NSAIDs Flashcards
Mechanism of action of NSAIDs ?
NSAIDs inhibit cyclo-oxygenase (COX) enzymes, decreasing production of prostaglandins, thus reducing inflammation, pain, and fever.
Types of COX?
COX-1: Constitutive (Its concentration remains stable)
Produces prostaglandins supporting platelets and protecting stomach.
Their reduction (as by salicylate) cause stomach ulcers and bleeding
COX-2: Induced (only formed as inflammatory response),
COX-3: in brain, mediate central action of prostaglandins (pain & fever
only)
Classification of NSAIDs according to COX selectivity ?
Nonselective COX-1,COX-2 Inhibitors: as acetyl salicylic acid, ibuprufen, indomethacin, diclofenac Preferential COX-2 inhibitors: Meloxicam Selective COX-2 Inhibitors: Celecoxib, rofecoxib COX-3 inhibitors: Paracetamol
Pharmacological actions of NSAIDs?
Analgesic:
- Reduce prostaglandins at nerve endings reducing pain
Anti-pyretic:
- Reduce prostaglandins at thermoregulatory center decreasing fever Anti-inflammatory: (all except paracetamol)
- Reduce prostaglandins causing signs of inflammation (redness,
hotness and swelling)
partial relief in the remaining.
Anti-platelet: (Mainly by salicylates in low dose)
- By interfering with platelet thromboxane A2 synthesis
Dysmenorrhoea:
- NSAIDs lower uterine PG levels—afford excellent relief in 60–70% and
Clinical uses of NSAIDs?
Treatment of mild to moderate pain: Headache and migraine Dental pain Dysmenorrhea Arthritis and myositis Treatment of fever Treatment of inflammatory conditions, especially to decrease
Common side effects of NSAIDs?
Gastrointestinal upset and Gastric ulceration
Bleeding:
Decrease renal blood flow causing sodium and water retention
Inhibition of uterine contraction
Asthma and anaphylaxis:
How can NSAIDs cause Gastrointestinal upset and Gastric ulceration? How can u counteract it?
If we use NSAIDS they will inhibit COX = Reduces the mucus = Mucosal ischaemia = mucosal damage = GI upset and gastric ulceration
- give PG analogues ( misoprostol ) administered concurrently with NSAIDs counteract their gastric toxicity
How can NSAIDs cause Bleeding ?
COX-1 will help in platelet function = due to inhibition of platelet thromboxane A2 synthesis
How can NSAIDs cause Decrease renal blood flow causing sodium and water retention?
COX1 helps in renal tract when it’s blocked
If someone is hypovolaemia, hepatic cirrhosis, renal disease and in patients receiving diuretics or antihypertensives
How can NSAIDs effect Inhibition of uterine contraction?
= causing delayed labor
How can NSAIDs cause Asthma and anaphylaxis ?
due to increased leukoterienes
General contraindications of NSAIDs?
Gastric ulcer
Patients taking anticoagulants drugs or hemophilic patients
Renal failure
Asthmatic patients
Beneficial actions due to PG
synthesis inhibition ?
- Analgesia: prevention of pain nerve ending sensitization • Antipyresis • Anti-inflammatory •Antithrombotic • Closure of ductus arteriosus in newborn
Shared toxicities due to PG
synthesis inhibition ?
• Gastric mucosal damage • Bleeding: inhibition of platelet function • Limitation of renal blood flow : Na+ and water retention • Delay/prolongation of labour • Asthma and anaphylactoid reactions in susceptible individuals
Salicylate mechanism of action?
- Non-selective irreversible COX inhibition. ( both COX 1 and 2 )
- Antiinflammatory action is exerted at high doses
Pharmacokinetics of Salicylate?
1. Gastric toxicity : Cause Salicylate is an acid = will be absorbed in an acidic medium - but when it enters the mucosal cell ( basic ) = It ionizes = Can’t diffuse ( ion trapping) = Enhance gastric toxicity
- Strongly bound to plasma protein
- Alkalinization ( basic ) of urine increase its excretion ( cause it acidic )
Specific uses of salicylate?
- Cardio-protective: reduces the incidence of myocardial infarction (in low dose aspirin
- post-infarct patients
- new onset’
- ‘sudden worsening’ angina
- Pregnancy-induced hypertension
- pre-eclampsia
Why is salicylate used in Pregnancy-induced hypertension and pre-eclampsia?
They are caused by = imbalance between TXA2 and PGI2 = When given aspirin = selectively suppressing TXA2 production = Restore balance
Specific side effects of salicylate?
- Effect on uric acid:
- Small dose = inhibiting urinary secretion of uric acid = hyperuricemia
- Large dose = due to reduced urinary re-absorption = hypouricemia
- Reye’s syndrome
- In children it is used in viral (varicella,
influenza) infection
- Progressive damage to the liver and brain- a rare form of hepatic
encephalopathy
Which medication is best suitable for children?
paracetamol
Toxicity of salicylate?
- Chronic toxicity (Salicylism) :
- Due to chronic use of large dose – Antiinflammatory doses - Acute salicylate intoxication :
- Start as salicylism followed by fever and convulsions.
Chronic toxicity (Salicylism) Symptoms and what happens to respiratory center.
- Symptoms: headache, dizziness, tinnitus, reversible decrease of hearing and vision, vertigo and vomiting
- dose has to be titrated to one which is just below that producing these symptoms; tinnitus is a good guide
- Early stimulation = respiratory center cause hyperventilation and respiratory alkalosis
- Late respiratory = accumulation of salicylate = metabolic acidosis= depression of respiratory center
Treatment of Acute salicylate intoxication
Gastric lavage and charcoal to reduce absorption
Monitor salicylate level and correct acid-base abnormalities
Reduce fever by ice packs
For convulsions, give intravenous (IV) diazepam
Forced alkaline diuresis (IV furosemide+sodium bicarbonate) increase
excretion and Hemodialysis in severe cases
Blood transfusion and vitamin K for bleeding
Precautions and contraindications for use salicylates (aspirin )
- People who are sensitive to it
- peptic ulcer, bleeding tendencies, in children suffering from chicken pox or influenza.
- Cautious use in chronic liver disease = hepatic necrosis have been reported.
- Aspirin should be stopped 1 week before elective surgery.
- It should be avoided by breastfeeding mothers.
- Avoid high doses in G-6PD deficient individuals—haemolysis can occur
