Analgesic drugs 2

Question 1

How do NSAIDS work?

one example enzyme inhibitor and enhancer

Answer 1

Will bind to cyclo-oxygenase enzymes (CO1 and CO2) to inhibit prostanoids production in the cells
(aspirin is only one irreverisble)

Effet

• decrease inflammation by decreasing prostaglandins
• relieve mild pain
• anticoagulation

example - cimetidine 0 enzyme inhibitor

enzyme enhancer- carbamazepine

Question 2

How to make prostaglandins

Answer 2

Stimuli will release AA from membrane

• COX1, COX2 - will make prostanoids and leukotrienes (cytokines and growth factors will promote this)
• only want COX2 to be inhibited because this is involved in inflammation

Question 3

What happens to the body when it gets the drug

Answer 3

-highly lipophilic
-rapid and complete absorption
-undergo very little first pass medtabolism - very high bioavailability
-high protein binding
-onset of action is slow - peak plasma conc occurs after a few hours
-

Question 4

Drug interactions with NSAIDS

Answer 4

e. g anti cancer agents - bad as these can bind to proteins as well , goign to increase amount in blood as they cannot bind to the proteins - so more active drug
- have to reconsider dose
- also can increase uric acid secretion - need to be careful of uric acid

Question 5

Side effects of NSAIDS

Answer 5

• bleedng, GI tract, renal, liver
• Aspirin is acetylsalicylic acid - absorbed in stomach and upper intestine by passive diffusion
• in blood - most is de-acetylated to become salicylic acid - responsible for most anti-inflammatory and analgesic effects
• joins to form glucuronic acid and is excreted in urine
• competes with uric acid secretion in kidneys , can get gout

Question 6

Aspirin - bleeding

Answer 6

Bleeding

• irreversibly acetylates platelets COX1 - inhibit formation of TXA2 , decrease platelet adhesion
• reduces the risk of heart attack and stroke to prevent clotting formation
• decrease thormbosis and increase vasodilation
• however can increase bleeding time - increase operative blood loss, epidurals - may be at risk of haematoma

Question 7

Aspiring - GI tract

Answer 7

Gastric epithelium - produces a gastric cycloprotective prostanoid - to protect against acid damage

• synthesis inhibited by aspirin
• this normally will decrease gastric acid secretion, decrease bicarb secretion, increase the pH, mucous synthesis ect.

Can also get nausea, vomiting, diarrhoea

Question 8

Asthma and aspirin

Answer 8

• Asthma induced aspirin (asthma will be triggered within 1-3 hours of ingestion of NSAIDs)
• starts off as aspirin intolerance - facial intollerance, then goes to severe asthma, then goes to nasal polyps (aspirin triad)

Mechanism - inhibition of Cox1, Cox2 enzymes - lead to decrease PGE2 which is a bronchodilator
-also get activation of lipoxygenases - increase inflammatory mediators - leukotrines, –> bronchospams

NSAID - may precipitate broncho-constriction in any asthmatic patient

Question 9

Pregnancy

Answer 9

Prostaglandins in pregnancy - establishing and maintaining labour

• increase in uterine smooth muscle contraction
• maintains patency of ductus arteriousus

Used NSAIDS - in premature labour - inhibits this, or to close the patent ductus arteriosis in premature infants

Question 10

Paracetamol

Answer 10

Analgesic and antipyretic

• not sure how it works, mild anti-inflammatory behaviour
• side effects mild
• overdose - fatal hepatic damage

Routes of administration
-PO, PR, IV

Paracetamol + codeine or paracetamol + NSAID