Lypressin

(BAN, USAN, rINN)
Lypressin Chemical formula
Synonyms: L-8; Lipresina; Lipressina; Lipresszin; LVP; Lypressiini; Lypressine; Lypressinum. [8-Lysine]vasopressin; Cys-Tyr-Phe-Gln-Asn-CysPro-Lys-Gly-NH 2 cyclic (1→6) disulphide.
Cyrillic synonym: Липрессин.

💊 Chemical information

Chemical formula: C46H65N13O12S2 = 1056.2.
CAS — 50-57-7.
ATC — H01 B A03 .
ATC Vet — QH01BA03.

Description.

Lypressin is the form of vasopressin present in the posterior pituitary of pigs.

Pharmacopoeias.

US includes Lypressin Nasal Solution.

Incompatibility.

Vasopressin was shown to be physically compatible (when injected at the Y-site in an intravenous tubing set) when tested in intravenous fluids with other drugs commonly used in cardiac arrest. 1 However, tests of vasopressin with drugs commonly used in septic shock showed physical incompatibility with phenytoin (when mixed in infusion bags). 2 Precipitation has also been reported 3 with vasopressin and furosemide together in intravenous fluids (tested at the Y-site). 1. Feddema S, et al. Physical compatibility of vasopressin with medications commonly used in cardiac arrest. Am J Health-Syst Pharm 2003; 60: 1271–2. 2. Barker B, et al. Visual compatibility of vasopressin with other injectable drugs. Am J Health-Syst Pharm 2005; 62: 1969, 1975–6. 3. Faria CE, et al. Visual compatibility of furosemide with phenylephrine and vasopressin. Am J Health-Syst Pharm 2006; 63: 906–8.

💊 Units

7.7 units of lypressin are contained in about 23.4 micrograms of synthetic peptide (with albumin 5 mg and citric acid) in one ampoule of the first International Standard (1978).

💊 Adverse Effects

Large parenteral doses of vasopressin may give rise to marked pallor, pounding headache, vertigo, sweating, tremor, nausea, vomiting, diarrhoea, eructation, cramp, and a desire to defaecate; some of these effects may also occur after large intranasal doses of lypressin. In women, vasopressin may cause uterine cramps of a menstrual character. Hyponatraemia with water retention and signs of water intoxication can occur. Hypersensitivity reactions have occurred and include urticaria and bronchoconstriction. Anaphylactic shock and cardiac arrest have been reported. Vasopressin may constrict coronary arteries. Chest pain, myocardial ischaemia, and infarction have occurred following injection, and fatalities have been reported. Other cardiovascular effects include occasional reports of arrhythmias and bradycardia, as well as hypertension. Peripheral vasoconstriction has resulted in gangrene, and thrombosis as well as local irritation at the injection site may occur. Nasal congestion, irritation, and ulceration have been reported occasionally after intranasal use, usually as lypressin; systemic effects at usual intranasal doses are mostly reported to be mild.

Effects on the heart.

Arrhythmias, including ventricular tachycardia and fibrillation,1 torsade de pointes,2-4 and asystole5 are among the adverse effects of vasopressin. Paradoxical bradycardia and hypotension have also been reported.6
1. Kelly KJ, et al. Vasopressin provocation of ventricular dysrhythmia. Ann Intern Med 1980; 92: 205–6
2. Eden E, et al. Ventricular arrhythmia induced by vasopressin: torsade de pointes related to vasopressin-induced bradycardia. Mt Sinai J Med 1983; 50: 49–51
3. Stein LB, et al. Fatal torsade de pointes occurring in a patient receiving intravenous vasopressin and nitroglycerin. J Clin Gastroenterol 1992; 15: 171–4
4. Faigel DO, et al. Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. Am J Gastroenterol 1995; 90: 822–4
5. Fitz JD. Vasopressin induction of ventricular ectopy. Arch Intern Med 1982; 142: 644
6. Kraft W, et al. Paradoxical hypotension and bradycardia after intravenous arginine vasopressin. J Clin Pharmacol 1998; 38: 283–6.

Ischaemia.

Reports of ischaemia and infarction associated with vasopressin.1-10
1. Greenwald RA, et al. Local gangrene: a complication of peripheral Pitressin therapy for bleeding esophageal varices. Gastroenterology 1978; 74: 744–6
2. Colombani P. Upper extremity gangrene secondary to superior mesenteric artery infusion of vasopressin. Dig Dis Sci 1982; 27: 367–9
3. Lambert M, et al. Reversible ischemic colitis after intravenous vasopressin therapy. JAMA 1982; 247: 666–7
4. Anderson JR, Johnston GW. Development of cutaneous gangrene during continuous peripheral infusion of vasopressin. BMJ 1983; 287: 1657–8
5. Reddy KR, et al. Bilateral nipple necrosis after intravenous vasopressin therapy. Arch Intern Med 1984; 144: 835–6
6. Brearly S, et al. A lethal complication of peripheral vein vasopressin infusion. Hepatogastroenterology 1985; 32: 224–5
7. Sweren BS, Bohlman ME. Gastric and splenic infarction: a complication of intraarterial vasopressin infusion. Cardiovasc Intervent Radiol 1989; 12: 207–9
8. Maceyko RF, et al. Vasopressin-associated cutaneous infarcts, alopecia, and neuropathy. J Am Acad Dermatol 1994; 31: 111–13
9. Lin RY, et al. Vasopressin-induced amber-like skin necrosis. Dermatology 1997; 195: 271–3
10. Dunser MW, et al. Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med 2003; 31: 1394–8.

💊 Treatment of Adverse Effects

The antidiuretic effects on water retention and sodium imbalance may be treated by water restriction and a temporary withdrawal of vasopressin. Severe cases may require osmotic diuresis alone or with furosemide.

Extravasation.

Localised intravenous and intra-arterial guanethidine was used in the treatment of a patient with extravasation of vasopressin.1 The intra-arterial use of guanethidine was considered to have helped to avoid necrotic changes.
1. Crocker MC. Intravascular guanethidine in the treatment of extravasated vasopressin. N Engl J Med 1981; 304: 1430.

💊 Precautions

Vasopressin should not be used in patients with chronic nephritis with nitrogen retention. It should be avoided or given only with extreme care, and in small doses, to patients with vascular disease, especially of the coronary arteries. It should be given with care to patients with conditions which might be aggravated by water retention including asthma, epilepsy, migraine, and heart failure. Fluid intake should be adjusted to avoid hyponatraemia and water intoxication. Care is also required in hypertension or other conditions that may be exacerbated by a rise in blood pressure. Nasal absorption of vasopressin may be impaired in patients with rhinitis.

Abuse.

Vasopressin or its analogues have been abused as socalled ‘smart drugs’ for their supposed effect on memory recall and cognition.

Resistance.

Antibodies to vasopressin were detected in 6 of 28 patients being treated for diabetes insipidus, all of whom had a decrease in antidiuretic effect with previously effective argipressin or lypressin therapy;1 desmopressin and chlorpropamide remained effective in these patients. There have been reports of patients with diabetes insipidus of pregnancy unresponsive to argipressin but responsive to desmopressin.2 This was probably due to excessive placental production of vasopressinase, an enzyme which degrades argipressin.
1. Vokes TJ, et al. Antibodies to vasopressin in patients with diabetes insipidus: implications for diagnosis and therapy. Ann Intern Med 1988; 108: 190–5
2. Shah SV, Thakur V. Vasopressinase and diabetes insipidus of pregnancy. Ann Intern Med 1988; 109: 435–6.

💊 Interactions

The antidiuretic effects of vasopressins might be expected to be enhanced in some patients receiving chlorpropamide, clofibrate, carbamazepine, fludrocortisone, urea, or tricyclic antidepressants. Lithium, heparin, demeclocycline, noradrenaline, and alcohol may decrease the antidiuretic effect. Ganglion-blocking drugs may increase sensitivity to the pressor effects of vasopressins.

Cimetidine.

A report of severe bradycardia and heart block leading to asystole in a patient given combined vasopressin and cimetidine therapy.1
1. Nikolic G, Singh JB. Cimetidine, vasopressin and chronotropic incompetence. Med J Aust 1982; 2: 435–6.

💊 Uses and Administration

Vasopressin is secreted by the hypothalamus and stored in the posterior lobe of the pituitary gland. It may be prepared from the gland of mammals or by synthesis. Vasopressin has a direct antidiuretic action on the kidney, increasing tubular reabsorption of water. It also constricts peripheral blood vessels and causes contraction of the smooth muscle of the intestine, gallbladder, and urinary bladder. It has practically no oxytocic activity. Vasopressin, which is usually given parenterally or intranasally in the synthetic forms of argipressin or lypressin, is used in the treatment of cranial diabetes insipidus due to a deficiency in antidiuretic hormone. It is ineffective in nephrogenic diabetes insipidus. Argipressin has also been used in the prevention and treatment of postoperative abdominal distension, and was formerly given to remove gas in abdominal visualisation procedures. Argipressin or lypressin are used in the treatment of bleeding oesophageal varices. Argipressin may have a role in cardiopulmonary resuscitation and shock due to vasodilatation. In the treatment of cranial diabetes insipidus to control polyuria, argipressin may be given subcutaneously or intramuscularly; the dose in the UK is 5 to 20 units every 4 hours. In the USA, 5 to 10 units given 2 or 3 times daily or more has been used. Alternatively, argipressin or lypressin has been given as a nasal spray; dosage should be individually adjusted as required. A long-acting oily suspension of vasopressin tannate was formerly used by intramuscular injection in diabetes insipidus. In the initial control of variceal bleeding argipressin is given in an initial dose of 20 units in 100 mL of glucose 5% infused intravenously over 15 minutes. Lypressin has also been given for bleeding oesophageal varices. Doses for children are given under Administration in Children, below. Vasopressin has also been used as a vasoconstrictor in local anaesthetic injections.

Administration.

Results1 suggesting that although intravenous argipressin produced much higher plasma concentrations than intranasal, the latter evoked a greater CNS response.
1. Pietrowsky R, et al. Brain potential changes after intranasal vs intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans. Biol Psychiatry 1996; 39: 332–40.

Administration in children.

Although not licensed in the UK for use in children, the BNFC includes a dose for adjunctive treatment of acute massive haemorrhage of the gastrointestinal tract or oesophageal varices in patients aged from 1 month to 18 years. An initial dose of 0.3 units/kg (up to 20 units) is given intravenously over 20 to 30 minutes, followed by a continuous infusion of 0.3 units/kg per hour adjusted according to response to a maximum of 1 unit/kg per hour. If the bleeding stops the infusion is continued at the same dose for 12 hours, then gradually withdrawn over 24 to 48 hours; the maximum duration of treatment should be 72 hours. Vasopressin given by continuous intravenous infusion in an average dose of 9 milliunits/kg per hour was safe and effective in 5 children who had diabetes insipidus as a manifestation of severe brain injury.1 A dose of 1.5 to 3 milliunits/kg per hour has also been used safely for postoperative diabetes insipidus in 2 children aged 3 years and under.2 Similar initial doses of argipressin were used in 3 comatose children with cranial diabetes insipidus,3 while a published algorithm for the management of acute cranial diabetes insipidus has recommended an initial dose of vasopressin of 0.25 to 1 milliunits/kg per hour, subsequently titrated to achieve an appropriate output and specific gravity of urine, and a serum sodium value of between 140 and 145 mmol/litre.4
1. Ralston C, Butt W. Continuous vasopressin replacement in diabetes insipidus. Arch Dis Child 1990; 65: 896–7
2. McDonald JA, et al. Treatment of the young child with postoperative central diabetes insipidus. Am J Dis Child 1989; 143: 201–4
3. Lee Y-J, et al. Continuous infusion of vasopressin in comatose children with neurogenic diabetes insipidus. J Pediatr Endocrinol Metab 1995; 8: 257–62
4. Lugo N, et al. Diagnosis and management algorithm of acute onset of central diabetes insipidus in critically ill children. J Pediatr Endocrinol Metab 1997; 10: 633–9.

Advanced cardiac life support.

Vasopressin (as argipressin) may be used as an alternative to adrenaline in cardiopulmonary resuscitation. In a preliminary study argipressin 40 units by intravenous injection appeared to be of value in the treatment of cardiac arrest due to ventricular fibrillation.1 Spontaneous circulation returned in 16 of 20 patients so treated; 14 were successfully resuscitated on arrival in hospital and 8 survived to be discharged. In comparison, of 20 patients treated with 1 mg of adrenaline intravenously only 7 were resuscitated and 3 survived till discharge. However, a larger study2 found no difference between vasopressin and adrenaline in the rates of survival to hospital admission for patients with ventricular fibrillation or pulseless electrical activity, although vasopressin was associated with a higher rate of hospital admission and discharge among patients with asystole. It also found that two doses of vasopressin followed by a single dose of adrenaline resulted in a better survival rate than three doses of adrenaline. Another large study3 of patients who experienced cardiac arrest while in hospital and were treated with either vasopressin 40 units or adrenaline 1 mg, found no difference in survival to discharge from hospital. A systematic review4 of 5 trials, including these 3, found no clear advantage for the use of vasopressin over adrenaline in the treatment of cardiac arrest.
1. Lindner KH, et al. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997; 349: 535–7
2. Wenzel V, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004; 350: 105–13
3. Stiell IG, et al. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet 2001; 358: 105–9
4. Aung K, Htay T. Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Intern Med 2005; 165: 17–24.

Diabetes insipidus.

For a discussion of diabetes insipidus and its management, including reference to the use of vasopressin analogues (particularly desmopressin).

Haemorrhagic disorders.

There are reports of vasopressin being used in the management of various haemorrhagic disorders including blood loss in abortion and caesarean section1,2 and haemoptysis.3,4 Infusion of vasopressin into the superior or inferior mesenteric artery has been used in the management of lower gastrointestinal bleeding, but modern embolisation techniques may be associated with fewer complications.5 For the use of va sopressin in upper gastrointestinal variceal haemorrhage, see below.
1. Schulz KF, et al. Vasopressin reduces blood loss from secondtrimester dilatation and evacuation abortion. Lancet 1985; ii: 353–6
2. Lurie S, et al. Subendometrial vasopressin to control intractable placental bleeding. Lancet 1997; 349: 698
3. Noseworthy TW, Anderson BJ. Massive hemoptysis. Can Med Assoc J 1986; 135: 1097–9
4. Bilton D, et al. Life threatening haemoptysis in cystic fibrosis: an alternative therapeutic approach. Thorax 1990; 45: 975–6. Correction. ibid. 1991; 46: 274
5. Darcy M. Treatment of lower gastrointestinal bleeding: vasopressin infusion versus embolization. J Vasc Interv Radiol 2003; 14: 535–43.

Nocturnal enuresis.

For references to the use of the vasopressin analogue, desmopressin, in nocturnal enuresis.

Shock.

Argipressin has been reported to have beneficial vasopressor effects in the management of shock due to vasodilatation. It has been given by continuous intravenous infusion at a dose of about 2 to 6 units/hour as supplemental therapy in patients who could not be adequately managed with conventional vasopressor therapy.1,2 In a retrospective study3 vasopressin given with or without catecholamines for haemodynamic support of shock did not increase the incidence of venous thromboembolism compared with catecholamines given alone. Further reports4,5 of the benefit of vasopressin in septic shock suggest that it may be of value in reducing doses of catecholamine vasopressors.
1. Dünser MW, et al. Management of vasodilatory shock: defining the role of arginine vasopressin. Drugs 2003; 63: 237–56
2. Dünser MW, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 2003; 107: 2313–19
3. Doepker BA, et al. Thromboembolic events during continuous vasopressin infusions: a retrospective evaluation. Ann Pharmacother 2007; 41: 1383–9
4. Obritsch MD, et al. Effects of continuous vasopressin infusion in patients with septic shock. Ann Pharmacother 2004; 38: 1117–22
5. Szumita PM, et al. Vasopressin for vasopressor-dependent septic shock. Am J Health-Syst Pharm 2005; 62: 1931–6.

Variceal haemorrhage.

However, terlipressin, and more recently octreotide, have been found to have some advantages over vasopressin, including bolus dosage and fewer adverse effects, and octreotide is increasingly preferred for this purpose. Glyceryl trinitrate has been given with the aim of counteracting the adverse cardiac effects of vasopressin while potentiating its beneficial effects on portal pressure.1-4
1. Stump DL, Hardin TC. The use of vasopressin in the treatment of upper gastrointestinal haemorrhage. Drugs 1990; 39: 38–53
2. Williams SGJ, Westaby D. Management of variceal haemorrhage. BMJ 1994; 308: 1213–17
3. Sung JJY. Non-surgical treatment of variceal haemorrhage. Br J Hosp Med 1997; 57: 162–6
4. McCormack G, McCormack PA. A practical guide to the management of oesophageal varices. Drugs 1999; 57: 327–35.

💊 Preparations

USP 31: Lypressin Nasal Solution; Vasopressin Injection.

Proprietary Preparations

Austral.: Pitressin; Canad.: Pressyn; Ger.: Pitressin†; Gr.: Pitressin†; Irl.: Pitressin; NZ: Pitressin; UK: Pitressin; USA: Pitressin.
Used as an adjunct in: Thai.: Neo-Lidocaton†.
Published May 08, 2019.