Narcotic Analgesics Flashcards
Opioids
Natural or synthetic morphine-like agents
Enkephalin Structure
Tyr-Gly-Gly-Phe- (Met/Leu)
Endorphins
30aa long- metenkephalin are last 5
Similar acting sites
Natural Opioids
Papaver Somniferum seed- morphine and codeine (3-methyl morphine)
Semi-Synthetic Opioid
Heroin (3,6 diacetyl morphine)
CNS Effects of Morphine
Dec. Pain perception- spinal effect Inc. pain tolerance- supraspinal effect Mood via Nucleus Acumbens- euphoria, dysphoria, restlesness Sedation via locus coeruleus Resp depression via medulla N&V at CTZ Miosis via occulomotor nuclei
Analgesic Effects of Opioids
Spinal- decreased ascending activity
Supraspinal- increased descending activity
Peripheral- opioid receptors expressed peripherally on chronic pain
Neuropathic- hyperalgesia & allodynia
Mu Opioid Receptors
Presynaptic inhibition: Dec. Ca influx
Postsynaptic inhibition: Inc. K influx
GPCR
Long-term: Activates MAP Kinase mediating physical dependence
GI Effects
Inc tone, dec. peristalsis
Delayed passage- increased water reabsorption
Constipation
Dec HCl secretion
Constriction of Sphincter of Oddi- increase bile pressure
Other Effects
Bronchoconstriction and vasodilation- increased histamine release
Urinary retention
Haemodynamic effects
Codeine
Weak agonist-no change in mood
1/10 analgesia of morphine
Antitussive at subanalgesic doses
Heroin
X3 analgesic potency of morphine
Easily passes through BBB
Hydrolysed to morphine and 6-monoacetylmorphine
Less emetic than morphine
Methadone
Slow onset, long duration >24 hours Stabilise addicts Cardiotoxicity risk Oral or IV Less euphoria Attenuates withdrawal syndrome
Remifentanil
Ultra-short acting Methyl ester hydrolysed by esterases IV analgesia in minor surgery Easily controlled T1/2: 5 minutes
Naloxone
Competitive antagonist at all receptors Short half-life: 30 minute duration Precipitates withdrawal symptoms Reduce stress-induced analgesia Rapidly metabolised by liver
