Октреотид: Соматостатин аналогы және оның қолданылуы

Octapeptide that mimics natural somatostatin pharmacologically

Octreotide, sold under the brand name Sandostatin among others, 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, and binds predominantly to the somatostatin receptors SSTR2 and SSTR5. It was approved for use in the United States in 1988.

Octreotide is used for the treatment of growth hormone producing tumors (acromegaly and gigantism), when surgery is contraindicated, pituitary tumors that secrete thyroid stimulating hormone (thyrotropinomata), diarrhea and flushing episodes associated with carcinoid syndrome, and diarrhea in people with vasoactive intestinal peptide secreting tumors (VIPomas). Octreotide is also used in mild cases of glucagonoma when surgery is not an option.

Octreotide is often given as an infusion for management of acute hemorrhage from esophageal varices in liver cirrhosis on the basis that it reduces portal venous pressure, though current evidence suggests that this effect is transient and does not improve survival.

Octreotide is used in nuclear medicine imaging by labeling with indium 111 (Octreoscan) to noninvasively image neuroendocrine and other tumours expressing somatostatin receptors. More recently, it has been radiolabeled with carbon 11 as well as gallium 68 (using edotreotide), enabling imaging with positron emission tomography (PET), which provides higher resolution and sensitivity. Octreotide (usually as the derivative edotreotide or DOTATOC) can also be labeled with a variety of therapeutic radionuclides, such as yttrium 90 or lutetium 177, to enable peptide receptor radionuclide therapy (PRRT) for the treatment of unresectable neuroendocrine tumours.

Octreotide can also be used in the treatment of acromegaly, a disorder of excessive growth hormone (GH). Octreotide, being a somatostatin analog, inhibits the release of GH from the pituitary gland through a process normally involved in negative feedback. In June 2020, Mycapssa (octreotide) was approved for medical use in the United States with an indication for the long term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide. Mycapssa is the first and only oral somatostatin analog (SSA) approved by the FDA. and sulphonylurea induced hypoglycemia in adults. It is useful in overdose management of sulfonylurea type antidiabetic medications, when recurrent or refractory to parenteral dextrose. Mechanism of action is the suppression of insulin secretion.

Octreotide is used in the palliative care setting to reduce gastrointestinal secretions, with the intention of alleviating vomiting associated with bowel obstruction.

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

The most common adverse effects are headache, hypothyroidism, cardiac conduction changes, gastrointestinal reactions (including cramps, nausea/vomiting and diarrhoea or constipation), gallstones, reduction of insulin release, hyperglycemia or sometimes hypoglycemia, and (usually transient) injection site reactions. Slow heart rate, skin reactions such as pruritus, hyperbilirubinemia, hypothyroidism, dizziness and dyspnoea are also fairly common (more than 1%). Rare side effects include acute anaphylactic reactions, pancreatitis and hepatitis. Rats which were treated by octreotide experienced erectile dysfunction in a 1998 study. A prolonged QT interval has been observed, but it is uncertain whether this is a reaction to the drug or the result of an existing illness. People with diabetes mellitus might need less insulin or oral antidiabetics when treated with octreotide, as it inhibits glucagon secretion more strongly and for a longer time span than insulin secretion.

On 15 September 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Mycapssa, intended for the treatment of adults with acromegaly. Mycapssa was approved for medical use in the European Union in December 2022.

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 meglitinide overdose. It has also been used with varying degrees of success in infants with nesidioblastosis to help decrease insulin hypersecretion. Several clinical trials have demonstrated the effect of octreotide as acute treatment (abortive agent) in cluster headache, where it has been shown that administration of subcutaneous octreotide is effective when compared with placebo. Octreotide has also been investigated in people with pain from chronic pancreatitis. 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 hepatorenal syndrome. By increasing systemic vascular resistance, these drugs reduce shunting and improve renal perfusion, prolonging survival until definitive treatment with liver transplant. Similarly, octreotide can be used to treat refractory chronic hypotension. While successful treatment has been demonstrated in case reports, larger studies have failed to demonstrate efficacy in treating chylothorax. A small study has shown that octreotide may be effective in the treatment of idiopathic intracranial hypertension.

Octreotide has been used experimentally to treat obesity, particularly obesity caused by lesions in the hunger and satiety centers of the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brain's feeding and satiety centers, respectively. The VMH is sometimes injured by ongoing treatment for acute lymphoblastic leukemia (ALL) or surgery or radiation to treat posterior cranial fossa tumors. "VMH dysfunction promotes excessive caloric intake and decreased caloric expenditure, leading to continuous and unrelenting weight gain. Attempts at caloric restriction or pharmacotherapy with adrenergic or serotonergic agents have previously met with little or only brief success in treating this syndrome."