NSAIDs Flashcards
(32 cards)
What is a drug?
A chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect.
Drugs are generally derived from…?
Plants or animals, created synthetically, or produced by genetic engineering.
What are medicines?
Contain drug/s plus other agents e.g. preservatives, bulking agents, solvents
What happens in Phase 1 trials?
First time in humans - a small number of healthy volunteers (50-200) take part to examine the pharmacologic actions and safe dosage range of a drug, how it is absorbed, distributed, metabolised and excreted.
What happens in Phase 2 trials?
Studies in volunteers (100-400) with the disease to assess if the drug has any effect and at what doses.
What happens in Phase 3 trials?
Determine efficacy; Randomised controlled trials of the drug among 1000-3000 highly-selected individuals with the disease. Compare the drug to placebo or to an alternative treatment.
What are the limitations of phase 3 trials?
Restricted population studied
Numbers are limited
Women and older people with multiple diseases often excluded
Children excluded
Duration of study limited
No information on benefits, risks, outcomes associated with long-term us
Outcome studied may be a surrogate not the clinical outcome of interest
Studies are not powered to determine adverse effects so knowledge about safety is very limited
People taking the drug are unlikely to all be like the phase 3 study population
What are phase 4 studies?
Studies of safety/pharmacovigilance
NSAIDs are effective as…?
Analgesics and for reducing inflammation
What was the first NSAID?
Aspirin
What was already being used in Roman times to treat inflammation?
Plants containing salicylic acid and its derivatives, e.g. willow bark
When was salicylic acid first synthesised?
When was it first registered?
1859
1899
How many aspirin tablets are consumed each year?
10 to the 11, e.g. 32,000 tons
When was the mechanism of action of aspirin first known?
1970s
Which NSAIDs prescription rate has increased significantly recently?
Naproxen
What is the Cyclo-oxygenase enzyme (Cox) involved in?
Prostaglandin synthesis from arachidonic acid and oxygen
What are the actions of prostaglandins?
Pyretic Pro-inflammatory Hyperalgesic Inhibit gastric acid secretion Generated by platelets Contract the uterus Increase renal blood flow
What are the actions of aspirin?
Antipyretic, anti-inflammatory, analgesic, GI side effects, anti-platelet effect, delays labour and may lead to kidney problems
What did John Vane demonstrate in 1971?
That aspirin, salicylate and indomethacin blocked the production of PGs in vitro.
When was ibuprofen launched (prescription only)?
When did it become available over the counter?
1969
1983
Which COX enzyme has physiological functions?
Which has an inflammatory role?
COX-1 (constitutive)
COX-2 (inducible)
What are the three broad categories of COX inhibition mechanisms?
Category 1 - rapid competitive reversible binding of COX-1 and COX- 2 (e.g. ibuprofen)
Category 2: rapid, lower-affinity reversible binding followed by time-dependent, higher-affinity, slowly reversible binding of COX-1 and COX-2 (e.g. diclofenac)
Category 3: rapid reversible binding followed by covalent modification of COX-1 and/or COX-2 (non-competitive, irreversible) (e.g. aspirin).
Why is low-dose aspirin cardio-protective?
It falls into category 3, where there is irreversible covalent modification. Platelet COX-1 is irreversibly inhibited for the lifetime of the platelet hence aggregation inhibited.
Give some examples of COX-2 selective NSAIDs.
Rofecoxib and celecoxib
