Opioids and their Effects

Opium Poppy
- Noted as a plant that has cultivated worldwide, with historical mention of flowers seen in Eastern Europe.

Key Opiates in Opium:
- Contains morphine, codeine, and other opiates.
- Morphine and codeine were the first drugs discovered, with morphine noted around 1884.

General Information:
- Opioid receptors mediate the effects of opiates.
- Types:
- Naturally occurring opiates: Morphine, Codeine, Heroin
- Semi-synthetic: Hydromorphone
- Fully-synthetic: Fentanyl
Therapeutic Uses:
- Pain management
- Induction of sleep
- Cough suppression
- Treatment of diarrhea

** Structure**:
- Proposed structure illustrated in Figure 11.8, indicating that Opioid receptors are G-protein-coupled receptors (GPCRs) with 7 transmembrane segments.

Receptor Activation:
- Cause opening of K+ channels (Postsynaptic inhibition).
- Close Ca2+ channels, which reduces neurotransmitter release (Presynaptic inhibition).
Consequences of Activation:
- Inhibitory actions of endogenous opioids:
- Visual representation indicated in Figure 11.11 on downstream inhibition, opening K+ channels leading to reduced activity in target cells.

Three receptor types:
- µ (Mu)
- δ (Delta)
- κ (Kappa)
Note on Variability:
- Expression levels of these receptors vary depending on cell type and specific brain regions.
Endogenous Opioid Proteins:
- Enkephalins, Endorphins, and Dynorphins bind specifically to each receptor type:
- Dynorphins bind to κ-receptors
- Endorphins bind to µ-receptors
- Enkephalins bind to δ-receptors

Morphine:
- Identified as a strong agonist of the µ-receptors.
- Administration methods: Injection or oral consumption.
- Recreational use noted for smoking opium due to rapid absorption from the lungs.
Effects of Morphine:
- Low/Moderate Doses: Pain relief and relaxation.
- Higher Doses: Euphoria and reinforcement.
- Very High Doses: Risk of respiratory failure, coma, and ‘death’, which characterizes an overdose.

Nociceptors:
- Receptor types embedded in skin, joints that respond to tissue damage, heat, and cold, transmitting signals via the ascending pain pathways to the brain.
Pain Perception:
- Divided into:
- Physical Component: Involves spinal cord, thalamus, somatosensory cortex.
- Emotional Component: Involves thalamus, limbic structures, anterior cingulate cortex.
Mechanism of Pain Management via Opioids:
- Inhibit pain pathways in the spinal cord through:
1. Inhibitory interneurons that mediate responses to the brain.
2. Direct action on spinal projection neurons.

Reinforcement Mechanisms:
- Activation of µ-receptors on GABAergic neurons in the VTA leads to inhibition of these neurons, resulting in disinhibition of VTA neurons, which enhances dopamine release in the mesolimbic pathway—critical for reinforcement and euphoria.

Statistical Overview:
- Graph depicting the causes of overdose deaths from 1999 to 2019 across different substances, including synthetic opioids, prescription opioids, heroin, psychostimulants, and antidepressants.
Breathing Regulation:
- Breathing regulated by brainstem respiratory nuclei that contain neurons responsible for generating inspiratory bursts essential for breathing.
- Binding of opioids to mu receptors in these nuclei diminishes the inspiratory neuronal activity leading to reduced respiratory drive.

Characteristics of Fentanyl:
- Defined as a synthetic opioid approximately 100 times more potent than morphine.
- Inexpensive to manufacture and frequently found mixed with other street drugs.

Administration of Naloxone (Narcan):
- Competitive opioid receptor antagonist.
- Mechanism: Competes for binding sites on opioid receptors, effectively displacing opioids such as fentanyl at high concentrations, allowing normal respiration to resume.

Consequences of Use:
- Re-administering opioids during withdrawal counteracts symptoms and is often necessary in treatment strategies.
- Methadone: Used as a MOR agonist to alleviate withdrawal symptoms, with a slower action when taken orally, providing no rapid dopamine release.

Summary of Effects:
- A comprehensive overview of the pharmacology, therapeutic uses, risks, mechanisms of action, and substances associated with opioid use, including the significance of receptors, signaling pathways, and treatment approaches for opioid use disorders.
This study guide acts as a definitive resource for understanding the complex interactions and implications associated with opioids, their effects, and the ongoing challenges related to their use in medical and recreational contexts.