Endorphins and Opioids

Endorphins are endogenous opioid peptides that function as natural painkillers and regulate mood, stress, and pleasure. Opioids, both endogenous and exogenous, act on opioid receptors to modulate pain perception.

Opioids can be classified into four major categories:

• Natural Opioids: Derived from the opium poppy (e.g., Morphine, Codeine)
• Semi-Synthetic Opioids: Chemically modified versions of natural opioids (e.g., Heroin, Oxycodone, Hydrocodone, Hydromorphone)
• Synthetic Opioids: Fully synthetic opioids created in the laboratory (e.g., Fentanyl, Methadone, Tramadol)
• Endogenous Opioids: Naturally occurring peptides in the body (e.g., Endorphins, Enkephalins, Dynorphins)

Opioids bind to opioid receptors in the CNS, including mu (μ), kappa (κ), and delta (δ) receptors, to produce their analgesic and side effects. These receptors inhibit neurotransmitter release, leading to pain relief, euphoria, and sedation.

Mechanism

Morphine and codeine act primarily on mu-opioid receptors to provide analgesia. Codeine is a prodrug, metabolized into morphine in the body.

Therapeutic Uses

• Morphine: Severe pain management, postoperative pain, cancer pain, and palliative care.
• Codeine: Mild to moderate pain, antitussive (cough suppressant) effects.

Adverse Effects

• Morphine: Sedation, respiratory depression, constipation, nausea, vomiting, hypotension.
• Codeine: Drowsiness, constipation, nausea, vomiting, potential for misuse.

Contraindications

• Morphine: Respiratory depression, acute or severe bronchial asthma, head injury, GI obstruction.
• Codeine: Children under 12 years old, respiratory issues, hypersensitivity.

Mechanism

These drugs are derived from morphine and bind to mu-opioid receptors. Heroin is metabolized to morphine in the body, while oxycodone and hydrocodone are semisynthetic opioids with modified structures.

Therapeutic Uses

• Heroin: Historically used for pain management but is now illegal in many places.
• Oxycodone: Severe pain management, postoperative recovery.
• Hydrocodone: Moderate to severe pain, often combined with acetaminophen.
• Hydromorphone: Severe pain relief in patients with opioid tolerance.

Adverse Effects

• Heroin: Euphoria, drowsiness, respiratory depression, overdose, addiction.
• Oxycodone: Constipation, dizziness, nausea, abuse potential.
• Hydrocodone: Drowsiness, constipation, dizziness, respiratory depression.
• Hydromorphone: Drowsiness, constipation, nausea, respiratory depression.

Contraindications

• Heroin: Respiratory depression, acute asthma, addiction potential.
• Oxycodone: Respiratory depression, severe asthma, GI obstruction.
• Hydrocodone: Respiratory disease, obstructive airway disease.
• Hydromorphone: Respiratory depression, GI obstruction.

Mechanism

Fentanyl and methadone are potent synthetic opioids that bind to mu-opioid receptors, while tramadol also inhibits serotonin and norepinephrine reuptake.

Therapeutic Uses

• Fentanyl: Severe pain management, especially in cancer patients.
• Methadone: Chronic pain management, opioid addiction treatment.
• Tramadol: Mild to moderate pain relief, osteoarthritis, neuropathic pain.

Adverse Effects

• Fentanyl: Respiratory depression, hypotension, bradycardia, addiction potential, overdose risk.
• Methadone: Respiratory depression, QT prolongation, constipation, dependence.
• Tramadol: Seizures, nausea, dizziness, constipation, serotonin syndrome.

Contraindications

• Fentanyl: Respiratory depression, acute asthma, hypersensitivity.
• Methadone: Respiratory depression, recent myocardial infarction, QT prolongation.
• Tramadol: History of seizures, serotonin syndrome, opioid intolerance.

Opioids are potent analgesics but carry significant risks such as addiction, overdose, and other serious adverse effects. Careful management and monitoring are essential for safe use in pain management.