O2ii: Compare and contrast the pharmacology of drugs that alter the pH of gastric fluid
Example
Proton Pump Inhibitors
Omeprazole
H2 Receptor Antagonist
Ranitidine
Antacids
Magnesium Hydroxide
Aluminium Hydroxide
Chemical
Proton Pump Inhibitors
Benzimadole derivative
H2 Receptor Antagonist
Furan derivative
Antacids
Weak base
Reacts with HCl to form water & salt
Lowering stomach pH
Presentation
Proton Pump Inhibitors
Capsules
Powder in a vial
H2 Receptor Antagonist
Tablets
Clear soln 25mg/ml
Antacids
Oral suspensions
Route
Proton Pump Inhibitors
IV/PO
H2 Receptor Antagonist
IV/PO
Antacids
PO only
MoA
Proton Pump Inhibitors
Irreversibly binds Parietal Cell H/K/ATPase pump on Apical memb
Non Competitive Inhibition
Prevents H+ excretion
↓gastric acid acidity
H2 Receptor Antagonist
Competitive Antagonist of H2 receptors on Parietal Cells
Prevents the potentiation of ACh & Gastrin to stimulate HCl by Histamine
↓volume and ↓gastric acidity
Antacids
Basic solution neutralises gut in the acid, raising pH
Weak base
Reacts with HCl to form water & salt
Lowering stomach pH
PK
Proton Pump Inhibitors
A
OBA 75%
Rapid peak 30min
D
95% PPB
Vd 0.4L/kg
M
Hepatic by CYTP450
Almost completely
E
Urinary
Metabolites excreted
T1/2 1hr
H2 Receptor Antagonist
A
OBA 60%
D
15% PPB
Vd 1.2L/kg
M
Small % metabolised by oxidation & methylation
E
Mostly unchanged by kidneys
Antacids
A
Aluminium & Magnesium not absorbed from gut
D
Not known
M
H+ acceptor
E
Eliminated in feces
Aluminium = constipation
Magnesium = osmotic diarrhoea
AE
Proton Pump Inhibitors
Increased risk of Pneumonia
Interstitial nephritis
Osteoporosis
Blurry vision
Dry mouth
Confusion
H2 Receptor Antagonist
Abnormal LFTs
Thrombocytopenia
Confusion
Antacids
Metabolic alkalosis
Diarrhoea
Constipation
Other:
PIRENZIPINE – muscarinic blocker – M1 competitive blockade, ↑↓IP3/DAG, ↓proton pump action
Less effective than PPI
MISOPROSTIL – prostaglandin E2 analogue – released when the gastric mucosa is damaged; mediate production of mucous layer that coats gastric epithelial cells. Also promotes production of bicarbonate which helps neutralise acid in stomach
↑uterine tone, severe diarrhoea, GI upset
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