Octreotide

Octreotide (brand name Sandostatin, Novartis Pharmaceuticals) is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer.

Approved uses
The Food and Drug Administration (FDA) has approved the usage of a salt form of this peptide, octreotide acetate, as an injectable depot formulation for the treatment of acromegaly, the treatment of diarrhea and flushing episodes associated with carcinoid syndrome, and treatment of diarrhoea in patients with vasoactive intestinal peptide-secreting tumors (VIPomas).

Radiolabelling
Octreotide is used in nuclear medicine imaging by labelling with indium-111 (Octreoscan) to non-invasively image neuroendocrine and other tumours expressing somatostatin-receptors. More recently, it has been radiolabelled with gallium-68 enabling imaging with positron emission tomography (PET) which provides higher resolution and sensitivity.

Octreotide can also be labelled with a variety of radionuclides, such as yttrium-90 or lutetium-177, to enable peptide receptor radionuclide therapy (PRRT) for the treatment of unresectable neuroendocrine tumours.

Off-label and experimental uses
Octreotide has also been used off-label for the treatment of severe, refractory diarrhea from other causes. It is used in toxicology for the treatment of prolonged recurrent hypoglycemia after sulfonylurea and possibly meglitinides overdose.

Octreotide has also been used with varying degrees of success in infants with nesidioblastosis to help decrease insulin hypersecretion.

In patients with suspected esophageal varices, octreotide can be given to help decrease bleeding.

Octreotide has been investigated for patients with pain from chronic pancreatitis.

It may be useful in the treatment of thymic neoplasms.

The drug has been used off-label, injected sub-cutaneously, in the management of hypertrophic pulmonary osteoarthropathy (HPOA) secondary to non-small cell lung carcinoma. Although its mechanism is not known it appears to reduce the pain associated with HPOA.

It has been used in the treatment of malignant bowel obstruction.

Octreotide may be used in conjunction with midodrine to partially reverse peripheral vasodilation in the hepato-renal syndrome. By increasing systemic vascular resistance, these drugs reduce shunting and improve renal perfusion, prolonging survival until definitive treatment with liver transplant.

The drug has also been shown to be effective in the treatment of chylothorax.

A small study has shown that octreotide may be effective in the treatment of idiopathic intracranial hypertension (IIH).

Contraindications
Octreotide has not been adequately studied for the treatment of children, pregnant and lactating women. The drug is given to these groups of patients only if a risk-benefit analysis is positive.

Adverse effects
Most frequent adverse effects (more than 10% of patients) are headache, hypothyroidism, cardiac conduction changes, gastrointestinal reactions (including cramps, nausea/vomiting and diarrhea or constipation), gallstones, reduction of insulin release, hyperglycemia (high blood sugar) or hypoglycemia (low blood sugar), and (usually transient) injection site reactions. Slow heart rate, skin reactions like pruritus, hyperbilirubinemia, hypothyreosis, dizziness and dyspnea are also fairly common (more than 1%). Rare side effects include acute anaphylactic reactions, pancreatitis and hepatitis.

Some studies reported alopecia in patients who were treated by octreotide. Rats who were treated by octreotide experienced erectile disfunction in a 1998 study. A prolonged QT interval has been observed in patients, but it is uncertain whether this is a reaction to the drug or part of the patients' illness.

Pharmacokinetics
Octreotide is absorbed quickly and completely after subcutaneous application. Maximal plasma concentration is reached after 30 minutes. The elimination half-life is 100 minutes (1.7 hours) on average when applied subcutaneously; after intravenous injection, the substance is eliminated in two phases with half-lives of 10 and 90 minutes, respectively.

Pharmacological effects
Since octreotide resembles somatostatin in physiological activities, it can:
 * inhibit secretion of many hormones, such as gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide
 * reduce secretion of fluids by the intestine and pancreas
 * reduce gastrointestinal motility and inhibit contraction of the gallbladder
 * inhibit the action of certain hormones from the anterior pituitary
 * cause vasoconstriction in the blood vessels
 * reduce portal vessel pressures in bleeding varices.

It has also been shown to produce analgesic effects, most probably acting as a partial agonist at the mu opioid receptor.

Interactions
Octreotide can reduce the intestinal resorption of ciclosporin, possibly making it necessary to increase the dose. Patients with diabetes mellitus might need less insulin or oral antidiabetics when treated with octreotide. The bioavailability of bromocriptine, is increased. Bromocriptine, besides being an antiparkinsonian, is also used for the treatment of acromegaly.