Prodrugs

acid labile therefore have enteric coating

dissolved in small intestine

short half life 1-1.5hrs

effects longer:

  • binds to H+/K+-ATPase protonn pump of parietal cells

  • prevents transport of H+ ions into gut lumen for 10-14 hours

takes 5 days to reach maximal effect

1/4 of proton pumps in each pareital cell remain active

when PPI used; Gatrin increased; when stopped ongoing Gastrin production; rebound acid secretion

  • similar efficacy

    • pantoprazole availbe in small tablets

PPI and NSAIDs

  • PPI indicated for prevention and treatement fo NSAID induced eroisions and ulcers in at risk patients

  • daily compared to “as needed”

  • 20mg once daily for duration of NSAID treatment

Risk factors

  • Age >65

  • Previous adverse reaction

  • use of other medicines that exacerbate adverse effects

  • history of cardiovascualr disaese

  • liver disease

  • chronic kidney disease

  • smoking

  • excessive eoth consumption

Stopping PPI

  • rebound acid secretion

    • 40% one week after = rebund dyspepsia

  • use rescue antacid

Adverse effects

  • rate = relatively low

  • headache and GI adverse effects

  • less frequent

    • dry mouth

    • peripheral oedema

    • dizziness

    • sleep disturbances

    • fatigue

    • paraesthesia

    • arthalgia

    • myalgia

    • rash

    • pruritus

    • interstital nephritis

  • associated with increase risk of infection

    • c.diff

      • 1.7x od

      • 2.4x bd

    • salmonella, campylobacter, shigella

      • 3x

    • pneumonia

Malabsorption

  • acid in gut increase solubility of elenebts

    • calcium and iron

  • makes protein bound vitamins (b12) available for abdorption

  • small increase # risk in long term use

  • severe hypomagnaesaemia associated use of ppi

    • + hypocalcaemia

    • magnsium -> decrease parathyroid PTH and decrease response of kidney and skeleton to PTH

    • especially if excessive etoh

    • other contributory medicines

      • diuretics

      • ciclosporin

      • aminoglycosides

    • routine testing not recommended

    • unexplained sympomts then consider

  • hyponatraemia associated with use of PPI in small amount of people

acute interstitial nephritis

  • sympotms/signs

    • fever

    • rash

    • eosinophilia

    • malaise

    • myalgia

    • arthralgia

    • weight loss

    • change urine output

    • haematuria

    • pyruia

    • high bp

  • if suspected:

    • urine microsocpy

    • renal function tests

Interactions

clopidogrel

  • unlikely to be clinically significant

  • pantoprazole less inhibitory effect on CYP2c19

Warfarin

  • increase in anticoagulant effect or decrease when PPI stopped