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At least 19 recordsLinked to original sources

Human pain thresholds after the application of lypressin, a vasopressin analogue.

Recent animal studies indicate that vasopressin has analgetic properties. The aim of this study was to find out if lypressin, a vasopressin analogue, produces analgesia in man. The effect of i.n. lypressin (5 and 10 I.U.) on experimental pain was tested in healthy humans. The lower dose proved high enough to produce a significant antidiuretic effect. Lypressin did not have any marked analgetic effect at these doses either on ischaemic, cutaneous thermal, or dental pain. The results indicate that lypressin cannot be used for pain relief in man at doses low enough not to produce a hazardous water retention.

Administration, Intranasal↗

[Influence of antianginal drugs on Lypressin induced T-wave enhancement in the electrocardiogram of the rat].

Lypressin enhances the T-wave in the ECG of the anesthetized Sprague-Dawley rat and this has been used in screening for antianginal activity. After oral administration the durations of action of the organic nitrates, glyceryl trinitrate, isosorbide dinitrate, glyceryl 1,2-dinitrate, glyceryl 1,3-dinitrate and of SIN-1 (3-morpholinosydnonimine), molsidomine and nicorandil were shorter than those of verapamil and nifedipine. The sequence of the durations of action of the substances examined was the same in the rat as in man.

Administration, Oral↗

The effect of 6-hydroxydopamine and some hypotensive drugs on lypressin induced hypertension in rats.

Intracerebroventricular injection of 6-hydroxydopamine (6-OH-DA) prevented the development of the lypressin (LVP)-induced hypertension. Administration of 6-OH-DA to hypertensive rats significantly decreased, but did not normalize, blood pressure. A fourteen-day treatment with clonidine, guanethidine, reserpine, dihydralazine, propranolol and furosemide produced a transient decrease in blood pressure in LVP-hypertensive rats. Eight weeks after the withdrawal of hypotensive drugs blood pressure again reached the value corresponding to that in untreated LVP-hypertensive rats.

Animals↗

Hemodynamic effects of lysine-vasopressin in orthostatic hypotension.

Previous investigations have demonstrated that the postural stimulation of arginine vasopressin (AVP) release is reduced in patients with Shy-Drager syndrome. We studied the effects of lypressin nasal spray on hemodynamic parameters in ten patients with chronic orthostatic hypotension. Heart rate, blood pressure, and stroke volume were measured at 0 degrees, 45 degrees and 70 degrees tilt before and one-half hour after two nasal sprays (four United States Pharmacopeia posterior pituitary pressor units, 7.4 micrograms) of lypressin. Lypressin did not significantly alter the effect of tilt on heart rate, stroke volume, and cardiac output but increased the blood pressure and total peripheral resistance. AVP analogues should be tested for treating chronic postural hypotension.

Administration, Intranasal↗

Treatment of diabetes insipidus with DDAVP.

The treatment of a patient with diabetes insipidus (DI) is described, and the general treatment of the syndrome is reviewed. The patient was a 16-year-old male who had experienced pain, inflammation and tenderness in the left gluteal region owing to an abcess at the site of intramuscular injection of vasopressin tannate in oil (VTO). (He had been diagnosed as having DI at age 8. Since then, he had been maintained on VTO, lypressin and posterior pituitary snuff.) After the abscess healed during hospital treatment, VTO was stopped and the patient's urinary output increased sharply; urine specific gravity and osmolarity decreased correspondingly. Three days after stopping VTO, the investigational drug, 1-deamino-8-D-arginine vasopressin (DDAVP), was begun at 10 microgram every 12 hours. The dose was eventually increased to 20 microgram every 12 hours, and the patient was discharged on this regimen which controlled his urine output, specific gravity and osmolarity. Other treatments reviewed include antidiuretic-hormone-replacement agents (vasopressin, lypressin) and drugs used to potentiate low ADH levels (chlorpropamide, clofibrate and carbamazepine).

Adolescent↗

Terlipressin: vasopressin analog and novel drug for septic shock.

OBJECTIVE: To review and assess available literature on chemistry, pharmacology, pharmacodynamics, pharmacokinetics, clinical studies, adverse events, drug interactions, and dosing and administration of terlipressin in septic shock. DATA SOURCES: A literature search of MEDLINE (1966-September 2006), International Pharmaceutical Abstracts (1970-September 2006), and Cochrane database (third quarter 2006) was conducted, using key terms of terlipressin, lypressin, triglycyl-lysine vasopressin, hemodynamic support, septic shock, vasopressor, and V1 receptor agonist. Bibliographies of relevant articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Available English-language literature, including abstracts, animal studies, preclinical studies, clinical trials, and review articles, were examined. DATA SYNTHESIS: Because of potentially favorable pharmacokinetics versus vasopressin and limited availability of vasopressin in some countries, the effects of terlipressin, a vasopressin analog, have been studied recently for the treatment of septic shock. When administered as a 1-2 mg intravenous dose in patients with septic shock, terlipressin increases mean arterial pressure, urine output, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work index while decreasing heart rate, cardiac output, lactate, and oxygen delivery and consumption index. It is unclear whether lower doses of terlipressin would produce a similar vasopressor response with fewer cardiopulmonary effects and whether the effects of the drug on oxygen transport indices are detrimental. CONCLUSIONS: Terlipressin is a promising investigational medication for treatment of septic shock. Small trials have shown terlipressin to have favorable effects on hemodynamics in patients with septic shock refractory to conventional vasopressor treatment. It should be used with extreme caution in patients with underlying cardiac or pulmonary dysfunction. Further studies are needed to verify safety, efficacy, and dosing of terlipressin in patients with septic shock, and its use cannot be recommended in lieu of vasopressin at this time.

Animals↗

Simulation of the fluid retention effects of a vasopressin analog using the Guyton model of circulation.

Fluid-loading (FL) consisting of water and salt tablets equivalent of 32 oz of isotonic saline is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during Shuttle reentry. However, the effectiveness of this countermeasure has been observed to decrease with the duration of space flight. Possible ways to improve fluid retention and thus the effectiveness of FL include use of analogs of vasopressin such as lypressin (LVP). This study used a computer simulation approach to analyze the potential benefits on fluid retention with LVP administered before FL.

Blood Volume↗

Altered renal handling of electrolytes in a child with central diabetes insipidus (CDI).

A 12-year-old female child, with a history of polyuria and polydipsia of about three years duration, was admitted to Ethio-Swedish Paediatric Hospital, in Addis Abeba. Urine output in 24 hours averaged 5-6 litres, with a frequency of 15 times during the day and 7-8 times during the night. Random urine analysis showed an osmolality of 60 mOsm/kg, Na+ 27.1 mmol/L and K+ was 7.6 mmol/L. Basal plasma osmolality was 313 mOsm/kg with Na+ being 156 mmol/L and K+ 4.06 mmol/L. Water deprivation for nine hours failed to produce a concentrated urine, which was only 138 mOsm/kg at the end of the test, with a corresponding plasma osmolality of 336 mOsm/kg. After nine hours of water deprivation, urine Na+ increased from 27.1 to 37.3 mmol/L while K+ increased from 7.1 to 18.7 mmol/L. Lypressin, a vasopressin analogue, at a concentration of 0.3 IU/kg injected intramuscularly, resulted in a marked increase in urine osmolality to 586 mOsm/kg within two hours, associated with relief of symptoms. Urinary excretion of K+ was markedly increased during the vasopressin test while Na+ excretion was little affected. A case of central diabetes insipidus of undefined etiology is presented and the possibility of altered renal handling of electrolytes and an abnormal response to vasopressin in such cases is noted. The problem of management and the currently available treatment options are summarized.

Child↗

SK&F 105494, a V2-vasopressin receptor antagonist, blocks oxytocin receptors in porcine myometrium.

AIM: To study the effects of SK & F 105494 (SK & F), a V2-vasopressin receptor antagonist, on lypressin (Lyp)- and oxytocin (Oxy)-induced increases in myometrial contractility. METHODS: Uterine strips isolated from sows in the luteal phase of the estrous cycle were used to study the contractility. The receptor binding assays were performed to study the Oxy receptor blocking activity. RESULTS: Lyp and Oxy caused a concentration-dependent increase in myometrial contractility with EC50 of 50 +/- 14 nmol.L-1 and 170 +/- 32 pmol.L-1, respectively. SK & F 30-300 nmol.L-1 antagonized the contractile effects of Lyp and Oxy in a concentration-dependent manner. When the concentration-dependent inhibition of [3H] Oxy binding by SK & F was compared with Lyp and L-366948 [(cyclo-(L-Pro-D-2-naphthyl-Ala-L-lle-D-pipecolic acid-L-pipecolic acid-D-His)], a potent antagonist specific for Oxy receptors, the Ki values for SK & F, Lyp, and L-366948 were 1.73 +/- 0.32, 14.36 +/- 1.73, and 1.79 +/- 0.35 nmol.L-1, respectively. CONCLUSION: SK & F has a potent Oxy receptor blocking activity in addition to its known V2-receptor blocking activity.

Animals↗

Biodegradation of and tissue reaction to 50:50 poly(DL-lactide-co-glycolide) microcapsules.

The biodegradation of the copolymer 50:50 poly(DL-lactide-co-glycolide)-lypressin microcapsules was studied by light and electron microscopic methods and 14C release. Intramuscular injection sites of microcapsules in rats were studied by dissecting and conventional light microscopy as well as scanning (SEM) and transmission electron microscopy. A minimal localized acute myositis was seen initially at the injection sites. By Day 4, a few small foreign body giant cells were present participating in the minimal foreign body response. Later the inflammatory cells decreased and the individual microcapsules were walled off by immature fibrous connective tissue and large syncytial foreign body giant cells. By Day 35, definitive changes in some microcapsules, consisting of a granular and slightly eroded appearance of the internal matrix, were seen by SEM. By Day 42, the outer rims of the microcapsules were extensively eroded. At Day 56, the inflammatory and connective tissue reactions were almost completely resolved and biodegradation continued so that only remnant pieces of the microcapsules were present at Day 63. The morphologic picture correlated well with loss of 14C radioactivity, which could no longer be detected at the injection sites on Day 56. Phagocytosis did not seem to be an important factor in the biodegradation.

Animals↗

Quantitative analysis of nonapeptides in pharmaceutical dosage forms by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method is described for determining oxytocin, lypressin and other nonapeptides and their by-products in liquid and solid pharmaceutical dosage forms. The use of injection volumes up to 750 microliter permits accurate determination of, e.g., oxytocin in injection solutions containing only 1 I.U. (international unit) per ml. Reproducibilities between 1.0 and 1.5% (relative S.D) have been obtained for liquid dosage forms and up to 3% (relative S.D.) for tablets. The correlation between results obtained by bioassay and by the proposed method is highly significant and suggests the use of HPLC as an alternative technique for stability and content-uniformity tests on dosage forms and concentrates.

Animals↗

Safety and tolerability of treatments for allergic rhinitis in children.

Allergic rhinitis is a common condition in adults and children and can have a large impact on patients' health and quality of life. The aim of current allergic rhinitis therapies is to treat the subjective symptoms and to improve objective measures of the disease. Of the available treatment options for paediatric allergic rhinitis, the newer oral antihistamines and intranasal corticosteroids are first-line treatments.First-generation antihistamines are associated with unwanted adverse effects such as cardiotoxicity, sedation and impairment of psychomotor function. Despite results from studies using first-generation antihistamines demonstrating impairment of cognitive and academic function in children, many of these agents are still commonly given to patients. The newer antihistamines, developed with the aim of being more specific for the histamine H(1) receptor and of overcoming these adverse effects, are the medication of choice in patients with mild intermittent allergic rhinitis. For children <12 years of age, three newer oral antihistamines are currently available: cetirizine, loratadine and fexofenadine. A lack of adverse effects with these antihistamines has been demonstrated in children using EEG and psychomotor performance tests, and in clinical studies. However, issues of receptor selectivity and the potential for CNS adverse effects still remain, and further studies are warranted.Intranasal corticosteroids are the most effective anti-inflammatory agents used for the treatment of paediatric allergic rhinitis; however, the safety of these compounds remains controversial. The safety implications associated with corticosteroids are long-term, dose-related systemic effects, such as suppression of adrenocortical function, growth and bone metabolism, and the extent of these effects is influenced by a number of factors including corticosteroid type, pharmacokinetic profile, mode of delivery and delivery device. Topical corticosteroids were introduced to reduce the systemic effects seen with the long-term use of oral agents. The intranasal corticosteroids currently available for the treatment of paediatric allergic rhinitis - beclometasone, budesonide, flunisolide, fluticasone propionate, mometasone and triamcinolone - have short half-lives and rapid first-pass hepatic metabolism; however, their pharmacokinetics vary in terms of systemic absorption, potency, binding affinity, lipophilicity, volume of distribution, and half-life. A number of studies - utilising hypothalamic-pituitary-adrenal axis function tests such as plasma cortisol levels, 24-hour urinary-free cortisol tests; stimulation tests with corticotropin (adrenocorticotropic hormone), lypressin, and corticotropin-releasing hormone; and growth assessment studies using knemometry and stadiometry - have indicated that these intranasal corticosteroids are well-tolerated in paediatric patients and do not significantly affect growth. The wealth of clinical data and the recommendations from evidence-based guidelines suggest that both antihistamines and intranasal corticosteroids have good safety profiles in children. Nevertheless, growth should be regularly monitored in children receiving intranasal corticosteroids. Other treatments such as immunotherapy, local chromones and decongestants can also be beneficial in managing paediatric allergic rhinitis, and therapies should be considered on an individual basis.

Administration, Intranasal↗

Computer simulation of the effect of dDAVP with saline loading on fluid balance after 24-hour head-down tilt.

Fluid loading (FL) before Shuttle reentry is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during reentry and postflight. The fluid load consists of water and salt tablets equivalent to 32 oz (946 ml) of isotonic saline. However, the effectiveness of this countermeasure has been observed to decrease with the duration of spaceflight. The countermeasure's effectiveness may be improved by enhancing fluid retention using analogs of vasopressin such as lypressin (LVP) and desmopressin (dDAVP). In a computer simulation study reported previously, we attempted to assess the improvement in fluid retention obtained by the use of LVP administered before FL. The present study is concerned with the use of dDAVP. In a recent 24-hour, 6 degree head-down tilt (HDT) study involving seven men, dDAVP was found to improve orthostatic tolerance as assessed by both lower body negative pressure (LBNP) and stand tests. The treatment restored Luft's cumulative stress index (cumulative product of magnitude and duration of LBNP) to nearly pre-bedrest level. The heart rate was lower and stroke volume was marginally higher at the same LBNP levels with administration of dDAVP compared to placebo. Lower heart rates were also observed with dDAVP during stand test, despite the lower level of cardiovascular stress. These improvements were seen with only a small but significant increase in plasma volume of approximately 3 percent. This paper presents a computer simulation analysis of some of the results of this HDT study.

Computer Simulation↗

Neurosarcoidosis. A report of 5 cases.

Neurological involvement in sarcoidosis occurs in about 5% of cases, and both the central and peripheral nervous systems may be affected. In the majority of patients, characteristic features of the disease are present in other systems. Five cases of neurosarcoidosis are described in which serious neurological involvement was the presenting manifestation of the disease. The chest radiographs were abnormal in all patients and this drew attention to the diagnosis. Evidence of sarcoid was obtained from biopsy specimens in each case; in 4 from lymph nodes and in 1 from a transbronchial biopsy specimen. All patients were treated with prednisone, although in 2 the dose had to be reduced because of side-effects and azathioprine was introduced. All became asymptomatic; in 2 cases therapy was withdrawn while in the other 3 maintenance therapy was necessary, 2 requiring replacement thyroxine and lypressin.

Adult↗

Vasopressin modulation of peritoneal, lymphatic, and plasma drug exposure following intraperitoneal administration.

i.p. administration of cytotoxic drugs for the treatment of regionally confined cancers results in a greater total drug exposure [area under the concentration x time curve (AUC)] for the peritoneal fluid and regional lymphatics than for plasma. We sought to augment the relative advantage of i.p. administration further through modulation of peritoneal clearance by reduction in splanchnic blood flow. Pigs were treated with 5-fluorouracil, etoposide (VP-16), and carboplatin (CBDCA) alone by the i.p. route or with the same drugs in combination with i.v. lypressin, a synthetic vasopressin analogue, which reduces splanchnic blood flow. Drug concentrations in peritoneal fluid, plasma, and thoracic duct lymph were monitored over the ensuing 6 h. The pharmacokinetics of 5-fluorouracil were not altered by vasopressin; however, vasopressin increased the peritoneal fluid:plasma AUC ratio for CBDCA from 30.6 +/- 5.6 to 70. 6 +/- 7.4 (P < 0.01) and increased the lymph:plasma AUC ratio from 1.1 +/- 0.4 to 2.6 +/- 0.22 (P < 0.05). In the case of VP-16, vasopressin increased the peritoneal fluid:plasma AUC ratio from 129 +/- 35 to 350 +/- 76 (P < 0.05) and the lymph:plasma AUC ratio from 2.1 +/- 0.6 to 10.6 +/- 3.5 (P < 0.05). Concurrent i.v. administration of vasopressin can increase the pharmacokinetic advantage of the i.p. route of administration of CBDCA and VP-16 markedly in the pig model. These data suggest that the strategy of concurrent i.p. administration of CBDCA or VP-16 plus an agent that reduces splanchnic blood flow may increase the dose intensity in the abdominal cavity and intraabdominal lymphatic tissue substantially without increasing systemic toxicity.

Animals↗