DRUGS ACTING ON GASTRO
INTESTINAL TRACT
Peptic ulcers-
A localised loss of gastric & duodenal mucosa leads to formation of
peptic ulcers. When mucosa is exposed to pepsin & acid.
It includes both gastric & duodenal ulcers.
3 Phases of gastric acid secretion are:-
Cephalic, Gastric & Intestinal phase.
3 main gastric secretagouges are:-
Ach from Vagus nerve (N.T)- Cephalic phase.
Gastrin from G-cells of antrum (endocrine-+ hormone)- Gastric & Intestinal phase.
Histamine from ECL (local hormone)- 3phases.
Somatostatin from D-cells of antrum- X gastrin secretion.
Antacids:-
• Neutralizes gastric HCl & raises gastric PH.
• Acid delivery to duodenum & pepsin.
• Don't reduce the HCl secretion.
• Promotes acid & pepsin secretion due to alkaline PH.
• + PG production & protective layer.
• Should be taken b/w meals & bed time.
• + nce of food prolongs the neutralizing action.
• Factors – formulation, duration & gastric emptying influence antacid action.
Uses of sodium bicarbonate-
1. Antacid- not preferred.
2. Metabolic acidosis- in poisoning cases & Diabetic ketoacidosis.
3. Urine Alkalinisation- acidic drug poisoning & also to facilitated the certain
antimicrobial agents which act better in alkaline medium.
4. One of the imp. ingredients of topical prep’s like eye, mouth washes & used for
gastric lavage.
Al(OH)3-It’s used to Rx of hyperphosphataemia & PO4 stones.
S/E’s
• Magnesium containing antacid-
• Diarrhea, dehydration, hypermagnesmia, renal stones.
• Aluminum containing antacid-
• Constipation, hypophosphataemia, osteodystrophy &
encephalopathy (Al3+ toxicity).
H2 Receptor Antagonists- Sir J.W.Black.
• Commonly prescribe drugs.
• Over -The-Counter Drugs.
M.O.A-
Competitively X H2R of parietal cells &
Blocks the actions of H released from ECL cells.
X direct + of parietal cells by gastrin/Ach.
Suppress basal & food + acid secretion.
Both acid & pepsin secretion are .
Blocks > 90% nocturnal acid & 70% food + secretion.
H2 Blockers Uses-
GERD & PUD (PPI’s)
NSAIDs induced ulcers
Prevention of stress induced gastric bleeding.
Prophylaxis against aspiration pneumonia.
Prevention of ulcer recurrence.
Zollinger- Ellison's syndrome (PPI’s/Surgical).
Rx of chronic urticaria.
A/E- Safe drugs.
Headache, Fatigue, Myalgia, Constipation.
Mental status changes on I.V Cimetidine.
Endocrinal effects- impotence & gynaecomastia.
Avoided during pregnancy & lactation.
H2 Blockers D.I-
1. Antacids X H2 blockers- 2hrs gap should be given.
2. H2 blockers X Ketoconazole, digoxin
3. Cimetidine is a potent inhibitor of Cyp-450.
Proton Pump Inhibitors- PPI’s
• Omeprazole is a prototype drug.
• Esomeprazole is s-isomer of Omeprazole.
• Rabeprazole & Pantoprazole- I.V route.
• These are acid labile & destroyed by HCL, so
available as E.C.T/C.
• X acid secretion in resting, food + &
secretogogues action .
• + nce of food the B.A- taken in empty stomach.
• So should be adm in morning just before break
fast.
• MOA-PPI’s irreversibly inhibits Proton Pump &
acid secretion starts only after synthesis of a new
pump.
E.C.T/C-Enteric coated tablet/capsule
PPI Uses-
Duodenal & Gastric ulcers.
GERD & NSAID’s induced ulcers.
Bleeding ulcers-I.V followed by oral PPI’s.
Prevention of ulcer recurrence.
ZE syndrome, Systemic mastocytosis & Endocrine adenomas- hyper secretory states.
H.Pylori associated ulcers- PPI’s+Antibiotics.
Stress-induced ulcers-I.V Pantoprazole
Prophylaxis for aspiration pneumonia.
PPI’s A/E-
• Extremely safe drugs.
• Headache, dizziness & diarrhea, Abd. Pain, muscle & joint pains.
• Not used during pregnancy/lactation.
• Gynaecomastia, erectile dysfunction, osteoporosis.
• Prolonged use- achlorohydria & hypergastrinemia
PPI D.I’s
• PPI’s X Ketoconazole, digoxin
• X CYP450 & also X metabolism of Warfarin, phenytoin.
• Lansoprazole X Theophylline – elimination.
• Clarithromycin X Omeprazole
• Pantoprazole & Rabeprazole have no significant interactions.
Prostaglandin analogs-
• PG plays imp role in gastric defence mechanism against PUD.
• PG X acid secretion, enhances mucosal blood flow & + mucus & bicarbonates secretion.
Misoprostol (PGE1 analogue)- NSAID’s induced P.U & chr. smokers.
Sucralfate -
• Its a aluminium salt of sulphated sucrose, undergoes polymerization in acid PH & forms a sticky
gel over the ulcer bed & acts as a acid resistant physical barrier.
• Also + mucosal PG & HCO3- secretion.
• Prevents its reflux to oesophagus.
• Promotes mucosal repair & ulcer healing.
• Doesn't neutralise the gastric acid.
• Uses PU in smokers, Stomatitis, Esophagitis & Stress ulcers. Burn dressing & bed sores- gel.
• Phosphate stone in kidney- high doses.
• Bile reflux, ICU pt’s, diabetic/radiation ulcers.
ANTIEMETICS
&
GERD
• Emesis/vomiting means expulsion of gastric contents through mouth due to
antiperistalsis.
• It is often preceded by Nausea.
• Retching is seen in b/w N & V.
• Vomiting can be life saving / side effect.
Types of emesis-
1. Motion sickness
2. Morning sickness
3. Chemotherapy induced emesis
4. Radiation induced emesis
5. Post operative vomiting
Classification-
1.Anticholinergics- Hyoscine, Dicyclomine
2. Antihistaminics- Promethazine, Diphenhydramine,
Dimenhydrinate, Doxylamine, Cyclizine,
Meclizine, Cinnarizine.
3.Neuroleptics- Chlorpromazine, Prochlorperazine, Haloperidol
4.Prokinetics- Metoclopramide, Domperidone,
Cisapride, Mosapride, Tegaserod,Prucalopride.
5. 5HT3 antagonists - Odansetrone, Granisetron,
6. Adjuvants- Benzodiazepines, Cannabinoids.
Macrolides, Loxiglumide
Anti-cholinergics
Hyoscine Most effective in motion sickness.
TD patch-1.5mg of hyoscine, placed behind the pinna, effective for 3days.
0.2-0.6mg orally Taken 30min before journey.
Dicyclomine Prophylaxis of motion & morning sickness.
10-20mg orally
H1 Antihistaminics
Promethazine Antiemetic activity due to antihistaminic, Anticholinergic & sedative effects..
Diphenhydramine Mostly useful in motion sickness.
Dimenhydrinate Given in combination with Pyridoxine for morning sickness.
Doxylamine
Neuroleptics Acts by X D2 R + in CTZ, M & H1blocker.
Procholoperazine Drug/ Disease induced & P.O.V.
Chemotherapy/ Radiation Induced vomiting.
Antivertigo & antiemetic.
Used as a antiemetic rather than antipsychotic.
Acute Muscle dystonia & Extra pyramidal S/E.
Pro-kinetics agents + GIT motility & Speed up gastric emptying
Metoclopramide Increases gastric & intestinal peristalsis.
Speeds gastric emptying & Opposes gastric reflux.
Acts both central and peripherally (D2 antagonism + 5-HT4 agonism + 5HT3 antagonism)
Antiemetic- P.O.V, D.I.V, C.I.N.V(Cisplatin) & R.I.N.V
Gastrokinetic –accelerate gastric emptying.
Dyspepsia , Functional G.I. disorders & hiccups.
GERD- symptomatic relief in mild cases.
Domperidone D2 antagonist
MOA is similar to Metoclopromide.
It’s antiemetic & pro-kinetic actions < metoclopramide.
Less Extrapyramidal side effects (only peripheral actions)
Domperidone + l-dopa/ Bromocriptine.
Ondansetron Prototype, newer antiemetic.
Useful in CINV/RINV/P.O.V.
Blocks 5HT3 R on vagal afferents of g.i.t, NTS & CTZ.
