Opioid renal effects

NEP inactivates a series of renal and CNS-active peptides, such as substance P, bradykinin, enkephalins and atrial natriuretic factor. It has been well underlined that inhibitors of NEP should be useful in the treatment of pain because of having a large spectrum of activities similar to that of opioid analgesics. In fact, inhibitors of NEP protect the endogenous atrial natriuretic factor degradation and enhance the typical renal effects of ANF on diuresis and natriuretic response (see Figure 28). 

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... 

Deaths, cardiac and resp have been reported during initiation and conversion of pain pts to methadone Tx from Tx w/ other opioids Uses Severe pain detox w/ maint of narcotic addiction Action Narcotic analgesic Dose Adults. 2.5-10 mg IM q3-8h or 5-15 mg PO q8h titrate as needed Feds. 0.7 mg/kg/24 h PO or IM -s- q8h T slowly to avoid resp depression X in renal impair Caution [B/D (prolonged use/high doses at term), + (w/ doses =/> 20 mg/24 h)], severe liver Dz Disp Tabs, inj SE Resp depression, sedation, constipation, urinary retention, T QT interval, arrhythmias Interactions T Effects W/ cimetidine, CNS depressants, protease inhibitors EtOH T effects OF anticoagulants, antihistamines, barbiturates, glutethimide, methocarbamol ... 

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. 

Renal function is depressed by opioids. It is believed that in humans this is chiefly due to decreased renal plasma flow. In addition, opioids have been found to have an antidiuretic effect in humans. Mechanisms may involve both the CNS and peripheral sites. Opioids also enhance renal tubular sodium reabsorption. The role of opioid-induced changes in antidiuretic hormone (ADH) release is controversial. Ureteral and bladder tone are increased by therapeutic doses of the opioid analgesics. Increased sphincter tone may precipitate urinary retention, especially in postoperative patients. Occasionally, ureteral colic caused by a renal calculus is made worse by opioid-induced increase in ureteral tone. 

Many nonsteroidal anti-inflammatory drugs of different chemical structures (Fig. 5) have been introduced for the treatment of inflammatory and painful conditions. Many years of clinical experience with these drugs have shown that there is no induction of tolerance or dependence and no respiratory depression as seen with opioids. The major side-effects of these compounds with COX-1 selectivity or balanced COX-1 and COX-2 inhibition are damage to the gastric mucosa, prolongation of bleeding time and renal failure. 

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