PHAR1101 Lecture Notes - Lecture 4: Cytochrome C Oxidase Subunit Ii, Salicylic Acid, Nonsteroidal Anti-Inflammatory Drug
Morphine & the quest for perfect pain control:
Morphine – the oldest drug?
- 1000AD – suggested by Avicenna to treat diarrhea
- 1522 – Paracelsus describes opium-based elixr
- a potet pai killer ut it e used sparigly.
- 1817 – distributed commercially by company for the first time
- 1827 – commercially sold by Merck, then a single chemist shop, which became a world-leading
pharmaceutical company.
Most systemic analgesics based on:
Salicylates: inhibit prostaglandin synthesis (NSAIDs and COX-2 inhibitors).
Opioids: activate inhibitory systems (selective ligands, delivery techniques).
Morphine:
Morphine and endorphins have structural similarities
Opioid receptors:
- 400 aminoacids
- 7 transmembrane domains
- 3 ajor lasses of reeptors ith 90% of AA’s idetial
Types:
µ - mu – MOR kappa – KOR Delta – DOR
find more resources at oneclass.com
find more resources at oneclass.com
Mu receptor:
- Supraspinal analgesia
- meiosis
- euphoria
- respiratory depression
- nausea/vomiting
- constipation
- urinary retention
- physical dependence
Location:
CNS
- Brain – brain stem (relevant for analgesia)
- limbic system (abuse, addiction)
- cortex (unclear function)
- Dorsal horn of spinal cord – presynaptic (relevant for analgesia)
- postsynaptic
Periphery
- On nociceptive fibers (relevant for analgesia, but only expressed after injury)
Pathways of opioid activity:
find more resources at oneclass.com
find more resources at oneclass.com
Attach at agent-receptor binding site on motor end plate of efferent motor neuron, inhibiting
nociception (release of neurotransmitter to create sensation of pain).
STRONG OPIOIDS
Effects of opioids:
- Respiratory depression – potentially fatal
- Nausea, vomiting
- Constipation
- Sedation
- Hallucinations, confusion
- Physical dependence and tolerance
- Psychological dependence/abuse
Strong opioids:
Morphine remains gold standard
Oxycodone a good alternative – no active metabolites
- additional kappa effect
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Morphine & the quest for perfect pain control: 1000ad suggested by avicenna to treat diarrhea. A (cid:862)pote(cid:374)t pai(cid:374) killer(cid:863) (cid:271)ut (cid:862)it (cid:271)e used spari(cid:374)gly(cid:863). 1817 distributed commercially by company for the first time. 1827 commercially sold by merck, then a single chemist shop, which became a world-leading pharmaceutical company. Salicylates: inhibit prostaglandin synthesis (nsaids and cox-2 inhibitors). Opioids: activate inhibitory systems (selective ligands, delivery techniques). 3 (cid:373)ajor (cid:272)lasses of re(cid:272)eptors (cid:449)ith 90% of aa"s ide(cid:374)ti(cid:272)al. Mu mor kappa kor delta dor. Brain brain stem (relevant for analgesia) Dorsal horn of spinal cord presynaptic (relevant for analgesia) On nociceptive fibers (relevant for analgesia, but only expressed after injury) Attach at agent-receptor binding site on motor end plate of efferent motor neuron, inhibiting nociception (release of neurotransmitter to create sensation of pain). Oxycodone a good alternative no active metabolites. Methadone a good alternative: - nmda antagonist effect.
