Trophic Hormones & Related Synthetic Drugs.
CONTENTS: Octreotide ( as free peptide ).
PRESENTATION: Amp 0.05 mg/mL x 5's. 0.1 mg/mL x 5's.
ACTIONS: Sandostatin is a synthetic octapeptide analogue of
naturally occurring somatostatin with similar pharmacological effects but
with a considerably prolonged duration of action. It inhibits the secretion
of peptides of the gastroenteropancreatic ( GEP ) endocrine sytem andof
growth hormone ( GH ).
Pharmacology: In animals, Sandostatin is a more potent inhibitor of growth hormone, glucagon and insulin release than somatostatin with greater selectivity for GH- and glucagon-suppression. Chronic administration (26 weeks) of doses up to 1 mg/kg a day (given intraperitoneally) in the rat and up to 0.5 mg/kg a day (given IV) in the dog is well tolerated.
In healthy subjects Sandostatin has been shown to inhibit:
Release of growth hormone (GH) stimulated by arginine, exercise and insulin-induced hypoglycaemia.
Postprandial release of insulin, glucagon, gastrin, other peptides of the GEP system, and the release of insulin and glucagon in response to arginine.
Thyrotropin releasing hormone (TRH) stimulated release of thyroid stimulating hormone (TSH).
In acromegalic patients (including those who have failed to respond to surgery, irradiation or dopamine-agonist treatment) Sandostatin lowers plasma levels of growth hormone and/or somatomedin C. A clinically relevant GH reduction (by 50% or more) occurs in all patients and normalization (plasma GH<5 ng/mL) can be achieved in about half of the cases. In most patients Sandostatin markedly reduces the clinical symptoms of the disease, eg headache, skin thickening, soft-tissue swelling, hyperhidrosis, arthralgia and paraesthesia. In patients with a large pituitary adenoma, Sandostatin treatment may result in some shrinkage of the tumour tissue.
In patients with tumours of the gastroenteropancreatic endocrine system, Sandostatin, because of its diverse endocrine effects, modifies various clinical features. Clinical improvement and symptomatic benefit occur in patients who have severe symptoms related to their tumours despite previous therapies which include surgery, hepatic artery embolisation and various chemotherapies, eg streptozocin and fluorouracil.
Sandostatin's effects in the different tumour types are as follows: Carcinoid tumours: Administration of Sandostatin may result in improvement of symptoms, particularly of flush and diarrhoea. In some cases this is accompanied by a fall in plasma serotonin and reduced urinary excretion of 5-hydroxyindole acetic acid. In the event of no beneficial response to Sandostatin treatment, continuation of therapy beyond 1 week is not recommended, although in non-responders no serious sustained adverse drug effects have been reported.
The biochemical characteristic of these tumours is overproduction of vasoactive intestinal peptide (VIP). In most cases, administration of Sandostatin results in alleviation of the severe secretory diarrhoea typical of the condition, with consequent improvement in quality of life. This is accompanied by an improvement in associated electrolyte abnormalities, eg hypokalaemia, enabling enteral and parenteral fluid and electrolyte supplementation to be withdrawn. In some patients, computer tomography suggests a slowing or arrest of progression of the tumour, or even tumour shrinkage, particularly of hepatic metastases. Clinical improvement is usually accompanied by a reduction in plasma VIP levels, which may fall into the normal reference range.
Administration of Sandostatin in most cases results in substantial improvement of the necrolytic migratory rash which is characteristic of the condition. In many cases it also exerts an effect on the slight diabetes mellitus to which these patients are prone. However, this effect is not very potent and does not generally result in a reduction of their requirement for insulin or oral hypoglycaemic agents. Sandostatin produces improvement of diarrhoea in those patients affected and weight gain. Although administration of Sandostatin often leads to an immediate reduction in plasma glucagon levels, this decrease is generally not maintained over a prolonged period of administration, despite continued symptomatic improvement.
Although therapy with selective H2-receptor blocking agents and antacids controls the recurrent peptic ulceration which results form chronic gastrin-stimulated hypersecretion of gastric acid, such control may be incomplete. Diarrhoea may also be a prominent symptom not alleviated by therapy. Sandostatin alone or in conjunction with H2-receptor antagonists, may reduce gastric acid hypersecretion and improve symptoms, including diarrhoea in 50% of the cases. Other symptoms possibly due to peptide production by tumour, eg flush, may also be relieved. Plasma gastrin levels fall in some patients.
Administration of Sandostatin produces a fall in circulating immunoreactive insulin which may, however, be of short duration (about 2 hrs). In patients with operable tumours it may help to restore and maintain normoglycaemia preoperatively. In patients with inoperable benign or malignant tumours, glycaemic control may be improved in a limited number of cases without concomitant sustained reduction in circulating insulin levels.
These rare tumours are characterised by production of growth hormone releasing factor (GRF) alone or in conjunction with other active peptides. Sandostatin produced an improvement in features and symptoms of resultant acromegaly in one of the two cases so far investigated. This is probably due to inhibition of GRF and growth hormone secretion, which may be followed by a reduction in pituitary enlargement.
Pharmacokinetics: After SC injection, Sandostatin is rapidly and completely absorbed. Peak plasma concentrations are reached 30 min after administration. Elimination after SC administration tykes place with a half-life of 100 min. After IV injection the elimination is biphasic with half-lives of 10 and 90 min, respectively. The volume of distribution is 6 L and the total body clearance is 160 mL/min. Plasma-, protein binding amounts to 65%. The amount of Sandostatin bound to blood cells is negligible.