Opiates absorption

The antiemetics and antivertigo drug may have additive effects when used with alcohol and other CNS depressants such as sedatives, hypnotics, antianxiety drugp, opiates, and antidepressants. There may be additive anticholinergic effects (see Chap. 25) when administered with drag s that have anticholinergic activity such as the antihistamines, antidepressants, pheno-thiazines, and disopyramide The antacids decrease absorption of the antiemetics. 

Inhalation (IH) The administration of volatile gases and vapours, followed by drug absorption in the lungs or nasal mucosa. Examples include general anaesthetics like nitrous oxide, nicotine from the tar droplets in tobacco smoke, cannabinoids from cannabis leaf smoke and various opiates from burning opium resin. 

Acute physiological responses to opiate administration occur rapidly and include constricted pupils, decreased pulse rate, reduced body temperature, slowed respiration rate and impaired reflexes. In addition, there is a marked slowing of the digestive system through an altering of the tonus and motility of the stomach and intestines, allowing for greater water absorption. This last effect is not subject to tolerance, and constipation is a common side effect even for chronic users. Indeed, some report that this is the worst side effect of opiate use. 

Opiates and opioid derivatives delay the transit of intraluminal content or increase gut capacity, prolonging contact and absorption. The limitations of the opiates are addiction potential (a real concern with long-term use) and worsening of diarrhea in selected infectious diarrheas. 

Loperamide, 4 mg initially, then 2 mg after each loose stool, not to exceed 8 mg daily Imodium A-D, various generic Loperamide, a synthetic opioid, acts on intestinal smooth muscle to decrease motility allowing for absorption of water and electrolytes. Poorly penetrates the CNS and has a lower risk of side effects compared with diphenoxylate or opiates. Not considered a controlled substance. 

Opiates produce constipation by affecting receptors in the intestines. Opium extracts were used in this capacity to treat diarrhea. Today there are other related compounds on the market which accomplish the peripheral task without affecting the CNS because of their poor absorption from the Gl tract when taken orally. Imodium A-D , an OTC, contains loperamide. It is also available as a generic OTC. The prescription mixture of diphenoxylate and atropine is called Lomotil . 

Most studies of the local actions of opioids on the intestinal mucosa have utilized muscle-stripped sheets of ileal mucosa with attached submucosa mounted in Ussing flux chambers. Peptidase-resistant enkephalin derivatives such as DPDPE decrease short-circuit current, an electrical measure of active transepithelial ion transport, across isolated mucosal sheets from the guinea pig ileum [46,127,128], rabbit ileum [129-131], mouse jejunum [132], and pig distal jejunum/ileum [133]. This effect, which occurs after the application of opioid agonists to the serosal aspect of epithelial sheets, is due to an increase in electroneutral salt absorption and a decrease in electrogenic chloride secretion [46,132,133], In contrast to enkephalin derivatives, opiate alkaloids have limited effects on active transepithelial transport of ions [69]. Pretreat-... 

Binder, H.J., Laurenson, I.P., and Doppins, J.W. 1984. Role of opiate receptors in regulation of enkephalin stimulation of active sodium and chloride absorption. Am. J. Physiol. 247, 432-436. 

Q6 Loperamide hydrochloride is an opioid. The starting dose will be 4 mg, which can be reduced to 2 mg, three times a day for five days if necessary. Opioids act on // opiate receptors in the myenteric plexus of the intestine and may modulate acetylcholine release to reduce peristalsis. They trigger mucosal transport of ions and water out of the lumen and cause a reduction in secretion. The absorption of fluid and electrolytes is increased since the stool remains in the colon for a longer period. Loperamide does not produce sedation or other central effects associated with opiates, since it does not cross the blood-brain barrier. 

In common with other phenolic opiate analgesics, buprenorphine shows low peroral potency, suggesting a high first-pass metabolism effect indeed, work in rats has shown this to be the case. Intravenous studies have estimated that the extraction ratio of buprenorphine is 85% and that peroral systemic availability is consequently expected to be 15% or less. Although absorption from the mouth is slow and, therefore, not as useful as parenteral administration in the treatment of acute pain, it offers a major bioavailability advantage over the peroral route for this drug. If required, the patient can be given a parenteral dose of buprenorphine to achieve rapid pain relief and... 

Opiate Use in the 19th Century Opiate Use in the 20th Century and Today Prescription Opiate Abuse Pharmacokinetics Absorption... 

Enkephalins are pentapeptides that bind to opiate receptors. In the gut, enkephalins promote the absorption of sodium, chloride and water (Dobbins et al 1980). Racecadotril is an oral enkephalinase inhibitor used in France and the Philippines for the treatment of acute diarrhea. It prevents the degradation of endogenous opioids (enkephalins) and thus promotes absorption of water and electrolytes from the intestinal lumen (Matheson Noble 2000). Studies have demonstrated the efficacy of racecadotril in two models of hypersecretory diarrhea infusion of cholera toxin and castor oil induced diarrhea. Moreover, unlike loperamide, racecadotril did not prolong transit time in the small intestine or colon. Further experiments have shown that racecadotril does not promote bacterial overgrowth in the small intestine (Duval-Iflah et al 1999). There are no reports on the use of racecadotril in horses. 

Opiates have effects on all segments of the bowel, but effects are most pronounced on the colon. The major mechanism by which opiates produce constipation has been proposed to be prolongation of intestinal transit time by causing spastic, nonpropulsive contractions. An additional contributory mechanism may be an increase in electrolyte absorption. 

Altered absorption Absorption can be increased or decreased by the actions of another drug Opiates slow intestinal transit time and increase absorption of other drugs Tetracycline can reduce absorption of iron salts... 

The subsequent introduction of naloxone s cyclopropylmethyl analog, naltrexone (Trexan, Fig. 5-9), with its ready oral absorption and considerably longer duration of action has made possible the use of a pure antagonist in the treatment of narcotic addicts. Naltrexone in once-a-day oral doses of 50 mg will produce satisfactory clinical blockade of intravenously administered opiates.10 In fact, a single dose of 100 or 150 mg can be used on a once, every other, or third-day basis. This drug may represent a small advance in the battle against opiate dependency. Naltrexone has been approved (1994) to obtund the cravings of alcohol abusers. 

The efflux transporter P-gp is a major determinant of the pharmacokinetics and pharmacodynamics of loperamide, a potent opiate. The main reason that loperamide does not produce opioid CNS effects at usual doses in patients is a combination of slow dissolution, first-pass metabolism, and P-gp-mediated efflux, which prevents brain absorption, perhaps contributing to its low addiction potential. Loperamide produced no respiratory depression when administered alone, but when administered with a P-gp inhibitor, respiratory depression occurred, which could not be explained by increased plasma loperamide concentrations. This effect demonstrates the potential for important drug interactions by inhibition of P-gp efflux transporter. The lack of respiratory depression produced by loperamide, which allows it to be safely used therapeutically, can be reversed by a drug causing P-gp inhibition, resulting in serious toxic and abuse potential. 

The addition of hydroxyde ion to nitrosobenzene produces azoxybenzene 6. Three techniques (electronic absorption spectroscopy, linear sweep voltammetry and d.c. polarography) have been used to study the equilibrium between nitrosobenzene and hydroxyde ions. The probable reaction pathway to obtain azoxybenzene is indicated by Scheme 4. The importance of the nitroso group in the reduction of nitro derivatives by alkoxide ions, when the electron-transfa- mechanism is opiating, has been explained. ... 

Metoclopramide increases the rate of gastric emptying so that the rate of morphine absorption from the small intestine is increased. An alternative idea is that both drugs act additively on opiate receptors to increase sedation. Droperidol may also enhance adverse effects such as sedation, and in some cases respiratory depression, possibly through opioid and other receptor sites in the CNS. In one case the respiratory depression was not reversed by naloxone, suggesting that the droperidol was at least partially if not completely responsible. ... 

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