The Risks of Overdose and Addiction Related to the Prescription of Analgesic Drugs

The prescription of analgesics aims at maximum effectiveness but must guard caution against the installation of a dependence and a tolerance which may lead to an increase of the administrered doses, up to an overdose, sometimes lethal, or to an addiction modifying negatively the patient’s life. Indeed, the so-called «opioid crisis» in the U.S.A. (70 000 annual deaths) has been largely driven by abusive prescriptions of the mu-type opioid receptor stimulating drugs. France still remains spared from this tragedy, owing to the prudence of her physicians and to the adherence to current legislation in force. Nevertheless, there is a massive misuse of buprenorphine; recurrent claims for the legalization of different drugs of abuse; excessive medication of various states of discomfort, including an irrepressible evolution towards a lower resistance to pain. This review will discuss the main analgesics, according to three «paliers» the main «landings» (I, II, III) defined by the World Health Organization. It will explain the substrates of tolerance and dependence concerning certain analgesics. It will explain the mechanisms of tolerance and dependence concerning certain analgesics. It will present several elements that may underlie a vulnerability to addiction which should be considered before choosing an analgesic. It will also recall the pharmacogenetic variations of cytochrome 2D6 that may influence the efficacy and addictivity of codeine, tramadol and hydrocodone. Some recommandations will be given with the purpose of preventing transforming pain relief into addiction, which would require continuous increase of the drug dose, with eventual culmination in strong opioids consumption such as heroin or anilinopiperidines (fentanyl and derivatives).