In-vivo catecholamine formation from phenylephrine.
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Biomedical subjects
Publications and source records attributed to J R Crowley.
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The metabolism of R-(-)-m-synephrine (administered orally and by inhalation in man and intraperitoneally in rats) was studied quantitatively by a gas chromatography-mass spectrometry-selected ion monitoring (g.c.-m.s.-s.i.m.) method using deuterated internal standards. When m-synephrine hydrochloride was administered orally to humans in normal dosage regimens four main metabolites were excreted in urine: (i) unconjugated m-hydroxymandelic acid (MHMA, 30%), (ii) m-hydroxyphenylglycol (MHPG) sulphate (6%), (iii) m-synephrine sulphate (47%) and (iv) m-synephrine glucuronide (12%). The comparable figures after inhalation of the drug were 24, 6, 56 and 5%. Intraperitoneal injection of m-synephrine into rats gave: unconjugated MHMA (5%), MHPG sulphate (35%), unconjugated m-synephrine (7%) and conjugates of m-synephrine (9%:4% as the glucuronide and 5% as the sulphate).
m-Hydroxyphenylglycol (MHPG) has been identified in mammalian urine by gas chromatography mass spectrometry selected ion monitoring. (2H0) MHPG and (2H5) MHPG were synthesized for use as authentic sample and internal standard, respectively. After acid hydrolysis or treatment with sulfatase, the glycol was extracted from urine with ethyl acetate, converted to its tris-pentafluoropropionyl (PFP) derivative and identified by comparison of the retention times and relative intensities of the characteristic ions, m/z 592, m/z 428 and m/z 415, with those from the authentic sample. Using the internal standard the following quantitative results were obtained: 10 normal human adults excreted 7 ng MHPG mg-1 creatinine (range 2-18) as a sulfate conjugate. Ten rats excreted 0.8 micrograms day-1 (range 0.5-1.1) of MHPG also in the conjugated form. Urinary m-hydroxymandelic acid (MHMA) was also measured quantitatively. The ratio MHMA:MHPG was 1:1 in the rat and 6:1 in the human. This indicates that the overall reductive pathway of m-octopamine and m-synephrine metabolism is more important in the rat than in the human. o-Hydroxyphenylglycol (OHPG) and the three isomeric monomethoxy phenylglycols could not be detected in human or rat urine by these techniques.
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o-Hydroxymandelic acid (OHMA), m-hydroxymandelic acid (MHMA) and p-hydroxymandelic acid (PHMA) were measured in the urine of 42 normotensive and 54 hypertensive patients. Patients having high urinary MHMA levels were all found to be ingesting medications containing m-synephrine (phenylephrine). These patients also had high levels of urinary m-synephrine which was excreted as the glucuronide. When patients ingesting m-synephrine were excluded from the analysis, no significant differences were observed between the two groups for the urinary excretion of OHMA, MHMA and PHMA.
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o-Hydroxymandelic acid has been found in large amounts in the urine of patients with phenylketonuria by gas chromatography mass spectrometry selected ion monitoring. Using deuterated o-hydroxymandelic acid as an internal standard, five patients were found to excrete 150-340 ng mg-1 creatinine. This may be compared with the excretion of 4-16 ng mg-1 creatine by normal subjects. Neither o-octopamine nor o-synephrine were found in urine under conditions by which 1 ng mg-1 creatinine would have been detected.
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o-Hydroxymandelic acid and m-hydroxymandelic acid have been identified in human urine by gas chromatography mass spectrometry selected ion monitoring. After solvent extraction the urinary acids were converted to their O-trifluoroacetoxy methyl ester derivatives which were identified by comparison of the retention times and relative intensities of the characteristic m/z 374 and m/z 315 ions with those from authentic samples. 4,6-[2H3]-o-hydroxymandelic acid and 2,4,6-[2H3]-m-hydroxymandelic acid were synthesized for use as internal standards in the quantitative estimation of the isomeric hydroxymandelic acids excreted in urine. In ten normal adults the following results were obtained: o-hydroxymandelic acid 4--16 ng mg-1 creatinine and m-hydroxymandelic acid 11--71 ng mg-1 creatinine. Acid hydrolysis of the urine or ingestion of a diet of known composition did not affect these results, indicating that these compounds are excreted as the free acids and probably arise by metabolism of the corresponding phenylethanolamine(s).
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The effectiveness of systematically designed print-based materials in teaching (a) knowledge of laboratory tests and (b) laboratory test skills to laboratory staff in small office practices was measured. Self-guided packets on Gram stain performance and interpretation, rapid streptococcal testing, and vaginal wet preparations were developed by a multidisciplinary team. A total of 21 staff members (14 treatment, 7 control) in 12 family practice offices with three or fewer physicians participated in the study. A posttest-only control group design was used to determine the effects of using the self-guided instructional packets. The treatment group, in relation to the control, scored significantly higher on tests of knowledge for all packets, demonstrated no difference in scores for Gram stain or streptococcal test skills, and scored significantly higher for identification of elements in photographs of vaginal wet preparations. Results affirmed both the usefulness and limitations of print-based instruction for knowledge level outcomes. For developing laboratory test skills additional forms of instruction are needed.
Laboratory workers and educators alike are challenged to support access to education that is current and provides opportunities for career advancement in the work place. The clinical laboratory science (CLS) program at the Medical College of Georgia in Augusta developed a clinical laboratory technician (CLT) to CLS articulation option, expanded it through distance learning, and integrated computer based learning technology into the educational process over a four year period to address technician needs for access to education. Both positive and negative outcomes were realized through these efforts. Twenty-seven students entered the pilot articulation program, graduated, and took a CLS certification examination. Measured in terms of CLS certification, promotions, pay raises, and career advancement, the program described was a success. However, major problems were encountered related to the use of unfamiliar communication technology; administration of the program at distance sites; communication between educational institutions, students, and employers; and competition with CLT programs for internship sites. These problems must be addressed in future efforts to provide a successful distance learning program. Effective methods for meeting educational needs and career ladder expectations of CLTs and their employers are important to the overall quality and appeal of the profession. Educational technology that includes computer-aided instruction, multimedia, and telecommunications can provide powerful tools for education in general and CLT articulation in particular. Careful preparation and vigilant attention to reliable delivery methods as well as students' progress and outcomes is critical for an efficient, economically feasible, and educationally sound program.