NSAIDs
Nonsteroidal anti-inflammatory drugs (NSAIDs)
CLASS
- non-selective COX inhibitors
Types – weak organic acids
- Salicylic acids – aspirin
- Acetic acids – diclofenac, ketorolac, indomethacin
- Propionic acids – ibuprofen, naproxen
- Fenamates – mefenamic acid
- Oxicams – tenoxicam, piroxicam
- Paracetamol
- Pyrazolones – phenylbutazone
MECHANISM OF ACTION
- cyclooxygenase (COX) is an enzyme that catalyses the synthesis of prostaglandins from arachidonic acid.
- prostaglandins mediate a large number of body processes including:
- inflammation
- pain
- secretion of a protective gastri layer
- maintenance of renal perfusion
- platelet aggregation
- NSAIDs block the action of COX -> reducing production -> results:
- analgesia
- anti-inflammation
- decreased gastric mucosa -> ulceration
- decreased renal perfusion
- bleeding
Main actions
- inhibition of biosynthesis of prostaglandins
- also:
- inhibition of chemotaxis
- down regulation of interleukin-1 production
- interference with Ca2+ mediated intracellular events
- decrease sensitivity of vessels to bradykinin & histamine
- affect lymphokine production from T lymphocytes
- reverse vasodilation
- inhibit platelet aggregation
ADVERSE EFFECTS
- bronchospasm
- hyperventilation
- GI ulceration, haemorrhage
- hepatic dysfunction -> transaminitis
- renal dysfunction from excretion of hypertonic metabolites -> papillary necrosis
- inhibition of platelet aggregation
- prolongation of bleeding time
- hyperglycaemia -> glycosuria
PHARMACOKINETICS
- Absorption – most are well absorbed, absorption not affected by food
- Distribution – highly protein bound (>98%), all are found in joints after repeated dosing
- Metabolism – hepatic
- Elimination – renal most important, biliary -> enterohepatic circulation
EVIDENCE
-> effective analgesics of similar efficacy for acute pain
-> NSAIDs + paracetamol = more analgesia
-> with careful selection of patients NSAID induced renal impairment is low
-> aspirin + some NSAIDs increase perioperative bleeding after tonsillectomy except in paediatrics
-> NSAIDs reduce opioid consumption
-> NSAIDs increase perioperative blood loss
References and Links
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
| INTENSIVE | RAGE | Resuscitology | SMACC