L16- Analgesics (1) Flashcards
What is an analgesic?
A remedy used to relieve pain, irrespective of case
How is pain felt?
- Peripheral noxious stimulation
- Nociception (sensory nerves)
- Pain (perception)
What are drugs with analgesic activity?
- Opioids (morphine-like)
- NSAIDs (aspirine- like)
- Paracetamol
- Local anaesthetics
What are opioid analgesics?
- Any substance whose actions are reversed by naloxone
- Including a number of opiates derived from opium
- Morphine-potent, Codeine- middle
What are the 3 types of opioid receptor?
- Mu (MOR)
- Delta (DOR)
- Kappa (KOR)
What are the 3 opioid peptides?
• Beta endorphins • Enkephalins • Dynorphins all derived from three pro-hormones all share the same N-terminal sequence
What are the cellular actions of opioids?
- Inhibiting adenylyl cyclase enzyme and causes MAP kinase activation
- Inhibits calcium entry into nerve terminals
- MOR/DOR open potassium channels and hyperpolarise nerve cells
- Inhibition of neurotransmitter release
How does descending inhibition work?
- The cortex of the brain detects pain
- Signals to the PAG
- PAG signals to the NRM which sends inhibitory signals to the dorsal horn synapse (5-HT)
- Prevents release of substance P to prevent transmission of signals conveying pain
How do opioids work?
- Inhibit release of substance P in dorsal horn from sensory nerves
- Hyperpolarise neuron in spinothalamic tract
- Produce disinhibition of transmission in PAG and NRPG, to increase output from these nerves to increase inhibition of pain transmission at dorsal horn
What are the effects seen following MOR/DOR activation?
- Spinal and supraspinal analgesia
- Respiratory depression
- Pupil constriction
- Reduced GI motility
- Euphoria and sedation
- Physical dependence
What are the effects seen following KOR activation?
• Spinal analgesia
• Respiratory depression
• Dysphoria and sedation
(removed from use)
What are some opioid drugs used clinically?
• Morphine • Diamorphine (heroine- more lipid soluble than morphine and crosses BBB faster) • Codeine • Methadone • Fentanyl all operate mainly via MOR
What is morphine at the different receptors?
MOR- partial agonist
DOR- agonist
KOR- agonist
What is pentazocine at the different receptors?
MOR- antagonist
DOR- agonist
KOR- agonist
What is buprenorphine at the different receptors?
MOR- partial agonist
DOR- agonist
KOR- antagonist
