The first reports of opioid use date to more than 6000 years ago, when a gummy substance known as opium was extracted from poppy plants known for its mind-altering effects. In 1805, a German chemist, Friedrich Serturner, identified the active ingredient in opium. He named it morphine, after Morpheus, the Greek God of dreams. In 1853, the hypodermic needle was introduced, and morphine could be administered intravenously. Morphine was used extensively during the American Civil War, and thousands of soldiers became addicted to the drug. In 1874, morphinewas modified by adding 2 acetyl groups to make heroin and in 1898 was marketed as a cough suppressant. In 1924, because of the addictive properties of opioids, nonmedical use was banned. In 1930, the synthetic opioid meperidine was introduced as an alternative to morphine to treat pain. During World War II another synthetic opioid, methadone, was developed as an alternative to morphine, and in the 1960s it was used as an adjunct to treat opioid addicts. In 1959, Janssen Pharmaceuticals developed another synthetic opioid, fentanyl, which was introduced into clinical care in 1960. Janssen went on to develop other fentanyl congeners, including sufentanil (1974) and alfentanil (1976). In 1992, Glaxo Smith Kline developed and marketed the newest of the fentanyl congeners, remifentanil.
Opioids activate opioid receptors present throughout membranes in the brain, spinal cord, and gastrointestinal system. Opioid receptors have been most extensively studied at synaptic junctions in the spinal cord. They consist of G protein–coupled receptors that activate ion channels and allow the flux of potassium and chloride, leading to a net negative polarization of a neuron membrane. In a hyperpolarized state, neurotransmission of pain signals are reduced especially in C and Aδ fibers that detect noxious stimuli.1 The main types of receptors are presented in Table 5–1.2 These receptors are similar; up to 70% of their protein sequence is identical. Other types of opioid receptors exist, but their role in pain control is not well defined.3
Table 5–1Opioid receptor site of action and effect. ||Download (.pdf) Table 5–1 Opioid receptor site of action and effect.
|Site of Action
|μ (μ1, μ2, μ3)
Reduced gastrointestinal motility
Inhibition of antidiuretic hormone release
Opioids are administered intravenously as a bolus and/or a continuous infusion and by mouth. Sample intravenous dosing regimens for commonly used opioids are ...