Opiates pharmacokinetics

All clinically used opiates have the same pharmacology since they all act on the mu receptor with the exception of the kappa agonist, pentazocine. Opiates are used to relieve moderate to severe pain whatever the cause (accidents, post-operative pain, cancer, etc.) and are used pre-, intra- and post-operatively. The mu opiates differ only in potency and pharmacokinetics. Examples are ... 

Mechanism of Action An opioid agonist that binds at opiate receptor sites in central nervous system (CNS). Therapeutic Effect Reduced intensity of pain stimuli incoming from sensory nerve endings, alteringpain perception and emotional response to pain. Pharmacokinetics Rapidly absorbed. Protein binding 40%-50%. Extensively distributed. Metabolized in liver. Excreted in urine. Half-life 11 hr. 

Rostami-Hodjegan A, Wohf K, Hay AWM, Raistrick D, Calvert R Tucker GT (1999). Population pharmacokinetics in opiate users characterization of time dependent changes. British Journal of Clinical Pharmacology, 47, 974-86... 

Busto, U., Bendayan, R., and Sellers, E.M., Clinical pharmacokinetics of non-opiate abused drugs, Clin. Phcirmcicokinet., 16, 1-26, 1989. 

Members of the group of natural, semisynthetic, or synthetic alkaloid compounds prepared from opium are referred to as opioids. This group includes natural compounds usually denoted opiates, such as morphine and codeine, and the synthetic and semi synthetic compounds such as oxycodone, buprenorphine, fentanyl, methadone, and tramadol. The pharmacological effects and pharmacokinetic parameters of these drugs share many common characteristics and are illustrated with the prototypic drug in this class, morphine. 

Courteix, C., Bourget, P., Caussade, F., Bardin, M., Coudore, F., Fialip, J., and Eschalier, A. (1998). Is the reduced efficacy of morphine in diabetic rats caused by alterations of opiate receptors or of morphine pharmacokinetics . Pharmacol. Exp. Ther. 285, 63—70. 

Prior use of benzodiazepines or opiates limits the psychotomimetic effects of ketamine. There has been a double-blind, placebo-controlled study of the role of lorazepam in reducing these effects after subanesthetic doses of ketamine in 23 volunteers who received lorazepam 2 mg or placebo, 2 hours before either a bolus dose of ketamine 0.26 mg/kg followed by an infusion of 0.65 mg/kg/hour or a placebo infusion (438). The ability of lorazepam to block the undesirable effects of ketamine was limited to just some effects. It reduced the ketamine-associated emotional distress and perceptual alterations, but exacerbated the sedative, attention-impairing, and amnesic effects of ketamine. However, it failed to reduce many of the cognitive and behavioral effects of ketamine. There were no pharmacokinetic interactions between subanesthetic doses of ketamine and lorazepam. 

Piischel, K., Thomasch, R, and Arnold, W., Opiate levels in hair. Forensic Sci. Int., 21, 181, 1983. Miyazawa, N., Uematsu, T., Mizuno, A., Nagashima, S., and Nakashima, M., Ofloxacin in human hair determined by high performance liquid chromatography. Forensic Sci. Int., 51, 65, 1991. Uematsu, T., Therapeutic drug monitoring in hair samples, Clin. Pharmacokinet., 25, 83, 1993. Tracqui, A., Kintz, R, and Mangin, R, Hair analysis a worthless tool for therapeutic compliance monitoring. Forensic Sci. Int., 70,183,1995. 

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

Hug C G (eds) Pharmacokinetics of anaesthesia. Blackwell, Boston, MA, p. 157 Riedesel D H, Hildebrand S V 1985 Unusual response following use of succinylcholine in a horse anesthetized with halothane. Journal of the American Veterinary Medical Association 187 507-508 Robertson S A, Carter S W, Donovan M et al 1990 Effects of intravenous xylazine hydrochloride on blood glucose, plasma insulin and rectal temperature In neonatal foals. Equine Veterinary Journai 22 43-47 Roger T, Bardon T, Ruckebush Y 1994 Comparative effects of mu and kappa opiate agonists on the cecocolic motility In the pony. Canadian Journal of Veterinary Research 58 163-166... 

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. 

If the nature of the time dependency is well understood and sampling is sufficient to identify model parameters, which define such expressions, a modification to the typical structural model can be explored. Specifically, as in the case of enzyme induction, changes in clearance may be expected to occur over typical time windows. By allowing the initial value of clearance, C1(0), to increase in a monoexponential manner until an asymptotic value, Cl(ss), is reached, the clearance at any time, t, can be expressed as a function of these boundary conditions and an induction rate constant, k,. Such a function (shown below) was proposed by Levy et al. and utilized by Rostami-Hodjegan et al. with certain assumptions to model methadone pharmacokinetics in opiate users. 

Rostami-Hodjegan, A. et ah, Population pharmacokinetics of methadone in opiate users characterization of time-dependent changes, Br. J. Clin. Pharmacol., 48 43-52, 1999. 

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