Peter H Tonner | Search PubMed

PubMed2003

Pathophysiological changes in the elderly.

Demographic data indicate an increasing workload of geriatric anaesthesia due to advancing life expectancy and reduced thresholds for high-invasive and high-risk surgery in the elderly. Chronological and biological age may be inconsistent, and the existence of age-related changes may vary between organ systems in the same individual. Age itself is not an illness, but is the most important contributing factor for perioperative complications and adverse outcome when the overall narrowed margins of organ function reserve are transgressed during the perioperative period. Age-related changes in the cardiovascular, pulmonary, nervous, metabolic and locomotive systems that are frequently present in the elderly are discussed with regard to their potential relevance to anaesthesiology. In conclusion, listing current diagnoses will not be sufficient in the assessment of the geriatric patient because age-related changes do not necessarily manifest as pathological entities. Rather, pre-operative examination should focus on determination of individual margins of organ function reserve.

Aged↗

PubMed2002

Meperidine exerts agonist activity at the alpha(2B)-adrenoceptor subtype.

BACKGROUND: The opioid agonist meperidine has actions, such as antishivering, that are more pronounced than those of other opioid agonists and that are not blocked with nonselective opioid antagonists. Agonists at the alpha(2) adrenoceptors, such as clonidine, are very effective antishivering drugs. Preliminary evidence also indicates that meperidine interacts with alpha(2) adrenoceptors. The authors therefore studied the ability of meperidine to bind and activate each of the alpha(2)-adrenoceptor subtypes in a transfected cell system. METHODS: The ability of meperidine to bind to and inhibit forskolin-stimulated cyclic adenosine monophosphate formation as mediated by the three alpha(2)-adrenoceptor subtypes transiently transfected into COS-7 cells has been tested. The ability of the opioid antagonist naloxone and the alpha(2)-adrenoceptor antagonists yohimbine and RX821002 to block the analgesic action of meperidine in the hot-plate test was also assessed. The ability of meperidine to fit into the alpha(2B) adrenoceptor was assessed using molecular modeling techniques. RESULTS: Meperidine bound to all alpha2-adrenoceptor subtypes, with alpha(2B) having the highest affinity (alpha(2B), 8.6 +/- 0.3 microm; alpha(2C), 13.6 +/- 1.5 microm, P < 0.05; alpha(2A), 38.6 +/- 0.7 microm). Morphine was ineffective at binding to any of the receptor subtypes. Meperidine inhibited the production of forskolin-stimulated cyclic adenosine monophosphate mediated by all receptor subtypes but was most effective at the alpha(2B) adrenoceptor (alpha(2B), 0.6 microm; alpha(2A), 1.3 mm; alpha(2C), 0.3 mm), reaching the same level of inhibition (approximately 70%) as achieved with the alpha2-adrenoceptor agonist dexmedetomidine. The analgesic action of meperidine was blocked by naloxone but not by the alpha 2-adrenoceptor antagonists yohimbine and RX821002. The modeling studies demonstrated that meperidine can fit into the alpha(2B)-adrenoceptor subtype. CONCLUSION: Meperidine is a potent agonist at the alpha2 adrenoceptors at its clinically relevant concentrations, especially at the alpha(2B)-adrenoceptor subtype. Activation of the alpha(2B) receptor does not contribute significantly to the analgesic action of meperidine. This raises the possibility that some of its actions, such as antishivering, are transduced by this mechanism.

Adenylyl Cyclase Inhibitors↗