Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
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PMID:Debut of a somatostatin analog: octreotide in review. 255 39

We have studied the metabolic and hormonal responses to surgery, and the pain scores and analgesic requirements in 24 patients undergoing cholecystectomy, allocated randomly to three groups to receive either general anaesthesia alone, or general anaesthesia with extradural diamorphine 0.1 mg kg-1, or general anaesthesia with extradural somatostatin to a total dose of somatostatin 3 mg. The only significant effect of extradural diamorphine was a decrease in the glucose response to surgery. Somatostatin 3 mg by the extradural route caused a significant increase in the concentration of circulating somatostatin which resulted in a significant decrease in plasma growth hormone and insulin after 60 min of surgery, together with an increase in plasma glycerol concentration. Patients in the diamorphine group required significantly less i.v. analgesia in the postoperative period than the other two groups. Intraoperative somatostatin failed to provide any postoperative analgesia.
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PMID:Hormonal and metabolic responses to cholecystectomy: comparison of extradural somatostatin and diamorphine. 197 53

Connective tissue cells proliferate actively when cultured in the presence of serum. Platelet-derived growth factor (PDGF), a basic protein of relative molecular mass approximately 30,000, has been identified as the major serum mitogen for these cells; its main physiological/pathophysiological role may be to initiate wound healing in connection with tissue injury. However, growth of cultured cells is also influenced by several other factors, including epidermal growth factor, fibroblast growth factor, insulin and somatomedins. Furthermore, Rozengurt and Sinnett-Smith recently showed that bombesin, a neuroendocrine peptide isolated from frog skin, stimulates DNA synthesis and cell division in cultures of a specific subtype of 3T3 cells. Substance P and substance K (also known as neurokinin A or neuromedin L) are mammalian peptides belonging to the tachykinin family. Substance P has been studied extensively; it is distributed widely throughout the central and peripheral nervous system, including primary sensory neurones, and can be released in the periphery from axon collaterals of stimulated pain fibres and contribute to the inflammatory response. Substance K is a member of the tachykinin family isolated from mammalian spinal cord; Nawa et al. determined the primary structure of two types of substance P precursors, one of which contained a sequence homologous to substance K, as well as the sequence of substance P. We report here that substance P and substance K stimulate DNA synthesis in cultured arterial smooth muscle cells and human skin fibroblasts, and that this stimulation is inhibited by the substance P-antagonist spantide.
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PMID:Stimulation of connective tissue cell growth by substance P and substance K. 258 Nov 42

The management of chronic pancreatitis continues to achieve only limited success. A lack of understanding of the basic pathogenic mechanism of this disease limits our therapy to treatment of symptoms, sequelae, and complications. The diagnosis of chronic pancreatitis usually is based on a history of classic pain plus some objective findings of pancreatic disease. Imaging techniques, such as ultrasonography or CT, are helpful in defining the size of the gland and the presence of masses and collections of fluid. Endoscopic pancreatography, however, remains the most helpful tool for diagnosis. The information that it provides about the pancreatic ductal system can help in selecting a procedure that achieves the best result with the lowest morbidity and mortality. The principle to follow in the surgical management of this condition is to tailor the procedure in each patient to preoperative clinical information, information provided by pancreatography, operative findings, exocrine and endocrine status of the patient, presence or absence of drug addiction and alcoholism, and the personality of the patient as well as his or her ability to manage the possible metabolic complications of surgery. Although management of pain is the main goal, the morbidity and late mortality that can result from different procedures must be a major consideration in selecting therapy. Pancreaticojejunostomy is the procedure of choice at this time for patients with a dilated pancreatic duct sphincterotomy or sphincteroplasty for the occasional patient with proved ampullary obstruction of the pancreatic duct, and internal drainage for pseudocyst. Different degrees of pancreatic resection are indicated for patients with severe disease and small pancreatic ducts, in patients in whom decompressive operations have failed, in patients with lateralized disease to the head or tail of the gland, in some instances of pseudocyst or pancreatic fistulas, and for some patients when cancer cannot be ruled out. Attempts are being made to improve the limited results of our current therapy. Endoscopic occlusion of the pancreatic duct, pancreatic segmental autotransplantation, islet cell autoimplantation, use of the pyloric-preserving operation, and use of continuous subcutaneous insulin infusion are being tried. Further experience with these techniques is required to determine their value in the management of patients with chronic pancreatitis.
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PMID:Surgical management of chronic pancreatitis. 258 27

A study was performed to assess the effect of xylazine HCl (0.1 mg/kg of body weight, IV) in heifers maintained at thermoneutrality (18 C, 42% humidity) or under heat stress (33 C, 63% humidity) conditions. Xylazine caused 50 and 70% decreases in serum insulin concentrations in the thermoneutral and heat-stressed heifers, respectively. Xylazine-induced hypoinsulinemia was associated with hyperglycemia. In the thermoneutral group, serum glucose concentrations increased from a basal concentration of 75 mg/dl to 150 mg/dl after 15 minutes. In the heat stress group, the serum glucose concentration increased from 65 mg/dl to 105 mg/dl. Hyperglycemia peaked at 2 hours and remained high for 6 hours after xylazine administration. Heat-stressed heifers took a longer time (107 minutes) to stand than did heifers under thermoneutral conditions (41 minutes). The time to regain sensation to pain was significantly prolonged in heat-stressed heifers. Xylazine had no effect on body temperature and respiration rate in heifers under the thermoneutral condition, whereas it markedly induced hyperthermia and suppressed respiration rate in the heat-stressed heifers. Furthermore, the pulse rate was slightly decreased in thermoneutral heifers and was markedly decreased in the heat-stressed heifers.
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PMID:Effect of xylazine in heifers under thermoneutral or heat stress conditions. 264 15

Twenty-five elderly patients with peripheral vascular disease and intermittent claudication were prospectively followed during a six-month session of physical training. Neuroendocrine and metabolic patterns as well as effects on walking performance were assessed during the training period. At the initial evaluation there was an inverse association between walking distance and serum cortisol and blood glucose levels. The walking distance increased during the training period. A positive effect on glucose homeostatis was seen with decreased basal fructosamine levels after training. During physical exercise a decrease in insulin and an increase in growth hormone was seen. Changes in growth hormone were, in contrast to insulin, more related to the pain level perceived than to the work load imposed. Apart from the marked effects on physical performance the results of the study suggest an improvement of hormonal and metabolic balance after physical training. This regularly applied exercise program improved the health status of rather old people.
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PMID:Longterm neuroendocrine and metabolic effects of physical training in intermittent claudication. 265 78

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects and drug interactions, dosage, availability and cost, and indications for use of octreotide, a new synthetic analogue of the peptide hormone somatostatin (SS), are reviewed. Like SS, octreotide suppresses secretion of pituitary growth hormone (GH) and thyrotropin and decreases release of a variety of pancreatic islet cell hormones including insulin, glucagon, and vasoactive intestinal peptide (VIP). Octreotide also reduces splanchnic blood flow, gastric acid secretion, GI motility, and pancreatic exocrine function and alters the absorption of water, electrolytes, and nutrients from the GI tract. The elimination half-life of i.v. octreotide is 72-98 minutes, compared with 2-3 minutes for i.v. SS. Usual administration of octreotide is by the i.v. or s.c. route. Octreotide has been studied in the treatment of hormone-secreting pituitary tumors and pancreatic islet cell tumors. Octreotide therapy lowers GH secretion and improves clinical symptoms in patients with acromegaly and may suppress clinical symptoms to a greater degree than bromocriptine. Patients with carcinoid syndrome and VIP-secreting tumors (vipomas) have had substantial improvement in clinical symptoms with administration of octreotide. This agent does not appear to be effective in the treatment of nonvariceal upper GI bleeding and acute pancreatitis; its relative usefulness in the treatment of variceal bleeding is not established. Adverse effects associated with octreotide therapy generally have been mild, including pain or burning at the injection site, abdominal pain, and diarrhea. Octreotide has been shown to interfere with absorption of oral cyclosporine. Standard initial therapy is octreotide acetate 50-100 micrograms s.c. every 8-12 hours, with titration based on clinical and biochemical effects. Up to 3000 micrograms/day of octreotide acetate has been administered to patients with acromegaly without serious adverse effect. Octreotide is marketed under the brand name Sandostatin and is available in 1-mL ampuls containing 50, 100, and 500 micrograms of octreotide acetate. Because the conditions for which octreotide appears to be most effective are uncommon, the drug should be considered for addition to the formulary in tertiary-care institutions only; addition of octreotide to the formulary of a community hospital is probably unnecessary. The synthetic analogue octreotide is longer acting and more specific in pharmacologic action than SS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Octreotide, a new somatostatin analogue. 265 11

The French Sandostatin/Acromegaly Study Group performed a multicentric, prospective, open-label trial of incremental doses with the aim of obtaining the best antisecretory effect. Forty-two patients (24 women, 18 men) aged 22-71 years were involved, either after unsuccessful surgery and/or radiotherapy (30 patients), or as primary treatment (12 patients). Doses were increased from 3 x 100 to 3 x 500 micrograms/day, according to the results of hormonal investigations (GH profiles and Sm-C) performed each month and for each dose, and tolerability. Four patients dropped out because of major digestive troubles. Recurrent pain at the injection site and minor gastrointestinal disorders were noted in some patients. Asymptomatic gallstones appeared in 4 patients. Carbohydrate tolerance and insulin secretion (determined by diurnal plasma glucose and insulin profiles) were not significantly altered by the various SMS doses. Clinical improvement was determined by the scoring of the symptoms. Mean plasma GH concentrations were significantly reduced for each SMS dose, compared to pretreatment values. Fifteen patients obtained 75% of GH values less than or equal to 2 micrograms/l. In 9 patients the highest dose failed to bring GH below 10 micrograms/l. Sm-C normalized in 17/31 patients. After 6 months of treatment a tumor reduction of 20-50% was found in 7 patients and greater than 50% in 5 patients. We conclude that (1) the tolerability of SMS is compatible with long-term treatments; (2) clinical improvement and biological criteria of efficacy are obtained in 3/4 acromegalic patients treated by SMS, and that (3) some patients are resistant to SMS and the increase in the dose does not improve the result.
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PMID:Experience of a six-month treatment with sandostatin at increasing doses in acromegaly. 265 68

With the ever-increasing population of cigarette smokers, the potential for cigarette smoke to affect drug therapy both pharmacokinetically and pharmacodynamically is significant. The overriding pharmacokinetic effect is increased drug metabolism through the induction of liver enzymes. The constituents of tobacco smoke, primarily nicotine, have their own pharmacological effects which may potentiate or antagonise the desired pharmacological effect of a particular drug, thereby affecting its efficacy. Furthermore, end-organ responsiveness may also be altered by tobacco. These latter 2 aspects constitute altered clinical pharmacodynamics. Approximately 30 drugs have been evaluated in terms of cigarette smoking. Induction of liver enzymes has been shown to increase the metabolism of imipramine, meprobamate, oestrogens, pentazocine, phenylbutazone, theophylline and warfarin. Nicotine has been shown to inhibit diuresis, alter ulcer healing, impair subcutaneous absorption, affect protein binding and stimulate catecholamine release; these effects have been evaluated in terms of therapy with frusemide (furosemide), histamine H2-antagonists, insulin, lignocaine (lidocaine) and beta-blockers, respectively. The interactions have not been correlated with clinical significance in all cases. Diminished end-organ responsiveness may account for reduced drowsiness in smokers receiving chlorpromazine and benzodiazepines, compared with non-smokers. Smoking has been associated with diminished pain tolerance, requiring increased dosages of morphine, pethidine (meperidine) and propoxyphene. Enzyme-inducers such as carbamazepine, phenytoin and phenobarbitone appear to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already maximally stimulated. Codeine, corticosteroids and nortriptyline do not appear to be affected by cigarette smoke. The bioavailability of glutethimide is higher in smokers, but this has not been associated with greater efficacy. The effect of smoking on paracetamol (acetaminophen) has been variable, depending on the extent of smoking, and does not appear to be of clinical significance.
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PMID:Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics. 267 8

Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life-threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin-dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief.
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PMID:Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. 268 36


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