Introduction to Opioids

• Historical Context

  • Opioids have a complex history: initially praised for their medicinal benefits, later criticized for their addictive properties.

  • Commonly prescribed for analgesia (pain relief).

Opium History

• Early Use

  • Opium usage dates back to the late 1800s, with products like laudanum and paragoric available over the counter.

  • Bayer company used to include heroin in their medications.

• Current Perceptions

  • Shifted from common medicinal use to scrutiny concerning addiction and overdose.

Types of Opioids

• Categories

  • Natural, semi-synthetic, and synthetic opioids.

  • Examples of natural derivatives: morphine and codeine.

  • Synthetic examples include fentanyl and methadone.

Mechanism of Action

• Opioid Receptors

  • Four primary receptor types: mu, delta, kappa, and nociceptin.

  • Mu receptors are primarily targeted by most clinically relevant opioids.

• Effects of Opioids

  • Produce analgesia and can induce euphoria.

  • Side effects: cough suppression, reduction of diarrhea, potential for addiction.

  • High tolerance potential; dependency and uncomfortable withdrawal symptoms.

Risks of Opioids

• Overdose Statistics

  • Overdose rates have increased significantly, particularly with synthetic opioids like fentanyl.

  • Comparisons show opioids to have higher mortality rates compared to other drugs.

• Health Risks

  • Risks include cognitive impairment and respiratory depression, especially when combined with other sedatives like alcohol.

  • Opioid overdose can lead to the opioid triad: coma, depressed respiration, and pinpoint pupils.

Pain Perception

• Pain Types

  • Acute pain: Immediate response, adaptive function post-injury.

  • Chronic pain: Ongoing, maladaptive, causes misery.

• Nociception

  • The process of sensing pain; nociceptors are the receptors involved in this process.

  • The body's response differentiates between early (acute) and late (chronic) pain pathways.

Brain Activation in Pain Responses

• Pain Pathways

  • Ascending pathways send pain signals to the brain.

  • Early pain activates the primary somatosensory cortex; late pain is processed in the anterior cingulate cortex.

• Descending Modulation

  • Periaqueductal gray (PAG) is crucial in modulating pain signals, rich in opioid receptors.

  • Opioids influence both ascending and descending pathways, blocking pain signaling.

Opioid Addiction

• Risk Factors

  • Family history, young age, prior substance abuse, high-risk environments.

  • Addiction onset occurs, on average, after a year of use.

• Statistics

  • Less than 5% of chronic pain patients prescribed opioids become addicted.

  • Around 25% of heroin users develop a full addiction.

Opioids and Reward Pathways

• Reward Circuitry

  • Involves the ventral tegmental area, which has connections to the nucleus accumbens and prefrontal cortex.

• Mechanism of Addiction

  • Opioids block GABAergic inhibition of dopamine neurons, leading to increased dopamine release and enhanced reward feelings.

Kratom

• Overview

  • An unregulated herbal substance that stimulates mu opioid receptors and affects serotonin and norepinephrine.

  • Used for anxiety, pain relief, and as a self-medication for opioid dependence.

Harmful Effects of Opioids

• Potential Risks

  • Impairment of cognition and high rates of addiction.

  • Respiratory depression, particularly risky in combination with CNS depressants.

Withdrawal Symptoms

• Characteristics

  • Pain sensitivity, insomnia, and anxiety during withdrawal compared to drug effects.

  • Withdrawals typically start within days of cessation and can last around five days.

Treatment for Opioid Dependence

• Options

  • Ultra Rapid Detox: Anesthetized patients receive clonidine and naltrexone to reduce withdrawal symptoms.

  • Methadone: A full agonist that requires daily administration for extended periods.

  • Buprenorphine: A partial agonist that can help wean individuals off opioids, with lower addictive risks.

  • Heroin Maintenance: Medically supervised heroin administration is available in certain regions, providing harm reduction.