GH Inhibitors

GH INHIBITORS

Somatostatin

This 14 amino acid peptide inhibits the secretion of GH, TSH and prolactin by pituitary; insulin and glucagon by pancreas and of almost all gastrointestinal secretions including that of gastrin and HCl. The g.i. action produces steatorrhoea, diarrhoea, hypochlorhydria, dyspepsia and nausea as side effect. Somatostatin constricts splanchnic, hepatic and renal blood vessels. The decreased g.i. mucosal blood flow can be utilized for controlling bleeding esophageal varices and bleeding peptic ulcer, but octreotide is preffered now due to longer duration of action. Its antisecretory action is beneficial in pancreatic, biliary or intestinal fistulae; can also be used to reduce complications after pancreatic surgery. It also has adjuvant value in diabetic ketoacidosis (by inhibiting glucagon and GH secretion).

Use of somatostatin in acromegaly is limited by its short duration of action (t½ 2–3 min), lack of specificity for inhibiting only GH secretion and GH rebound on discontinuation.

Dose: (for upper g.i.bleeding) 250 μg slow i.v. injection over 3 min followed by 3 mg i.v. infusion over 12 hours.

STILMEN, SOMATOSAN 250 μg and 3 mg amps.

Octreotide 

This synthetic octapeptide surrogate of somatostatin is 40 times more potent in suppressing GH secretion and longer acting (t½ ~90 min), but only a weak inhibitor of insulin secretion. It is being preferred over somatostatin for acromegaly and seretory diarrhoeas associated with carcinoid, AIDS, cancer chemotherapy or diabetes. Control of diarrhoea is due to suppression of hormones which enhance intestinal mucosal secretion.

Dose: Initially 50–100 μg s.c. twice daily, increased upto 500 μg TDS.

Adverse effects are abdominal pain, nausea, steatorrhoea, diarrhoea, and gall stones (due to biliary stasis).

Octreotide injected i.v. (100 μg followed by 25–50 μg/hr) reduces hepatic blood flow and helps stop esophageal variceal bleeding.

SANDOSTATIN, OCTRIDE 50 μg, 100 μg in 1 ml amps.

Pegvisomant 

This polyethylene glycol complexed mutant GH binds to the GH receptor but does not trigger signal transduction: acts as a GH antagonist. It is indicated in acromegaly due to small pituitary adenomas.