pharmacology of GORD/peptic ulcer disease

Question 1

some examples of NSAIDS

Answer 1

ibuprofen
naproxen
diclofenac

Question 2

primary mechanism of action of NSAIDs

Answer 2

inhibit cyclo-oxygenase which is rate limiting step for all prostanoids( prostaglandins and thromboxanes) from parent arachidonic acid. prostanoids act through large number of prostanoi receptors to produce array of actions.
thought that antiinflammatory actions and most of the analgesic and antipyretic actions are related to inhibiton of cox2, while unwanted effects are result of cox1 inhibition

Question 3

what is target of NSAIDs

Answer 3

cyclo oxygenase enzyme

Question 4

common unwanted effects of NSAIDs

Answer 4

gastric irritation
ulceration 
bleeding
in extreme cases - perforation, reduced creatinine clearance and possible nephritis and bronchoconstriction in susceptible individuals (contraindicated in asthma)
skin rashes, dizziness, tinnitus

Question 5

what side effects can occur following prolonged use of NSAIDs or in patients with pre existing cv risk?

Answer 5

cardiovascular effects - hypertension, stroke, mi

renal complications

Question 6

what is prolonged analgesic abuse of NSAIDs associated with

Answer 6

chronic renal failure

aspirin has been linked with rare but serious post viral encephalitis - reyes syndome in children

Question 7

what is the main use of NSAIDs

Answer 7

1.analgesics - for relief of mild to moderate pain e.g musculo-skeletal pain, headache, dysmenorrhoea
2. antipyretics - to reduce fever
3. anti inflammatory - for control of inflammatory disease (e.g ra, oa)
aspirin only - is an antiaggregatory agent to inhibit platelet aggregation in patients who are at risk of stroke /mi

Question 8

what are some examples of proton pump inhibitors

Answer 8

omeprazole

lansoprazole

Question 9

what is the mechanism of action of ppis

Answer 9

irreversible inhibitors of h+/k+ ATPase in gastric parietal cells. They are weak bases and accumulate in acid environment of canaliculi of parietal cells. concentrates their actions there and prolongs duration of action

Question 10

what is the plasma half-life of omeprazole

Answer 10

1hr but single dose affects acid secretions for 2-3 days

Question 11

by how much % do ppis inhibit basal and stimulated gastric acid secretions

Answer 11

> 90%

Question 12

what is the target of ppis

Answer 12

h+/k+ ATPase (proton pump)

Question 13

what are some unwated but common side effects of ppis

Answer 13

headache, diarrhoea, abdominal pain and rashes. use of these drugs could mask symptoms of gastric cancer.

Question 14

how is omeprazole related to cytochrome p2c19

Answer 14

it is an inhibitor of cytochrome p2c19 and has reported to reduce activity of e.g clopidogrel when platelet function is monitored.

Question 15

what is meant by ppis ar epro drugs

Answer 15

at low ph are converted into 2 reactive species which react with sulphydryl groups in h+k+atpase responsible for transport of h+ ions out parietal cells.

Question 16

how are ppis generally given

Answer 16

orally but degrade rapidly at low ph so administered as capsule containing enteric coated granules

Question 17

what are some examples of h2 receptor antagonists

Answer 17

ranitidine

Question 18

what is the mechanism of action of hr receptor antagonists

Answer 18

are competitive antagonists of h2 receptors. inhibit stimulatory action of histamine released from enterochromaffin like cells on gastric parietal cells. inhibit gastric secretion by ~60%

Question 19

target for ranitidine

Answer 19

histamine h2 receptor

Question 20

side effects of h2 receptor antagonists

Answer 20

incidence is low
diarrhoea, dizziness, muscle pains and transient rashes.
cimetidine - inhibits cytochrome p450 and may retard metabolism and potentiate effects of range of drugs incl. oral anticoagulants and tcas

Question 21

what is the half life of ranitidine

Answer 21

~ 2-3hrs
- well tolerated so twice daily dosing is effective
undergo 1st past metabolism - 50% bioavailability
low dose over the counter formulations available from pharmacies for short term use.

Question 22

what is paracetamol also known as

Answer 22

acetaminophen

Question 23

what is mechanism of action of paracetamol

Answer 23

appears to be largely restricted to nervous tissue but mechanism of action is unclear.
current hypotheses - suggest both central and peripheral action possibly involving interaction with cox 3 isoform (inhibition of pg synthesis), cannabinoid receptors or endogenous opioids. interaction at 5ht and adenosine receptors have also been proposed.

Question 24

target of paracetamol

Answer 24

not yet well defined

cox3 isoform?

Question 25

side effects of paracetamol

Answer 25

generally safe drug
few side effects
doesnt cause gastric irritation but in overdose serious hepatotoxicity may occur.
occasional allergic skin lesions

Question 26

is paracetamol an nsaid?

Answer 26

no - has little anti-inflammatory activity.
however is a good analgesic for mild to moderate pain and also has antipyretic activity.
legal restrictions on sales have greatly reduced overdose fatalities.

Question 27

how do prostaglandins in gastric mucosal cells protect from acid

Answer 27

increase bicarbonate release
increase mucus production
increase blood flow

Question 28

what can be co prescribed with an nsaid to reduce its gi effects

Answer 28

proton pump inhibitor