Morphine renal effects

In most cases the mechanism is not known. Stimulators of vasopressin secretion include vincristine, cyclophosphamide, tricyclic antidepressants, nicotine, epinephrine, and high doses of morphine. Lithium, which inhibits the renal effects of vasopressin, also enhances vasopressin secretion. Inhibitors of vasopressin secretion include ethanol, phenytoin, low doses of morphine, glucocorticoids, fluphenazine, haloperidol, promethazine, oxilorphan, and butorphanol. Carba-mazepine has a renal action to produce antidiuresis in patients with central diabetes insipidus but actually inhibits vasopressin secretion via a central action. 

Morphine and its derivatives continue to be considered the gold standard for alleviating pain. Morphine is metabolized in the liver via N-dealkylation and glu-coronidation at the third (M3G) or sixth position (M6G). Although M3G are the most common metabolites (accounts for 50% of the metabolites produced), they elicit no biological activity when bound to MOR. It is the M6G metabolite (accounts for 10% of the metabohtes produced) that elicits the nociceptive/analgesic effect upon binding to the p opioid receptor (Dahan et al. 2008). M6G is predominately eliminated via renal excretion. 

Analgesics are given to reduce abdominal pain. In the past, parenteral meperidine (50 to 100 mg) every 3 to 4 hours was usually used because it causes less spasm of the sphincter of Oddi than other opioids. Meperidine is used less frequently today because it is not as effective as other opioids and is contraindicated in renal failure. Parenteral morphine is sometimes used, but it is thought to cause spasm of the sphincter of Oddi, increases in serum amylase and, rarely, pancreatitis. Hydromorphone may also be... 

Codeine phosphate is still used for diarrhea predominantly based on hypermotility but the longer-acting loperamide is more convenient and has less central nervous system effects. Codeine has an exceptionally low affinity for opioid receptors and its effects are due to the fact that it is converted for approximately 10% to morphine. The active metabolite of morphine, morphine-6-glucuronide, may also accumulate during repeated administration of codeine to patients with impaired renal function. 

The majority of their metabolites are inactive with a few notable exceptions, such as morphine-6-glucuronide, which produces an analgesic effect normeperidine and norpropoxyphene, which produce excitatory but not analgesic effects and 6-(3-naltexol, which is less active than naltrexone as an antagonist but prolongs the action of naltrexone. Excretion of the metabolites requires adequate renal function, since excretion by routes other than the urine are of minor importance. 

Contraindications are similar to those of morphine. In addition, because normeperidine accumulates in renal dysfunction and meperidine accumulates in hepatic dysfunction, meperidine is contraindicated in such patients because of convulsant effects. Similarly, the use of meperidine is contraindicated in patients who have a... 

The effects of these active metabolites should be considered in patients with renal impairment before the administration of morphine or hydromorphone, especially when given at high doses. 

M6G, on the other hand, is pharmacologically active and exerts important clinical opioid effects, especially when it is allowed to accumulate in the plasma of patients who have renal failure. However, after short-term morphine administration, the contribution of M6G to both analgesia and... 

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. 

Pethidine causes vomiting about as often as does morphine it has atropine-Hke effects, including dry mouth and blurred vision (cycloplegia and sometimes mydriasis, though usually nviosis). Overdose or use in renal failure can cause central nervous system stimulation (myoclonus, convulsions) due to norpethidine. 

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