Summary
Somatostatin was originally isolated from the hypothalamus, but has subsequently been found throughout the whole gastrointestinal tract. It exerts an inhibitory effect upon numerous functions of the body, and, therefore, increasing attention has been focused on its potential as a therapeutic agent with cytoprotective properties and a potent inhibitory action on a wide variety of functions in endocrine diseases, cancer and gastrointestinal haemorrhage, including bleeding from oesophageal varices. As somatostatin has a very short plasma half-life and requires administration by continuous infusion to maintain therapeutic levels, stable long-acting analogues have been developed. The analogue octreotide has been shown to have a plasma half-life of 113 minutes and to produce a profound selective inhibition of growth hormone. Hepatic excretion of octreotide has been estimated to be between 30 and 40% in healthy volunteers; no data are available in cirrhotic patients.
A review of published data assessing systemic and hepatic haemodynamics in animals and humans over varying dosage regimens of somatostatin and octreotide reveals that cardiac output, arterial pressure and peripheral resistance are modified more in animals than in humans. Hepatic haemodynamics are significantly altered in animals as well as in humans in most of the studies.
Circumstantial evidence is provided indicating that the mechanisms of action of somatostatin and octreotide in the therapy of bleeding oesophageal varices are mainly mediated by a splanchnic vasoconstrictive effect.
Furthermore, gastric acid suppression and potential enhancement of platelet aggregation may contribute to the beneficial outcome after treatment of oesophageal varices with somatostatin.
Similar content being viewed by others
References
Arimura A, Fishback JB. Somatostatin: regulation of secretion. Neuroendocrinology 33: 246–256, 1981
Baldissera FGA, Munoz-Perez MA, Holst JJ. Somatostatin 1-28 circulates in human plasma. Regulatory Peptides 6: 63–69, 1983
Battershill PE, Clissold SP. Octreotide — a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. Drugs 38: 658–702, 1989
Bauer W, Briner U, Doepfner W, Haller, R, Huguenin R, et al. SMS 201-995: A very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sciences 31: 1133–1140, 1982
Becker RHA, Scholtholt J, Scholkens BA, Wolfgang J, Speth O. A microsphere study on the effects of somatostatin and secretin on regional blood flow in anesthetized dogs. Regulatory Peptides 4: 341–351, 1982
Bories P, Pomier-Layrargues G, Chotard J-P, Jacob C, Michel H. La somatostatine diminue l’hypertension portale chez le cirrhotique. Gastroenterologie Clinique et Biologique 4: 616–617, 1980
Bosch J, Kravetz D, Rodes J. Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of the liver: comparison with vasopressin. Gastroenterology 80: 518–525, 1981
Brazeau P, Vale W, Burgus R, Ling N, Butcher M, et al. Hypo-thalamic polypeptide that inhibits the section of immunoreactive pituitary growth hormone. Science 179: 77–79, 1973
Burroughs AK, McCormick A, Hughes MD, Sprengers D, D’Heygere F, et al. Randomized, double blind, placebo-controlled trial of somatostatin for variceal bleeding. Gastroenterology 99: 1388–1395, 1990
Burroughs AK, Santana IA, Dux T, Dick R, Mclntyre N. Effect of a long acting analogue of somatostatin (SMS 201-995) on hepatic venous pressures and azygós blood flow in cirrhotics. Gut 26: A562, 1985
Cambia RP, Neville R, Ballantyne GH, Zdon MJ, Zucker KA, et al. Somatostatin and analogs lack splanchnic vasoconstrictive effects in anesthetized pigs. Journal of Surgical Research 43: 452–459, 1987
Cerini R, Lee SS, Hadengue A, Koshy A, Girod C, et al. Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension. Gastroenterology 94: 703–708, 1988
Clements D, Rhodes JM, Elias E. Effect of somatostatin on oesophageal variceal pressure assessed by direct measurement. Journal of Hepatology 2: 262–266, 1986
Cohen M, Rosing E, Wiley KS, Slater IH. Somatostatin inhibits adrenergic and cholinergic neurotransmission in smooth muscle. Life Sciences 23: 1659–1664, 1978
del Pozo E, Neufeld M, Schlüter K, Tortosa F, Clarenbach P, et al. Endocrine profile of a long-acting somatostatin derivative SMS 201-995. Study in normal volunteers following subcutaneous administration. Acta Endocrinologica 111: 433–439, 1986
Doertenbach JG, Hottenrott EC. Hämodynamische Veränderungen nach Somatostatingabe. Fortschritte der Medizin 105: 634–636, 1987
Doertenbach JG, Hanisch E, Wenisch HJC. Erstmaliger Nachweis von Somatostatinzellen in der Gallenblase. Eine immunhisto-chemische Studie beim Menschen. Zeitschrift für Gastroenterologie 25: 444, 1987
Eriksson LS, Brundin T, Söderlund C, Wahren J. Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis. Scandinavian Journal of Gastroenterology 22: 919–925, 1987
Eriksson LS, Law D, Sato Y, Wahren J. Influence of somatostatin on splanchnic haemodynamics in patients with liver cirrhosis. Clinical Physiology 4: 5–11, 1984
Esch F, Böhlen P, Ling N, Benoit R, Brazeau P, et al. Primary structure of ovine hypothalamic somatostatin-28 and somatostatin-25. Proceedings of the National Academy of Sciences of the United States of America 77: 6827–6831, 1980
Folkow B, Lewis DH, Lundgren O, Mellander S, Wallentin J. The effect of graded vasoconstrictor fibre stimulation on the intestinal resistance and capacitance vessels. Acta Physiologica Scandinavica 61: 445–457, 1964a
Folkow B, Lewis DH, Lundgren O, Mellander S, Wallentin J. The effect of the sympathetic vasoconstrictor fibres on the distribution of capillary blood flow in the intestine. Acta Physiologica Scandinavica 61: 458, 1964b
Furness JB. The adrenergic innervation of the vessels supplying and draining the gastrointestinal tract. Zeitschrift für Zellforschung 113: 67–82, 1971
Fuse I, Ito S, Takagi A, Shibata A. Different effects of three kinds of somatostatin (15-28, 1-14, 1-28) on rabbit’s platelet aggregation. Life Sciences 36: 2047–2052, 1985
Gazzaniga PP, Di Macco G, La Mancusa R, Oddi A, Pappalardo G, et al. In vitro enhancement of human platelet aggregation by somatostatin. Experientia 44: 892–894, 1988
Gerich JE. Somatostatin and diabetes. American Journal of Medicine 70: 619–626, 1981
Girod C, Dubois MP, Durand N. Immunocytochemical evidence for the presence of somatostatin-like immunoreactivity in scattered cells of the duct system of the submandibular glands in the monkey, Macaca irus. Histochemistry 69: 137–143, 1980
Giugliano D, Coppola L, Misso L, Tirelli A, Passariello N, et al. Further studies on the significance of circulating platelet aggregates induced by somatostatin in man. Metabolism 30: 172–175, 1981
Granger DN, Richardson DJ, Kvietys PR, Mortillaro NA. Intestinal blood flow. Gastroenterology 78: 837, 1980
Hanisch E, Hawlicek J, Jakobi R, Falk S. In-vitro-Aktivitätsmuster der Gallenblasenmuskulatur von Steinträgern und NichtSteinträgern-Differenzierte Antwort auf Cholezystokinin, Motilin und Neurotensin. Zeitschrift für Gastroenterologie 30: 5–11, 1992
Hanisch E, Strasse R, Wenzel M, Hawlizcek J, v. Loh D, et al. Rat portal vein in vitro — effects of SRIF and SMS 201-995 upon contractility. Journal of Hepatology (Suppl. 1): S160, 1989
Hanisch E, Wenisch HJC, Schumm-Draeger P-M, Hottenrott Ch, Encke A. Reduction of urinary calcium excretion by a long acting somatostatin analog. Results of a study using human parathyroid tissue transplanted to athymic nude mice. Acta Endocrinologica 114 (Suppl. 283): 50, 1988
Hirst BH, Conlon JM, Coy DH, Holland J, Shaw B. Comparison of the gastric exocrine inhibitory activities and plasma kinetics of somatostatin-28 and somatostatin-14 in cats. Regulatory Peptides 4: 227–237, 1982
Hökfeld T, Elfvin LG, Elde R, Schultz M, Goldstein M, et al. Occurrence of somatostatin-like immunoreactivity in some peripheral sympathetic noradrenergic neurons. Proceedings of the National Academy of Sciences of the United States of America 74: 3587, 1977
Holman ME. Electrophysiology of vascular smooth muscle. Ergebnisse der Physiologie 61: 137, 1969
Jaspan J, Polonsky K, Lewis M, Moossa R. Reduction in portal vein blood flow by somatostatin. Diabetes 28: 888–892, 1979
Jenkins SA, Baxter JN, Corbett WA, Shields R. The effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the cirrhotic rat. British Journal of Surgery 72: 864–867, 1985a
Jenkins SA, Baxter JN, Corbett WA, Shields R. The effects of a somatostatin analogue SMS 201-995 on hepatic haemodynamics in the pig and on intravariceal pressure in man. British Journal of Surgery 72: 1009–1012, 1985b
Jenkins SA, Devitt P, Day DW, Baxter JN, Shields R. Effects of somatostatin on hepatic haemodynamics in the cirrhotic rat. Digestion 33: 126–134, 1986
Keller U, Sonnenberg GE, Kayasseh L, Gyr K, Perruchoud A. Doisisabhängigkeit der Wirkung von Somatostatin auf die splanchnische Durchblutung beim Menschen. Schweizerische Medizinische Wochenschrift 109: 595–596, 1979
Kleber G, Sauerbruch T, Fischer G, Paumgartner G. Somatostatin does not reduce oesophageal variceal pressure in liver cirrhotics. Gut 29: 153–156, 1988
Konturek SJ, Tasler J, Cieszkowski DH, Coy A, Schally AV. Effect of growth hormone release-inhibiting hormone on gastric secretion, mucosal blood flow and serum gastrin. Gastroenterology 70: 737–741, 1976
Konturek SJ, Tasler J, Jaworek J, Pawlik W, Walus KM, et al. Gastrointestinal secretory, motor, circulatory and metabolic effects of prosomatostatin. Proceedings of the National Academy of Sciences of the United States of America 78: 1967–1971, 1981
Kravetz D, Bosch J, Arderiu MT, Pizcueta MP, Casamitjana R, et al. Effects of somatostatin on splanchnic hemodynamics and plasma glucagon in portal hypertensive rats. American Journal of Physiology 254: G322–G328, 1988
Kusterer K, Rohr G, Schwedes U, Usadel KH, Szabo S. Gastric mucosal protection by somatostatins. Klinische Wochenschrift 64 (Suppl. VII): 97–99, 1986
Kutz K, Nüesch E, Rosenthaler J. Pharmacokinetics of SMS 201-995 in healthy subjects. Scandinavian Journal of Gastroenterology (Suppl. 119): 65-72, 1986
Lebrec D, DeFleury P, Rueff B. Portal hypertension, size of esophageal varices, the risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterology 79: 1139–1144, 1980
Lin TM, Evans DC, Shaar CJ, Root MA. Action of somatostatin on stomach, pancreas, gastric mucosal blood flow and hormones. American Journal of Physiology 244: G40–G45, 1983
Macdougall BRD, Williams R. A controlled clinical trial of cimetidine in the recurrence of variceal hemorrhage: implications about the pathogenesis of hemorrhage. Hepatology 3: 69–73, 1983
McCormick PA, Dick R, Siringo S, Wagstaff D, Chesta J, et al. Octreotide reduces azygos blood flow in cirrhotic patients with portal hypertension. European Journal of Gastroenterology and Hepatology 2: 489–492, 1990
McCuskey RS, Reilly FD, McCuskey PA. ’In vivo’ microscopy studies of the hepatic microvascular system. Bibliotheca Anatomica 18: 73–76, 1979
Mclntosh Ch, Arnold R. The radioimmunoassay and physiology of somatostatin in the pancreas and gastrointestinal tract. Zeitschrift für Gastroenterologie 16: 330–340, 1978
Merkel C, Gatta A, Zuin R, Finucci GF, Nosadini R, et al. Effect of somatostatin on splanchnic hemodynamics in patients with liver cirrhosis and portal hypertension. Digestion 32: 92–98, 1985
Naeije R, Hallemans R, Mois P, Mélot Ch, Reding P. Effects of vasopressin and somatostatin on hemodynamics and blood gases in patients with liver cirrhosis. Critical Care Medicine 10: 578–582, 1982
Navasa M, Bosch J, Chesta J, Bru C, Pizcuela P, et al. Haemodynamic effects of subcutaneous administration of SMS 201-995, a long acting somatostatin analog, in patients with cirrhosis and portal hypertension. Journal of Hepatology 123: 64, 1988
Polonsky K, Jaspan J, Berelowitz M, Pugh W, Moossa A, et al. The in vivo metabolism of somatostatin-28: possible relationship between diminished metabolism and enhanced biological action. Endocrinology 111: 1698–1703, 1982
Pringle SD, McKee RF, Garden OJ, Lorimer AR, Carter DC. The effect of a long-acting somatostatin analogue on portal and systemic haemodynamics in cirrhosis. Alimentary Pharmacology and Therapeutics 2: 451–459, 1988
Rao GS, Lemoch H, Kessler H, Damm I, Eiermann V, et al. Prevention of pahalloidin-induced lesions on isolated rat hepatocytes by novel synthetic analogues of somatostatin. Klinische Wochenschrift 64 (Suppl. VII): 79–86, 1986
Resnick RH. Somatostatin for variceal bleeders (editorial). Gastroenterology 99: 1524–1526, 1990
Reichlin S. Somatostatin (first of two parts). New England Journal of Medicine 309: 1495–1556, 1983a
Reichlin S. Somatostatin (second of two parts). New England Journal of Medicine 309: 1556–1563, 1983b
Romeo JM, Novo C, Fernández-Cruz A, Lòpez-Novoa JM. Hemodynamic effects of somatostatin in the rat: relationship with plasma glucagon levels. Heart Vessels 5: 219–223, 1990
Rosenthal J, Raptis S, Zoupas Ch, Escobar-Jimenet F. Inhibition by somatostatin of renin, blood pressure, and cardiac and stroke index in essential hypertension. Circulation Research 43 (Suppl. 1): 69–75, 1978
Rueger JM, Hanisch E, Encke A, Pannike A. Effects of a long-acting somatostatin analogue upon bone. Histomorphometric results of a rat pilot study. Calcified Tissue International 46 (Suppl. 2): A46, 1990
Rümenapf G, Hanisch E, Schwüle PO. Low-dose infusion of somatostatin in man — no effect upon intestinal calcium absorption but a fall in blood insulin. Experimental and Clinical Endocrinology 87: 306–312, 1986
Saari A, Kivilaakso E, Inberg M, Pääkkönen M, Lahtinen J, et al. Comparison of somatostatin and vasopressin in bleeding esophageal varices. American Journal of Gastroenterology 85: 804–807, 1990
Samnegard H, Thulin L, Andreen M, Tyden G, Hallberg D, et al. Circulatory effects of somatostatin in anesthetized dogs. Acta Chirurgica Scandinavica 145: 209–212, 1979
Schölkens BA. Influence of somatostatin on blood pressure and plasma renin activity in the rat. Arzneimittel-Forschung 28: 802–803, 1978
Schusdziarra V. Somatostatin — A regulatory modulator connecting nutrient entry and metabolism. Hormone and Metabolic Research 12: 563–577, 1980
Schwüle PO, Hanisch E, Engelhardt W, Scholz D. Basal plasma somatostatin in biliary stone patients. Klinische Wochenschrift 62: 595–597, 1984
Sherlock S. Esophageal varices. American Journal of Surgery 160: 9–13, 1990
Sonnenberg GE, Keller U, Perruchoud A, Burckhardt D, Gyr K. Effect of somatostatin on splanchnic hemodynamics in patients with cirrhosis of the liver and in normal subjects. Gastroenterology 80: 526–532, 1981
Strazzulla G, Gabbrielli G, Lo Sapio P, Lo Russo D, Brocchi A, et al. Evidence for the release of somatostatin from human thyroid. Hormone Research 20: 126–127, 1988
Tulassay T, Tulassay Z, Rascher W, Szücs L, Seyberth HW, et al. Effect of somatostatin on kidney function and vasoactive hormone systems in healthy subjects. Klinische Wochenschrift 69: 486–490, 1991
Tydén G, Samnegard H, Thulin L, Friman L. Treatment of bleeding esophageal varices with somatostatin. New England Journal of Medicine 299: 1466–1467, 1978
Tydén G, Samnegard H, Thulin L, Muhrbeck O, Efendic S. Circulatory effects of somatostatin in anesthetized man. Acta Chirurgica Scandinavica 145: 443–446, 1979
Usadel K-H, Kessler H, Rohr G, Kusterer K, Palitzsch KD, et al. Cytoprotective properties of somatostatins. Klinische Wochenschrift (Suppl. VII): 59-63, 1986
Uvnäs-Wallenstein K, Efendic S, Luft R. Occurrence of somatostatin-like immunoreactivity in vagal nerves. Acta Physiologica Scandinavica 102: 248, 1978
Valenzuela JE, Schubert T, Fogel MR, Strong RM, Levine J, et al. A multicenter, randomized, double-blind trial of somatostatin in the management of acute hemorrhage from esophageal varices. Hepatology 10: 658–661, 1989
Vinik AI, Gaginella TS, O’Dorisio TM, Shapiro B, Wagner L. The distribution and characterization of somatostatin-like immunoreactivity in epithelial cells, submucosa, and muscle of the rat stomach and intestine. Endocrinology 109: 1921–1926, 1981
Wahren J, Felig P. influence of somatostatin on carbohydrate disposal and absorption in diabetes mellitus. Lancet 2: 1213–1216, 1976
Yamada Y, Ito S, Matsubara Y, Kobayashi S. Immunohistochemical demonstration of somatostatin-containing cells in the human, dog and rat thyroids. Tohoku Journal of Experimental Medicine 122: 87–92, 1977
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hanisch, E., Doertenbach, J. & Usadel, K.H. Somatostatin in Acute Bleeding Oesophageal Varices. Drugs 44 (Suppl 2), 24–35 (1992). https://doi.org/10.2165/00003495-199200442-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199200442-00005