PUD

Question 1

Classes of drugs

Answer 1

Reduce gastric acidity, mucosal protective agents, triple therapy for H.pylori eradication

Question 2

Agents that reduce gastric acidity

Answer 2

Antacids, H2-receptor antagonist, PPI

Question 3

Antacids

Answer 3

NaHCo3, CaCO3, Mg(OH)2, Al(OH)3

Question 4

MoA of antacids

Answer 4

DO not prevent acid production, but REDUCE acidity
Neutralize gastric acid to form salt and H2O
For those with CO3, CO2 is formed too

Question 5

Rate of neutralization by antacids

Answer 5

Na > Ca > Mg > Al

Question 6

SE of antacids

Answer 6

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)

Question 7

Precautions of antacids

Answer 7

Avoid LT use in renal insufficiency

Do not take within 2h of other medications — affect absorption

Question 8

H2-receptor antagonist/H2-blocker

Answer 8

Famotidine, cimetidine, ranitidine

Question 9

MoA of H2-R antagonist

Answer 9

Competitive inhibition of H2 receptors on parietal cells –> suppress gastric acid secretion and pepsin concentration induced by histamine, gastrin, Ach

Question 10

Efficacy of H2-R antagonist

Answer 10

Very effective at inhibiting nocturnal acid secretion due to histamine, modest effect on meal-induced acid secretion
Famotidine most potent

Question 11

SE of H2-R antagonist

Answer 11

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)

Question 12

DDI of H2-R antagonist

Answer 12

CYP450 inhibitor — prolongs half-life of drugs such as warfarin, theophylline

Question 13

PPI

Answer 13

Omeprazole, esomeprazole

Question 14

MoA of PPI

Answer 14

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

Question 15

PK of PPI

Answer 15

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

Question 16

Instructions for PPI

Answer 16

1x daily, 1h before breakfast

Takes 3-4d to achieve full inhibition of acid secretion

Question 17

SE of PPI

Answer 17

Generally good safety profile
Cause headaches, nausea, constipation/diarrhoea

May cause Ca deficiency (pH change affecting absorption), osteoporosis risk, fractures (chronic high dosing)

Question 18

Mucosal protective agents

Answer 18

Sucralfate, bismuth compounds, misoprostol

Question 19

MoA of sucralfate

Answer 19

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

Question 20

SE of sucralfate

Answer 20

Minimal systemic effect as compound is not absorbed

SE: constipation (presence of Al), affect absorption of other drugs

Question 21

Instructions for sucralfate

Answer 21

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

Question 22

Bismuth compounds

Answer 22

Bismuth subsalicylate (dyspepsia, acute diarrhoea), bismuth subcitrate potassium (quadruple therapy for H.pylori)

Question 23

MoA of bismuth

Answer 23

Forms (mechanical) protective layer and protects ulcer from acid and pepsin
Stimulate mucus and bicarbonate secretion
DIrect anti-microbial activity against H.pylori

Question 24

SE of bismuth compounds

Answer 24

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

Question 25

MoA of misoprostol

Answer 25

Synthetic PGE1 analogue –> binds to PGE2 receptor
Low-dose: cytoprotective — promotes bicarbonate, mucus secretion, mucosal blood flow
High-dose: anti-secretory —inhibit acid secretion

Question 26

SE of misoprostol

Answer 26

Most important: uterine contraction that can cause abortion

Others: abdominal pain, diarrhoea, bone pain & hyperostosis

Question 27

Use of misoprostol

Answer 27

Limited use due to adverse effects, potential for abuse as abortifacient, non-compliance (multiple dosing), advent of COX-2 selective NSAIDs

Question 28

Contraindication of misoprostol

Answer 28

Pregnant women due to risk of abortion

Question 29

H.pylori eradication triple therapy

Answer 29

2 antibiotics (clarithromycin and amoxicillin/metronidazole), 1 PPI (omeprazole/esomeprazole) —for 7-14days

Question 30

Use of PPI in H.pylori eradication

Answer 30

Raise intra-gastric pH to lower minimum inhibitory concentration (MIC) of antibiotics against H.pylori
Also, minimal antimicrobial properties

Question 31

Instructions for triple therapy

Answer 31

After completion of triple therapy, must continue PPI for 4-6w to ensure complete healing

Question 32

Quadruple therapy for H.pylori eradication

Answer 32

2 antibiotics + 1 PPI/H2 antagonist, 1 bismuth — for 14days (longer than triple therapy)

Question 33

SE of triple therapy

Answer 33

Diarrhoea, N&V