GI: Peptic Ulcers & GERD

Question 1

Peptic Ulcer is a result of?

Answer 1

Imbalance between acid-pepsin secretion and mucosal defense factors

Question 2

Gastric Acid Secretion is Regulated by which chemicals and what are their receptors?

Answer 2

Acetylcholine: M1 Receptor
Gastrin: G Receptor
Histamine (Released by enterochromaffin cells under influence of Ach and G): H2 Receptors

Question 3

H. pylori is associated with which disease?

Answer 3

Helicobacter pylori : Chronic gastritis, Peptic Ulcers, and their recurrence.

Question 4

Classification of Drugs used in Peptic Ulcer:

Answer 4

1) Drugs for neutralization of Acid
2) Drugs that reduce gastric acid secretion
3) Ulcer Protectives

Question 5

Antacids pH, how are they given, MOA

Answer 5

Antacids are Basic Substances, which are given orally and raise the pH of the gastric contents.

Question 6

Types of Antacids, with examples; Basis of classification

Answer 6

1) Systemic Antacids: Eg Sodium Bicarbonate
2) Nonsystemic Antacids: Eg: Aluminium hydroxide, Magnesium trisilicate, Magnesium hydroxide, calcium carbonate.
3) Others: Simethicone

Based on absorption in circulation.

Question 7

Systemic Antacid: Sodium Bicarbonate, Its Onset of Action, Duration of Action , MOA.

Answer 7

Fast Acting,
Short-Acting,
Neutralizes HCl to form Nacl and CO2

Question 8

Systemic Antacid: Sodium Bicarbonate, Its Uses, ADRs

Answer 8

Uses: In Peptic Ulcers and Hyperacidity, To Alkanise urine in treatment of poisoning due to acidic drugs, Metabolic Acidosis

ADRs: NaHCO3 gets absorbed from intestines-> Systemic Alkalosis. Rebound Hyperacidity due to increase gastrin levels. Increase sodium load -> Troublesome to Patients w/ Cardiovascular Diseases
In high doses may cause MILK-ALKALI SYNDROME: Hypercalcaemia, metabolic Alkalosis & Renal Dysfunction.

Question 9

Systemic Antacids examples?

Answer 9

Sodium Bicarbonate
Sodium Citrate

Question 10

Nonsystemic Antacids: Examples, MOA

Answer 10

Examples: Aluminium hydroxide, Magnesium salts and Calcium carbonate

MOA: They are insoluble substances which react with HCl to form Chloride Salts (Non absorbable) & H2O

Question 11

Nonsystemic Antacids: AL(OH)3. MOA & ADRs

Answer 11

It is a slow acting neutralizing substance which also forms a protective layer over the ulcers.

ADRs: Relaxes smooth muscles which leads to constipation
Binds with phosphate which leads to hypophosphataemia on prolonged use.

Question 12

Nonsystemic Antacids: Mg Salts, MOA & ADRs

Answer 12

Mg(OH)2, MgTrisilicate, MgO, MgCO3.
Neutralizes the acid to form MgCl2.
Quick action and prolonged action.

ADRs: MgCl2 is purgative and may cause diarrhoea
MgTrisilicate may get absorbed in small amounts.
It may lead to hypermagnesaemia in renal dysfunction.

Question 13

What is Magaldrate?

Answer 13

Hydrated complex of hydroxymagnesium aluminate, it reacts with acid to release Al(OH)3. which has prolonged effect.

Question 14

Nonsystemic Antacids: CaCO3 MOA,ADRs

Answer 14

Quick and prolonged action.
Liberates CO2 which may cause discomfort.

ADRs: May cause constipation
Hypercalcaemia which may cause rebound acidity.
Long term use may cause Renal stones and Milk Alkali Syndrome.

Question 15

Antacid Combinations: Examples and reasons.

Answer 15

Examples: GELUSIL Liquid, GELUSIL Tablet, DIGENE Gel & Tablet.

Advantages:
1) Quick and prolonged Effect: Mg(OH)2 :Fast acting, Al(OH)3 long acting.
2)Canceling out side effects: Mg:Laxative, Al: Constipation
3) Additive Effect: Cancels out side effects but increases the effect without increasing the individual doses..

Question 16

Antacid Drug Interaction:

Answer 16

They form complexes with Iron, tetracyclines, digoxin, ranitidine, sulfonamides and antimuscarinic drugs.
Antacids should be taken 2 hours before or after these drugs

Question 17

Drugs that reduce gastric acid secretion: H2 Receptor Blockers. MOA And Pharmacokinetics.

Answer 17

They Bind to H2 Receptor and competitively inhibit action of histamine. Both Volume and acidity are reduced. Single dose can cause 60-70% reduction in secretion.

Rapidly absorbed but undergoes first pass meta.

Question 18

Gastric acid secretion: H2 Receptor Blockers: ADRs

Answer 18

Diarrhoea, Dizziness, Muscle Pain, headache. Crosses placenta and +nt in milk ergo should be avoided in pregnancy and lactation.

Question 19

Examples of gastric acid secretion: H2 Receptor Blockers (CENFRR)

Answer 19

Cimetidine
Ebrotidine
Nizatidine
Famotidine
Ranitidine
Roxatidine

Question 20

ADRs of Cimetidine

Answer 20

It is antiandrogenic, increases prolactin levels and inhibits estrogen metabolism in liver.
Results in Gynaecomastia, dec. sperm count, impotence, loss of libido and galactorrhoea in women.

CNS effects: Confusion, restlessness, delirium and hallucinations.
Headache, dizziness, rashes, diarrhoea

CVS Effects: Bradycardia, AV block, C.Arrest, A Fribli.

Interferes with metabolism of many drugs (Cyt.)

Ergo not preferred.

Question 21

Advs and ADR of Ranitidine

Answer 21

Preferred over cimetidine cause:
More potent and long acting.
No ADRs like in Cimetidine

Only ADR : Dizziness and headache

Question 22

Advs and ADR of Famotidine

Answer 22

Similar to Ranitidine but more potent.

ADRs: Headache, Dizziness, Bowel disturbances and rashes, QT Prolongation

Question 23

Advs and ADR of Roxatidine

Answer 23

Similar to Ranitidine but twice as potent; Same ADRs

Question 24

Advs and ADR of Nizatidine

Answer 24

Same as Ranitidine:

More potent and long acting.
No ADRs like in Cimetidine
90% Excreted thru kidney
Only ADR : Dizziness and headache

Question 25

Uses of H2 Blockers wrt GIT

Answer 25

1) Peptic ulcer: Rapid relief from pain and ulcers heal in 80-90% patients within 6-8 weeks. 2) Gastritis: First line drugs for non ulcer dyspepsia 3) Prevention of Stress induced Ulcers 4) Zollinger Elison Syndrone: Gastrin Secreting Tumor 5) GERD 6) Preanaesthetic: Ranitidine

Question 26

Gastric acid secretion: M1 Receptor Blockers. Which drugs are used and why is atropine not used.

Answer 26

Pirenzepine and Telenzepine are used as they have no CNS side effects like atropine as they cannot cross BBB and is specific to gastric M1 Receptors ADRs: Dryness of Mouth and Blurring of Vision

Question 27

Gastric acid secretion: Proton Pump Inhibitors: Examples (OPREDL)

Answer 27

Omeprazole (Prototype) Pantoprazole (Most acid stable, Oral And IV) Rabeprazole (Fastest onset of action) Esomeprazole (S enantiomer of ome.) Dexlansoprazole (Higher oral bioavailability than Ome.) Lansoprazole (Higher oral bioavailability than Ome.)

Question 28

Gastric acid secretion: PPI: MOA

Answer 28

They are prodrugs which get activated in parietal cells in acidic environment to Sulfenamide. Sulfenamide binds with the proton pump inactivating it irreversibly. Single dose can decrease upto 90-95% secretion. It takes 3-4 days for the onset of action.

Question 29

Gastric acid secretion: PPI: Pharmacokinetics

Answer 29

They are acid labile. Ergo are enteric coated. They are lipid soluble and are absorbed in intestines rapidly. It reaches parietal cells due to its acidic nature. Conc of the drug is 1000 times more as its trapped. *Pantoprazole and Esomeprazole can be used as IV* T1/2 is 1-2 hours but the action is for 2-3 days. Metabolised in Liver CytP450 Food interferes therefore PPI should be taken 1hr before.

Question 30

Gastric acid secretion: PPI: ADRs

Answer 30

Well Tolerated 1) Prolonged acid suppression : Infections 2) Dizziness headache diarrhoea abd. pain nausea 3) Long term use: VitB12 Def., Decreased Iron, magnesium and calcium absorption (Osteoporosis) Atrophic changes in stomach after 3-4 years of use

Question 31

Gastric acid secretion: PPI:Uses

Answer 31

1)Peptic Ulcers 2)GERD 3) Dyspepsia 4)Drug induced ulcers 5) H. pylori regimen 6) Zollinger Ellison Syndrome 7) Gastrinoma 8) Preanesthetic Medication

Question 32

Gastric acid secretion: PPI: Drug Interactions

Answer 32

1) PPI decrease drug absorption of drugs which need acid environment 2) Enzyme inhibition by Omeprazole and Esomeprazole which inhibit meta. of diazepam, phenytoin and warfarin.

Question 33

Ulcer Protectives: Sucralfate: MOA and Uses

Answer 33

Salt of Sucrose and Sulfated aluminium hydroxide. In acidic medium it polymerizes to form viscid layer over the ulcer. Negative charged sucralfate is attracted to positively charged proteins in ulcer. Remains for 6 hours. Also stimulates PG syn. to secrete Mucus. Uses: Peptic Ulcer healing, Prevent Stress Induced ulcer ADR: Dryness of mouth and constipation (Al)

Question 34

Ulcer Protectives: Bismuth Salts: MOA and Uses

Answer 34

Colloidal Salts of Bismuth subcitrate and subsalicylate. Chelates and forms a layer on ulcer base. Also inhibits H. pylori growth. And stimulates Mucus sec. and PG syn. Uses: P. Ulcer healing, Prevents Travellers diarrhoea ADRs: Constipation, Black stools, darkening of tongue and dizziness.

Question 35

Other P. Ulcer Drugs: Prostaglandins: Examples and MOA

Answer 35

MOA : Decrease gastric secretion and stimulates mucus secretion Examples: Misoprostol, enprostil, rioprostil Also Prevents NSAID induced gastric ulcers.

Question 36

What is Simethicone:

Answer 36

Aka Dimethylpolysiloxane, silicone polymer. Pharmacologically inert. Helps in proper dispersion of antacids. Also decreases flatulence as it reduces surface tension (Prevents bubbles).