Opioids

Original Editor - Michael Caruso Top Contributors - Justin Bryan, Claire Knott, Lucinda hampton, Michael Caruso and Tony Lowe

Introduction

An opioid (exogenous opioid) refers to any substance from a group of analgesic agents derived from the ingredient opium. Opioids are a type of depressant, analgesic drug that slows down the messages being sent through the central nervous system between the body to the brain. Although used to treat pain, opioids can entice euphoric feelings and sedative effects which can be addictive, which makes abuse of this drug group increasingly common.

Opioids can be naturally occurring, synthetic, or semi-synthetic depending how they are derived. Natural and semi-synthetic opioids utilize substances extracted from opium, which is produced from the dried seeds of the opium poppy. Fully synthetic opioids, on the other hand, are derived using laboratory methods to produce the same compounds naturally found in opium through controlled chemical processes. A least 20 different compounds are found in opium; these biologically active substances can either produce analgesic effects directly (i.e. morphine), or act as precursors that can be used to produce other analgesic drugs including semi-synthetic opioids.

Clinical Pharmacology

Production of opioids begins with four naturally occurring alkaloids which can be isolated from the opium poppy seed (papaver somniferum). These plant-derived amines, which include morphine, codeine, papaverine and thebaine, can then be used to produce many varieties of semi-synthetic opioids useful in clinical medicine. Common semi-synthetic opioids derived from these four substances include diamorphine, dihydrocodeine, buprenorphine, nalbuphine, naloxone and oxycodone.

Opioids exert their analgesic properties by binding to specialized "opioid" receptors that already exist on the neurons at specific sites in the central nervous system. These receptors exist in concert with endogenous (produced by within the body) opioid-like substances, both of which act as part of the body's natural process of controlling pain and inflammation. The three groups of endogenous opioid-like substances include endorphins, enkephalins, and dynorphins. In addition to pain control, endogenous opioid-like substances are believed to play a role in other processes including response to stress, immune modulation, GI function, eating and others.

Opioid Receptors

There are three major types of opioid receptor, 𝜇, 𝛿, and 𝜅 (mu, delta and kappa), found throughout the body. Other opioid receptors do exist, i.e. nociceptin/orphanin FQ peptide receptors, however no know exogenous opioid has been found to specifically act upon them. As such, opioids are commonly classified by their ability to exert an effect by binding to one of the three main receptors (𝜇, 𝛿, and 𝜅). All 3 receptors will produce analgesia when binded with an opioid substance, but the degree of effect is determined by how strongly a given opioid binds to a given receptor. This degree of "affinity" produces further sub classifications under each receptor type.

Of the three opioid receptor types, each produces analgesic effects when a substance binds to it. That being said, each receptor type a produce unique and distinct spectrum of impacts when activated. This specificity can be useful in choosing a specific opioid to target a patient's unique symptoms. Common unique effects of each receptor are listed below:

• Mu (𝜇) - Sedative effects, depression of respiratory function, constipation, reduction in release of neurotransmitters
• Delta (𝛿) - Sedative effects, constipation, psychoactive effects
• Kappa (𝜅) - Heightened release of hormones, reduction in release of neurotransmitters

Opioid Mechanisms of Action

Opioids produce their analgesic effect by acting directly on the synapses of neurons in the brain, spinal cord, and other tissues of the body. Each of these three areas are unique in their characteristics and how opioids specifically exert their effect.

• Spinal Cord: Opioid action at the level of the spinal cord impacts the transmission of pain signals from peripheral nerves to the brain. This occurs mainly by through the binding of presynaptic receptors of pain neurons, resulting in a reduction of the release of pain-mediating neurotransmitters including Substance P
• Brain: Opioid action in the brain occurs by altering the action of neurons responsible for interpretation and transmission of pain signals. A common belief is that opioids facilitate increased activity of descending pain pathways by blocking the signals of interneurons that would typically inhibit these pathways. When this process occurs it is known as disinhibition. At the same time, increased descending pathway activity also blocks the transmission of pain signals in the spinal cord through the same mechanism as opioids acting on this region
• Peripheral Tissue: Opioid receptors have been found on peripheral sensory neurons, allowing opioids to act directly in these areas. When the receptors on these peripheral nerves are bound by opioids, the excitability of the neurons in reduced. In this way, analgesia is achieved preventing pain signals from even being produced

Benefits & Drawbacks of Opioids

Opioids can produce profound analgesia for patients with acute pain. Opioids are very effective at treating acute pain due to their ability to inhibit pain signal transmission at multiple stages in the pain pathway and their ability to enhance the inhibitory pain fibres.

There are many adverse effects associated with opioids. Kappa receptor stimulation is associated with side effects such as hallucinations, dysphoria, anxiety and restlessness. Delta and mu receptor stimulation is often dangerously associated with respiratory depression as the body is unable to regulate carbon dioxide levels in the body effectively. Other drawbacks associated with opioid use in general include sleep apnoea, hypothalamic-pituatory axis supression (hormonal changes with the potential for decreased libido, infertility & fluid retention), urinary retention, nausea & vomiting, physical dependence and addiction, opioid-induced hyperalgesia, dental pathology, constipation, increased mortality and tolerance.

Considerations in Physiotherapy

Opioids are regularly administered for the treatment of pain; many patients that present to physical therapists may have already been prescribed them. Our role within any multidisciplinary management team treating a person who has pain is to ensure that we are monitoring the safe and clinically indicated use of opioids if required, identifying the potential for adverse effects and recognising these in a timely manner. The video clip below highlights the signs to look for re addiction to opioids    

Opioid use is also linked to increased falls risk. A 2018 retrospective, observational, multicentre cohort study the findings were that recent opioid use is associated with a greater risk of falls in older adults and a greater likelihood of death in those with fall-related injuries.

Opioids alone are not a solution for chronic pain as supported by an abundance of literature.

The image below shows the many areas involved in the brain with pain processing.