Case Study: Aspirin Flashcards
What is the chemical name of aspirin?
2-acetoxybenzoic acid
Or
Acetylsalicylic acid
What is the chemical formula of aspirin?
C9 H8 O4
Why is drug stability important?
- important for the patient: if the medicine decomposes, treatment will be ineffective or decomposition products may be toxic
- important for pharmaceutical industry, NHS and community pharmacy - financial loss if stock is beyond its sell date
- important to have correct storage conditions
Describe aspirin hydrolysis.
- slow under neutral conditions
- catalysed by a base
- hydrolysis products are salicylic acid and ethanoic acid
What are he industrial unit process of medicine manufacturing?
- comminution
- mixing
- granulation
- drying
- tableting
- coating
- filtration
What is aspirin used to treat?
- headaches
- heart attacks
What happens when you swallow a tablet?
- tablet goes down through the oesophagus and enters the stomach
What are the steps associated with the workings of aspirin?
- absorption
- distribution
- metabolism
- excretion
Describe the first step of the workings of aspirin when it enters the body?
- absorption
- little aspirin is absorbed in the stomach
- most of the absorption occurs in the small intestine
Describe absorption in the small intestine.
- absorption occurs across the gut wall into the blood
- small intestine has a large surface area to maximise absorption
- aspirin molecules move across the small intestinal epithelium entering the bloodstream
- blood plasma levels start to rise ~20 mins following ingestion and peaks after ~2 hours
Describe the second step in the workings of aspirin.
- distribution
- main occurs via the circulatory system
- following absorption medicines are carried to the liver by the hepatic
portal vein
Describe the third step in the workings of aspirin.
- metabolism
- most drugs undergo extensive metabolism in the liver
- some are activated, deactivate, broken down
- some are conjugated i.e. covalently attached to other molecules
What happens to aspirin during metabolism?
- at least 50% of ingested aspirin is hydrolysed by esterase enzymes in the gut wall and the liver
- salicylates are then further metabolised in the liver to a variety of metabolites, many of which are conjugated
- up to 80% of a therapeutic dose of aspirin is metabolised in the liver
Describe stage 4 in the workings of aspirin.
- excretion
- most drugs leave the body via the kidneys
- ~50-80% of salicylate in the blood is bound by serum protein while
the rest remains in the active ionised state - salicylate metabolites are excreted mainly via the kidneys
What is the action of aspirin in the body?
- it suppresses the production of prostaglandins and thromboxanes
What are prostaglandins and thromboxanes?
They are members of the eicosanoid family of signalling molecules
What are eicosanoids?
- signalling molecules made from essential fatty acids contain 29 carbon atoms
- they derive from omega-3 or omega-6 fatty acids in the diet
- exert control over many body systems e.g. inflammation and immunity, and act as messengers in the CNS
What are some examples of eicosanoids?
- prostaglandins
- leukotrienes
- thromboxanes
- cysteinyl leukotrienes
How do prostaglandins work?
- involved in transmitting pain information to the brain and dilation of blood vessels
- therefore suppressing its production is an effect treatment for headaches
How do thromboxanes work?
- involved in the aggregation of platelets that form blood clots
- therefore suppression production is an effective treatment for heart attacks
How does aspirin suppress the production of prostaglandins and thromboxanes?
- by irreversibly inactivating the cyclo-oxygenase (COX) enzymes that make them
- acts as an acetylating agent i.e. an acetyl group is covalently bound to an (serine) amino acid in the active site of COX
- once the COX has been acetylated it can no longer catalyse the formation prostaglandin and thromboxane molecules
What is the difference between aspirin and other related analgesics, such as ibuprofen?
- aspirin binds irreversibly while the others are reversible enzyme inhibitors
What was aspirin originally developed from?
The leaves of willow trees
