Peripheral and central analgesia Flashcards
List 5 methods of pain relief
Remove peripheral stimulus
Interrupt nociceptive input
stimulate nociceptive inhibitory mechanisms
Modulate central appreciation of pain
Block or remove secondary factors maintaining pain
What substances are released to activates nociceptors?
Algogenic substances
What 2 algogenic substances can be exploited by analgesics?
Substance P
Prostaglandins
Other than activate nociceptive pathways, what is the function of the release of allogenic substances?
Activate inflammatory cascade
What cascade do analgesics tens to target?
Inflammatory cascade through inhibition of algogenic substances at or near the site of injury
List 2 types of analgesics commonly used
Paracetamol
NSAIDs
COX-2 inhibitors
How is paracetamol an anti-pyretic?
Prostaglandin inhibition in hypothalamus
Is paracetamol an anti-inflammatory?
No
In what type of patients should paracetamol should be avoided?
Patients with pre-existant liver disease
Where is paracetamol metabolised?
liver
How can paracetamol be harmful for people with pre-existant liver disease?
10% of paracetamol is metabolised via conjugation to NAPQI
This is hepatotoxic
It is normally inactivated by glutathione, but in people with liver disease glutathione is reduced/non-existant, so NAPQI build up causing liver cell death
How is paracetamol normally metabolised?
In the liver, 90% into a harmless product and excreted, 10% via conjugation to NAPQI, a hepatotoxic compound, normally inactivated by glutathione into a safe compound that can be excreted
What are the immediate clinical manifestations of paracetamol overdose?
No immediate manifestations
What should you do if a patient coming in complaint about dental pain says they have taken more than the recommended dose of paracetamol?
Dental problem should take a back seat and they should be taken to A&E
What are the risk factors for paracetamol overdose?
Liver disease e.g. less glutathione
Alcohol abuse, malnourished
How can paracetamol be treated?
Activated charcoal (absorbs excess paracetamol in the system) and give them a precursor for glutathione to increase glutathione production
Name 2 NSAIDs
Aspirin Ibuprofen
Generally, how do NSAIDs work?
Non-selective block of cyclo-oxygenase (COX) enzyme
Name the 2 forms of COX that NSAIDs non-selectively inhibit
COX1 COX2
Explain the role of COX1
Production of prostaglandins that help synthesis of gastric mucosal mucus and regulate gastric acid
Explain the role of COX2
Helps the production of prostaglandins and other inflammatory mediators that cause acute pain
List 4 beneficial effects of NSAIDs
Anti-pyretic
Analgesic
Anti-inflammatory
Anti-platelet (aspirin only)
How do NSAIDs cause an anti-pyretic effect?
Inhibit prostaglandin production in the hypothalamus
List 4 unwanted effects fo NSAIDs?
Gastric ulceration
Platelet effects
Induce asthmatic attacks
Non-selective COX inhibitor causes dysregulation of gastric acid and renal toxicity
What is ‘safe aspirin’, why is it named so?
Selective COX-2 inhibitor, decreased gastric side-effects
Disadvantages of safe aspirin?
Increased risk of MI
Why should ibuprofen be taken with meals?
Better absorption in the stomach with food
Name a centrally acting analgesic?
Opioids
How are opioids classified?
Strength - weak = codeine, strong = morphine
How do opioids work?
Pure or partial agonists to opioid receptors
How is the strength of an opioid determined?
Strong = pure agonist at opioid receptor Intermediate = partial
What are the side-effects of opioids?
Respiratory depression, depression, decrease gut mobility, dependence, nausea
Describe the opioids mode of action?
Bind to opioid receptors centrally and peripherally
This activates descending inhibitory control over nociception
Also inhibits propagation of impulse though stopping neurotransmitter release peripherally
When are opioids prescribes?
Pain is moderate to severe
Pain has significant impact on function
Pain has significant impact on quality of life
Other treatments have been tried and failed
Patient has consented to be closely monitored
How quickly does dependence begin?
24 hours
How does chronic exposure to opioids effect receptors?
Increase no. and sensitivity = increase cellular response
What are the 4C’s involved in additction?
Compulsive use
Impaired control over use
Continued use despite consequences
Craving
Where is morphine metabolised?
Hepatic and renal metabolism
Why is morphine not effective given orally?
Extensive first pass metabolism
