Case Study: Aspirin

Question 1

What is the chemical name of aspirin?

Answer 1

2-acetoxybenzoic acid
Or
Acetylsalicylic acid

Question 2

What is the chemical formula of aspirin?

Answer 2

C9 H8 O4

Question 3

Why is drug stability important?

Answer 3

• 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

Question 4

Describe aspirin hydrolysis.

Answer 4

• slow under neutral conditions
• catalysed by a base
• hydrolysis products are salicylic acid and ethanoic acid

Question 5

What are he industrial unit process of medicine manufacturing?

Answer 5

• comminution
• mixing
• granulation
• drying
• tableting
• coating
• filtration

Question 6

What is aspirin used to treat?

Answer 6

• headaches

- heart attacks

Question 7

What happens when you swallow a tablet?

Answer 7

• tablet goes down through the oesophagus and enters the stomach

Question 8

What are the steps associated with the workings of aspirin?

Answer 8

• absorption
• distribution
• metabolism
• excretion

Question 9

Describe the first step of the workings of aspirin when it enters the body?

Answer 9

• absorption
  
  • little aspirin is absorbed in the stomach
  • most of the absorption occurs in the small intestine

Question 10

Describe absorption in the small intestine.

Answer 10

• 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

Question 11

Describe the second step in the workings of aspirin.

Answer 11

• distribution
  
  • main occurs via the circulatory system
  • following absorption medicines are carried to the liver by the hepatic
    portal vein

Question 12

Describe the third step in the workings of aspirin.

Answer 12

• 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

Question 13

What happens to aspirin during metabolism?

Answer 13

• 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

Question 14

Describe stage 4 in the workings of aspirin.

Answer 14

• 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

Question 15

What is the action of aspirin in the body?

Answer 15

• it suppresses the production of prostaglandins and thromboxanes

Question 16

What are prostaglandins and thromboxanes?

Answer 16

They are members of the eicosanoid family of signalling molecules

Question 17

What are eicosanoids?

Answer 17

• 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

Question 18

What are some examples of eicosanoids?

Answer 18

• prostaglandins
• leukotrienes
• thromboxanes
• cysteinyl leukotrienes

Question 19

How do prostaglandins work?

Answer 19

• involved in transmitting pain information to the brain and dilation of blood vessels
• therefore suppressing its production is an effect treatment for headaches

Question 20

How do thromboxanes work?

Answer 20

• involved in the aggregation of platelets that form blood clots
• therefore suppression production is an effective treatment for heart attacks

Question 21

How does aspirin suppress the production of prostaglandins and thromboxanes?

Answer 21

• 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

Question 22

What is the difference between aspirin and other related analgesics, such as ibuprofen?

Answer 22

• aspirin binds irreversibly while the others are reversible enzyme inhibitors

Question 23

What was aspirin originally developed from?

Answer 23

The leaves of willow trees