Pain III: Adjuncts - McDougall 3 Flashcards Preview

Pharmacology 3001 > Pain III: Adjuncts - McDougall 3 > Flashcards

Flashcards in Pain III: Adjuncts - McDougall 3 Deck (23)
1

Advantages of smoked cannabis

Pain relief, improved sleep, reduced anxiety

2

Disadvantages of smoked cannabis

Not appropriate for al patients
Psychotropic effects
Smoking is not safest mode of administration

3

Phytocannabinoids

Derived from cannabis plant

4

Synthetocannabinoids

Man made
Can reduce nociception in arthritic joints locally

5

Endocannabinoids

Present naturally in the body
Ie. Anandamide
May be an effective system to control arthritis pain naturally
Local inhibition of breakdown reduces nociception and inflammation

6

Cannabinoid receptors

CB1, CB2

7

CB1

Located on central and peripheral nerves
Agonist decreases signal in OA joint mechanosensitivity

8

CB2

Associated with immunocytes

9

Endocannabinoid synthesis

Phospholipids - phospholipase C _ archidonic acid- anandamide, 2AG, Noladin, NADA, Virodhamine

10

Limitations of endocannabinoids

Only switched on when we need them
Enzymes are produced that chew then up pretty quickly

11

FAAH inihibition

Fatty acid amide hydrolase
Increase bioavailability of Anandamide, reducing mechanosensitivity of joints

12

AMT

Anandamide membrane transporter

13

FAAH

Fatty acid amide hydrolase
Processes anandamide into ethanol amine and arachidonic acid

14

NAPE

N-arichidonyl-phosphatidylehtanolamine
Hydrolyzed into anandamine

15

Leukocyte rolling and inflammation

Endocannabinoids decrease rolling
Prevents leukocytes from entering tissue and releasing compounds to cause inflammation and sensitization of the peripheral nerve

16

TRPs

Transient receptor potential channels
Molecular sensors of taste, temperature and pain

17

TRPV1

Chilli receptor
Expressed on C-fibres and Adelta-fibres, in laminae I/II of spinal cord
Non-selective cation channel
Endogenous ligands: anandamide, endovanilloids
Exogenous ligands: capsaicin, resiniferatoxin

18

Capsaicin

Hot component of chilli peppers
Acts on sensory nerves
Initial sensitization followed by prolonged desensitization

19

Acute low concentration (TRPV1)

Sensitization, followed by Ca2+ dependent phosphorylation of ion channel causing desensitization

20

Prolonged exposure/high concentration (TRPV1)

Destruction of C- and Adelta-fibres
Destruction recovers in adults but nerve loss is permanent in neonates

21

Therapeutic potential of TRPV1

Topical capsaicin creams or patch for peripheral neuropathic pain
Found greater pain relied than oral medications
Adverse effects: skin irritation, burning oedema

22

Therapeutic potential of TRPV1 antagonists

AMG517
Highly potent, selective, oral bioavailability
HOWEVER, systemic TRPV1 blockade, causing concentration dependent hyperthermia lasting days: blocked thermoregulatory centres in CNS

23

TRPM8

Cool TRP
Melastatin TRP family
Non-selective cation channel
15% of small diameter sensory neurons
Expression increases in models of neuropathic pain
Exogenous ligands: menthol, icilin, spearmint