The effect of H2-blockade on plasma gastrin concentration in patients with an achlorhydric stomach.
The mechanisms of hypergastrinaemia during H2-receptor antagonist therapy remain unclear. In addition, the effect of food stimulation in conditions of hypergastrinaemia is poorly understood. These effects may be important when considering long-term therapy with potent acid inhibitory agents. To investigate this we studied the effect of H2-receptor antagonist therapy on basal and meal-stimulated plasma gastrin concentrations in 9 patients with pentagastrin fast gastric achlorhydria associated with pernicious anaemia. The subjects received in double-blind randomized fashion 28-day courses of 300 mg ranitidine q.d.s. and placebo, with one-month wash-out between. The fasting and peptone meal-stimulated gastrin concentrations were studied on the final day of each course of treatment. The median fasting gastrin concentrations (ng/L) were similar following placebo (1100, range 25-2100), and 300 mg ranitidine q.d.s. (1075, range 15-2600) and both markedly elevated when compared with our laboratory's normal range of 0-100. Despite the elevated basal levels the pernicious anaemia patients still showed a further increase in response to the peptone meal. Their median peak percentage rise over basal in response to the meal was similar following placebo (96%, range 0-375) and 300 mg ranitidine q.d.s. (100%, range 25-425) (both P less than 0.02 c.f. basal). This study shows that: (a) in hypergastrinaemia in pernicious anaemia subjects, meal stimulation leads to a marked and prolonged increase in plasma gastrin concentrations; (b) H2-receptor antagonists have no effect on plasma gastrin in the neutral stomach and this is consistent with their gastrin effect being entirely secondary to acid inhibition.
University Department of Surgery, Western Infirmary, Glasgow, UK.
G M
GM
Fullarton
J E
JE
Ardill
K E
KE
McColl
D000126:Achlorhydria / Q000097:blood* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000752:Anemia, Pernicious / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000097:blood* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010461:Peptones / Q000494:pharmacology; D011899:Ranitidine / Q000009:adverse effects / Q000494:pharmacology
D005755:Gastrins; D006635:Histamine H2 Antagonists; D010461:Peptones; D011899:Ranitidine