Proton pump inhibitors (PPI)

Question 1

what are PPIs

Answer 1

drugs that inhibit H+ secretion

Question 2

examples

Answer 2

-prazoles

omeprazole
lansoprazole
these both are pro-drugs, only activated at very low pH

esomeprazole
pantoprazole

Question 3

used for

Answer 3

conditions caused by excessive gastro-oesophageal acidity

Question 4

MOA

Answer 4

• PPIs irreversibly inhibit H+/K+ ATPase in parietal cells (stop H+ in for K+ out)
• reduce H+ secretion, no gastric acid produced
• increases stomach pH (more alkaline)

Question 5

overall function of PPIs is

Answer 5

to suppress H+ gastric acid secretion

Question 6

PPIs given in an inactive form

Answer 6

which is activated
and takes effect in an acidic envt (eg. the canaliculi of the apical parietal cells)

Question 7

why does it take 2-3 days to completely work - max efficacy?

Answer 7

PPI given in inactive form, then are activated in acidic envt

not all H+/K+ pumps are active all of the time, so not all are inhibited

quick symptomatic relief takes abt 48hrs

Question 8

dosing regime

Answer 8

PPIs given daily
doses given 30mins before bfast and dinner, to control gastric pH

Question 9

indications

Answer 9

• GORD
• peptic ulcer disease (GU, DU) + prevent stress ulcers
• H.pylori eradication as combination therapy
• gastritis
• ZES (gastrinoma)
• gastropathy caused by NSAIDs
• ! MALT lymphoma (stages I,II)

Question 10

cautions when prescribing PPIs for

Answer 10

• increases risk of GI infections eg. C difficile
• reduces absorption of Ca2+, Mg2+ so long term use increases risk of osteoporosis and high dose increases risk of fractures
• reduces absorption of Vitamin B12 and iron in long-term use, so anaemia
• can mask symptoms of gastric cancer (alarm features)

Question 11

how to prescribe carefully to certain pts

Answer 11

• pts at risk of osteoporosis - maintain enough Ca2+ and Vit D intake, and give additional bone-sparing therapy
• pts at risk of hypomagnesaemia - esp if taking drugs causing it (digoxin, diuretics) so check serum Mg levels before starting PPI therapy and intermittently if long-term use

Question 12

common side effects

Answer 12

• abdo pain
• GI upset - c,n,v,d
• dizziness
• dry mouth
• headache
• GI disorders
• insomnia
• skin reactions

Question 13

uncommon side effects

Answer 13

• arthralgia
• bone fractures
• confusion
• depression
• drowsiness
• leucopenia
• malaise
• myalgia
• paraesthesia
• peripheral oedema
• thrombocytopenia
• vertigo
• vision disorders

Question 14

interactions

Answer 14

• omeprazole + esomeprazole INHIBIT CYP2C19 enzyme
• clopidogrel converting into active metabolite, so pt swapped to lanzoprazole if co-prescribed clopidogrel + omeprazole : this CYP2C19 enzyme converts drugs into their active metabolite so inhibiting enzyme - reduces clinical efficacy of drugs

CYP2C19 responsible for clearing
- WARFARIN, PPI inhibits enzyme so less clearance so increased risk of bleeding
- PHENYTOIN (AED/ASD), PPI inhibits enzyme so less clearance so phenytoin toxicity can be fatal
-
OVERALL, PPI enhances effects of warfarin + phenytoin so monitor INR levels

measure serum Mg before and during PPIs, especially when used with drugs that cause hypoMgaemia or with digoxin

Question 15

contraindications

Answer 15

PPIs mask symptoms of upper GI malignancy so not for
* pts with red flags for upper GI malignancy
* pts with red flags before endoscopy
* pts already taking PPIs and needing endoscopy - stop their PPI atleast 2 weeks before the procedure

fine to use in pregnancy, breast-feeding - not harmful