Our data confirm a ceiling effect of buprenorphine but not fentanyl with respect to respiratory depression.
The data indicate that the OPRM1:c.118A>G polymorphism affects opioid analgesic and respiratory effects differentially. Despite reduced analgesic responses to M6G the OPRM1:c.118A>G single-nucleotide polymorphism does not protect against the toxic effects of the tested opioid. However, some caution in the interpretation of the data is needed because of the small sample size. Further studies are needed to explore the link between this polymorphism and respiratory/analgesic responses beyond the small human sample. In OPRM1:c.118AA homozygotes, the potency parameters differed by a factor of 2 for analgesic versus respiratory effect. In this respect, M6G differs favorably from morphine.
Our data indicate that systems involved in morphine-induced analgesia and respiratory depression share important pharmacodynamic characteristics. This suggests similarities in central mu-opioid analgesic and respiratory pathways (e.g., similarities in mu-opioid receptors and G proteins). The clinical implication of this study is that after morphine administration, despite lack of good pain relief, moderate to severe respiratory depression remains possible.
The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo-controlled double-blind study we measured the effect of an intravenous dose (4 mg kg −1 ) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83-85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid I.V. and 200 mg α-tocopherol P.O.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O 2 -CO 2 interaction, i.e. the increase in O 2 sensitivity with rising P CO 2 . Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo-and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O 2 -CO 2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen-sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude.
We compared the effects of the carbonic anhydrase inhibitors methazolamide and acetazolamide (3 mg kg -1 , I.V.) on the steady-state hypoxic ventilatory response in 10 anaesthetized cats. In five additional animals, we studied the effect of 3 and 33 mg kg -1 methazolamide. The steady-state hypoxic ventilatory response was described by the exponential function:whereV I is the inspired ventilation , G is hypoxic sensitivity, D is the shape factor and A is hyperoxic ventilation. In the first group of 10 animals, methazolamide did not change parameters G and D, while A increased from 0.86 ± 0.33 to 1.30 ± 0.40 l min -1 (mean ± S.D., P = 0.003). However, the subsequent administration of acetazolamide reduced G by 44% (control, 1.93 ± 1.32; acetazolamide, 1.09 ± 0.92 l min -1 , P = 0.003), while A did not show a further change. Acetazolamide tended to reduce D (control, 0.20 ± 0.07; acetazolamide, 0.14 ± 0.06 kPa -1 , P = 0.023). In the second group of five animals, neither low-nor high-dose methazolamide changed parameters G, D and A. The observation that even high-dose methazolamide, causing full inhibition of carbonic anhydrase in all body tissues, did not reduce the hypoxic ventilatory response is reminiscent of previous findings by others showing no change in magnitude of the hypoxic response of the in vitro carotid body by this agent. This suggests that normal carbonic anhydrase activity is not necessary for a normal hypoxic ventilatory response to occur. The mechanism by which acetazolamide reduces the hypoxic ventilatory response needs further study.
In contrast to the ample literature demonstrating sex differences in morphine analgesia, neither sex nor subject expectation (i.e., placebo) contributes to the large between-subject response variability with alfentanil analgesia. The difference in alfentanil analgesia onset and offset between pain tests is discussed.
List of abstacts and authors:1. Integrating the art and science of psychiatryEugene Allers2. Chronic pain as a predictor of outcome in an inpatient Psychiatric populationEugene Allers and Gerhard Grundling3. Recent advances in social phobiaChrister Allgulander4. Clinical management of patients with anxiety disordersChrister Allgulander5. Do elephants suffer from Schizophrenia? (Or do the Schizophrenias represent a disorder of self consciousness?) A Southern African perspectiveSean Exner Baumann6. Long term maintenance treatment of Bipolar Disorder: Preventing relapseCharles L. Bowden7. Predictors of response to treatments for Bipolar DisorderCharles L. Bowden8. Aids/HIV knowledge and high risk behaviour: A Geo-graphical comparison in a schizophrenia populationP Buckley, S van Vuuren, L Koen, J E Muller, C Seller, H Lategan, D J H Niehaus9. Does Marijuana make you go mad?David J Castle10. Understanding and management of Treatment Resistant SchizophreniaDavid J Castle11. Workshop on research and publishingDavid J Castle12. From victim to victor: Without a self-help bookBeatrix Jacqueline Coetzee13. The evaluation of the Gender Dysphoric patientFranco Colin14. Dissociation: A South African modelA M Dikobe, C K Mataboge, L M Motlana, B F Sokudela, C Kruger15. Designated smoking rooms...and other "Secret sins" of psychiatry: Tobacco cessation approaches in the severely mentally illCharl Els16. Dual diagnosis: Implications for treatment and prognosisCharl Els17. Body weight, glucose metabolism and the new generation antipsychoticsRobin Emsley18. Neurological abnormalities in first episode Schizophrenia: Temporal stability and clinical and outcome correlatesRobin Emsley, H Jadri Turner, Piet P Oosthuizen, Jonathan Carr19. Mythology of depressive illnesses among AfricansSenathi Fisha20. Substance use and High school dropoutAlan J. Flisher, Lorraine Townsend, Perpetual Chikobvu, Carl Lombard, Gary King21. Psychosis and Psychotic disordersA E Gangat 22. Vulnerability of individuals in a family system to develop a psychiatric disorderGerhard Grundling and Eugene Allers23. What does it Uberhaupt mean to "Integrate"?Jürgen Harms24. Research issues in South African child and adolescent psychiatryS M Hawkridge25. New religious movements and psychiatry: The Good NewsV H Hitzeroth26. The pregnant heroin addict: Integrating theory and practice in the development and provision of a service for this client groupV H Hitzeroth, L Kramer27. Autism spectrum disorderErick Hollander28. Recent advances and management in treatment resistanceEric Hollander29. Bipolar mixed statesM. Leigh Janet30. Profile of acute psychiatric inpatients tested for HIV - Helen Jospeh Hospital, JohannesburgA B R Janse van Rensburg31. ADHD - Using the art of film-making as an education mediumShabeer Ahmed Jeeva32. Treatment of adult ADHD co-morbiditiesShabeer Ahmed Jeeva33. Needs and services at ward one, Valkenberg HospitalDr J. A. Joska, Prof. A.J. Flisher34. Unanswered questions in the adequate treatment of depressionModerator: Dr Andre F JoubertExpert: Prof. Tony Hale35. Unanswered questions in treatment resistant depressionModerator: Dr Andre F JoubertExpert: Prof. Sidney Kennedy36. Are mentally ill people dangerous?Sen Z Kaliski37. The child custody circusSean Z. Kaliski38. The appropriatenes of certification of patients to psychiatric hospitalsV. N. Khanyile39. HIV/Aids Psychosocial responses and ethical dilemmasFred Kigozi40. Sex and PsychiatryB Levinson41. Violence and abuse in psychiatric in-patient institutions: A South African perspectiveMarilyn Lucas, John Weinkoove, Dean Stevenson42. Public health sector expenditure for mental health - A baseline study for South AfricaE N Madela-Mntla43. HIV in South Africa: Depression and CD4 countM Y H Moosa, F Y Jeenah44. Clinical strategies in dealing with treatment resistant schizophreniaPiet Oosthuizen, Dana Niehaus, Liezl Koen45. Buprenorphine/Naloxone maintenance in office practice: 18 months and 170 patients after the American releaseTed Parran Jr, Chris Adelman46. Integration of Pharmacotherapy for Opioid dependence into general psychiatric practice: Naltrexone, Methadone and Buprenorphine/ NaloxoneTed Parran47. Our African understanding of individulalism and communitarianismWillie Pienaar48. Healthy ageing and the prevention of DementiaFelix Potocnik, Susan van Rensburg, Christianne Bouwens49. Indigenous plants and methods used by traditional African healers for treatinf psychiatric patients in the Soutpansberg Area (Research was done in 1998)Ramovha Muvhango Rachel50. Symptom pattern & associated psychiatric disorders in subjects with possible & confirmed 22Q11 deletional syndromeJ.L. Roos, H.W. Pretorius, M. Karayiorgou51. Duration of antidepressant treatment: How long is long enough? How long is too longSteven P Roose52. A comparison study of early non-psychotic deviant behaviour in the first ten years of life, in Afrikaner patients with Schizophrenia, Schizo-affective disorder and Bipolar disorderMartin Scholtz, Melissa Janse van Rensburg, J. Louw Roos53. Treatment, treatment issues, and prevention of PTSD in women: An updateSoraya Seedat54. Fron neural networks to clinical practiceM Spitzer55. Opening keynote presentation: The art and science of PsychiatryM Spitzer56. The future of Pharmacotherapy for anxiety disordersDan J. Stein57. Neuropsychological deficits pre and post Electro Convulsive Therapy (ECT) thrice a week: A report of four casesUgash Subramaney, Yusuf Moosa58. Prevalence of and risk factors for Tradive Dyskinesia in a Xhosa population in the Eastern CapeDave Singler, Betty D. Patterson, Sandi Willows59. Eating disorders: Addictive disorders?Christopher Paul Szabo60. Ethical challenges and dilemmas of research in third world countriesGodfrey B. Tangwa61. The interface between Neurology and Psychiatry with specific focus on Somatoform dissociative disordersMichael Trimble62. Prevalence and correlates of depression and anxiety in doctors and teachersH Van der Bijl, P Oosthuizen63. Ingrid Jonker: A psychological analysisL. M. van der Merwe64. The strange world we live in, and the nature of the human subjectVasi van Deventer65. Art in psychiatry: Appendix or brain stem?C W van Staden66. Medical students on what "Soft skills" are about before and after curriculum reformC W van Staden, P M Joubert, A-M Bergh, G E Pickworth, W J Schurink, R R du Preez, J L Roos, C Kruger, S V Grey, B G Lindeque67. Attention deficit hyperactivity disorder (ADHD) - Medical management. Methylphenidate (Ritalin) or Atomoxetine (Strattera)Andre Venter68. A comprehensive guide to the treatment of adults with ADHDW J C Verbeeck69. Treatment of Insomnia: Stasis of the Art?G C Verster70. Are prisoners vulnerable research participants?Merryll Vorster71. Psychiatric disorders in the gymMerryl Vorster72. Ciprales: Effects on anxiety symptoms in Major Depressive DisorderBruce Lydiard
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