/min. The physical examination was significant for regular tachycardia, mydriasis, moist mucus membranes, suprapubic tenderness to palpation, and an obviously distended bladder verified by clinical examination and bedside ultrasonography. The patient had no alteration in sensorium, decreased bowel sounds, or lack of axillary sweat to suggest an anticholinergic syndrome. Upon insertion of a Foley catheter, approximately 1.6 L of clear, yellow urine were obtained, which resulted in marked improvement of his discomfort.
e Keywords—amphetamine; methamphetamine; MDMA; ecstasy; urinary retention
INTRODUCTION Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), or “ecstasy,” have become increasingly popular drugs of abuse among adolescents and young adults. As their popularity has grown, a better understanding of the adverse health effects associated with their use has emerged. These include tachycardia, hypertension, hyperthermia, rhabdomyolysis, serotonin syndrome, seizures, intracranial hemorrhage, myocardial infarction, hyponatremia, and death (1,2). We report a case
RECEIVED: 11 October 2002; FINAL ACCEPTED: 27 May 2003
SUBMISSION RECEIVED:
30 April 2003; 173
174
J. H. Delgado et al.
Laboratory evaluation showed normal renal function parameters and a leukocytosis (WBC 25,700/mL). Urinalysis showed trace proteinuria and trace hematuria. At the request of the urology consultant, an abdominal/ pelvis CT scan was obtained that demonstrated no structural abnormality or extravasation of contrast from the bladder. A urine radioimmunoassay (RIA) screen for drugs of abuse (Abbott Laboratories, Abbott Park, IL) was positive for amphetamines. No ethanol was detected by this method, which has a limit of detection of 12 mg/dL. Subsequent analysis by thin-layer chromatography (Ansys Technologies, Lake Forest, CA) showed the presence of MDMA and its metabolite methylenedioxyamphetamine (MDA). The patient denied ingesting any illegal substances but did state that he had taken two Sudafed威 tablets (pseudoephedrine hydrochloride 30 mg) within the previous day. He also said that he had been drinking alcohol the previous night and perhaps someone had “spiked” his drink. He was observed in the ED for approximately 8 h, during which time the signs of sympathetic excess resolved. The catheter was removed and the patient was able to void spontaneously. He returned the following day for scheduled follow-up. He was urinating without pain or hesitancy and had no further complaints. Subsequent confirmatory analysis by gas chromatography-mass spectrometry demonstrated the presence of methamphetamine (⬎ 25,000 ng/mL), MDMA (⬎ 5000 ng/mL), amphetamine (1404 ng/mL), and MDA (3700 ng/mL) in his urine. A comprehensive urine drug screen showed no additional substances other than caffeine.
DISCUSSION The micturition reflex involves a complex interaction of detrusor contraction accompanied by relaxation of the urinary sphincter (3). Drugs interfering with either of these processes can result in pharmacologically mediated urinary dysfunction. Anticholinergic agents, for example, inhibit detrusor contraction, whereas alpha-adrenergic agents stimulate bladder neck contraction. Methamphetamines and MDMA exert an alpha-agonist effect indirectly by increasing the release of endogenous norepinephrine stores (2). Because the bladder neck is innervated primarily by alpha-adrenergic receptors, excessive and prolonged stimulation of these receptors by norepinephrine can lead to urinary retention (4). These effects can occur even in the absence of underlying structural or functional abnormalities. The paucity of information on this subject relative to the frequency of methamphetamine and MDMA use argues that the effects are typically short-lived, mild, or both. Two previous reports have described urinary retention
in young men who admitted to ingesting ecstasy tablets before the onset of symptoms (5,6). In addition, two cases of acute urinary retention associated with intravenous amphetamine use have been reported, one of which resulted in bladder rupture (7,8). In none of these cases was laboratory confirmation of MDMA or amphetamine use reported. This is especially important in cases of suspected illicit substance use for two reasons. First, “street drugs” often contain contaminants that can have significant effects on their own. For instance, one series found that 21% of pills sold as ecstasy contained dextromethorphan in much higher concentrations than the usual therapeutic dose (9). Second, the substance purchased is frequently different than what the buyer believes is being purchased. Analyses of purported ecstasy tablets have shown that up to half do not contain any MDMA or one of its derivatives (10). The most reasonable explanation for the clinical presentation and laboratory results in our patient is that he ingested a mixture of methamphetamine and MDMA. Both substances are primarily excreted as parent drug in urine (11). Both also undergo N-demethylation as an initial metabolic step, yielding the active metabolites amphetamine and MDA, respectively (Figure 1). Additional amino and hydroxylated metabolites and their conjugates are excreted in the urine but in relatively low concentrations. Although the patient’s use of pseudoephedrine could have contributed to his symptoms, this is unlikely because he had no detectable pseudoephedrine in his urine at the time of presentation to the ED. Another consideration is the possibility that the patient co-ingested an anticholinergic drug. Again, this is unlikely because the TLC assay employed in this case screens for a number of common anticholinergic agents, none of which was present in detectable amounts. Due to these considerations, the patient’s symptoms are almost certainly related solely to methamphetamine and MDMA use and not to other causes. CONCLUSION MDMA and other amphetamine derivatives may cause bladder dysfunction, most likely from alpha-adrenergic stimulation of the bladder neck. Their use should be considered in the differential diagnosis of young persons presenting with acute urinary retention in whom no structural abnormality of the genitourinary tract is evident. Acknowledgments—The authors would like to thank Robert Palmer, PhD for reviewing the manuscript and providing the chemical structures.
Urinary Retention and Ecstasy Use
175
Figure 1. Principal metabolic pathways for methamphetamine and MDMA. Oxidation of the parent compounds via N-demethylation results in the detectable metabolites, amphetamine and MDA.
REFERENCES 1. White SR. Amphetamine toxicity. Semin Respir Crit Care Med 2002;23:27–36. 2. Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. Can Med Assoc J 2001;165:917–28. 3. Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Campbell MF, Walsh PC, Retik AB, eds. Campbell’s urology, 8th edn. Philadelphia: Elsevier Science; 2002:887– 8. 4. Awad S, Bruce AW, Carro-Ciampi G, Downie JW, Lin M, Marks GS. Distribution of alpha and beta adrenoreceptors in human urinary bladder. Br J Pharmacol 1974;50:525–9. 5. Bryden AA, Rothwell PJ, O’Reilly PH. Urinary retention with misuse of “ecstasy.” BMJ 1995;310:504.
6. Inman DS, Greene D. “The agony and the ecstasy:” acute urinary retention after MDMA abuse. BJU Int 2003;91:123. 7. Worsey J, Goble NM, Stott M, Smith PJ. Bladder outflow obstruction secondary to intravenous amphetamine abuse. Br J Urol 1989; 64:320 –1. 8. Bennett AH, Delrio A. Idiopathic rupture of the bladder: association with methamphetamine and alcohol. J Urol 1980;124:429 –30. 9. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J. Chemical analysis of ecstasy pills. JAMA 2000;284:2190. 10. Cole JC, Bailey M, Sumnall HR, Wagstaff GT, King LA. The content of ecstasy tablets: implications for the study of their long-term effects. Addiction 2002;97:1531– 6. 11. Baselt RC. Disposition of toxic drugs and chemicals in man, 6th edn. Foster City, CA: Chemical Toxicology Institute; 2002.
doi:10.1016/j.jemermed.2003.05.007
Selected Topics: Toxicology
ACUTE, TRANSIENT URINARY RETENTION FROM COMBINED ECSTASY AND METHAMPHETAMINE USE Joa˜o H. Delgado,
MD,*,†
Michael J. Caruso, MD,* Javier C. Waksman, MD,‡ and Dan Stillman, MD‡
MD,†,‡,§
Benjamin Honigman,
*Denver Health Medical Center, Denver, Colorado, †Rocky Mountain Poison and Drug Center, Denver, Colorado, ‡University of Colorado Health Sciences Center, Denver, Colorado, and §Toxicology Associates, Denver, Colorado Reprint Address: Joa˜o H. Delgado, MD, Rocky Mountain Poison and Drug Center, 1001 Yosemite St., Suite 200, Denver, CO 80230
e Abstract—Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”) are synthetic amphetamine analogs that have become increasingly popular, particularly among adolescents and young adults. Many deleterious physiologic effects arising from the use of these agents have been well documented in the medical literature. Urinary retention, however, has rarely been reported as an effect of MDMA or methamphetamine use and is thought to occur as a result of alpha-adrenoceptor stimulation of the bladder neck. We report a case of acute, transient urinary retention due to combined MDMA and methamphetamine use with laboratory confirmation. © 2004 Elsevier Inc.
of acute, transient urinary retention associated with methamphetamine and MDMA with laboratory confirmation of their use.
CASE REPORT An 18-year-old man presented to the ED for evaluation of acute-onset urinary retention. According to the patient, he had attended a party the previous evening, where he consumed large amounts of alcohol. When he awoke the following morning he developed lower abdominal pain and the inability to void. On presentation, he was in mild distress and complained of suprapubic pain and a feeling of bladder fullness. His temperature was 38.3°C, heart rate 144 beats/min, blood pressure 145/93 mm Hg, and respiratory rate 18 breaths/min. The physical examination was significant for regular tachycardia, mydriasis, moist mucus membranes, suprapubic tenderness to palpation, and an obviously distended bladder verified by clinical examination and bedside ultrasonography. The patient had no alteration in sensorium, decreased bowel sounds, or lack of axillary sweat to suggest an anticholinergic syndrome. Upon insertion of a Foley catheter, approximately 1.6 L of clear, yellow urine were obtained, which resulted in marked improvement of his discomfort.
e Keywords—amphetamine; methamphetamine; MDMA; ecstasy; urinary retention
INTRODUCTION Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), or “ecstasy,” have become increasingly popular drugs of abuse among adolescents and young adults. As their popularity has grown, a better understanding of the adverse health effects associated with their use has emerged. These include tachycardia, hypertension, hyperthermia, rhabdomyolysis, serotonin syndrome, seizures, intracranial hemorrhage, myocardial infarction, hyponatremia, and death (1,2). We report a case
RECEIVED: 11 October 2002; FINAL ACCEPTED: 27 May 2003
SUBMISSION RECEIVED:
30 April 2003; 173
174
J. H. Delgado et al.
Laboratory evaluation showed normal renal function parameters and a leukocytosis (WBC 25,700/mL). Urinalysis showed trace proteinuria and trace hematuria. At the request of the urology consultant, an abdominal/ pelvis CT scan was obtained that demonstrated no structural abnormality or extravasation of contrast from the bladder. A urine radioimmunoassay (RIA) screen for drugs of abuse (Abbott Laboratories, Abbott Park, IL) was positive for amphetamines. No ethanol was detected by this method, which has a limit of detection of 12 mg/dL. Subsequent analysis by thin-layer chromatography (Ansys Technologies, Lake Forest, CA) showed the presence of MDMA and its metabolite methylenedioxyamphetamine (MDA). The patient denied ingesting any illegal substances but did state that he had taken two Sudafed威 tablets (pseudoephedrine hydrochloride 30 mg) within the previous day. He also said that he had been drinking alcohol the previous night and perhaps someone had “spiked” his drink. He was observed in the ED for approximately 8 h, during which time the signs of sympathetic excess resolved. The catheter was removed and the patient was able to void spontaneously. He returned the following day for scheduled follow-up. He was urinating without pain or hesitancy and had no further complaints. Subsequent confirmatory analysis by gas chromatography-mass spectrometry demonstrated the presence of methamphetamine (⬎ 25,000 ng/mL), MDMA (⬎ 5000 ng/mL), amphetamine (1404 ng/mL), and MDA (3700 ng/mL) in his urine. A comprehensive urine drug screen showed no additional substances other than caffeine.
DISCUSSION The micturition reflex involves a complex interaction of detrusor contraction accompanied by relaxation of the urinary sphincter (3). Drugs interfering with either of these processes can result in pharmacologically mediated urinary dysfunction. Anticholinergic agents, for example, inhibit detrusor contraction, whereas alpha-adrenergic agents stimulate bladder neck contraction. Methamphetamines and MDMA exert an alpha-agonist effect indirectly by increasing the release of endogenous norepinephrine stores (2). Because the bladder neck is innervated primarily by alpha-adrenergic receptors, excessive and prolonged stimulation of these receptors by norepinephrine can lead to urinary retention (4). These effects can occur even in the absence of underlying structural or functional abnormalities. The paucity of information on this subject relative to the frequency of methamphetamine and MDMA use argues that the effects are typically short-lived, mild, or both. Two previous reports have described urinary retention
in young men who admitted to ingesting ecstasy tablets before the onset of symptoms (5,6). In addition, two cases of acute urinary retention associated with intravenous amphetamine use have been reported, one of which resulted in bladder rupture (7,8). In none of these cases was laboratory confirmation of MDMA or amphetamine use reported. This is especially important in cases of suspected illicit substance use for two reasons. First, “street drugs” often contain contaminants that can have significant effects on their own. For instance, one series found that 21% of pills sold as ecstasy contained dextromethorphan in much higher concentrations than the usual therapeutic dose (9). Second, the substance purchased is frequently different than what the buyer believes is being purchased. Analyses of purported ecstasy tablets have shown that up to half do not contain any MDMA or one of its derivatives (10). The most reasonable explanation for the clinical presentation and laboratory results in our patient is that he ingested a mixture of methamphetamine and MDMA. Both substances are primarily excreted as parent drug in urine (11). Both also undergo N-demethylation as an initial metabolic step, yielding the active metabolites amphetamine and MDA, respectively (Figure 1). Additional amino and hydroxylated metabolites and their conjugates are excreted in the urine but in relatively low concentrations. Although the patient’s use of pseudoephedrine could have contributed to his symptoms, this is unlikely because he had no detectable pseudoephedrine in his urine at the time of presentation to the ED. Another consideration is the possibility that the patient co-ingested an anticholinergic drug. Again, this is unlikely because the TLC assay employed in this case screens for a number of common anticholinergic agents, none of which was present in detectable amounts. Due to these considerations, the patient’s symptoms are almost certainly related solely to methamphetamine and MDMA use and not to other causes. CONCLUSION MDMA and other amphetamine derivatives may cause bladder dysfunction, most likely from alpha-adrenergic stimulation of the bladder neck. Their use should be considered in the differential diagnosis of young persons presenting with acute urinary retention in whom no structural abnormality of the genitourinary tract is evident. Acknowledgments—The authors would like to thank Robert Palmer, PhD for reviewing the manuscript and providing the chemical structures.
Urinary Retention and Ecstasy Use
175
Figure 1. Principal metabolic pathways for methamphetamine and MDMA. Oxidation of the parent compounds via N-demethylation results in the detectable metabolites, amphetamine and MDA.
REFERENCES 1. White SR. Amphetamine toxicity. Semin Respir Crit Care Med 2002;23:27–36. 2. Kalant H. The pharmacology and toxicology of “ecstasy” (MDMA) and related drugs. Can Med Assoc J 2001;165:917–28. 3. Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Campbell MF, Walsh PC, Retik AB, eds. Campbell’s urology, 8th edn. Philadelphia: Elsevier Science; 2002:887– 8. 4. Awad S, Bruce AW, Carro-Ciampi G, Downie JW, Lin M, Marks GS. Distribution of alpha and beta adrenoreceptors in human urinary bladder. Br J Pharmacol 1974;50:525–9. 5. Bryden AA, Rothwell PJ, O’Reilly PH. Urinary retention with misuse of “ecstasy.” BMJ 1995;310:504.
6. Inman DS, Greene D. “The agony and the ecstasy:” acute urinary retention after MDMA abuse. BJU Int 2003;91:123. 7. Worsey J, Goble NM, Stott M, Smith PJ. Bladder outflow obstruction secondary to intravenous amphetamine abuse. Br J Urol 1989; 64:320 –1. 8. Bennett AH, Delrio A. Idiopathic rupture of the bladder: association with methamphetamine and alcohol. J Urol 1980;124:429 –30. 9. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J. Chemical analysis of ecstasy pills. JAMA 2000;284:2190. 10. Cole JC, Bailey M, Sumnall HR, Wagstaff GT, King LA. The content of ecstasy tablets: implications for the study of their long-term effects. Addiction 2002;97:1531– 6. 11. Baselt RC. Disposition of toxic drugs and chemicals in man, 6th edn. Foster City, CA: Chemical Toxicology Institute; 2002.