NSAIDS and Paracetemol Flashcards
Prostaglandins are inflammatory mediators. What are their other functions? 4
Prostaglandins have house keeping functions in the :
- GIT
- Vasculature
- Platelets
- Kidneys
What do NSAIDs do?
NSAIDS inhibit the synthesis of prostaglandins by inhibit cyclooxygenase I and II
Describe the synthesis of prostaglandins
- Cyclooxygenase converts arachidonic acid into PGG2
- PGG2 is converted into PGH2
- PGH2 is converted into :
A) PGF2; uterine contraction
B) PGI2: vasodilation, gastric cytoprotection and decreased platelet aggregation
C) Thromboxane A2: increased platelet aggregation
D) PGE2: vasodilation in the kidney and gastric cytoprotection
E) PGD2
Describe the actions of PGF2
Uterine contraction
Describe the actions of PGI2 (prostacyclin)
- Gastric cytoprotection
- Vasodilation
- Decreased platelet aggregation
Describe the action of thromboxane A2
Increased platelet aggregation
Describe the action of PGE2
- Vasodilation in the kidneys
2. Gastric cytoprotection
Arachidonic acid is broken down by cyclooxygenase I and II. What is the difference.
- Cyclooxygenase I breaks down arachidonic acid into PG that produce housekeeping functions
- Cyclooxygenase II breaks down arachidonic acid into inflammatory PG
Elaborate the function of cyclooxygenase I 7
- House keeping enzymes
- Synthesis of housekeeping prostaglandins
- Gastric cytoprotection: mucous formation
- Platelet thromboxane A2 thrombus formation
- Uterine contraction
- GIT contraction
- Vasodilation
Elaborate the function of cyclooxygenase II 7
- Inducible enzyme
- Induces: cytokines, growth factors, bacterial lipopolysaccharides
Functions include: - Increased PG at inflammatory site
- House keeping
- Renal vasodilation
- Synthesis of PGI2
- Cardio-protective function
What are the adverse effects of non selective NSAIDs?
- GIT minor —> major e.g. ulceration, perforation, bleeding
- Prolonged bleeding time
- Renal vasoconstriction = ischaemia (nephrotoxicity)
- Pregnancy: prolonged gestation and bleeding
- Hypersensitivity reactions
- Tinnitus
- Drug interactions
What are the adverse effects of Cox II selective inhibitors? 4
- Inhibition of PGI2 -> increased TXA2 : increased risk MI and stroke
- Contra-indicated in heart failure! Also COX I inhibitors changes in BP -> Na+/H2O retention
- Inhibition of PG in renal vasculature -> vasoconstriction-> decrease GFR -> renal ischaemia
There is also a 50% reduction in GIT - ADR
How are NSAIDs classified?
- Non-selective
2. COX II selective
What are the categories of NSAIDS? 5
- Salicylates
- Acetic acid derivatives
- Propionic acid derivatives
- Oxicams
- Fenamates
Names the drugs in the group salicylates 1
Aspirin
Names the drugs in the group acetic acid derivatives 2
- Diclophenac (Coxib)
2. Indomethacin
Names the drugs in the group oxicams 1
Piroxicam
Names the drugs in the group propionic acid derivatives 2
- Ibuprofen
2. Naporxen
Names the drugs in the group fenamates 1
Mefanamic acid
What are the coxibs?
- Diclophenac
- Celecoxib
- Etoricoxib
Describe the MOA of aspirin? 2
Aspirin adds an acetyl group to the active site of COX and causes irreversible inhibition of COX I and COX II.
Used to prevent platelet aggregation
Describe the Kinetics of Aspirin
- Oral administration: water soluble so never IV
- Absorption: rapid; stomach, small intestine, pH dependent
- Binds plasma proteins (50% -90%)
- Biotransformation in the liver; glycine conjugation
- Urinary excretion; alkaline increased, acidic decreased
- T1/2 300mg = 2.4hours
- Toxic at T1/2 > 19 hours
What are the adverse effects of aspirin at analgesic dose? 6
- GIT
- Heamatological
- Hypersensitivity
- Renal effects
- Children
- Pregnancy
What are GIT adverse effects of aspirin? 6
- Epigastric distress
- N&V
- Occult blood loss
- Mucosal irritation
- Ulceration
- Haemorrhage
What are heamatological adverse effects of aspirin? 2
- Prolonged bleeding time
2. Inhibits platelet aggregation
What are hypersensitivity reactions adverse effects of aspirin? 2
- Angiooedema
2. Rashes
What are renal adverse effects of aspirin?
- Salt and water retention
- Aggravate renal dysfunction
- Renal ischaemia
- Inhibit uric acid excretion
Why is aspirin contraindicated in children
Underlying infection leads to Reys syndrome
Why is aspirin CI in pregnancy?
- Causes premature closure of the ductus arteriosis
2. Not safe especially in the 3rd trimester
What is the MOA of paracetamol? 3
- Inhibits cox 1 & 2 in the brain
- Poor peripheral cox inhibition
- No anti-inflammatory properties
What are the advantages of using paracetamol? 3
- No GIT effects
- No bleeding
- Safe at therapeutic doses
What are the kinetics of paracetamol?
- Rapid absorption
2. Hepatic conjugation
What are the adverse effects of paracetamol at therapeutic doses?
- Skin rash
2. Allergic reactions
What are the contraindicated of paracetamol?
Hepatic cirrhosis/ liver damage
What is the overdosage of paracetamol?
> 10g
In paracetamol toxicity, what causes death?
Hepatic necrosis
- GSH depletion causes accumulation of toxic metabolite (N acetyl benzoquinone)
- Treat with N acetylcysteine
What are the uses of NSAIDs? 8
- Anti-pyretic
- Inflammatory diseases
- Pain
- Post-operative pain
- Closure of ductus arteriosus
- Primary dismenorrhea
- Prevention - colon cancer
- Aspirin - anti-platelet
What are the strategies to prevent GIT problems associated with NSAIDS?
- Always take with food
- Combine NSAID with misoprostol (PGE2)
- Inhibitor of gastric acid secretin
