Pharmacology of pain Flashcards
Which drugs are used to treat pain?
Paracetamol
Opioids
Co-amoxiclav
Lactulose
What is the drug target for paracetamol?
Unclear
- 5HT3 receptor
- Cannabinoid reuptake proteins
- Peroxidase
What is the primary mechanism of action of paracetamol?
At peripheral sites, may inhibit a peroxidase enzyme which converts arachidonic acid to prostaglandins (1st step in this pathway involves the enzyme, cyclooxygenase). The ability of paracetamol to inhibit peroxidase can be blocked if excessive levels of peroxide build up (as is commonly seen in inflammation)
Activation of descending serotonergic pathways possibly via 5HT3 receptor activation
Inhibits reuptake of endogenous endocannabinoids, which would increase activation of cannabinoid receptors - this may contribute to activation of descending pathways
What are the main side effects of paracetamol?
Relatively safe drug with few common side effects
OVERDOSE:
Liver damage and less frequently renal damage
Nausea and vomiting early features of poisoning (settle in 24h).
Onset of right subcostal pain after 24hindicates hepatic necrosis.
What are examples of weak opioids?
Codeine
Tramadol
What are examples of strong opioids?
Morphine, fentanyl
What is the target of opioids?
Opioid receptor
What is the primary mechanism of action of opioids?
Over-arching mechanism at a cellular level is a depressant effect on cellular activity. Multiple sites within pain pathway, where activation of the opioid receptor leads to decreased perception or increased tolerance to pain.
Anti-tussive effect due to decreased activation of afferent nerves relaying cough stimulus from airways to brain
What are the side effects of opioids?
Mild – nausea & vomiting (increase activity in chemoreceptor trigger zone) and constipation (opioid receptors in GIT can reduce gut motility)
OVERDOSE - respiratory depression (direct and indirect inhibition of respiratory control centre.)
What is the drug target for co-amoxiclav?
Amoxicillin = penicillin binding proteins Clavulanate = beta lactamase
What is the primary mechanism of action of co-amoxiclav?
Amoxicillin binds to bacterial penicillin binding proteins. This prevents transpeptidation (the cross linking process for bacterial cell wall synthesis)
Clavulanate is an inhibitor of beta lactamase. Beta lactamase is a bacterial enzyme that can degrade beta lactam anti-biotics and thus confer resistance to these anti-biotics.
What are the side effects of co-amoxiclav?
Amoxicillin is well tolerated. Most common side effects are nausea and diarrhoea.
What is the drug target for lactulose?
No drug target
What is the primary mechanism of action of lactulose?
Lactulose is a non-absorbable disaccharide. It reaches the large bowel unchanged. This causes water retention via osmosis and an easier to pass stool. It can also be metabolised by colonic bacteria. The colonic metabolism of sugars has an additional laxative effect.
What are the side effects of lactulose?
Abdominal pain, diarrhoea, flatulence, nausea
What are the 3 rungs of the WHO pain ladder?
- Mild pain
- Mild to moderate pain
- Moderate to severe pain
What is the treatment of mild pain?
Non opioid with/without adjuvant therapy
What is the treatment of mild to moderate pain?
Weak opioid
+/- nonopioid
+/- adjuvant therapy
What is the treatment of moderate to severe pain?
Strong opioid
+/- non opioid
+/- adjuvant therapy
What are the parts of the pain pathway?
Transduction
Transmission
Perception
Modulation
Why are NSAIDS anti-inflammatory but Paracetamol is not?
NSAIDS stop the productions of prostaglandins. Prostaglandins normally cause sensory neurones to fire at a faster rate. Removing prostaglandins desensitises them
Paracetamol acts on the peroxidase which converts the PG intermediate to a PG
In a normal tissue with no inflammation you are going to have the prevention of PG synthesis with either Paracetamol and NSAIDs
The difference comes when we are the tissue is inflamed
When is lactulose often prescribed?
prior to commencement of opioid therapy to improve symptoms associated with constipation
How long does lactulose take to work?
Begins working within 8-12 hours but may take up to 2 days to improve constipation.
What type of AB is amoxicillin?
Semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms
