Opioids and Pain Flashcards
Nociception
The physiological processes in response to a noxious stimulus
Very immediate
Activates particular sensory nerve
Allodynia
Pain in response to a normally innocuous stimulus
Hyperalgesia
Enhanced pain to a normally painful stimulus
Nociceptive Pain
Direct activation of nociceptors by noxious stimuli
Ex: touching something hot
Inflammatory Pain
Activation by inflammatory mediators
Ex: rheumatoid arthritis
Neuropathic Pain
Pain arising from nerve damage
Ex: Postherpetic neuralgia
Patient looks normal, but damage to nervous system causes extreme pain
Opiate
Drug derived from opium
Opioid
Agents with opiate-like actions
- synthetic drugs
- proteins that mimic opiate actions
(endorphins)
Narcotic
2 Definitions
- Sleep inducing (Pharmacological)
- Drugs producing dependence (Legal)
During acute inflammation…
Upregulation of opioid receptors
Opioid analgesia very effective
During chronic inflammation…
Downregulation of opioid receptors
Opioid analgesia less effective
Negative Side Effects of Opioids
Severe constipation, somnolescence, cardiorespiratory depression
Tolerance
Dependence (Addiction)
Physical Dependence
Drug withdrawal produces physical abstinence syndrome:
Mild: lacrimation, sweating, yawning
Severe: anorexia, cramps, nausea, vomiting, restlessness, irritability, tremor, HR/BP changes, chills, spasms, PAIN
Psychological Dependence
Compulsive drug seeking behaviour
Occurs with drugs with mood enhancing properties
Activates dopaminergic circuits (endogenous reward systems)
Treatment of Dependence
Cessation of drug intake
Naltrexone (μ-antagonist)
Methadone (μ-agonist – good oral availability (no more injections), selective, long-lasting/slow withdrawal
Peripherally restricted opioids
Can target pain at the source
Reduce sensitization of nociceptors
Do not pass the blood brain barrier therefore less likely to cause addiction issues, centrally-mediated side-effects (e.g. respiratory depression)
How to improve opioid receptor levels
Inhibit β-arrestin activity = reduced receptor internalization
Inhibit receptor degradation (protease inhibitors)
Promote receptor recycling
4 Opioid receptor subtypes and their function
Mu, kappa delta (inhibit neuronal depolarization)
NOP (neuronal depolarization
2 Ways to reduce pain transmission
- On presynaptic nerve terminal: opioid binds, reduces release of excitatory NTs and reduce Ca input which feeds back into inhibition of release
- On postsynaptic nerve terminal: increase K permeability (hyperpolarization)
