Pain III - Adjunct Analgesics Flashcards
List three advantages and three disadvantages to smoking cannabis for analgesia
Advantages
- Pain relief
- Improved sleep
- Reduced anxiety
Disadvantages
- Not appropriate for all patients
- Psychotropic side effects
- Smoking is not very safe mode of administration
Give a brief history of cannabis
8000 BC: clothing use
2700 BC: Gout and malaria treatment in China
1611: Colonial settlers bring cannabis to N america
1800s: Explosion of cannabis studies in Europe
1850: Used in US pharmacy
1935: Cannabis in 28 treatment programs, research is being done
1937: Marihuana Tax Act (stop)
1970: THC isolated as active compound
List the uses for medical cannabis from most to least prevalent
- Arthritis
- Spinal cord injury
- AIDS/HIV
- Multiple sclerosis
- Spinal cord disease
- Cancer
- Epilepsy
List the main types of cannibinoids
- Phytocannabinoids (derived from Cannabis sativa)
- Synthetocannabinoids
- Endocannabinoids (eg. anandamide)
Contrast the two cannabinoid receptors
CB1: Central and peripheral nerves
CB2: Associated with immunocytes
List the steps of endocannabinoid synthesis from tissue damage.
- Tissue damage
- Phospholipids are metabolized by phospholipase C and phospholipase A2
Phospholipase C facilitates synthesis of endocannabinoids from phospholipids
Phospholipase A2 synthesizes arachidonic acid from phospholipids, which goes on to become endocannabinoids
What is the effect of CB1 agonists on osteoarthritic joint mechanosensitivity?
It inhibits the spike activity of nociceptors after noxious movement (and normal movement, to some extent)
What are some limits of endocannabinoid use for pain management?
Endocannabinoids are metabolized and cleared very quickly. Therefore it may be beneficial to block endocannabinoid breakdown.
How can endocannabinoid breakdown be inhibited for pain management?
FAAH (fatty acid amide hydrolase) can be inhibited pharmaceutically.
ECBs are transported into the cell with transporters, where they are metabolized to ethanolamine and arachidonic acid via FAAH.
FAAH inhibition reduces osteoarthritic joint nociception but does not inhibit mechanosensitivity on control joints (better than just agonists)!
Can endocannabinoids alter joint inflammation?
Yes. Local endocannabinoid administration effectively blocks leukocyte trafficking and adhesion to endothelium.
What are transient receptor potential channels (TRPs)?
- Named after the role of these channels in Drosophila phototransduction
- 30 different TRPs grouped into 6 families
- Molecular sensors of taste, temperature and pain
List the taste TRP channels in order of coldest to hottest.. (6)
- TRPA1 (garlic, cinnamon)
- TRPM8 (mint)
- TRPV4
- TRPV3 (camphor)
- TRPV1 (chili peppers)
- TRPV2
What is the chili receptor? Where is it found peripherally?
TRPV1
- A non-selective cation channel (depolarizer)
Capsaicin causes initial sensitization followed by prolonged desensitization (that can last a long time) through calcium dependent phosphorylation of ion channels.
Expressed on C-fibres and Aδ-fibres
Also found in lamina I and II of spinal cord (consistent with C and Aδ fibre expression)
What are two endogenous and two exogenous ligands for TRPV1?
Endogenous
- Anandamide
- Endovanilloids
Exogenous
- Capsaicin
- Resiniferatoxin
What happens when there is prolonged exposure to TRPV1 channels, of high concentrations of agonist (eg. capsaicin)?
Destruction of C and Aδ fibres as well as receptor desensitization through calcium dependent ion channel phosphorylation. This destruction is recoverable in adults, but can be permanent for neonates.
This can be exploited for pain therapy. Topical capsaicin creams (0.025 - 0.07%) or 8% capsaicin patches (which need to be administered along with local analgesia).
