Hydrocodone abuse

Hydrocodone is a widely prescribed (and abused) pharmaceutical designed as a pain-reliever. The drug works by converting into a form of morphine once it enters the body. Hydrocodone can be derived from either codeine or thebaine and is three times more powerfiil than codeine. Hydrocodone has various trade names. 

Side-effects Hydrocodone induces side-effects similar to codeine and morphine and has an appreciable abuse and dependence potential (Morrison, 1979). 

The abuse of marketed medications has been at the forefront of public awareness in recent years, mostly due to widespread reports concerning OxyContin and hydrocodone.1 While these are highly regulated, prescription-only medications with recognized potential for abuse, even some over-the-counter (OTC) medications have become problematic, either because of their own effects (e.g., ephedrine) or because they are used in the manufacture of other abused substances (e.g., pseudoephedrine, used to make methamphetamine).2 3... 

Friedman RA, House JW, Luxford WM, Gherini S, Mills D. Profound hearing loss associated with hydrocodone/acetami-nophen abuse. Am J Otol 2000 21(2) 188-91. 

Heroin was first synthesized from morphine over a century ago. Since then, it has become one of the most abused substances. Research into why it produces such powerful effects has led to the discovery of specific opiate receptors and endogenous opioids (enkephalins and endorphins). These peptides appear to be neurotransmitters involved with the sensation of pain and pleasure. A number of opiates and synthetic opioids are available and can lead to dependency, including morphine, heroin, propoxyphene (Darvon), methadone, meperidine (Demerol), pentazocine (Talwin), hy-dromorphone (Dilaudid), oxycodone (Percodan), and hydrocodone (Vicodin, Damason-P), and codeine. 

Opioids cause a release of endorphins producing a feeling of pleasure. Examples of abuse include heroin, a highly addictive opioid that metabolizes to morphine and readily passes into the brain producing an immediate euphoria. Pharmaceutical or medicinal abused opioids include oxycontin, hydrocodone, codeine, methadone, and propoxyphene. 

Hydrocodone is used as an analgesic and as an anti-tussive. It has also been diverted as a drug of abuse. 

Ingestion is the most common route of exposure to hydrocodone. It is available as tablets and syrup. Hydrocodone has been solubilized and used parente-rally as a drug of abuse. 

Hydrocodone has the potential for abuse. Chronic users may develop tolerance, thus necessitating larger doses for the desired effect. Abrupt cessation can cause withdrawal, yielding restlessness, insomnia,... 

A number of drugs of abuse are known substrates (e.g., codeine, hydrocodone, p-methoxyamphetamine, amphetamine) or inhibitors (e g., (-)-cocaine, pentazocine) of CYP2D6. For some of these drugs, the pharmacokinetic differences due to the polymorphism will be so profound that they are likely to exceed pharmacodynamic sources of variation in response. For other drugs (e.g., hydrocodone to hydromorphone, codeine to morphine, oxycodone to oxymorphone), CYP2D6 may not contribute importantly to the overall clearance of the drug, but may catalyze the formation of highly active metabolites. 

The establishment that CYP2D6 converts hydrocodone to its active metabolite hydromorphone in vivo. This drug was subsequently selected as the prototypical pro-drug opiate used to study the role of CYP2D6 activity variants in opiate plasma kinetics and in responses related to abuse (Otton et al. 1993a). 

With respect to treatment, depending on the particular biotransformation pattern and the activity of the metabolites, several therapeutic approaches are evident. For example, EMs (93 percent of the Caucasian population) could receive an inhibitor as part of a therapeutic regimen. Such inhibition will alter the kinetics, toxicity, drug-reinforcing properties, and physical dependence liability of some drugs of abuse (e g., hydrocodone, oxycodone, codeine) and make the drug less pharmacologically attractive. 

Hydrocodone bitartrate is approximately threefold more effective on a weight basis as an oral antitussive medication compared to codeine. Hydrocodone also has greater analgesic activity and abuse potential than codeine. Hydrocodone is only available as a Schedule III prescription agent in combination formulations for cough suppression. 

The number of Americans abusing prescription drugs doubled from 7.8 million in 1992 to 15.1 million in 2003. The painkiller hydrocodone was used by 7.4% of college students in the United States in 2005. It is a semisynthetic opioid derived from two of naturally occurring opiates, codeine and thebaine. Production of this drug has increased in recent years. In Scandinavia, flunitrazapam, a sedative, is sold as Rohypnol, and it is widely known as a date-rape drug. ... 

Coles, R., M. M. Kushnir, G. J. Nelson, A. Gwendolyn, cuid F. M. Urry. 2007. Simultaneous determination of codeine, morphine, hydrocodone hydromor-phone, oxycodone, and 6-acetylmorphine in urine, serum, plasma, whole blood, and meconium by LC-MS/MS. Journal of Analytical Toxicology 31 (1) 1-14. Drummer, O. H. 2004. Postmortem toxicology of abused drugs. Forensic Science International 142 (2-3) 101-113. 

Other constraints are important for more complex products, for which mass is not central, but value. For example, central nervous system stimulants are a new class of substances addressed by production with engineered baker s yeast. Expressing the biosynthetic pathways for the opioids thebaine and hydrocodone, and parts of the morphine pathway in yeast, a first step is taken for easy production of opiates [21, 22]. This opens the possibility for the development of new painldllers with less addictive potential. However, it clearly is a new technology that could be abused with many negative consequences - so some contemplation about how to control these developments seems advisable [23]. Not only are narcotics in the center of interest but stimulants such as caffeine and theobromine have also recently been produced with genetically engineered 5. cerevisiae strains [24]. 

In an observational study in 1818 patients intended to discover whether the abuse potential of opioids matches the preference for non-therapeutic abuse in the real world, fentanyl, despite being predicted to have the greatest abuse potential, did not rank as high choice, owing to fear of toxicity and overdose hydrocodone and oxycodone were the drugs of choice in 75% of patients [10 ). 

Absolute history of previous severe allergic reaction to hydrocodone or acetaminophen. Relative head injury, increased intracranial pressure, elderly patient, severe liver or renal impairment, acute abdominal conditions, hypothyroidism, Addison s disease, prostatic hypertrophy, urethral stricture, history of drug abuse, and patients with respiratory depression [8]. 

---