Introduction to Analgesic Drugs - Other Flashcards
How are TRPV1 agonists relevant for analgesia?
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.
How are TRPV1 antagonists relevant for analgesia?
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.
What evidence/treatment is there for TRPV1 agonists?
Topical capsaicin; 0.075% cream licensed for symptomatic treatment of post-herpetic (shingles) neuralgia, 8% pathc for peripheral neuropathic pain (non-diabetic).
What must topical capsaicin treatment be co-administered with?
EMLA cream; intense burning w/capsaicin (TRPV1 activation)
What are tramadol’s multiple targets/actions for analgesia?
- Weak μ-opioid receptor agonist
- 5-HT (serotonin) releaser
- Noradrenaline reuptake inhibitor
What is tramadol metabolised to/what effect does this have on its activity?
- Metabolised to O-desmethyltramadol; a much more potent μ-opioid agonist (greater analgesia).
How does tramadol add to its opioid effects in regards to monoamine control?
Potentiation (increasing strength of nerve impulses) of descending monoamine control of pain transmission.
Where does tramadol show antagonist activity? (list up to 6)
- NMDA receptors
- 5HT2C receptors
- (α7)5 nAChR
- M1 and M3 mAChR
Where else does tramadol show agonism?
TRPV1.
What properties of tramadol reduce its abuse potential?
Long half-life due to pharmacokinetics; there is no rapid washout/come down as a result.
What might tramadol overdose increase risk of?
Seizures.
What is the dual mode of action of Tapentadol?
- μ-opioid receptor agonist
- Noradrenaline reuptake (NET) inhibitor
How does tapentadol potentiate pain?
Via the descending pathway.
What are the benefits of using tapentadol compared with traditional opioids?
- 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
What are the cautions associated with Tapentadol?
Hint: like Tramadol
- Caution in seizure-prone patients.
Where do α2-adrenoceptor agonists exert an analgesic effect?
- Act on presynaptic receptors to reduce NT release e.g. clonidine
Why are α2-adrenoceptor agonists not commonly used for analgesia (and when would they be?)
Lack of selectivity; there are many α2 receptors in the body, thus not used apart from migraine prevention.
How may neuropathic pain come about?
Via damage to neural tissue: trauma, herpes, diabetes, chemotherapy, HIV, alcoholism.
What is ‘central pain’ in regards to stroke and neuropathic pain?
Pain w/o a stimulus.
What is neuropathic pain caused/accompanied by?
- Peripheral and central sensitisation of pain pathways
- Accompanied by allodynia
What is allodynia?
Pain due to normally innocuous stimuli
What is common treatment for neuropathic pain?
Tricyclic antidepressants and anti-epileptics.
How do tricyclic antidepressants (such as amitriptyline) operate as an adjuvant analgesic?
They enhance descending monoaminergic pain control (e.g. serotonin, dopamine, and noradrenaline)
How do doses differ for tricyclic antidepressants in treating pain and depression?
The dose for pain is less than for depression; 10mg at night increasing to 75mg if necessary; depression target dose = 150-200mg daily).
