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.
Fullarton
G M
GM
University Department of Surgery, Western Infirmary, Glasgow, UK.
Ardill
J E
JE
McColl
K E
KE
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