GIT Drugs Flashcards
1
Q
Acid-peptic diseases
A
- Comprises of gastric ulcer & duodenal ulcer, gastroesophageal reflux disease and stress related mucosal injury.
- Hyper-secretory condition: like Zollinger- Ellison syndrome.
2
Q
Acid-peptic disease Etiopathogenesis
A
- Gastric acid
- Decreased mucosal resistance to acid
- H. pylori
- Drugs –high dose nonselective NSAIDS (due to COX inhibition and direct irritation). Concurrent use of other drugs –warfarin & corticosteroids
- Risk factors of >65 years, Stress
- Lifestyle
- Gastrinoma – a rare gastrin secreting tumor (ZES)
3
Q
Antacids
A
- Gastric antacids: they are weak bases that react with gastric HCl to form salt and water. The end result is increased gastric pH. Provide quick relief of symptoms.
- Commonly used antacids are:
- Magnesium hydroxide (Milk of Magnesia)
- Aluminum hydroxide and
- Calcium carbonate (Tums)
Adverse
- Magnesium hydroxide produce Mg salt, which is very poorly absorbed and cause diarrhea.
- Aluminum hydroxide reacts with HCl to form Aluminum chloride, which is insoluble and cause constipation. Hypophosphatemia
- Calcium carbonate: Hypercalcemia, nephrolithiasis and constipation –fecal compaction.
- Ca, Mg, Al molecules can chelate tetracyline
Factors that enhance gastric acid secretion are:
- three fundamental agonists that control the gastric acid secretion –histamine, acetylcholine and gastrin.
- Final pathway of these compounds is activation of the H+/K+ ATPase pump
4
Q
Regulation of gastric acid secretion
A
- Dicyclomine: cholinergic receptor blocker
- Cimetidine: H2-R blocker
- Misoprostol: stimulates Prostaglandin-R
- Omeprazole: PPI
- Octreotide: long-acting SST analogue to decr gastric acid
- Clinical uses: carcinoid tumors, VIPoma, acute variceal bleeding and acromegaly.
- Adverse effects: Abdominal cramps, nausea, steatorrhea, and gall stones.
- reduce endocrine and exocrine pancreatic activity.
5
Q
H2 receptor blockers
A
- Preoperatively, they are used to prevents aspiration pneumonia.
- Ranitidine, Famotidine and Nizatidine (Axid) are longer acting and more potent than older cimetidine.
- Unlike cimetidine, newer drugs does not produce the anti-androgenic or prolactin- stimulating effects.
- They do not inhibit the mixed-function oxygenase system in the liver (CYP450 enzymes).
Adverse
- Most common side effects are nausea, headache, and dizziness.
- Cimetidine is notorious to present unwanted endocrinal adverse effects, for instance gynecomastia, elevated serum prolactin levels and confusion in elderly people.
6
Q
PPI – Proton Pump Inhibitors:
- Omeprazole (Prilosec),
- Lansoprazole (Prevacid),
- Pantoprazole (Protonix),
- Esomeprazole (Nexium)
- Rabeprazole (Aciphex)
A
- **MOA: **reacts with a cysteine residue of the H+/K+-ATPase, forming a stable covalent bond leading to irreversible inactivation of enzyme.
Indications:
- GERD, duodenal and gastric ulcers, multiple endocrine neoplasia (MEN-1) or Zollinger-Ellison syndrome.
- contribute in combination with antibiotics to eradicate H Pylori.
- NSAID-induced ulcers should be treated with PPIs. They support platelet aggrega7on & maintain clot integrity used in hemorrhagic ulcers.
7
Q
1st line regimen for H pylori eradication
A
- PPI + Clarithromycin + Amoxicillin: 10 to 14 d
- PPI + Clarithromycin + metronidazole: 10 to 14 d
- Bismuth subsalicylate + metronidazole + tetracycline + ranitidine or PPI: 10 to 14 d
8
Q
Mucosal Protec1ve Agents:
A
- Sucralfate: sulfated disaccharide used in PUD.
- Bismuth: by selectively binding to an ulcer it forms a coating and protects from acid and pepsin.
- Misoprostol: prevention of gastric ulcers induced by NSAIDs.
MOA
- drug undergoes polymerization and selective binding to necrotic tissue where it acts as a barrier to acid. It is also s7mulates endogenous prostaglandin synthesis.
- Sucralfate requires acidic pH to be activated therefore it should not be administered simultaneously with H2 – blockers, PPI or other antacids.
- Therapeutic actions of Bismuth: It appears to have some antimicrobial effect on H Pylori. When it is administered along with metronidazole and tetracycline antomicrobial drugs, ulcer healing rate of up to 90% have been reported.
Adverse effects of Misoprostol:
- Diarrhea in up to 30% of patients who take this drug.
- Abortions due to induction of uterine contractions during pregnancy
- Exacerbations of inflammatory bowel disease (IBD).
9
Q
Metoclopramide
A
PROKINETIC DRUGS USED IN GI DISORDERS;
- also indicated in Diabetic, Parkinson’s and post-op
- reduces nausea and vomiting associated with chemotherapeutic agents.
MOA: 3 mechanisms
- 5-HT3 and D2 receptors blocker – acts as anti-emetic.
- prokinetic activity of metoclopramide is mediated by muscarinic activity via 5-HT4 receptor agonist activity. It accelerates gastric emptying and intestinal motility.
- At higher doses, 5-HT3 antagonist activity may also contribute to the anti-emetic effect.
Adverse
due to anti-dopaminergic –sedation, diarrhea, and Parkinsonian effects limit its high-doses and long term use.
10
Q
Cisapride
A
- Prokinetic agent
- 5HT4 agonist. Use: gastroparesis, GERD and constipation via stimulatinng Ach.
- ADR: arrhythmias
11
Q
Macrolide
A
- acting as a prokinetic agent
- Erythromycin acts on motilin receptors of GIT used I.V.
- Used for gastric emptying before upper GI endoscopic procedures.
- Tolerance may develop in gastroparesis.
12
Q
Emesis pharmacology
A
- D2, 5HT3, Opioid / Ach and substance P receptors
- Muscarinic and H1 receptors.
- GI distention, or acute GI infections, activates the 5-HT3
13
Q
ANTIEMETIC AGENTS
A
- 5-HT3 inhibitors – Ondansetron
- H1 antihistamines & antimuscarinics –
- Diphenhydramine & Scopolamine
- Corticosteroids – Dexamethasone
- NK1–receptor blocker – Aprepitant
- D2 Receptor antagonist – Prochlorperazine
- Benzamide – Metoclopramide
- Marijuana – Dronabinol (Marinol)
14
Q
Ondansetron and other 5-HT3 antagonists:
A
- block 5-HT3 in the gut and CNS
- Clinical indications of the anti-emetics are:
- Chemotherapy induced – moderate to severe emesis or post-operative nausea and vomiting.
- Route of administration usually I.V. and for prophylaxis they are given orally.
15
Q
Aprepitant
A
- NK1 –receptor blocker in CNS
- Effective in both decreasing the early and delayed emesis in cancer chemotherapy.
- Route of administration is PO.
- Fosaprepitant is for I.V.
- Adverse effects are dizziness, fatigue, diarrhea CYP interaction may occur.
