CHAPTER 68: Opioid Pharmacotherapy

INTRODUCTION

Analgesics are drugs that relieve pain without significant loss of other sensations. The word analgesic is from the Greek an, without + algesis, sensation of pain. Opioid analgesics are the most effective and commonly used pharmacotherapy for moderate to severe pain.¹ Not all pain patients benefit from opioid therapy; however, more patients benefit from strong analgesics when the drugs are used as an element of multimodal therapy.

Opioids include all compounds that bind to opioid receptors; these include exogenous opioid receptor agonists and antagonists as well as the endogenous opioid peptides. The term opiate originally was used to describe a drug derived from opium but now includes the natural opium products (e.g., morphine), the semisynthetic derivatives (e.g., hydromorphone), and completely synthetic congeners (e.g., methadone).

The differences between exogenous opioids, such as morphine, and endogenous opioids, such as β-endorphin, do not justify differing terminology. Opioid accurately describes both types of compounds and is generally considered the preferred term in both clinical and scientific dialogue.

Narcotic, from the Greek narkotikos, benumbing, was originally used to describe opium derivatives. Today, narcotic has become a legal term that includes a broad range of sedating and potentially abused drugs, many of which are not related to opium. Because the word narcotic has negative connotations, physicians should not use it when talking with patients.

The last 30 years have seen a marked increase in our knowledge of the sites and mechanisms of action of opioids.¹ New analytical methods reveal pharmacokinetic (PK) data on the disposition and fate of opioids in humans. Recently elucidated opioid receptor-related genetic polymorphisms provide a greater understanding of how genetics can help predict responses to opioids.²

BRIEF HISTORY OF OPIOID ANALGESICS

The word opium is derived from the Greek opion, poppy juice. Opium is the milky exudation derived from the unripe capsules of the opium poppy, Papaver somniferum. Opium contains over 20 different alkaloids and has been used to control human discomfort for over five millennia. Opium was used clinically in the early days of European medicine, but it fell into disfavor because of toxic outcomes from nonstandardized forms that were not used with necessary care. Paracelsus repopularized the use of opium in the 16th century, and by the second half of that century, clinical use of opium was understood and adopted by physicians throughout the continent.

The French pharmacist Jean-François Derosne isolated a crystalline precipitate from opium in 1803, a mixture of morphine and narcotine. It was not until 3 years later that the German pharmacist Friedrich Wilhelm Sertürner isolated morphine, the pure alkaloid, and named it after ...