PUD Flashcards
Classes of drugs
Reduce gastric acidity, mucosal protective agents, triple therapy for H.pylori eradication
Agents that reduce gastric acidity
Antacids, H2-receptor antagonist, PPI
Antacids
NaHCo3, CaCO3, Mg(OH)2, Al(OH)3
MoA of antacids
DO not prevent acid production, but REDUCE acidity
Neutralize gastric acid to form salt and H2O
For those with CO3, CO2 is formed too
Rate of neutralization by antacids
Na > Ca > Mg > Al
SE of antacids
Na: fluid retention, HTN, CHF
Ca: hyperCa, rebound acid secretion
HCO3, CO3: CO2 gas formation –> distension, belching [some agents contain simethicone as anti-foaming agent to ease release of gas]
Can cause metabolic alkalosis, Milk-Alkali syndrome
Mg: osmotic diarrhoea
Al: constipation
Combined formulation reduces impact on bowel function (Mylanta)
Precautions of antacids
Avoid LT use in renal insufficiency
Do not take within 2h of other medications — affect absorption
H2-receptor antagonist/H2-blocker
Famotidine, cimetidine, ranitidine
MoA of H2-R antagonist
Competitive inhibition of H2 receptors on parietal cells –> suppress gastric acid secretion and pepsin concentration induced by histamine, gastrin, Ach
Efficacy of H2-R antagonist
Very effective at inhibiting nocturnal acid secretion due to histamine, modest effect on meal-induced acid secretion
Famotidine most potent
SE of H2-R antagonist
Relatively safe with high therapeutic index
For cimetidine: mental confusion in critically ill Px or those with renal/hepatic dysfunction, anti-androgenic (increase serum prolactin –> gynaecomastia, galactorrhoea)
DDI of H2-R antagonist
CYP450 inhibitor — prolongs half-life of drugs such as warfarin, theophylline
PPI
Omeprazole, esomeprazole
MoA of PPI
Enteric-coated formulation to protect activation before absorption
Released and absorbed in intestines –> protonated, activated, concentrated in parietal cell canaliculi
Forms irreversible covalent disulphide bonds with H/K ATPase –> inhibit proton pump
Some antimicrobial activity against H.pylori
PK of PPI
Bioavailability decreased by food
Inactivates active pumps not quiescent pumps
Short serum T1/2: 1-2h, DoA 24h (due to irreversible block)
Takes 3-4d to fully inhibit acid secretion
Instructions for PPI
1x daily, 1h before breakfast
Takes 3-4d to achieve full inhibition of acid secretion
SE of PPI
Generally good safety profile
Cause headaches, nausea, constipation/diarrhoea
May cause Ca deficiency (pH change affecting absorption), osteoporosis risk, fractures (chronic high dosing)
Mucosal protective agents
Sucralfate, bismuth compounds, misoprostol
MoA of sucralfate
Negatively charged sucrose sulphate binds to positive-charge proteins at ulcer crater –> forms viscous gel that prevents further acid attack
Stimulates mucosal PG and bicarbonate secretion
SE of sucralfate
Minimal systemic effect as compound is not absorbed
SE: constipation (presence of Al), affect absorption of other drugs
Instructions for sucralfate
At least 1h before meals, on empty stomach
Limited use due to H2-R antagonist, PPI being more effective BUT still use for preventing stress-related bleeds
Bismuth compounds
Bismuth subsalicylate (dyspepsia, acute diarrhoea), bismuth subcitrate potassium (quadruple therapy for H.pylori)
MoA of bismuth
Forms (mechanical) protective layer and protects ulcer from acid and pepsin
Stimulate mucus and bicarbonate secretion
DIrect anti-microbial activity against H.pylori
SE of bismuth compounds
Generally good safety profile for ST use but LT use could be harmful for Px with renal impairment due to slow renal excretion
SE: harmless blackening of stool, reversible darkening of tongue
Prolonged use may rarely cause bismuth toxicity –> encephalopathy (ataxia, h/a, confusion, seizures); avoid LT use and use in Px with renal impairment
MoA of misoprostol
Synthetic PGE1 analogue –> binds to PGE2 receptor
Low-dose: cytoprotective — promotes bicarbonate, mucus secretion, mucosal blood flow
High-dose: anti-secretory —inhibit acid secretion
SE of misoprostol
Most important: uterine contraction that can cause abortion
Others: abdominal pain, diarrhoea, bone pain & hyperostosis
Use of misoprostol
Limited use due to adverse effects, potential for abuse as abortifacient, non-compliance (multiple dosing), advent of COX-2 selective NSAIDs
Contraindication of misoprostol
Pregnant women due to risk of abortion
H.pylori eradication triple therapy
2 antibiotics (clarithromycin and amoxicillin/metronidazole), 1 PPI (omeprazole/esomeprazole) —for 7-14days
Use of PPI in H.pylori eradication
Raise intra-gastric pH to lower minimum inhibitory concentration (MIC) of antibiotics against H.pylori
Also, minimal antimicrobial properties
Instructions for triple therapy
After completion of triple therapy, must continue PPI for 4-6w to ensure complete healing
Quadruple therapy for H.pylori eradication
2 antibiotics + 1 PPI/H2 antagonist, 1 bismuth — for 14days (longer than triple therapy)
SE of triple therapy
Diarrhoea, N&V
