The use of aspirin and opiates by Dumfries and Galloway general practitioners in the management of acute myocardial infarction.

In March 1994 a study in the British Medical Journal indicated a low rate of administration of aspirin and opiates by general practitioners in cases of suspected myocardial infarction. A retrospective analysis was made of 120 consecutive admissions to the medical intensive care unit of Dumfries and Galloway Royal Infirmary, by general practitioners, with a primary diagnosis of acute myocardial infarction. Of these 120 cases, 24% were given aspirin by their G.P. prior to admission and 64% were given opiate (IV or IM). Thirty-three percent were already on regular aspirin and of these 18% received further aspirin prior to admission. These figures were considerably better than those previously quoted and they showed that prior regular aspirin therapy did influence the GPs' decision on further administration of aspirin in the acute event. A questionnaire sent to all GPs in Dumfries and Galloway revealed that 100% carried aspirin in their medical bags, 62% claimed to give aspirin to patients with suspected MI, 95% used a British Heart Foundation approved dose of aspirin and 83.3% administered the aspirin using one of the approved methods.

Selectivity and potency of 2-alkyl analogues of the alpha 2-adrenoceptor antagonist idazoxan (RX 781094) in peripheral systems.

The profiles of four analogues of idazoxan have been examined at alpha-adrenoceptors and the results compared to those obtained with idazoxan and yohimbine. The compounds possessed either a methyl (RX 801079), ethyl (RX 811033), n-propyl (RX 811054) or isopropenyl (RX 811005) group at the two position of idazoxan. The rank order of antagonist potency against UK-14,304 at prejunctional alpha 2-adrenoceptors of the rat isolated vas deferens was RX 811054 greater than RX 811033 greater than idazoxan greater than RX 811005 greater than yohimbine = RX 801079. All compounds were competitive antagonists. The rank order of antagonist potency against noradrenaline at postjunctional alpha 1-adrenoceptors of the rat isolated anococcygeus muscle was RX 811054 = RX 811033 = idazoxan = yohimbine greater than RX 811005 = RX801079. All compounds were competitive antagonists. The rank order of alpha-adrenoceptor selectivity (alpha 2/alpha 1) was RX 811005 greater than RX 801079 greater than RX 811054 greater than RX 811033 greater than idazoxan greater than yohimbine. In pithed rats, intravenous administration of all compounds fully reversed the prejunctional alpha 2-adrenoceptor agonist effects of clonidine and guanabenz on electrically-induced contractions of the vas deferens and anococcygeus muscle respectively. In pithed rats the rank order of antagonist potency against UK-14,304 at cardiac prejunctional alpha 2-adrenoceptors was RX 811054 greater than RX 811033 greater than idazoxan greater than yohimbine greater than RX 811005 greater than RX 801079. In contrast, the rank order of antagonist potency against cirazoline pressor effects (vascular postjunctional alpha 1-adrenoceptors) was RX 811054 greater than RX 811033 greater than yohimbine greater than idazoxan greater than RX 811005 greater than RX 801079. The rank order of alpha 2-adrenoceptor selectivity was RX 811033 = RX 801079 = RX 801005 greater than RX 811054 greater than idazoxan greater than yohimbine. Although idazoxan produced contractions of the anococcygeus muscle and increased blood pressure in pithed rats, three of the analogues (RX 811005, RX 801079 and RX 811033) were inactive. In conclusion, alkyl substitution in the 2-position of idazoxan can enhance either alpha 2-adrenoceptor antagonist potency or selectivity or both and furthermore, the weak partial alpha 1-adrenoceptor agonist properties of idazoxan can be removed.

Sleeping times evoked by alpha adrenoceptor agonists in two-day-old chicks: an experimental model to evaluate full and partial agonists at central alpha-2 adrenoceptors.

The ability of a series of alpha adrenoceptor agonists to induce a sleep-like state (as measured by the time interval between the loss and regaining of the righting reflex) has been assessed in 2-day-old chicks in order to understand their pharmacological profile better. Guanabenz, guanoxabenz, UK-14,304, guanfacine and xylazine produced dose-related increases in sleeping time, the highest dose of these agonists causing the chicks to sleep for over 120 min. In contrast, the dose-response curves to tiamenidine and clonidine were flatter and bell-shaped with maxima of 30 and 60 min, respectively. The effects of all these compounds were antagonized by idazoxan (RX781094) and yohimbine (two selective alpha-2 adrenoceptor antagonists) but were moderately enhanced or unaffected by prazosin (a selective alpha-1 adrenoceptor antagonist) confirming that the state of arousal in chicks can be depressed by stimulation of alpha-2 adrenoceptors. In particular, idazoxan displaced significantly the guanoxabenz dose-response curve to the right without affecting its slope and apparent maximum and blocked the sleep induced by clonidine. However, idazoxan failed to affect the sleep evoked by ethanol, etorphine or pentobarbital. Naloxone antagonized the effects of etorphine but not those of guanoxabenz, ethanol or pentobarbital. The relatively selective alpha-1 adrenoceptor agonist, cirazoline, given in doses up to 20 mg/kg i.m., produced in chicks behavioral manifestations suggestive of enhanced arousal.(ABSTRACT TRUNCATED AT 250 WORDS)