Pharm - GORD

Question 1

What are NSAIDs?

Answer 1

non steroidal anti-inflammatory drugs

Question 2

What are some examples of NSAIDS?

Answer 2

ibuprofen
naproxen
diclofenac

aspirin

Question 3

What is the primary mechanism of action for NSAIDs?

Answer 3

inhibit the enzyme cyclo-oxygenase (COX), which is the rate-limiting step for the production of all prostanoids (prostaglandins & thromboxanes) from the parent arachidonic acid
Prostanoids act through a large number of prostanoid receptors to produce a highly complex array of actions

Question 4

What is the drug target of NSAIDs?

Answer 4

Cyclo-oxygenase (COX) enzyme

Question 5

What are the side effects of NSAIDs?

Answer 5

gastric irritation
ulceration and bleeding
in extreme cases, perforation;

reduced creatinine clearance
possible nephritis;

bronchoconstriction in susceptible individuals (contraindicated in asthma)

Skin rashes & other allergies, dizziness, tinnitus.

Adverse cardiovascular effects (hypertension, stroke, MI) may occur following prolonged use or in patients with pre-existing CV risk.

Prolonged analgesic abuse over a period of years is associated with chronic renal failure.

Aspirin has been linked with a rare but serious post-viral encephalitis (Reye’s syndrome) in children.

Question 6

When are NSAIDs used?

Answer 6

• analgesics for the relief of mild to moderate pain (e.g. musculoskeletal pain, headache, dysmenorrhoea); as antipyretics to reduce fever
• anti-inflammatory drugs for chronic control of inflammatory diseases (e.g. rheumatoid arthritis, osteoarthritis)
• (aspirin only) as an anti-aggregatory agent to inhibit platelet aggregation in patients who are at risk of stroke or myocardial infarction

Question 7

What causes most of the unwanted side effects of NSAIDs?

Answer 7

anti-inflammatory actions, and probably most of the analgesic & antipyretic actions, of the NSAIDs are related to inhibition of COX-2, while their unwanted effects are largely a result of inhibition of COX-1

Question 8

What are PPIs?

Answer 8

proton pump inhibitors

Question 9

What are some examples of PPIs?

Answer 9

Omeprazole

Lansoprazole

Question 10

What is the primary mechanism of action of PPIs?

Answer 10

Irreversible inhibitors of H+/K+ ATPase in gastric parietal cells.
Proton pump inhibitors inhibit basal and stimulated gastric acid secretion by >90%.

Question 11

What prolongs the duration of action for PPIs?

Answer 11

weak bases and accumulate in the acid environment of the canaliculi of the parietal cells - this concentrates their actions there

Question 12

What is the drug target for PPIs?

Answer 12

H+/K+ ATPase (‘proton pump’)

Question 13

What are the side effects?

Answer 13

uncommon but may include:
- headache
- diarrhoea
- bloating
- abdominal pain
- rashes
Omeprazole = inhibitor of cytochrome P2C19 and has been reported to reduce the activity of e.g. clopidogrel, when platelet function is monitored

Question 14

Why do you have to be careful with PPIs?

Answer 14

can mask the symptoms of gastric cancer

Question 15

Why do PPIs have to be administered in capsules containing enteric-coated granules?

Answer 15

PPIs are pro-drugs which, at low pH, are converted into 2 reactive species which react with sulphydryl groups in the H+/K+ ATPase responsible for transporting H+ ions out of the parietal cells.

Generally given orally but degrade rapidly at low pH so they need the capsules

Question 16

What is an example of a H2 receptor antagonist?

Answer 16

Ranitidine

Cimetidine

Question 17

What is the primary mechanism of action for H2 receptor antagonist?

Answer 17

• competitive antagonists of H2 histamine receptors (structural analogues of histamine)
• inhibit the stimulatory action of histamine released from enterochromaffin-like (ECL) cells on the gastric parietal cells
• inhibit gastric acid secretion by approximately 60%

Question 18

What is the drug target for H2 receptor antagonists?

Answer 18

H2 receptors

Question 19

What are the side effects of H2 receptor antagonists?

Answer 19

Incidence of side-effects is low:
- Diarrhoea
- dizziness
- muscle pains
- transient rashes
Cimetidine (but not other H2 antagonists) inhibits cytochrome P450 and may retard the metabolism and potentiate the effects of a range of drugs incl. oral anticoagulants and TCAs.

Question 20

What is the primary mechanism of action for paracetamol?

Answer 20

Still not totally clear.

At peripheral sites, may inhibit a peroxidase enzyme which is involved in the conversion of arachidonic acid to prostaglandins (involves COX).

Activation of descending serotonergic pathways possibly via 5HT3 receptor activation.

Inhibits reuptake of endogenous endocannabinoids, which would increase activation of cannabinoid receptors - this may contribute to activation of descending pathways.

Question 21

What are the drug targets of paracetamol?

Answer 21

Unclear.

• 5HT3 receptors
• Cannabinoid reuptake proteins
• Peroxidase

Question 22

What are the side effects of paracetamol?

Answer 22

Relatively safe drug with few common side effects.

Question 23

What are the features of paracetamol overdose?

Answer 23

Liver damage and less frequently renal damage.

Nausea and vomiting early features of poisoning (settle in 24h).

Onset of right subcostal pain after 24 hrs - hindicates hepatic necrosis.

Question 24

What are the uses of paracetamol?

Answer 24

Analgesic and anti-pyretic.

Does NOT possess anti-inflammatory activity.