Gastrointestinal Pharmacology

Inhibitors of Gastric Acid secretion

Proton Pump Inhibitors (PPIs)

Gastric Acid Secretion

Receptors

H2 histamine receptors
Gs

Histamine

M3 Muscarinic
Gq

Ach

EP3 Prostaglandin receptors
Gi

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PG Prostaglandin

MOA

Inhibit H+/K+ ATPase proton pump that controls H+ secretion from the parietal cell

PKs

Pro-drug activated in acidic env

Rapidly absorbed, highly protein bound

Metabolised by CYP450 2C19 and CYP 3A4

Drugs

Omeprazole

Lansoprazole

Pantoprazole 🥇

Rabeprazole

Esomeprazol

ADs

CYP 2C19 genotype hav greater efficiacy and adverse effects

Indications

  1. Gastric and duodenal ulceration
  1. H. pylori eradicatoin (Triple Therapy)
  1. Dyspepsia
  1. GORD
  1. NSAID ass ulceration

7. Zollinger - Ellison syndrome
Tumors cause too much acid, resulting in peptic ulcers

  1. Nausea
  1. Abdominal pain
  1. Constipation
  1. Diarrhoea
  1. Risk of bone fracture
  1. Susceptibility to certain infx (C.dif and HAP) 🍫⛲

Interactions

Esomeprazole + Omeprazole - Clopidogrel

  1. Hypomagnesia 🧲

Decreased efficacy of clopidogrel

H2RA Histamine H2 Receptor Antagonists

Drugs

Cimetidine

RoyKentTedLassoGIF

선서다짐걸스카우트GIF

Ranitidine

Famotidine

Nizatidine

MOA

Competitive antagonism of H2 receptors

Prevents ↑cAMP and gastric acid secretion

Indications

  1. Gastric / duodenal ulceration
  1. H. pylori eradication
  1. Dyspepsia
  1. GORD
  1. NSAID ass ulceration
  1. Zollinger-Ellison syndrome

Adverse Effects

  1. GIT disturbance
  1. Headache
  1. Dizziness
  1. Altered LFTs
  1. Bradycardia
  1. Confusion
  1. Depression
  1. Hallucinations
  1. ↑ Prolactin
  1. Galactorrhoea
  1. Impotence
  1. CYP450 inhibiton - Cimetidine

Interactions

Cimetidine - Warfarin (CYP2C9), Phenytoin (CYP3A4), Theophylline (CYP1A2)

Cimetidine inhibits drug metabolism

  1. Secondary hypergastrinaemia

Prostaglandin Analogues

Drug

Misoprostol

MOA

E1 Prostaglandin analogue

Antisecretory and cytoprotective properties vie EP3 receptor

Increases mucin and bicarbonate secretion

Indications

  1. Gastric / duodenal ulceration
  1. NSAID ass ulceration

Adverse Effects

Nausea and vomiting

Abdominal pain

Diarrhoea

Abdnormal vaginal bleeding

Women of childbearing age must take contraception

Contraindicated in pregnancy

Exacerbates inflammatory bowel disease (IBD)

Chelates & Complexes

Sulcralfate

Bismuth Chelates

Indications

Gastic / duodenal ulceration

Indications

Gastric / duoudenal ulcers

H. pylori eradication

Antacids

Drugs

Aluminium hydroxide (MAALOX)

Magnesium carbonate (ANDRES ANTACID TAB)

Indications

Symptom relief in ulcer dyspepsia

Non erosive GORD

Adverse Effects

Aluminium hydroxide : Constipation

Magnesium carbonate : Diarrhoea

H. Pylori Eradication

1st Line 🥇
Triple Therapy

  1. PPI (Pantoprazole 🥇)
  2. Amoxicillin
  3. Metronidazole

Penicillin allergy

Amoxicillin → Lymecycline

2nd Line 🥈

  1. PPI
  2. Levofloxacin
  3. Amoxicillin

Penicillin allergy

Amoxicillin → Clarithromycin

Treatment of Dyspepsia

  1. Inhibitors of Gastric Acid Secretion
  1. Antiacids
  1. Mucosal Protectants / Chelates & Complexes

Laxatives

Causes of Constipation

β Blockers

Ca+ channel blockers

Neuroleptics

SSRIs

SNRIs

Tricyclic antidepressants

Ostrogens

Codeine

Levodopa

Managment of Constipations

🥇Dietary fibre , fluids, exercise

🥈Laxatives

Types

  1. Bulk forming laxatives
  1. Stimulant laxatives
  1. Faecal softeners
  1. Osmotic Laxatives

Bulk forming Laxatives

  1. Peripheral opioid receptor antagonists

Methylcellulose

Ispaghula

Steruclia

Stimulant laxatives

Sennoside

Bisacodyl

Na Picosulphate sachet

Faecal Softeners

Na+ Lauryl Sulfoacetate

Na+ Citrate

Glycerol enema

Sorbic acid enema

Osmotic Laxatives

Lactulose

Macrogols

Peripheral Opiod Receptor Antagonists

Naloxegol

Methylnaltrexone bromide solution

Antidiarrheals

Definition of Acute Diarrhoea

Lasts less than 14 days but symptoms improve within 2-4 days

Causes

Infection

Chronic GIT condition (IBD)

Drugs

β blockers

Antibiotics

HIV protease inhibitors

SSRIs

PPIs

Oestrogens

Methyldopa

Misoprostol

Methotrexate

Management

  1. Rehydration - Dioralyte
  1. Loperamide
  1. Diphenoxylate
  1. Cholestyramine

Loperamide

MOA

Piperidine derivative

Opiate agonist slows GIT moltility

Reduces GIT secretions

Adverse Effects

QT prolongation

Torsades de points

Cardiac arrest

Diphenoxylate

Piperidine derivative

Given in combo w/ anticholinergic agent

Cholestyramine

MOA

Ion-exchange resin

Indication

Diarrhoe due to ileal resection

Crohn's

Diabetic vagal neuropathy