NSAIDS and Paracetamol Flashcards
Importance of pain
- tells you when there is danger in the environment
- induce spinally mediated withdrawal reflex
- linked to the defensive instinct of supraspinally mediated perception
Acute pain
- perceived and communicated through peripheral pathways
- considered as the healing process
- usually associated with the autonomous response
non- malignant pain - 4
- pain persists beyond the precipitating injury
- no autonomous symptoms
- no evidence of the underlying pathology
- characterised by myofascial, visceral and neurologic causes
malignant
- both acute and chronic pain
- definable cause such as tumor reccurrence
neuropathic pain -3
- damage to the nerve
- burning, stinging, tingling
- DOES NOT RESPOND WELL TO STANDARD ANALGESICS
what is the pain in C fibres generated by
cancer and damaged tissue
fast pain
sharp and localised
- a delta
slow pain
dull and more diffuse
- c fibres
where are nociceptors located
at the peripheral terminations of lightly myelinated free nerve endings of type a delta and c fibres transmitting pain
chemical mediators of pain response include
pottasium - damaged cells
prostaglandins - damaged cells
serotonin - platelets from injury
histamine - mast cells
bradykini - blood plasma
neutrotransmitter release first when pain is encountered
GLUTAMATE (associated with acute pain)
suppress pain signals = 3
glycine
opioids
serotonin
inflammatory mediators - 4
chemokines
cytokines (IL-1, 6, TNFa)
plasma mediators (bradykinin)
LIM
COX other name
Prostaglandin endoperoxide synthase (PTGS) - responsible for the formation of prostanoids
isoforms of COX
cox 1,2 and 3
COX-1 - 3
- constituitive enzyme
- present in almost all the tissues
- involved in physiological processes - platelet aggregration, vascular homeostasis, maintenance of BP, gastric protection
COX 2
- inducible
- induced by cytokines
- found on sites where there is inflammation
- EXPRESSED IN CNS AND PLAYS A ROLE IN CENTRAL MEDIATION OF PAIN AND FEVER
General MOA of NSAIDs
reduces:
pain, fever, platelet aggregration, inflammation
General indications of NSAIDS
- chronic joint disease (osteo and rhemuatoid athritis)
- acute inflammatory conditions such as fractures, sprains, sport and sof tissue injury
- post operative pain
- dental
- headache and migraines
- menstrual pain
NSAIDS MOA detailed
- they bind and inactivate one monomer of the COX dimer which is enough to shut down prostanoid formation
are NSAIDS competetive or non?
They are competetive active site inhibitors of both COXs
Anti inflammatory effects - 2
- inhibit the production of pg, histamine, thromboxane and leukotrines
- reduce pain and swelling and increase blood flow in response to inflammation
Analgesic effects -3
- reduce pain in the area of inflammation
- inhibit the release of prostaglandins which sensitise nociceptors to bradykinin
- used with opioids for post operative pain
Antipyretic effects -2
- the hypothalamus is responsible for maintaining temperature
- it inhibits prostaglandins effects on the thermoregulatory centre, thus returning temperature to normal
General A/E
- GIT
- Kidney
- Skin conditions
- CNS
- Haematopoetic effects
GIT A/E
- inhibition of cox-1 decreases prostaglandins that protect the mucosa and inhibit acid secretion
- ABUDAN
Kidney A/E
inhibitition of prostaglandins responsible for renal blood flow
Skin condition A/E
SJS
CNS A/E
HDV
Haematopoetic effects
thrombocytopoenia, prolonged bleeding due to poor clotting, leukopoenia
Traditional nonselective cox inhibitors - SPAA OPIP
Salicylic acid = aspirin
Propionic acid = Ibuprofen, Ketoprofen, Flurbiprofen, Naproxen, Oxaprozin
Anthracilic acid = mefenamic acid
Arryl-acetic acid derivatives = diclofenace, aceclofenac
Oxicam derivatives = piroxicam, tenoxicam
Pyrrolo-pyrrole derivatives = ketoralac, indomethacin, nabumetone
Indole derivative = indomethacin, sulindac
Pyrazolone derivative = phenylbutazone, oxyphenbutazone
preferential cox-2
Nabumetone
Nimesulide
Diclofenac
Aceclofenac
Meloxicam
selective cox 2
all coxibs
antipyretic, analgecis but POOR anti-inflammatory - 3
- Paraaminophenol derivative = paracetamol
- Pyrazolone derivative = propihenazone, metamizole
- Benzoxazocine derivative = nefopam
comments about cox-1 inhibitors
= inhibit platelet aggregrations
= CAUSE gastric ulcers
comments about cox 2 inhibitors
= less inhibition of platelet aggregration compared to cox 1
= increase platelet aggregration (through inhibition of prostacyclin)
another indication of aspirin
cardiovascular disorders
aspirin pk
- oral or rectal formulation
- absorption delayed by food intake
- rapidly hydrolysed to salicylate in plasma and tissue (which is anti inflammatory)
- metabolised in liver and eliminated in kidneys
aspirin A/E
- gastric ulcers
- allergic reactions
- anticoagulatory effects
- reye’s syndrome
probenecid and sulfinpyrazone
inteferes with uricosuric agents and reduces urate secretions
paracetamol therapeutic effects - 3
- antipyretic and antiinflammatory = by inhibiting pg synthesis
- weak anti inflammatory = poor effect on COX in peripheral tissues (but they say WEAK)
- no effect on platelet function or clotting
Paracetamol indications
- fever
- mild to moderate pain
- post op pain
- childern with fever and pain (first line)
Principles of pain management
- Comprehensive pain assessments
- Appropriate pain management targets
- Individualised pain management regiments
- Monitoring
Please what is paracetamol not indicated in
in inflammation!! NOT!!
If aspirin is contradicted
give paracetamol… esp in gastric ulcers, pregnancy and children
Paracetamol OOA
rapidly absorbed and exerts effects within 30 mins
INACTIVATED in the liver and then conjugated (sulfation and glucurnidation)
NAPQI
- toxic form that forms via the cyp450 pathway and it is neutralized by glutathione
- its accumulation leads to liver and kidney cerosis
specific opoids for moderate to severe pain
codeine and tramadol
1st line
paracetamol/ NSAID/ aspirin, but start with paracetamol
2nd line
paracetamol + weak opioid
NSAID + weak opioid
3rd line
paracetamol + NSAID + weak opioid
4th line
paracetamol + NSAID + strong opioid
epidural nerve block
