Pharmacology of GORD

Question 1

What are some examples of NSAIDS?

Answer 1

• ibuprofen
• naproxen
• diclofenac

Question 2

What is the primary mechanism of action of NSAIDS?

Answer 2

inhibition of cyclo-oxygenase (COX) enzyme - the rate limiting step of the production of prostaglandins and thromboxanes from arachidonic acid.
Leading to the anti-inflammatory and antipyretic actions of NSAIDS - tend to be due to inhibition of COX2. Side effects due to COX1 inhibition.

Question 3

What is the drug target of NSAIDS?

Answer 3

cyclo-oxygenase (COX) enzyme

Question 4

What are the main side effects of NSAIDS?

Answer 4

• gastric irritation
• gastric ulceration
• gastric bleeding
• gastric perforation (extreme)
• reduced creatine clearance
• nephritis
• bronchoconstriction
• skin rashes
• dizziness
• tinnitus
• hypertension, stroke, MI
• chronic renal failure

Question 5

What are NSAIDS contraindicated with?

Answer 5

asthma due to possible bronchoconstriction

Question 6

What has aspirin been linked with?

Answer 6

post-viral encephalitis

Reyes syndrome in children

Question 7

What are the main uses of NSAIDS?

Answer 7

• analgesia
• antipyretics
• anti-inflammatories
• anti-aggregatory agent (aspirin ONLY)

Question 8

What are some examples of Proton Pump Inhibitors?

Answer 8

• omeprazole

- lansoprazole

Question 9

What is the primary mechanism of action of PPIs?

Answer 9

irreversible inhibition of H+/K+ ATPase in the gastric parietal cells.
weak bases that accumulate in the canaliculi of the parietal cells - increases concentration and duration of action
Inhibit basal and stimulated gastric acid secretion by >90%

Question 10

What is the main drug target of PPIs?

Answer 10

H+/K+ ATPase (proton pump)

Question 11

What are the main side effects of PPIs?

Answer 11

• headache
• diarrhoea
• bloating
• abdominal pain
• rashes

Question 12

What is omeprazole and inhibitor of?

Answer 12

cytochrome P2C19 and reduced the activity of eg clopidogrel when platelet function is monitored

Question 13

How are PPIs administered?

Answer 13

• orally
• degrade rapidly at low pH
• therefore capsules contain enteric-coated granules

Question 14

What does it mean that PPIs are pro-drugs?

Answer 14

at a low pH are converted into 2 reactive species withreact with the sulphydryl groups in the H+/K+ ATPase responsible for getting H+ out the parietal cell

Question 15

What is an example of a Histamine (H2) receptor antagonist?

Answer 15

• ranitidine

Question 16

What is the primary mechanism of action of Histamine (H2) receptor antagonists?

Answer 16

competetive antagonist of H2 receptors

• inhibits the stimulatory action of histamine released from enterochromaffin-like (ECL) cells on the gastric parietal cells
• inhibit gastric acid secretion by around 60%

Question 17

What is the drug target of H2 receptor antagonists?

Answer 17

Histamine H2 receptors

Question 18

What are the side effects of H2 receptor antagonists?

Answer 18

• diarrhoea
• dizziness
• muscle pains
• transient rashes

Question 19

What happens in Climetidine?

Answer 19

• inhibits cytochrome P450
• can retard the metabolism and potentiate the metabolism and the effects of a range of drugs (TCAs and oral anti-coagulants).

Question 20

What is the normal dose of ranitidine?

Answer 20

2 x daily 
well tolerated 
half life: 2-3 hours 
1st metabolism = 50% bioavailability
low dose available over the counter

Question 21

What is the primary mechanism of action of Paracetamol?

Answer 21

• actions restricted to nervous tissue
• unclear mechanism of action
  current hypothesis: central and peripheral action and interaction with COX3 isoform (inhibition of PG synthesis), cannabinoid receptors or the endogenous opiods.
  Interactions at 5HT and adenosine receptors have also been proposed.

Question 22

What is the possible drug target of paracetamol?

Answer 22

unknown - COX 3 isoform

Question 23

What are the main side effects of Paracetamol?

Answer 23

few side effects at therapeutic dosage
at overdose:
- hepatoxicity
occasionally: skin reactions

Question 24

Why is paracetamol not considered an NSAID?

Answer 24

it has very little anti-inflammatory activity

Question 25

What are the main effects of Paracetamol?

Answer 25

• anti-pyretic

- analgesic (mild to moderate)