Morphine histamine release

Therapeutic doses of morphine cause dilation of cutaneous blood vessels. The skin of the face, neck, and upper thorax frequently becomes flushed. These changes may be due in part to the release of histamine and may be responsible for the sweating and pruritus that occasionally follow the systemic administration of morphine. Histamine release probably accounts for the urticaria commonly seen at the site of injection, which is not mediated by opioid receptors and is not blocked by naloxone. It is seen with morphine and meperidine but not with oxymorphone, methadone, fentanyl, or sufentanil. 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Opioids. Reactions to morphine, codeine phosphate, meperidine, fentanyl and its derivatives are uncommon. Because of their direct histamine-releasing properties, especially regarding morphine and codeine, distinction between anaphylaxis and non-immune-mediated histamine release is not always easy. Only 12 cases were recorded in the last 2 years epidemiologic survey in France, 9 of them being related to morphine administration [9]. 

Avoid drugs that cause histamine release (e.g., morphine sulfate, codeine, atracurium, metocurine, mivacurium, and tubocurarine)... 

Morphine can cause constipation, spasms of the sphincter of Oddi, urinary retention, and pruritus (secondary to histamine release) (see Table 54-4). In head trauma patients who are not ventilated, morphine-induced respiratory depression can increase intracranial pressure and cloud the neurologic examination results. 

As for all opioids common adverse effects are constipation, slowed gastric emptying and biliary spasm. Urinary retention may occur. There is an increased risk of respiratory depression in young children and in the elderly. Allergic reactions are rare, but wheals and pain at the injection site due to histamine release may occur. CNS depressants will potentiate the depressant effects of morphine and that of other opioids. 

Less potent opioids have fallen into disfavor because of the prominence of the untoward effects they produce when given in high doses. Meperidine hydrochloride (Demerol) causes tachycardia, while morphine produces hypotension and bronchoconstriction as a consequence of its histamine-releasing action. 

Drugs, particularly organic bases, may release histamine from mast cells by physically displacing the amine from its storage sites. Morphine, codeine, d-tubocu-rarine, guanethidine, and radiocontrast media can release histamine from mast cells. Basic polypeptides, such as bradykinin, neurotensin, substance P, somatostatin, polymyxin B, and the anaphylatoxins resulting from complement activation, also stimulate histamine release. Venoms often contain basic polypeptides as well as the histamine-releasing enzyme phospholipase A. 

Other smooth muscle Morphine causes bronchoconstriction which is due to histamine release and may be dangerous in patients suffering from bronchial asthma. 

Morphine also cause flushing and itching of skin due to histamine release. 

Most of the haemodynamic effects of opioids are related to decreased central sympathetic outflow, specific vagal effects or, in the case of morphine and pethidine, histamine release. Fentanyl and its analogues do not cause histamine release. All opioids, with the exception of pethidine, produce bradycardia by actions on the afferent fibres of the vagus and the nucleus tractus solitarius and nucleus commissuralis, which have very high densities of opioid receptors. Pethidine often produces tachycardia, possibly due to its structural similarity to atropine. In isolated heart or heart-muscle preparations, opioids produce a dose-related negative inotropic effect, but only at concentrations 100 to several thousand times those found clinically. 

Therapeutic doses of the opioid analgesics produce flushing and warming of the skin accompanied sometimes by sweating and itching CNS effects and peripheral histamine release may be responsible for these reactions. Opioid-induced pruritus and occasionally urticaria appear more frequently when opioid analgesics are administered parenterally. In addition, when opioids such as morphine are administered to the neuraxis by the spinal or epidural route, their usefulness may be limited by intense pruritus over the lips and torso. 

Morphine by releasing Histamine causes Orthistatic Hypotension... 

Bronchial muscle is constricted, partly due to histamine release, but so slightly as to be of no importance, except in asthmatics in whom morphine should be avoided anyway because of its respiratory depressant effect. 

Other effects of morphine include sweating, histamine release, pruritus and piloerection. 

Treuren BC, Galletly DC, Robinson BJ, Short TG, Ure RW. The influence of the HI and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine. Anaesthesia 1993 48(9) 758-62. 

Urticaria at the site of injection is due to histamine release. It is seen with pethidine and morphine, but not with oxymorphone, methadone, fentanyl, or sufentanil. Wheal and flare responses to various opioids differ (41). 

Pruritus is not due to preservatives in formulations, as it occurs with non-preservative-containing opioid solutions (176). It is unlikely to be due to histamine release, as the effect occurs about 3 hours after spinal or epidural administration (154,177-179) and occurs with fentanyl, which does not cause histamine release, in contrast to morphine (180). 

Rosow CE, Moss J, Philbin DM, Savarese JJ. Histamine release during morphine and fentanyl anesthesia. Anesthesiology 1982 56(2) 93-6. 

Shuto H, Sueyasu M, Otsuki S, Kara T, Tsuruta Y, Kataoka Y, Oishi R. Potentiation of vancomycin-induced histamine release by muscle relaxants and morphine in rats. Antimicrob Agents Chemother 1999 43(12) 2881. ... 

The opioids are considered relahvely safe from a cardiovascular standpoint. Myocardial depression is minimal. Changes in heart rate are species dependent and usually manifest as a mild decrease in heart rate however, a significant increase in heart rate can be seen in horses, which is consistent with the central excitatory effect that often occurs. Opioids inhibit the baroreceptor reflex response to changes in blood pressure. Certain opioids may cause systemic vasodilatation, decreased peripheral vascular resistance and hypotension secondary to histamine release. Morphine and meperidine (pethidine) are the opioids most likely associated with this effect. This is typically seen after rapid i.v. administration, is dose dependent and does not result from mast cell... 

Dextromethorphan is the methylated dextro-isomer of levorphanol. Unlike the L-isomer, it has no analgesic properties. Dextromethorphan acts on the central nervous system (CNS) to elevate the cough threshold. It retains only the antitussive activity of other morphine derivatives. Administration of dextromethorphan may be associated with histamine release. Dextromethorphan is often present in multisymptom products with a combination of ingredients. Toxic effects of concurrent agents such as antihistamines, decongestants, analgesics, and/or alcohol may be exhibited. 

Morphine p agonist— strong (full) +++ +++ +++ Prototype of the class, marked sedation, poor oral bioavailability, histamine release... 

The histamine release in the brain, and perhaps other sites, involves exocytosis, as this potassium-induced release is a calcium-dependent process. Histamine is released by many factors. For example, histamine is released by numer-ons drugs including reserpine, codeine, meperidine, hydralazine, morphine, d-tnbocurarine, dextrans, papaverine, and compound 48/80. However, the different histamine storage sites show certain degrees of specificity. For example, the histamine in mast cells is not released following potassium-induced depolarization or by reserpine, factors that release histamine from nenrons. Conversely, compound 48/80, which releases histamine from mast cells, is not able to release histamine from nenrons. 

Morphine causes histamine release, which can cause bronchoconstriction and vasodilation, and should be avoided in patients with a history of asthma. Other /i-receptor agonists that do not release histamine, such as the fentanyl derivatives, may be better choices for such patients. 

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