Morphine biliary effects

Morphine decreases the propulsive contractions of the gastrointestinal tract, and biliary and pancreatic secretions are reduced. The end result, especially when morphine is administered over extended time periods, is constipation. Morphine-induced spasms of the sphincter of Oddi have been observed. However, the clinical significance of such an occurrence should be assessed on an individual basis. Although morphine s effect on the urinary bladder varies, urinary... 

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Opiates can effect serum levels of enzymes and other substances whose homeostatic control depends on clearance through the liver (F8, G12, M15, N4, S19). In one reported case, the aspartate aminotransferase was within normal limits before the administration of codeine, but within 2 hours after the drug, the enzyme activity had risen to two times the normal value by 8 hours to eight times the normal activity, and within 24 hours it had returned to normal (F8). Increases in transaminase to levels 5-85 times the control value have been reported in 6 of 16 patients with disease of the biliary tree following the administration of codeine phosphate (2 grains) (B7, F8). Gross has shown that morphine, codeine, or mepheridine administration produce elevations of serum amylase or lipase (G12). These elevations have been attributed to constriction of the sphincter of Oddi and increased intraductal pressure on the pancreatic duct (G12, N4). 

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. 

Meperidine differs from morphine in that it has far less antitussive effect and little constipative effect. The drug is particularly useful in cancer patients and in pulmonary patients, in whom the cough reflex must remain intact. However, it does have more seizure-inducing activity than morphine. Although meperidine produces spasms of the biliary tract and colon, such spasms are of shorter duration than those produced by morphine. 

Meperidine has replaced morphine to a large extent in medical practice because of the physician s reluctance to use an opiate and the belief that meperidine manifests less undesirable side effects than does morphine. However, both of these assumptions are ill founded. Addiction to meperidine is much less amenable to treatment than is addiction to morphine. Meperidine, similar to morphine and codeine, causes spasm of the upper gastrointestinal tract and typical attacks of biliary colic in biliary tract disease. Meperidine, in doses giving an equal analgesic effect, induces as much respiratory depression as does morphine. Similar to morphine, it also crosses the placental barrier and must therefore be used cautiously in the latter stages of labor. 

Pain due to spasm of visceral smooth muscle, e.g. biliary, renal colic, when severe, requires a substantial dose of morphine, pethidine or buprenorphine. These drugs themselves cause spasm of visceral smooth muscle and so have a simultaneous action tending to increase the pain. Phenazocine and buprenorphine are less liable to cause spasm. An antimuscarinic drug such as atropine or hyoscine may be given simultaneously to antagonise this effect. 

Intrabiliaiy pressure may rise substantially after morphine (as much as 10 times in 10 minutes), due to spasm of the sphincter of Oddi. Sometimes biliary colic is made worse by morphine, presumably in a patient in whom the dose happens to be adequate to increase intrabiliary pressvue, but insufficient to produce more than slight analgesia. In patients who have had a cholecystectomy this can produce a syndrome sufficiently like a myocardial infarction to cause diagnostic confusion. Naloxone may give dramatic symptomatic relief, as may glyceryl trinitrate. Another result of this action of morphine is to dam back the pancreatic juice and so cause a rise in the serum amylase concentration. Morphine is therefore best avoided in pancreatitis but buprenorphine has less of this effect. 

In general, when morphine is used and the smooth muscle effects are objectionable, atropine may be given simultaneously to antagonise spasm. Unfortunately this does not always effectively oppose the rise of pressure induced in the biliary system, nor does it restore bowel peristalsis. Glyceryl trinitrate will relax morphine-induced spasm. 

Smooth muscle is relaxed. In the gastrointestinal tract there is reduction of tone and peristalsis. Muscle spasm of the intestinal tract induced by morphine is reduced, but such spasm in the biliary tract is not significantly affected. Atropine relaxes bronchial muscle, an effect that is useful in some asthmatics. Micturition is slowed and urinary retention may be induced especially when there is pre-existing prostatic enlargement. 

Butorphanol is generally believed to have a much smaller effect on biliary pressure than morphine, fentanyl, or pethidine, but 2 mg has caused biliary spasm (3). 

Answer C. Morphine continues to be used in pulmonary congestion, in part because of its sedative (calming) and analgesic effects and also because of its vasodilating actions, which result in favorable hemodynamics in terms of cardiac and pulmonary function. Similarly, morphine is of value in an acute MI, especially its ability to relieve pain. However, morphine is not suitable for pain of biliary origin because it causes contraction of the sphincters of Oddi, leading to spasms. None of the other proposed indications are appropriate. 

Morphine and certain other central analgesics have a contractile action on the sphincter of Oddi (M18). Increased biliary pressure arrests the secondary phase of BSP disappearance from the circulation the initial rapid phase is unaffected. This effect is not demonstrable in patients with intact gallbladders since the gallbladder has some capacity to regulate pressure. Codeine phosphate has a similar effect to morphine in cholecys-tectomized patients, causing biliary colic and elevated BSP retention. Pholcodine and l-(2,12-benzylphenoxyl-l-methylethyl) piperidine has no such effect. Papaverine exerts a counter-effect, relieving colic and BSP stasis (H26). 

BSP retention is usually increased in acute cholecystitis, but only occasionally is it increased in acute peritonitis and other acute abdominal conditions (B60, W21). The mechanism in these conditions is either partial biliary obstruction or alteration in hepatic blood flow. The effect of morphine in causing BSP retention by constriction of the sphincter of Oddi is relevant (see Section 7.12). Burnett (B60) found increased BSP retention ranging from 5 to 20% in 5 out of 6 patients with minor ailments given morphine, all of whom had shown normal BSP retention on the previous day. 

The outstanding properties of methadone are its analgesic activity, its efficacy by the oral route, its extended duration of action in suppressing withdrawal symptoms in physically dependent individuals, and its tendency to show persistent effects with repeated administration. Miotic and respiratory-depressant effects can be detected for more than 24 hours after a single dose, and on repeated administration, marked sedation is seen in some patients. Effects on cough, bowel motility, biliary tone, and the secretion of pituitary hormones are qualitatively similar to those of morphine. 

The relief of pain by morphine-like opioids is relatively selective, in that other sensory modalities are not affected. Patients frequently report that the pain is still present, but they feel more comfortable. Continuous dull pain is relieved more effectively than sharp intermittent pain, but sufficient amounts of opioid can relieve even the severe pain associated with renal or biliary colic. 

BILIARY TRACT After the subcutaneous injection of 10 mg morphine sulfate, the sphincter of Oddi constricts, and the pressure in the common bile duct may rise more than tenfold within 15 minutes this effect may persist for 2 hours or more. Fluid pressure also may increase in the gallbladder, producing symptoms that vary from epigastric distress to typical biliary cohc. All opioids can cause biliary spasm. Atropine only partially prevents morphine-induced biliary spasm, but opioid antagonists prevent or relieve it. Nitroglycerin (0.6-1.2 mg) administered sublingually also decreases the elevated intrabiliary pressure. 

UNTOWARD EFFECTS AND PRECAUTIONS Morphine and related opioids produce a wide spectrum of unwanted effects, including respiratory depression, nausea, vomiting, dizziness, mental clouding, dysphoria, pruritus, constipation, increased pressure in the biliary tract, urinary retention, hypotension, and rarely dehiium. Increased sensitivity to pain after analgesia has worn off also may occur. 

Intravenous morphine relieves the dyspnea of pulmonary edema associated with left ventricular failure. The mechanism may involve a decrease in perception of shortness of breath, relief of anxiety, and reductions in cardiac preload (decreased venous tone) and afterload (decreased peripheral resistance). Opioids cause exaggerated effects in Addison s disease and hypothyroidism, are contraindicated in head injuiy because they increase intracranial pressure, and may cause biliary muscle spasm. If given during labor, they may cause respiratory depression in the newborn. The answer is (E). 

The narcotic analgesics tend to produce euphoria which is an important factor in their addietive property which limits their use. Other limitations include respiratory depression, decreased gastrointestinal motility leading to constipation, increase biliary tract pressure and pruritus due to histamine release. Beeause of these setbacks in the use of morphine there has been a eonstant effort to develop analgesies with fewer side-effects and minimal addictive actions. 

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