Exemption of chemical mixtures containing the List I chemicals ephedrine, N-methylephedrine, N-methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and pseudoephedrine. Final rule. (17/147)

On September 16, 1998, the Drug Enforcement Administration (DEA) published a Notice of Proposed Rulemaking (NPRM) to implement provisions of the Controlled Substances Act (CSA) pertaining to the regulation of chemical mixtures which contain any of 34 listed chemicals. The NPRM was published to implement CSA requirements that only those chemical mixtures identified by regulation be exempt from applicable regulatory controls. The NPRM proposed criteria for the determination of whether a chemical mixture shall qualify for automatic exemption from CSA regulatory controls. Additionally, the NPRM defined an application process by which manufacturers may apply for an exemption for chemical mixtures that do not qualify for automatic exemption. Due to concerns regarding the potential illicit use of chemical mixtures which contain ephedrine, N-methylephedrine, N- methylpseudoephedrine, norpseudoephedrine, phenylpropanolamine, and/or pseudoephedrine (as precursor material for the production of methamphetamine and related amphetamines), DEA is hereby finalizing the portion of the NPRM pertaining to these six chemicals. Final regulations for all remaining listed chemicals will be published under separate rulemaking, upon completion of a thorough review of applicable comments.  (+info)

Major risk factors for aneurysmal subarachnoid hemorrhage in the young are modifiable. (18/147)

BACKGROUND AND PURPOSE: To identify risk factors for subarachnoid hemorrhage (SAH) and intracerebral hemorrhage, we designed a case-control study of men and women 18 to 49 years of age (the Hemorrhagic Stroke Project [HSP]). This report focuses on SAH. METHODS: Patients were recruited from 44 hospitals in the United States. Cases with SAH must have had a ruptured aneurysm documented by angiography or surgery. Two controls, identified by random digit dialing and matched to each patient for age, sex, race, and telephone exchange, were sought for each case subject. RESULTS: Between 1994 and 1999, 425 patients with SAH were enrolled in HSP, and 312 cases met the criteria for aneurysmal SAH. The present analyses also included 618 matched controls. Of the 312 cases, 66% were current cigarette smokers compared with 30% of controls (adjusted odds ratio [OR], 3.73; 95% CI, 2.67 to 5.21). Cocaine use within the previous 3-day period was reported by 3% of cases and no controls (bivariate exact OR, 24.97; 95% exact CI, 3.95 to infinity; adjusted estimate not calculable). Other independent risk factors in the multivariable model included hypertension (adjusted OR, 2.21; 95% CI, 1.48 to 3.29), low body mass index (OR, 1.59; 95% CI, 1.08 to 2.35), primary family history of hemorrhagic stroke (OR, 3.83; 95% CI, 1.73 to 8.46), caffeine in pharmaceutical products (OR, 2.48; 95% CI, 1.19 to 5.20), lower educational achievement (OR, 2.36; 95% CI, 1.44 to 3.87), and nicotine in pharmaceutical products (adjusted estimate not calculable). CONCLUSIONS: Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use). The association of caffeine and nicotine in pharmaceutical products and aneurysmal SAH warrants further study.  (+info)

Stroke associated with sympathomimetics contained in over-the-counter cough and cold drugs. (19/147)

BACKGROUND AND PURPOSE: Phenylpropanolamine (PPA) and pseudoephedrine are sympathomimetics contained in over-the-counter cold preparations. A case-control study linked PPA use with hemorrhagic stroke in women. Twenty-two patients with stroke associated with use of these drugs are described. METHODS: In a consecutive stroke registry since 1988, 22 patients had stroke associated with over-the-counter sympathomimetics. Sympathomimetic dosage and type, time interval until stroke onset, and neuroimaging findings are described. RESULTS: Ten male and 12 female patients were included. Intracerebral hemorrhage occurred in 17 patients, subarachnoid hemorrhage in 4, and ischemic stroke in 1. Stroke was associated with PPA use in 16 patients (dose 75 to 675 mg), with pseudoephedrine in 4 (dose 60 to 300 mg), and with others administered by the nasal route in 2 (oxymetazoline and phenylephrine). Stroke occurred after a single dose in 17 patients and after daily use during several days in 5. The interval between drug exposure and clinical onset varied from 30 minutes to 24 hours. Stroke occurred after recommended doses of PPA (50 to 75 mg) in 32% and pseudoephedrine (60 mg) in 50% of patients. Eight patients had acute hypertension at stroke onset. Cerebral angiography was normal in 8 cases and showed diffuse vasospasm or beading in 10 patients. CONCLUSIONS: Stroke related to over-the-counter sympathomimetics was associated with acute hypertension and/or vasospasm or angiitis mechanisms, most related to the use of PPA; however, stroke also occurred with the use of other sympathomimetics, particularly pseudoephedrine. Although stroke complications occurred when doses were used that were higher than recommended doses, apparently there is also a stroke risk when these agents are taken properly.  (+info)

Pharmacokinetics of cathinone, cathine and norephedrine after the chewing of khat leaves. (20/147)

AIM: The stimulating herbal drug khat is habitually used in East Africa and the Arabian peninsula but is also imported into other countries. The aim was to study the pharmacokinetics of its alkaloids cathinone, cathine and norephedrine. METHODS: Four volunteers chewed khat leaves in an amount equivalent to one-quarter of that used in a typical khat session. Blood samples were collected up to 80 h and the alkaloids were assayed using gas chromatography-mass spectrometry. The data were evaluated using computerized pharmacokinetic compartmental analysis. RESULTS: The plasma concentration-time data for the alkaloids could be described using a two-compartment model with two-segment absorption. The mucosa of the oral cavity is considered to be the first absorption segment, where the major proportion of the alkaloids is absorbed (mean +/- SD 59 +/- 21% for cathinone and 84 +/- 6% for cathine). The extraction of the alkaloids from the leaves by chewing was very effective with only 9.1 +/- 4.2% remaining as a residue. Cathinone was eliminated from the central compartment with a mean half-life of 1.5 +/- 0.8 h. The half-life of cathine was 5.2 +/- 3.4 h. The metabolism of cathinone to norephedrine had a substantial influence on its plasma concentration profile. Psychophysical functions were essentially unaffected by the chewing of khat. CONCLUSIONS: The pharmacokinetics of khat alkaloids in humans explain why chewing is the preferred form of khat ingestion. Subjects absorbed a mean dose of 45 mg of cathinone, and did not suffer any severe adverse reactions.  (+info)

Phenylpropanolamine-induced intraventricular hemorrhage. (21/147)

Intracranial hemorrhage is an uncommon complication of phenylpropanolamine. There is an increasing awareness of this complication in the West. However, to the best of our knowledge there have been no cases reported from India. Here we report a patient who developed Intraventricular hemorrhage following ingestion of Phenylpropanolamine, from which he made an uneventul recovery over the next two weeks.  (+info)

Efficient synthesis of B-alkylated oxazaborolidines derived from ephedrine and norephedrine. (22/147)

[reaction: see text] Representative B-butyl- and B-methyl-1,3,2-oxazaborolidines derived from ephedrine and norephedrine were prepared in good yield and excellent purity by one-pot treatment of B-H oxazaborolidines with the corresponding organolithium reagent and subsequent hydrolysis of the cyclic borohydride intermediate with anhydrous ammonium chloride.  (+info)

Overview of adrenergic anorectic agents. (23/147)

Adrenergic anorexic agents of the amphetamine class suppress appetite and reduce body weight via activation of beta-adrenergic and/or dopaminergic receptors within the perifornical hypothalamus (PFH). Although phenylpropanolamine (PPA) is often considered to be a member of the amphetamine class of anorexiants, this drug is an atypical adrenergic anorexiant. Unlike amphetamine, microinjection of PPA into the PFH does not suppress feeding. Moreover, PPA anorexia is not reversed by the dopamine antagonist haloperidol. The anorexic action of PPA may result, in part, from its interaction with alpha 1-adrenergic receptors within the paraventricular medial hypothalamus (PVN). This hypothesis is supported by prior research, which documents that PPA is a direct-acting agonist predominantly at alpha 1 adrenoceptors, that microinjections into the PVN of the alpha 1-adrenoceptor agonists PPA and l-phenylephrine suppress feeding, and that injections of alpha 1-adrenoceptor antagonists within the PVN enhance feeding behavior.  (+info)

Determination of ephedrine alkaloids in human urine and plasma by liquid chromatography/tandem mass spectrometry: collaborative study. (24/147)

A collaborative study was conducted to evaluate the accuracy and precision of a method for ephedrine-type alkaloids (i.e., norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, methylephedrine, and methylpseudoephedrine) in human urine and plasma. The amount of ephedrine-type alkaloids present was determined using liquid chromatography (LC) with tandem mass selective detection. The test samples were diluted to reflect a concentration of 5.00-100 ng/mL for each alkaloid. An internal standard was added and the alkaloids were separated using a 5 microm phenyl LC column with an ammonium acetate, glacial acetic acid, acetonitrile, and water mobile phase. Eight blind duplicates of human urine and eight blind duplicates of human plasma were analyzed by 10 collaborators. In addition to negative controls, test portions of urine and plasma were fortified at 3 different levels with each of the 6 ephedrine-type alkaloids at approximately 1, 2, and 5 microg/mL for urine and 100, 200, and 500 ng/mL for plasma. On the basis of the accuracy and precision results for this collaborative study, it is recommended that this method be adopted Official First Action for the determination of 6 different ephedrine-type alkaloids in human urine and plasma.  (+info)