Octreotide
Encyclopedia
Octreotide 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.
(FDA) has approved the usage of a salt form of this peptide, octreotide acetate
, as an injectable depot formulation for the treatment of acromegaly
, diarrhea
and flushing
episodes associated with carcinoid syndrome
, and diarrhea in patients with vasoactive intestinal peptide
-secreting tumors (VIPoma
s).
(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.
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. It 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. It has been investigated for patients with pain from chronic pancreatitis
, and it may be useful in the treatment of thymic neoplasms.
The drug has been used off-label, injected subcutaneously, 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 hepatorenal syndrome
. By increasing systemic vascular resistance, these drugs reduce shunting and improve renal perfusion, prolonging survival until definitive treatment with liver transplant.
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
.
is positive.
, cardiac conduction
changes, gastrointestinal reactions (including cramps, nausea/vomiting and diarrhea or constipation), gallstone
s, reduction of insulin
release, hyperglycemia
or hypoglycemia
, and (usually transient) injection site reactions. Slow heart rate, skin reactions such as 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 which 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' illnesses.
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.
It has also been shown to produce analgesic
effects, most probably acting as a partial agonist
at the mu opioid receptor
.
, 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; besides being an antiparkinsonian, bromocriptine is also used for the treatment of acromegaly.
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
that mimics natural somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
pharmacologically, though it is a more potent inhibitor of growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
, glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
, and insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer.
Approved uses
The Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) has approved the usage of a salt form of this peptide, octreotide acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...
, as an injectable depot formulation for the treatment of acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
and flushing
Flushing (physiology)
For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
episodes associated with carcinoid syndrome
Carcinoid syndrome
Carcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction...
, and diarrhea in patients with vasoactive intestinal peptide
Vasoactive intestinal peptide
Vasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...
-secreting tumors (VIPoma
VIPoma
A VIPoma is a rare endocrine tumor, usually originating in the pancreas, that produces vasoactive intestinal peptide ....
s).
Radiolabelling
Octreotide is used in nuclear medicine imaging by labelling with indium-111 (Octreoscan) to noninvasively image neuroendocrine and other tumours expressing somatostatin receptors. More recently, it has been radiolabelled with gallium-68, enabling imaging with positron emission tomographyPositron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET), which provides higher resolution and sensitivity.
Octreotide can also be labelled with a variety of radionuclides, such as yttrium-90
Yttrium-90
Yttrium-90 is a medically significant isotope of yttrium.It emits beta rays of 2.3 MeV.Yttrium-90 is a decay product of Strontium-90 which makes up about 5% of the Nuclear daughter isotopes when Uranium is fissioned....
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-labelOff-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
for the treatment of severe, refractory diarrhea from other causes. It is used in toxicology for the treatment of prolonged recurrent hypoglycemia after sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
and possibly meglitinides overdose. It has also been used with varying degrees of success in infants with nesidioblastosis
Nesidioblastosis
Nesidioblastosis is beta cell hyperplasia, consisting of the proliferation of islet cells from pancreatic ducts. It is a cause of hypoglycemia and hyperinsulinemia in a number of infants and newborns. Recently, this condition has been recognized in adolescents and adults and occurs in 5% of...
to help decrease insulin hypersecretion.
In patients with suspected esophageal varices
Esophageal varices
In medicine , esophageal varices are extremely dilated sub-mucosal veins in the lower esophagus...
, octreotide can be given to help decrease bleeding. It has been investigated for patients with pain from chronic pancreatitis
Chronic pancreatitis
Chronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption....
, and it may be useful in the treatment of thymic neoplasms.
The drug has been used off-label, injected subcutaneously, in the management of hypertrophic pulmonary osteoarthropathy
Hypertrophic pulmonary osteoarthropathy
Hypertrophic pulmonary osteoarthropathy is a medical condition combining clubbing and periostitis of the long bones of the upper and lower extremities. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen...
(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
Midodrine
Midodrine is a vasopressor/antihypotensive agent. Midodrine was approved in the United States by the Food and Drug Administration in 1996 for the treatment of orthostatic hypotension...
to partially reverse peripheral vasodilation in the hepatorenal syndrome
Hepatorenal syndrome
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
. By increasing systemic vascular resistance, these drugs reduce shunting and improve renal perfusion, prolonging survival until definitive treatment with liver transplant.
While successful treatment has been demonstrated in case reports, larger studies have failed to demonstrate efficacy in treating chylothorax
Chylothorax
A chylothorax is a type of pleural effusion. It results from lymphatic fluid accumulating in the pleural cavity.-Causes:...
.
A small study has shown that octreotide may be effective in the treatment of idiopathic intracranial hypertension
Idiopathic intracranial hypertension
Idiopathic intracranial hypertension , sometimes called by the older names benign intracranial hypertension or pseudotumor cerebri , is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases...
.
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 analysisRisk-benefit analysis
Risk–benefit analysis is the comparison of the risk of a situation to its related benefits. Exposure to personal risk is recognized as a normal aspect of everyday life. We accept a certain level of risk in our lives as necessary to achieve certain benefits. In most of these risks we feel as though...
is positive.
Adverse effects
The most frequent adverse effects (more than 10% of patients) are headache, hypothyroidismHypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, cardiac conduction
Electrical conduction system of the heart
The normal intrinsic electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node through both atria and forward to the Atrioventricular Node. Normal/baseline physiology allows further propagation from the AV node to the ventricle or Purkinje Fibers...
changes, gastrointestinal reactions (including cramps, nausea/vomiting and diarrhea or constipation), gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s, reduction of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
release, hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
or hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, and (usually transient) injection site reactions. Slow heart rate, skin reactions such as pruritus, hyperbilirubinemia, hypothyreosis, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
and dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
are also fairly common (more than 1%). Rare side effects include acute anaphylactic reactions, pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
and hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
.
Some studies reported alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
in patients who were treated by octreotide. Rats which were treated by octreotide experienced erectile disfunction in a 1998 study.
A prolonged QT interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
has been observed in patients, but it is uncertain whether this is a reaction to the drug or part of the patients' illnesses.
Pharmacokinetics
Octreotide is absorbed quickly and completely after subcutaneousSubcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...
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 gastrinGastrinIn humans, gastrin is a peptide hormone that stimulates secretion of gastric acid by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the antrum of the stomach, duodenum, and the pancreas...
, cholecystokininCholecystokininCholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein...
, glucagonGlucagonGlucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
, growth hormoneGrowth hormoneGrowth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
, insulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, secretinSecretinSecretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn...
, pancreatic polypeptidePancreatic polypeptidePancreatic polypeptide is a polypeptide secreted by PP cells in the endocrine pancreas predominantly in the head of the pancreas. It consists of 36 amino acids and has molecular weight about 4200 Da....
, TSHTSHTSH may refer to:* Tanzanian shilling, the currency of Tanzania* Thyroid-stimulating hormone, a hormone synthesized and secreted by thyrotrope cells* Tshiuetin Rail Transportation, a Canadian railway between Labrador and Quebec...
, and vasoactive intestinal peptideVasoactive intestinal peptideVasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...
, - reduce secretion of fluids by the intestine and pancreasPancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
, - reduce gastrointestinal motility and inhibit contraction of the gallbladderGallbladderIn vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated....
, - inhibit the action of certain hormones from the anterior pituitaryAnterior pituitaryA major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
, - cause vasoconstrictionVasoconstrictionVasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
in the blood vessels, and - reduce portal vessel pressures in bleeding varices.
It has also been shown to produce analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
effects, most probably acting as a partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
at the mu opioid receptor
Mu Opioid receptor
The μ-opioid receptors are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. They are also referred to as μ opioid peptide receptors. The prototypical μ receptor agonist is the opium alkaloid morphine; μ refers to morphine...
.
Interactions
Octreotide can reduce the intestinal resorption of ciclosporinCiclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, possibly making it necessary to increase the dose. Patients with diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
might need less insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
or oral antidiabetics when treated with octreotide. The bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
of bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
is increased; besides being an antiparkinsonian, bromocriptine is also used for the treatment of acromegaly.