pharmacology GORD

Question 1

Why can NSAIDs cause peptic ulcers/stomach injury?

Answer 1

NSAIDS inhibit COX1 & COX2 and therefore inhibits production of prostaglandins. Inhibit PG protection of gastric mucosa - PGs protect from acid by increasing bicarbonate production, increasing mucus production and increasing blood flow. Stomach wall more vulnerable to acid causing peptic ulcers.

Question 2

BMJ algorithm for those with peptic ulcer disease caused by NSAIDS? Dose?

Answer 2

Stop NSAIDS when possible. Full dose PPI therapy for 4-8wks (options include omeprazole 20mg orally once daily)

Question 3

Why are PPIs hard to stop taking?

Answer 3

Because cause rebound effect when stopped causing stomach pain

Question 4

Why do PPIs increase risk of fracture?

Answer 4

Absorption of calcium salts is pH dependent so change in pH due to PPIs may decrease calcium available for bone

Question 5

Examples of NSAIDs?

Answer 5

Ibuprofen, naproxen, diclofenac

Question 6

Mechanism of NSAIDS?

Answer 6

Inhibit COX enzyme (cyclo-oxygenase) which produced prostaglandins from arachidonic acid. Prostaglandins act on PG receptors for many actions. NSAIDS used for anti-inflammatory, analgesic & antipyretic actions. These actions due to inhibition of COX-2, side effects due to COX-1 inhibition

Question 7

Target of NSAIDS?

Answer 7

(COX-2 and COX-1)

Question 8

Side effects of NSAIDS?

Answer 8

Gastric irritation, ulceration, bleeding, perforation. Reduced creatinine clearance & possible nephritis. Bronchoconstrition in susceptible (contraindicated in asthma). Skin rashes & allergies, dizziness, tinnitus. Adverse CV effects (hypertension, stroke MI) in prolonged use. Prolonged abuse associated with CKD.

Question 9

What are NSAIDS commonly used for?

Answer 9

Mild - moderate pain - antipyretics & anti-inflammaotry drugs for chronic control of inflammatory diseases

Question 10

What is aspirin used for + side effects?

Answer 10

Anti-aggregatory agent to inhibit platelet aggregation in those with risk of stroke/MI. reye’s syndrome in children (post-viral encephalitis)

Question 11

Examples of PPIs?

Answer 11

Omeprazole, lansoprazole

Question 12

Mechanism of PPIs? half life? effects?

Answer 12

Irreversibly inhibit H+/K+ ATPase (proton pump) on gastric parietal cells, decreasing acid secretion. They are weak bases so accumulate in acid environment of parietal cells. Omeprazole plasma half life 1h but daily dose affects acid secretion for 2-3days. Inhibit basal and stimulated gastric secretion by >90%

Question 13

Target of PPIs?

Answer 13

H+/K+ ATPase (proton pump)

Question 14

Side effects of PPIs?

Answer 14

Headache, diarrhoea, bloating , abdominal pain & rash. May mask symptoms of gastric cancer. Omeprazole inhibitor of cytochrome P2C19 & reduces activity of clopidogrel.

Question 15

Interactions of PPIs?

Answer 15

Inhibitor of cytochrome P2C19 and reduces activity of clopidogrel

Question 16

How are PPIs given and why?

Answer 16

Pro-drugs converted into 2 reactive species at low PH that react with sulphydryl group in proton pump. Given orally but degrade quickly at low pH so given as capsulated containing enteric-coated granules

Question 17

Histamine-2 receptor antagonist example?

Answer 17

ranitidine

Question 18

H2 receptor antagonists mechanism?

Answer 18

competitive antagonists of H2 histamine receptors. Inhibit stimulatory action of histamine released from ECL cells on gastric parietal cells, inhibiting gastric acid secretion by about 60%

Question 19

Target of H2 receptor antagonists?

Answer 19

H2 histamine receptor

Question 20

Side effects of H2 receptor antagonists?

Answer 20

Diarrhoea, dizziness, muscle pain, rash.

Question 21

Interactions of H2 receptor antagonists?

Answer 21

Climetidine (but not other H2 antagnonists) inhibits cytochrome p450 so may slow metabolism/potentiate effects of oral anticoagulants & TCAs

Question 22

Structure/half-life of ranitidine?

Answer 22

Plasma half life 2-3h - twice daily dosing effective. Undergo first pass metabolism (50% bioavailability)

Question 23

Paracetamol mechanism?

Answer 23

Maybe interaction with COX-3 isoform inhibiting PG synthesis, cannabinoid receptors or exogenous opiods, interactions at 5HT & adenosine receptors.

Question 24

Paracetamol target?

Answer 24

COX-3 isoform

Question 25

Paracetamol side effects?

Answer 25

No gastric irritation but overdose can cause serious heptatotoxicity

Question 26

What is paracetamol commonly used for?

Answer 26

Little anti-inflammatory activity but good analgesic and anti-pyretic. Sadly common way of suicide