opioids

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).

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.

Categories
- Natural, semi-synthetic, and synthetic opioids.
- Examples of natural derivatives: morphine and codeine.
- Synthetic examples include fentanyl and methadone.

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.

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 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.

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.

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.

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.

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.

Potential Risks
- Impairment of cognition and high rates of addiction.
- Respiratory depression, particularly risky in combination with CNS depressants.

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.

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.