Pharmacology of Opioids Opioids on the market Codeine, fentanyl, hydromorphone, oxycodone, meperidine, methadone, pentazocine, buprenorphine, loperamide Endogenous opiate peptides

Enkephalin δ opioid receptor

Dynorphin κ opioid receptor

β-endorphin μ opioid receptor

Endomorphins μ opioid receptor selective Opioid antagonists Naloxone, naltrexone, methylnaltrexone, alvimopan Opioid receptors

G protein coupled receptors located in brain, spinal cord, & periphery

Three types o μ opioid receptor: analgesia & euphoria o δ opioid receptor: analgesia o κ opioid receptor: analgesia & dysphoria

Opioid receptor activation leads to o Gi: (–) adenylyl cyclase o Go: (+) K+ channels o Go: (–) Ca2+ channels

Effects of opioids

Analgesia: produces absence of pain without causing loss of consciousness o Mechanism

Stimuli (mechanical, chemical, electrical) activates nociceptors in dorsal root ganglion travels through spinothalamic tract information received by sensory afferent neuron

(+) Opioid receptors stop pain transmission

(–) Presynaptic Ca2+ channels ↓ neurotransmitter release

(+) Postsynaptic K+ channels hyperpolarization prevents activation of neuron

Respiratory depression o Depresses brainstem’s respiratory center o Effects: ↓rate, ↓minute volume, ↓tidal exchange o Dangerous: main cause of death in opioid toxicity

↑Risk: combination of opioids with alcohol, sedatives, hypnotics, anesthetics, tranquilizers

Euphoria: effect of μ opioid receptor, responsible for addictive property (dysphoria: effect of κ opioid receptor)

Drowsiness: “opium dream”

Antitussive: depresses cough reflect

N&V: stimulates CTZ, not GI related

Miosis: pupil constriction, activation of parasympathetic system

Neuroendocrine effect: (–)GRH + (–)CRF ↓LH, ↓FSH, ↓ACTH, ↑ADH

Hypotension: ↓sympathetic outflow, ↓baroreceptor reflexes, ↓PVR

Thermoregulation: affects hypothalamic heat regulation o Normal doses + μ receptors hypothermia (↓temp) o High doses + δ hyperthermia (↑temp)

Pruritus: possibly mediated by histamine release

GI effects: constipation due to ↓GI smooth muscle contractions, ↓motility, ↑emptying time, ↓HCl secretion