pharmacology of pain Flashcards
paracetamol primary mechanism of action
Paracetamol Still not totally clear.
At peripheral sites, may inhibit a peroxidase enzyme which is involved in the conversion of 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.
drug target of paracetamol
Unclear.
5HT3 receptors/Cannabinoid reuptake proteins/Peroxidase
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.
oaracetamol extra info
Analgesic and anti-pyretic.
Does NOT possess anti-inflammatory activity.
A number of medications contain paracetamol, so care must be taken to avoid accidental overdose. Legal restrictions on sales of paracetamol have significantly reduced the number of fatalities from overdose in the UK although, regrettably, ingestion of large amounts of paracetamol remains a common method of suicide.
In 2020, paracetamol was the 14th most commonly prescribed drug in the West London area.
Probably the most commonly prescribed over the counter (OTC) medicine in the world.
opiods strength
Opioids:
Weak – codeine, tramadol
Strong – morphine, fentanyl, (heroin)
opiods mechnism of action
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
opiod mechanism of action
opioid receptor
side effects of opioid
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.)
opiods extra info
Prescriptions for opioids in the UK have more than doubled in the last 20 years.
In 2020, several ‘weak’ opioids or weak opioid/paracetamol combinations were among the most commonly prescribed drugs in the West London area.
Co-codamol (paracetamol + codeine) = 26th
Co-dydramol (paracetamol + dihydrocodeine) = 60th
Tramadol = 69th
co amoxiclav mechnism of action
Amoxicillin (like all penicillin like drugs) 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.
co amoxiclav site of action
Amoxicillin = penicillin binding proteins
Clavulanate = beta lactamase
co amoiclav side effects
Amoxicillin is well tolerated. Most common side effects are nausea and diarrhoea.
co amoxiclav side effects
Amoxicillin is a semisynthetic antibiotic with a broad spectrum of bactericidal activity against many gram-positive and gram-negative microorganisms
Hypersensitivity to penicillins is relatively common. Usually associated with rash but can lead to anaphylactic reactions.
Co-amoxiclav is a commonly prescribed antibiotic in hospital settings.
lactulose mechanism of action
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.
lactulose drug target
no drug target
lactulose side effects
Abdominal pain, diarrhoea, flatulence, nausea.
lactulose extra info
Begins working within 8-12 hours but may take up to 2 days to improve constipation.
Constipation is a very common side effect of opioids. Lactulose is often prescribed prior to commencement of opioid therapy to improve symptoms associated with constipation.
How do we feel pain
1.pain stimulus switches on nocicereceptor
2.transmission where peripheral sensory nerve goes to spinal chord and synapses at the level of the spinal chord
3.spinothalamic-thalamus receives info and distribution
4.modulation is where drug will target by activating descending inhibitory targets
NSAIDS vs paracetamol
Anandamide produced by the brain when pain occurs causing activation of descending pain pathways
Is converted to arachidonic acid then other metabolites via cox and peroxide
NSAIDS inhibit cox and paracetamol inhibits peroxides
Paracetamol more effective for non inflammatory pain as it more lipid soluble so crosses the BBB quickly
Morphine effect on a cellular level
Increases potassium efflux hyperpolarising the cell thus no exocytosis occurs and adenyltye cyclase inhibited
Thus slows down cell thus interrupts pain transmission
Opioids cause euphoria ,GABA usually inhibits this but the endorphins now shut down gaba
GABA usually shuts down inhibitory modulation pathway but this is switched on due to endorphins reducing pain
How do opioids enter brain
Send to be lipid soluble in order to diffuse
Need to be able to bind to the receptors
OH ground and teritary nitrogen
Morphine antagonist
Naldo one has a longer side chain which can bind to opioid receptor but doesn’t switch it on
Morphine to codein conversion
Morphine to codeine dose conversion
Divide the total daily dose of morphine by 0.1 to obtain an equivalent dose of codeine.
Total morphine = 2.5 x 4 = 10 mg per day
Morphine to codeine conversion = 10/0.1 = 100 mg codeine per day
Codeine dose (given QDS) = 100/4 = 25mg per dose
Equivalent codeine = 25mg QDS
It is generally recommended that the dose is reduced by 30% to reduce the risk of overdose. Hence 25mg x 0.7 = 17.5mg. However, dose reduction may not be necessary in a young man like Mr Chow who has no other underlying medical conditions. In this case, no dose reduction was applied.
Codeine comes in 15mg, 30mg and 60mg.
Discharge TTA (to take away) = Codeine, 30mg, PO, QDS PRN
