💊Pharmacology💊 - Pain Flashcards
What is the pain ladder?
What is the management for gastroenteritis?
Oral rehydration - can manage oral fluids, but at risk of dehydration due to diarrhoea/vomiting
Analgesia - complaints of abdominal pain
How do the mechanisms of action of NSAIDs compare to paracetamol?
Both inhibit prostaglandin production
NSAIDs inhibit cyclo-oxygenase
Paracetamol inhibits peroxidase activity
Compare the effects of NSAIDs vs paracetamol
Both analgesic and anti-pyretic
Only NSAIDs are anti-inflammatory
Why is paracetamol not anti-inflammatory?
Paracetamol’s action depends on peroxidase activity
Paracetamol works by inhibiting the enzyme cyclooxygenase (COX), specifically in the brain.
However, COX requires peroxidase activity to function properly.
Endogenous peroxides block paracetamol’s effect
During inflammation, the body produces high levels of peroxides in inflamed tissues.
These peroxides counteract paracetamol’s inhibition of COX, meaning paracetamol becomes ineffective as an anti-inflammatory drug.
What are the signs of appendicitis?
umbilical → right iliac fossa, guarding, rebound tenderness, febrile
What is the management for acute appendicitis?
Surgery - open laparoscopy
Hydration (nil by mouth) - intravenous crystalloids
Analgesia - move up the pain ladder as necessary
Antibiotics - obstructed appendix could lead to bacterial overgrowth, plus risk of post-surgical infection
What effect does morphine have on neuron synapses?
Presynaptic neuron
reduces Ca²⁺ influx - reduces neurotransmitter exocytosis
Postsynaptic neuron
Increases K⁺ efflux, hyperpolarizing the neuron and reducing excitability
What effect might morphine have on the nervous system as a whole?
Inhibit signal transduction from stimulus
Inhibit transmission through spinal cord
Activate (disinhibit) modulation pathway from brain (lessens pain)
How do opioids effect pain perception and tolerance?
Pain tolerance (descending pathway):
Opioids (e.g., morphine) bind to mu-opioid receptors (MORs) in the brainstem
Inhibit GABAergic interneurons, removing inhibition on descending pain-modulating neurons
Pain perception (ascending pathways):
Reduces neurotransmitter release and hyperpolarises postsynaptic neurons
What allows opioids (or any drugs for that matter) to produce affects within the brain?
Access brain tissue - permeation through the blood brain barrier
Lipid solubility for passive diffusion
In a patient in recovery with IV morphine, how can acute renal failure arise?
Low resp rate and 02 sats - poor perfusion of kidneys
Sedentary and immobile - muscle breakdown - release of urea and creatininie = Rhabdomyolysis
This can also contribute to kidney damage
Which chemical features achieve affinity and efficacy in opioids?
OH group and terminal N chain for affinity
Short terminal chain for efficacy
How does acute renal failure lead to opiate overdose?
Morphine and opiates are excreted in kidneys
What are some classic signs/symptoms of opioid overdose?
Bilateral pupil constriction
Low resp rate
Bradycardia
Hypotension
Give an opioid receptor antagonist
Naloxone
What is important for affinity of a molecule to an opioid receptor?
OH at position 3 and tertiary nitrogen to bind to opioid receptors
What is needed for efficacy of a molecule at an opioid receptor?
Short terminal chain off the nitrogen for efficacy
What is codeine?
Pro-drug for morphine
What can codeine be metabolised into?
Both norcodeine (inactive metabolite) AND morphine (active metabolite)
Which liver enzymes are responsible for metabolism of codeine?
CYP3A4 is responsible for ‘fast’ metabolism of codeine to norcodeine and CYP2A6 is responsible for ‘slow’ metabolism of codeine to morphine
What is the significance of the fast and slow metabolism of codeine?
Only 10% of codeine forms active metabolites, so called weak opioid - morphine(strong opioid)
Why is codeine more suitable than morphine for post-discharge pain management?
Even though 100 mg of codeine per day metabolizes into roughly 10 mg of morphine, it does so slowly and in a controlled manner, making it safer and more appropriate for managing post-discharge pain. If stronger pain relief is needed, then oral morphine (e.g., Oramorph) can be considered instead
What is the mechanism of action of paracetamol?
Not totally clear
May block peroxidase in peripheral sites - ability is blocked if excessive levels of peroxidase build up, such as in inflammation
Activation of descending serotonergic pathways
Inhibits reuptake of endogenous endocannabinoids - increases activation of descending pathways
What is the mechanism of action of opioids?
Over-arching mechanism is a depressant on cellular activity - multiple sites in pain pathways
Both ascending and descending, inhibiting pain perception and disinhibiting pain modulation
What is the mechanism of action of co-amoxiclav?
Amoxicillin binds to bacterial penicillin binding proteins
What is the mechanism of action of lactulose?
Non-absorbable disaccharide
Reaches large bowel unchanged so stimulates water retention in lumen - easier to pass stool
Also can be metabolised by colonic bacteria - additional laxative effect
What is the drug target of paracetamol?
Unclear
5HT3 receptors
Cannabinoid reuptake proteins
Peroxidase
What is the drug target of opioids?
Opioid receptor
What is the drug target of co-amoxiclav?
Amoxicillin = penicillin binding proteins
Clavulanate = beta lactamase
What is the drug target of lactulose?
n/a
What are the main side effects of paracetamol?
Relatively safe with few common side effects
Overdose - liver damage (sometimes renal damage)
Nausea and vomiting early signs - onset of right subcostal pain after 24h indicates hepatic necrosis
What are the main side effects of opioids?
Mild - nausea and vomiting, constipation
Overdose - respiratory depression
What are the main side effects of co-amoxiclav?
Well tolerated
Common side effects are nausea and diarrhoea
What are the main side effects of lactulose?
Abdominal pain
Diarrhoea
Flatulence
Nausea
Why is lactulose given with opioids?
Opioids cause constipation
Lactulose is a laxative
