Cimetidine, a new H2‐receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half‐life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended.
Aims-To assess whether r-HuEPO (recombinant human erythropoietin) has any effect on thrombopoiesis in patients with chronic renal failure.Methods-This was a retrospective study of 78 patients with chronic renal failure undergoing either haemodialysis (n = 57) or intraperitoneal dialysis (n = 21). All patients had a full blood count (in EDTA) me before stling r-HuEPO and at monthly intervals thereafter up to six months. Variables studied were haematocrit, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW). Other groups of control patients were also studiedpatients with chronic renal failure receiving dialysis but not r-HuEPO (n = 40) and a group of patients with normal renal function who were receiving aspirin (n = 30). Results-There was a significant increase in mean haematocrit (p < 0.01) and in mean platelet volume (p < 0-001) over the six month period, but no change in either total platelet count or platelet distribution width in the patients with chronic renal fiilure receiving r-HuEPO. In contrast, both the control groups showed no significant change in MPV. Conclusions-The results suggest that r-HuEPO affects thrombopoiesis and may be part of a group of humoral factors contributing to megakaryocyte development and maturation. Larger platelets are more reactive and may contribute to the increased risk of thrombosis associated with r-HuEPO. The dose of r-HuEPO began at 50 IU/kg twice weekly (by subcutaneous injection), increasing to 75 IU/kg twice weekly after two to three months if there was an insufficient rise in haematocrit and haemoglobin. It is the policy of the renal unit to give aspirin to all patients starting r-HuEPO. Twelve out of the 78 patients did not receive aspirin during the six month period of study as they had been given r-HuEPO before the establishment of this policy.All the patients had a full blood count (in EDTA) measured on a Coulter STKS (Coulter Electronics, Northwell Drive, Luton, Beds) at monthly intervals from baseline (before starting r-HuEPO) up to six months. As a result of organisational procedure both within the renal wards and the haematology laboratory, most of the samples would have been analysed within 4 hours of venepuncture, but we cannot exclude a few samples having been analysed at a later time.The variables studied were haematocrit, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW).Changes in these variables were compared with baseline values and statistically analysed using Student's paired t test. A measure of the difference between the maximum value of a variable achieved over the six month period and baseline was calculated and used in the 159 on 7 May 2018 by guest. Protected by copyright.
Abstract. We have compared the effects of cimetidine and SK&F 92994, a new more potent histamine H2 receptor antagonist, on serum prolactin, and also assessed the effect of the H2 receptor agonist impromidine on the response to cimetidine. As previously reported, cimetidine 200 mg given as an iv bolus dose produced a marked rise in serum prolactin, but 50 mg and 200 mg of SK&F 92994 given by the same route had no effect. Iv infusion of impromidine 10 μg kg−1h−1 failed to modify the prolactin response to cimetidine. It is concluded that the rise in serum prolactin following iv administration of cimetidine may be due to a specific property of cimetidine. An effect mediated via histaminergic pathways within the central nervous system, although less likely, cannot be excluded.
Intrinsic factor (IF) secretion in healthy male subjects was studied in response to pentagastrin stimulation with and without cimetidine, and to impromidine, a histamine H2 receptor agonist. Peak and total IF output were reduced by cimetidine, but the concentration was unchanged and the response was unaffected by administration of the compound for 1 week. The IF secretory response to impromidine was similar to that to pentagastrin. It is suggested that the acid and IF components of the parietal cell secretory response are mediated via different intracellular pathways, that histamine H2 receptors do not fulfill and obligatory role in the secretion of IF and that synthesis of IF is probably not altered by cimetidine.
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