6.6 Centrally Acting Analgesics Flashcards
What are analgesics
Analgesics are a class of drugs that are pain killers, they can either be centrally acting (on the CNS) or non-steroidal anti inflammatory drugs. Most analgesics are derived from plants, e.g morphine and aspirin
What is opiate
natural compounds found in the opium poppy
What is an opioid
Any substance, whether natural, endogenous or synthetic, that produces morphine-like effects via opioid receptors
Give some notable opioids
-Morphine (acute & chronic pain, oral & IV admin, many side effects)
-Codeine (mild pain, less potent, pro-drug, oral admin, constipation)
-Pethidine (acute pain, oral & IM admin, used in labour pain, hallucinogenic)
-Oxycodone (acute & chronic pain, oral admin, street drug)
-Fentanyl (acute & chronic pain, pre/post-surgery, IV admin, highly potent)
-Methadone (used in addicts, oral admin, long duration, less withdrawal, no euphoria)
-Loperamide (treatment of diarrhoea, does not cross BBB)
Describe the family of endogenous opioid peptides
They are all small peptides with a tyrosine residue at the N terminus. They include endorphins, dynorphins, metenkephalin and leuenkephalin. A common feature of them is the amine group separated from the phenyl ring by 2 carbon atoms
Describe the primary mechanism of opioid analgesics
They act as agonists at opioid receptors. Opioid receptors are inhibitory G protein coupled receptors, they are coupled to Gi or Go proteins. These agonists either block adenylate cyclase, activate potassium channels, inhibit calcium channels or activate MAPK cascade, all of these will reduce neuronal excitability.
What are some central nervous system mediated effects of opioids
analgesia, euphoria, respiratory depression, depression of cough reflex, nausea & vomiting and pupillary constriction
Describe some of the sites of action on opioid analgesics
The analgesic effects can be mediated in the periphery, spinal cord or brain.
-they inhibit nociceptive afferents
-they inhibit spinal reflexes and transmission of nociceptive impulses through the dorsal horn
-they cause localised release of endorphins in the brain and the spinal cord
-they can also affect the descending pain pathways, acting on the raphe nucleus to induce release of 5-HT in the spinal cord
Describe opioid receptors
There are multiple opioid receptors, the main one being Mu receptor which is the receptor for endorphins and the main site for opioid analgesics (other receptors include delta, kappa and ORL1)
What are some non central nervous system mediated effects of opioids
reduced gastrointestinal motility, itching, bronchoconstriction, hypotension, depression of immune system
What are some opioid antagonists
naxalone - has the greatest affinity for mu receptors, is fast acting and for a short duration. It is used to treat overdoses
naltrexone is similar but for a longer duration
What are some non opioid derived analgesics
antidepressants - neuropathic pain is severe and debilitating, opioids have some effect but tricyclic antidepressents are widly used, they act in the CNS to inhibit noradrenaline and seratonin reuptake
anti seizure drugs - e.g carbamazepine (used to treated trigeminal neuraglia) and gabapentine and pregabalin widely used in neuropathic pain - they block voltage gated calcium channels, hence inhibiting nt releas in spinal cord
cannabinoids - Acts at CB1 receptors in CNS; relieves acute, nociceptive, inflammatory and neuropathic pain in animal models
