13.3: Opioid Analgesics: Morphine and Other Natural Cogeners

Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a complex structure that allows it to interact with opioid receptors. It specifically binds to the μ opioid receptor (MOR), triggering a cascade of reactions resulting in pain relief and euphoria. While morphine effectively relieves pain, it is not without its adverse effects, including miosis, drowsiness, constipation, respiratory depression, and nausea or emesis. Prolonged use of opioids, including morphine, can result in tolerance, where the body requires higher doses to achieve the same effect. Opioids also carry a risk of addiction, characterized by compulsive use despite negative consequences. When opioid use is reduced or stopped, the body may experience withdrawal symptoms, which occur as it adjusts to the absence of the drug. These symptoms can include physical effects such as nausea, sweating, muscle pain, and tremors, as well as psychological effects like anxiety, irritability, and intense cravings. It's important to note that opioids have been invaluable in managing pain, but their potential for side effects and addiction necessitates careful prescribing and monitoring. Other opioids, such as codeine, act as weak μ opioid agonists and are used for mild to moderate pain. However, it's crucial to know the risk of life-threatening respiratory depression and death, particularly in children.

Understanding the pharmacokinetic profile of opioids is vital. Morphine, for example, has a linear profile and is usually administered orally, subcutaneously, or intravenously. It undergoes conjugation in the liver to form active glucuronide metabolites excreted via urine. In summary, opioids like morphine play a crucial role in pain management. Still, their use must be balanced with the potential for adverse effects, addiction, and the need for careful monitoring.

Opioids are a diverse group of pain-relieving drugs categorized as natural, synthetic, or semisynthetic compounds.

Natural opioids, known as opiates, are alkaloids derived from the poppy plant.

Morphine, a benzylisoquinoline, possesses a complex three-dimensional pentacyclic structure with a distinct T-shaped X-ray conformation, enabling interaction with opioid receptors.

It binds strongly to the μ opioid receptor, triggering a cascade of reactions that relieve pain and induce euphoria.

Morphine has a linear pharmacokinetic profile and is rapidly distributed in the body tissues. In the liver, it conjugates with glucuronic acid to undergo renal excretion.

However, morphine can yield adverse effects, including nausea, miosis, drowsiness, constipation, respiratory depression, and cough reflex.

Codeine, a milder μ receptor agonist, is an analgesic and antitussive. However, it can cause respiratory depression and pose a risk of death in children.

Prolonged opiate use fosters tolerance, demanding higher doses for comparable effects, causing addiction, and culminating in withdrawal symptoms upon cessation.