Pharmacokinetics heroin

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

The use of prodrugs with higher lipophrlicity compared to the parent molecule is realized in the classical example of heroin and morphine. Heroin, the di-acetyl derivative of morphine, penetrates the BBB by one log order better than morphine and is cleaved by tissue esterases to release the active parent drug. As follows from fhe pharmacokinetic principles shown in Section 2.3.2.1 (Eq. 2.3), brain concentration is a function of bofh BBB permeability, reflected by and plasma area under the curve ... 

Pharmacokinetics plays a very important role in the manner in which opioids are abused. Morphine and many of its derivatives are slowly and erratically absorbed after oral administration, which makes this route suitable for long-term management of pain but not for producing euphoria. In addition, opioids undergo considerable first-pass metabolism, which accounts for their low potency after oral administration. Heroin is more potent than morphine, although its effects arise primarily from metabolism to morphine. The potency difference is attributed to heroin s greater membrane permeability and resultant increased absorption into the brain. 

Mechanism of Action An opioid agonist-antagonist that binds with opioid receptors in the CNS. Therapeutic Effect Alters the perception of and emotional response to pain blocks the effects of heroin and produces minimal opioid withdrawal symptoms. Pharmacokinetics Rapidly absorbed following IM administration. Protein binding Very high. Metabolized in liver. Primarily excreted in feces minimal excretion in urine. Half-life 2 hr... 

Cook, C.E., Pyrolytic characteristics, pharmacokinetics, and bioavailability of smoked heroin, cocaine, phencyclidine and methamphetamine, NIDA Research Monograph 99, 6-23. DHHS Pub. No. 1990. 

Gyr, E., R. Brenneisen, D. Bourquin, T. Lehmann, et al., Pharmacodynamics and pharmacokinetics of intravenously, orally and rectally administered diacetylmoiphine in opioid dependents, a two-patient pilot study within a heroin-assisted treatment program, Int. J. Clin. Pharmacol. Ther., 38(10), 486—491, 2000. 

Girardin, F., K.M. Rentsch, M.A. Schwab, M. Maggiorini, et al., Pharmacokinetics of high doses of intramuscular and oral heroin in narcotic addicts, Clin. Pharmacol. Ther., 74(4), 341-352, 2003. 

Many heroin users use heroin and alcohol together. There has been an evaluation of the pharmacokinetic interaction between heroin and alcohol and the role of that interaction in the cause of 39 heroin-related deaths that were attributed to either heroin or heroin + ethanol (69). The... 

Polettini A, Groppi A, Montagna M. The role of alcohol abuse in the etiology of heroin-related deaths. Evidence for pharmacokinetic interactions between heroin and alcohol. J Anal Toxicol 1999 23(7) 570-6. 

Inturrisi CE, Max MB, Eoley BCM, Schultz M, Shin SU, Houde RW. The pharmacokinetics of heroin in patients with chronic pain. N Engl J Med 1984 310 1213-7. 

Cook, C.E. Pyrolytic characteristics, pharmacokinetics, and bioavailability of smoked heroin, cocaine, phencyclidine, and methamphetamine. In Miller, M.A., and Kozel, N.J., eds. Methamphetamine Abuse Epidemiologic Issues and Implications. National Institute on Drug Abuse Research Monograph 115. DHHS Pub. No. (ADM) 91-1896. Washington, DC Supt. of Docs., U.S. Govt. Print. Off,... 

Pharmacokinetics and phanuacodynamics of smoked heroin. J Anal Toxicol 18 317-330, 1994. 

Peginterferon alfa does not affect the pharmacokinetics of methadone, but an isolated report describes a patient who relapsed to heroin use following treatment with peginterferon. Methadone maintenance does not appear to affect the pharmacokinetics of peginterferon alfa or the virological response to interferons. Similarly, buprenorphine does not appear to influence the effect of interferon. 

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