analgesics Flashcards
how do we know we are in pain? what does the body need to feel pain?
- a receptor to detect pain
- pathways to brain to inform there is a painful stimulant
what detects pain in the body?
nociceptors - detects mechanical, thermal, chemical damage
*a potentially tissue damaging stimulus is required to activate nociceptors
name three kinds of sensory afferents
- Aσ (delta) fibres
- C fibres
- Aß (beta) fibres
describe A σ (delta) fibres
- mechanical, thermal (< 5°c, >43°c) chemical
- fast (5-30m/s) myelinated 2-4µm
- sharp, localised pain
describe C fibres
- mechanical, thermal, chemical
- slow (0.5-2 m/s) - non- myelinated < 1µm
- dull burning pain
describe A ß (beta) fibres
- pressure, touch, position
- fast (10-85m/s) - myelinated 6-22µm
- gate control theory of pain
nociceptor activation leads to what?
inflammation via the kinin system
how is inflammation caused?
release of various chemicals at the site of injury including histamine, bradykinin, prostaglandins which are activated by bradykinin
what is the action of bradykinin?
- local vasodilation
- stimulation of nerve ending causing pain
- arachidonic acid release - this is precursor to prostaglandins, leuotrienes and thromboxanes
what is the first step in takling inflammation?
- block production of inflammatory mediators → prostaglandins can sensitive afferent C fibres to bradykinin
how could prostaglandins be inhibited to treat inflammation?
Non -Steroidal Anti Inflammatory drugs (NSAIDs)
describe the roles of the COX 1 and 2 enzyme in inflammation
COX 1 - always produced - has protective effect, converts arachidonic acid into prostaglandins
COX 2 - responsible for pain and inflammation - active at site of traum/injury
how do NSAIDs reduce inflammation?
- block COX 1 and 2 - blocks many signs/symptoms of inflammation
why is it important to block COX 1 and 2 to reduce inflammation?
- COX 1 and 2 activate convertion of arachidonic acid to prostaglandins (PGs)
- PGs increase sensitivity of nociceptors to other stimuli
name the three pharmacological actions of NSAIDs
- antipyretic
- analgesic - relieves pain ass. with production of PGs
- anti - inflammatory - reduces oedema, sensitisation of nociceptors and musculoskeletal pain
what are the side effects of NSAIDs?
* in chronic treatment - high dose, prolonged use
- indigestion
- diarrhoea
- nausea/vomiting
- gastric bleeding and ulceration
what do NSAIDs inhibit and why does this cause gastric bleeding and ulceration?
PG1 and PG2 → these produce mucus and HCO3 secretion, reduced acid secretion and increased blood flow to stomach
how can the side effects of NSAIDs be reduced?
- develop drugs which only inhibit COX 2
- enteric coating of tablets
- give drugs with protective agent
- prodrugs
name 2 drugs which only inhibit COX 2
- celecoxib
- etoricoxib
name 2 drugs with a protective agent which reduce the side effects of NSAIDs
- misoprostol (PGE1 analogue)
- omeprazole (H+ pump inhibitor)
what is a prodrug?
drug which is administered in an inactive form - when given prodrug is metabolised into active metabolite
name 3 NSAIDs prodrugs
- sulindac
- nabumetone
- fenbufen
what is aspirin an example of?
NSAIDs
what is aspirin effectice for?
mild pain and fever
which enzyme does aspirin target?
non selective COX inhibitor
who should not be given aspirin?
- patients who are allergic to aspirin
- under 16s - can cause Reye’s syndrome if given for viarl illnesses
- patient with history of peptic ulcer, haemophilia or bleeding disorders
- patients taking anticoagulants
- patients with liver disease
what is ibuprofen an exaqmple of?
NSAIDs
what is ibuprofen’s mechanism of action? and why is it the drug of choice for inflammation?
- nonselective COX inhibitor
- low risk of side effects
what is naproxen?
NSAIDs - similar to ibuprofen but more potent and longer lasting (fewer doses needed)
name 7 NSAIDs other than aspirin, ibuprofen and naproxen
- dexibuprofen
- fenbufen
- ketoprofen
- diclofenac
- indometacin
- mefenamic acid
- prioxicam
is paracetamol a NSAID?
no - it is a class of analgesic of its own
what is paracetamol used for?
- antipyretic (excellent)
- analgesic
*limited anti inflammatory action
when doses paracetamol become toxic?
2-3times the therapeutic dose - toxic to liver
aspirin and paracetamol can be combined with weak opiatea, give 2 examples
- co-codapirin (aspirin and codiene)
- co-codamol (paracetamol and codiene)
why are opiods given with NSAIDS?
- less chance of dependency - but not shown to give greater relief
- increased side effects
what are opiod analgesics and what effect do they have?
- opium derivatives
- cause: euphoria, analgesia, sleep
what is the mechanism of action of opiods?
*enkephalins, endorphins and dynorphins are produced naturally by body
- bind to opiod receptors on the A(delta) and C fibres
- substance P release from A(delta) and C fibres inhibited (inhibits Ca+ influx)
- signal not transmitted to thalamus
- opiods promote opening of potassium channels and inhibit opening of voltage gated Ca+ channels
what are opiods used for?
visceral pain origin following surgery or in terminal illness
which opiods may be given for mild to moderate pain?
- codeine
- dihydrocodiene
- meptazinol
which opiods may be given for moderate to severe pain?
- morphine
- diamorphine (heroin)
- pethidine
- buprenorphine
- tramadol
which opoids may be give intraoperatively and postoperatively?
intra - fentanyl, alfentanil
post - morphine
in opiod overdose which caused respiratory depression which drug would be given to reverse the affects?
naloxone
when would morphine be given?
acute or chronic pain - causing euphoria and mental detachment
how would morphine be administered?
- IV, IM, subcutaneous or rectal
- infusion by syringe pump
slowly absorbed orally - sustained release
what are the side effects of morphine?
- constipation - 100%
- nausea/ vomiting (stimulates chemoreceptors in brain) - 30%
- sedation - 30%
- confusion, nightmares, hallucinations - 1%
- potentail dependency
- patients can become tolerant
- respiratory depression - occurs at therapeutic doses - not so much of prob when used as analgesic as pain stimulates respiration
morphine is a cough supressant, why and which drug?
- not know why
- pholcodeine
which fibres do local anaesthetics act on?
small diameter fibres - A (delta) / C fibres
describe the difference between lipid soluble and lipid insoluble local anaesthetics
lipid soluble - can dissolve across membrane
lipid insoluble - drug requires injection into nerve axon
give some methods of administration for local aneasthetics
- topically to skin/ mucosal surface
- subcutaneous injection - act on nerve endings
- nerve block - infiltrated around nerve ending
- intravenous regional anaesthesia
give 4 examples of local anaesthetics
- lidocaine
- bupivicaine
- prilocaine
- tetracaine
