Opioids are naturally occurring substances that have several effects on the central nervous system that are mainly mediated by opioid receptors.

Opioid receptors

There are three important classes of opioid receptors and these are denoted by Greek letters:

• μ receptor or Mu receptors

  There are three subtypes of this receptor (μ1, μ2 and μ3). Present in the brainstem and the thalamus of the brain, these receptors are involved in pain relief, respiratory depression, sedation, euphoria, constipation and physical dependence. Mu2 is also associated with itching, prolactin release and anorexia.

• κ receptor or kappa receptor

  Present in limbic and other diencephalic areas of the brain, brainstem and spinal cord, these receptors are involved in pain relief, sedation, loss of breath and dependence.

• δ receptor or delta

  This type of receptor is present in the brain and acts to induce psychiatric effects.

Around 17 types of opioid receptors have been reported in scientific literature. Other less important types include the ε (Epsilon), ι (Iota), λ (Lambda) and ζ (Zeta) receptors. These receptors all have a high affinity for the laevo isomers of opioids. Another type of receptors is the opioid-receptor-like receptor 1, which has the opioid receptor-like property of providing pain relief.

Mechanism of action of opioids

The main effects of opioids result from their binding to opioid receptors and these effects vary depending on which type of receptor an opioid binds to. There are three basic ways in which an opioid receptor is activated:

• Agonist – An agonist molecule causes the full effect of receptor activation to be mediated. For example, morphine activates the μ1 receptor and leads to pain relief. Similarly, morphine acts on the μ2 receptor to cause depression of the respiratory drive as well as addiction or dependence. Furthermore, sedation or sleepiness caused by morphine is mediated via the κ receptor. Morphine has a higher affinity for the μ receptor while ketazocine binds favourably to the κ receptors.
• Antagonist – In contrast to an agonist, an antagonist molecule opposes the action of opioids. Examples of opioid antagonists include naloxone and naltrexone.
• Partial agonists – These molecules produce a less than maximal effect when they bind to opioid receptors.

Pharmacokinetics of opioids in the body

Opioids are absorbed orally as well as by other routes of administration. They are then metabolized by enzymes present in the body, opioid metabolites. This metabolism mainly occurs in the liver. The rate of opioid metabolism is dependent on factors such as age, gender, diet, other medication use, disease states and genetic makeup. Metabolism is usually via glucuronidation or the P450 (CYP) system. The molecules and their metabolites are usually excreted by the kidneys.

Drug	Relative Potency	Nomionized Fraction	Protein Binding	Lipid Solubility
"Morphine"	"1"	++	++	+
Merperidine	0.1	+	+++	++
Hydromorphone	10
Alfentanyl	10 – 25	++++	++++	+++
Fentanyl	75 – 125	+	+++	++++
Remifentanyl	250	+++	+++	++
Sufentanyl	500-1000	++	++++	++++
		+ very low, ++ low, +++ high, ++++ very high

Further Reading

• All Opioids Content
• Opioids – What are Opioids?
• Opioid Uses
• Opioid Side Effects
• Opioid Types

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.