Introduction to Analgesic Drugs - Other

Question 1

How are TRPV1 agonists relevant for analgesia?

Answer 1

TRPV1 is stimulated by vanilloids (e.g. capsaicin); agonists rapidly desensitising the channel with a decrease in TRPV1 activity, where a burning sensation is felt followed by analgesia - over-activation.

Question 2

How are TRPV1 antagonists relevant for analgesia?

Answer 2

TRPV1 is a nonselective cation channel highly expressed in sensory nerves + the CNS too; activated by inflammatory conditions such as > 43 °C, low pH/acidic conditions, capsaicin (chili), and allyl isothiocyanate (mustard/wasabi).

This produces a painful, burning sensation; antagonists thus reduce this.

Question 3

What evidence/treatment is there for TRPV1 agonists?

Answer 3

Topical capsaicin; 0.075% cream licensed for symptomatic treatment of post-herpetic (shingles) neuralgia, 8% pathc for peripheral neuropathic pain (non-diabetic).

Question 4

What must topical capsaicin treatment be co-administered with?

Answer 4

EMLA cream; intense burning w/capsaicin (TRPV1 activation)

Question 5

What are tramadol’s multiple targets/actions for analgesia?

Answer 5

• Weak μ-opioid receptor agonist
• 5-HT (serotonin) releaser
• Noradrenaline reuptake inhibitor

Question 6

What is tramadol metabolised to/what effect does this have on its activity?

Answer 6

• Metabolised to O-desmethyltramadol; a much more potent μ-opioid agonist (greater analgesia).

Question 7

How does tramadol add to its opioid effects in regards to monoamine control?

Answer 7

Potentiation (increasing strength of nerve impulses) of descending monoamine control of pain transmission.

Question 8

Where does tramadol show antagonist activity? (list up to 6)

Answer 8

• NMDA receptors
• 5HT2C receptors
• (α7)5 nAChR
• M1 and M3 mAChR

Question 9

Where else does tramadol show agonism?

Answer 9

TRPV1.

Question 10

What properties of tramadol reduce its abuse potential?

Answer 10

Long half-life due to pharmacokinetics; there is no rapid washout/come down as a result.

Question 11

What might tramadol overdose increase risk of?

Answer 11

Seizures.

Question 12

What is the dual mode of action of Tapentadol?

Answer 12

• μ-opioid receptor agonist

- Noradrenaline reuptake (NET) inhibitor

Question 13

How does tapentadol potentiate pain?

Answer 13

Via the descending pathway.

Question 14

What are the benefits of using tapentadol compared with traditional opioids?

Answer 14

• Provides analgesia comparable w/ other opioid analgesics such as oxycodone and pethidine, but with a more tolerable side effect profile
• Dual action; different components of pain pathway

Question 15

What are the cautions associated with Tapentadol?

Hint: like Tramadol

Answer 15

• Caution in seizure-prone patients.

Question 16

Where do α2-adrenoceptor agonists exert an analgesic effect?

Answer 16

• Act on presynaptic receptors to reduce NT release e.g. clonidine

Question 17

Why are α2-adrenoceptor agonists not commonly used for analgesia (and when would they be?)

Answer 17

Lack of selectivity; there are many α2 receptors in the body, thus not used apart from migraine prevention.

Question 18

How may neuropathic pain come about?

Answer 18

Via damage to neural tissue: trauma, herpes, diabetes, chemotherapy, HIV, alcoholism.

Question 19

What is ‘central pain’ in regards to stroke and neuropathic pain?

Answer 19

Pain w/o a stimulus.

Question 20

What is neuropathic pain caused/accompanied by?

Answer 20

• Peripheral and central sensitisation of pain pathways

- Accompanied by allodynia

Question 21

What is allodynia?

Answer 21

Pain due to normally innocuous stimuli

Question 22

What is common treatment for neuropathic pain?

Answer 22

Tricyclic antidepressants and anti-epileptics.

Question 23

How do tricyclic antidepressants (such as amitriptyline) operate as an adjuvant analgesic?

Answer 23

They enhance descending monoaminergic pain control (e.g. serotonin, dopamine, and noradrenaline)

Question 24

How do doses differ for tricyclic antidepressants in treating pain and depression?

Answer 24

The dose for pain is less than for depression; 10mg at night increasing to 75mg if necessary; depression target dose = 150-200mg daily).

Question 25

What is first-line for diabetic neuropathy?

Answer 25

Pregabalin and gabapentin.

Question 26

How do the antileptics pregabalin/gabapentin carry out their analgesic effect?

Answer 26

• Interact with VGCCs (Ca2+)
• Presynaptic NMDA receptors
• Enhance descending noradrenergic pain control

Question 27

What is carbamazepine effective in treating and how does it work?

Answer 27

• Trigeminal neuralgia (chronic pain in face)

- Acts on VGSCs

Question 28

What can the anticonvulsant lamotrigine also be used to treat?

Answer 28

• Post-stroke pain

- HIV/AIDS-related neuropathy

Question 29

How does the placebo effect work in favour of acupuncture?

Answer 29

• Descending control is under a certain amount of cognitive control; can be very strong.