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.
16
Q
Phenothiazines –Prochlorperazine
A
- Antagonist at D2 receptors and muscarinic receptors
- Side effects: Extrapyramidal symptoms, hypotension and sedation.
- Metoclopramide (MCP): Effective at high doses against the highly emetogenic cisplatin
- Anti-dopaminergic side effects of MCP: Sedation, diarrhea, and extrapyramidal symptoms, limit its high-dose use.
17
Q
Benzodiazepines:
A
- Anti-emetic potency of lorazepam, alprazolam and diazepam is low.
- Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties
- Useful for anticipatory vomiting
18
Q
Anti-emetic drug combo
A
- Dex
- Ondansetron
- Aprepitant
Choice of CINV (Chemotherapy induced nausea & vomiting):
19
Q
INFLAMMATORY BOWEL DISEASE –IBD
A
- Crohn’s disease and Ulcera1ve coli1s
- Drugs used in IBD are: Sulfasalzine, glucocorticoids (Budesonide), azathioprine, Methotrexate, Cyclosporine, Infliximab and Natalizumab
20
Q
Sulfasalazine
A
- inhibits the pro-inflammatory mediators –IL1, and TNF-α
- It is a sulfa derivative. So, it should be avoided in pt with sulfa allergy.
- In the GIT, sulfapyridine (anti-bacterial) and 5- Aminosalicylic acid (5-ASA) (anti-inflammatory) released from sulfasalazine by colonic bacteria.
- It is used in mild to moderate Crohn’s disease or UC
Adverse
- Nausea, vomiting, diarrhea,
- hypersensitivity
- reversible oligospermia.
- Bone morrow suppression is related to the sulfapyridine release from sulfasalazine.
21
Q
Mesalamine (5-ASA)
A
- Balsalazide: releases mesalamine (5-ASA) in the large intestine at the active site of UC
- Sulfasalazine: Proximal, distal colon and rectum.
22
Q
6-mercaptopurine (6-MP) and Methotrexate (MTX)
A
- Indications: moderately severe to severe Crohn’s disease and UC
- GI mucositis, myelosupression. Hepatotoxicity can occur with 6-MP. Toxicities are rare with MTX at low doses.
23
Q
Infliximab
A
- monoclonal antibody targets TNF-α, a principal mediator in Crohn’s disease.
- Used in conditions associated with flare up of IBD –particularly in Crohn’s related fistulas and acute flares.
- Also used in rheumatoid arthritis
Adverse
- reactivation of latent tuberculosis and other infections (CMV). It is given IV
- fever, chills, urticarial reaction, hypotension may occur. Antibodies to infliximab may develop.
- Adalimumab: TNF-α inhibitor
- Natalizumab **blocks leukocyte integrins can produce multifocal leukoencephalopathy. **
24
Q
Drugs used for IBS
A
Alosetron:
- 5-HT3 antagonist with long duration of action, has high potency.
- Reduces smooth muscle activity in the gut (For IBS-D).
- Recommended for sever diarrhea associated IBS.
- Rare, serious constipation; ischemic colitis and infarction may occur.
Anticholinergics: non-selective action on the gut can be used in IBS
• Hyoscyamine, Dicyclomine, Glycopyrrolate, Methscopalamine
Chloride channel activator: Lubiprostone used in constipation-associated IBS (IBS-C).
25
Q
ANTIDIARRHEAL DRUGS:
A
- Loperamide and Diphenoxylate are opiate derivatives. They slow gut motility with negligible CNS effects
- Acts via GI mu-opioid receptors. Inhibit acetylcholine release and decrease peristalsis.
- Diphenoxylate is formulated with atropine to reduce abuse potential. High doses of Diphenoxylate can cause CNS effects.
- Risk of toxic megacolon in children or pts. with severe colitis.
- Kaolin + Pectin: are adsorbents available as OTC
26
Q
Bile salt-binding resins –cholesterol lowering agents valuable in diarrhea:
A
- Prevent diarrhea of IBS & IBD by blocking osmotic and irritating actions of bile salts.
- form insoluble complexes with bile acids in the intes1ne
27
Q
LAXATIVES:
A
Classified by mechanism of action as Stimulants, Osmotic agent, Bulk forming agents and Stool Sofeners.
- Stimulants: Castor oil, Senna (Senokot), Bisacodyl (Dulcolax).
- May cause cramping.
- Chronic use may lead to habit of perceived need for laxatives.
- Bulk forming agents: These are insoluble indigestible derivatives from fruits and vegetables; hydrophilic colloids. Methycellulose, Psyllium, Bran
- They are non-absorbable; increase water retention and stools become bulky. The disten7on of bowel leads to peristaltic stimulation of gut.
- Osmotic agents:
- Magnesium citrate, Magnesium hydroxide are saline cathartics. Lactulose and sorbitol are non-digestible sugars.
- They osmotically draw water into the lumen of GIT, which then stimulate motility.
- Used in simple constipation, bowel prep for endoscope.
- Lactulose is a semi-synthetic disaccharide sugar acts as an osmotic laxative. Large doses are degraded by colonic bacteria to form lactic, formic and acetic acid –which increases osmotic effect too.
- Lactulose also used in hepa1c encephalopathy. It helps to “draw out” ammonia (NH3) from the body and is useful for preventing hyperammonia.
- PEG (polyethylene glycol) is used for colonic lavage for endoscopic and radiological procedures.
- Lubiprostone –prostanoic acid derivative, stimulates chloride secretion into GI – increase fluid content.
28
Q
Pancreatic insufficiency drugs
A
Pancrelipase:
- A replacement enzyme from animal pancreatic extract
- Improve the digestion of dietary fat, protein and carbohydrates. ↑A, D, E, K vit absorp7on
- Use: patients with chronic pancreatitis, afer pancreatectomy, steatorrhea and cystic fibrosis associated insufficiencies.
29
Q
Bile acid resin (cholestyramine, colestipol, colesevelam) therapy for Gallstones:
A
Prevent intestinal absorption of bile acids; liver must use cholesterol to make more Side effects: Bad taste, GI discomfort, decrease fat soluble vitamins
30
Q
Ursodiol
A
- has enterohepatic circulation
- It reduces cholesterol absorption by breaking up micelles containing cholesterol.
- Used in patient who refuses or not eligible for surgery.
- Adverse effect: diarrhea.
31
Q
Drugs used in Variceal hemorrhage:
A
- Non-selective β-blockers (Propranolol & Nadolol) are effective in reducing portal pressures.
- β1 & β2 blockade result in ↓CO &↑VC -> Improves GI blood vessel tone -> ↑systemic vasoconstriction & ↓vasodilation
