Pharmacology - Treatment of PUD
Terms in this set (44)
What are the properties of an ideal antacid?
A prolonged and effective neutralizing action following an acceptable oral dose
No cause of systemic disturbances i.e. acid base and electrolyte imbalance
No interference with digestion and absorption
No constipation/laxative side effects
What is the difference between systemic antacids and nonsystemic antacids?
Systemic can cause metabolic alkalosis after absorbing of their cationic moiety (positively charged ion molecules) with long, excessive dosage
Non systemic antacids are physically, physiochemically, chemically acting. Their cationic moiety forms unabsorbable, insoluble basic compounds in the intestine.
What are examples fo nonsystemic antacids?
Aluminium salts, magnesium salts, calcium salts, bismuth salts.
What is an antacid, its MoA, DoA and clinical importance?
Weak bases that neutralize acid & inhibit formation of pepsin (pepsinogen is -> to pepsin at acidic pH)
Not part of Physician prescribed regimen
OTC drug for symptomatic relief of dyspepsia
Duration of action : 30 min empty stomach, 2 hrs after a meal
Clinical importance- Interactions avoided by taking
2 hrs before or after other drugs .
What are the side effects and interactions of antacids?
Al3+ antacids - constipation (relax GI smooth muscle & delay emptying)
Mg2+ antacids - Osmotic diarrhea
In renal failure Al3+ antacid - Aluminium toxicity & encephalopathy
Interaction: Absorb drugs and form insoluble complexes that are not absorbed
Common additives in antacids are:
Simethicone :- Decrease surface tension ,thereby reduce bubble formation - Added to prevent reflux
Alginates:- Form a layer of foam on top of gastric contents & reduce reflux
Oxethazaine: - Surface anaesthetic
Most potent and commonly used
Insoluble and prolonged duration of action
Mg(OH)2 + 2HCl = MgCl2 + 2H2O
With renal impairment - neurological, neuromuscular and cardiovascular effects
Decreased total acid load
Inactivates pepsin by absorption and precipitation
Stimulates mucus secretion
Partially absorbed and distributed in bone and lung
Binds and precipitates phosphate
Side effects: Hypophosphataemia , hypophosphaturia , hypercalciuria , urinary calculi, osteomalacia , osteoporosis . Decreased absorption of tetracycline's , pencillins , Sulphonamides, digoxin, Isoniazid, acetylsalicylic acid etc.
What is a Histamin H2 Receptor Antagonist?
Reversible competitive inhibitors of H2 receptor
Highly selective-not H1 or H3 receptors
Very effective in inhibiting nocturnal acid secretion as it depends on Histamine
Modest impact on meal stimulated acid secretion as it depends on gastrin, acetylcholine and histamine
What are the three Histamine H2 Receptor Antagonists?
Cimetidine Ranitidine Famotidine
What are the side effects of H2 blockers?
Cimetidine - gynecomastia, galactorrhea (antiandrogenic & increases Prolactin)
Inhibits CYP450 & increases concentration of Warfarin, Theophylline, Phenytoin, Ethanol.
Cimetidine: Action, absorption, % protein bound, % liver inactivation, % excreted thru urine and half life
H2 receptor Competitive antagonist
Inhibits basal and stimulated acid secretion
Decreases pepsin output
Water soluble, cross placenta not BBB
< 25% bound to plasma proteins
30% inactivated by liver P450 enzyme system
60% excreted unchanged in urine
T ½ -2 hours.
Uses and side effects of Cimetidine
Uses: Duodenal ulcer, benign gastric ulcer, reflux esophagitis, prophylaxis of gastrointestinal bleed due to gastric erosions, Before anaesthesia for emergency surgery. In chronic pancreatic insufficiency.
Headache, dizziness, diarrhoea , muscle pain
Sexual dysfunction & gynaecomastia
Bone marrow dysfunction
Liver enzyme changes, cholestasis, hepatitis.
Liver enzymes suppression
CNS changes confusion (elderly), fits (young).
Famotidine: Action, absorption, % protein bound, % liver inactivation, % excreted thru urine and half life
Slowly reversible competitive H2 receptor antagonist
Antisecretory activity lasts for 10-12 hours after single dose
< 45% oral dose absorbed
30% of oral dose and 70% of I/V dose excreted unchanged
T ½ 3 hours
More potent than cimetidine
Decreased 94% nocturnal acid secretion
Low binding to androgen receptors/P450 system
Increased bacterial flora
Proton Pump Inhibitors: MOA, how and where activated
Most effective drugs in antiulcer therapy
Irreversible inhibitor of H+ K+ ATPase
Prodrugs requiring activation in acid environment
Weakly basic drugs & so accumulate in canaliculi of parietal cell
Activated in canaliculi & binds covalently to extracellular domain of H+ K+ ATPase
Acid secretion resumes only after synthesis of new molecules
Proton Pump Inhibitors - how given, halflife, dose timing and contraindications
Given as enteric coated capsule or tablets
Pantoprazole also given intravenously
Half life - 1.5 hrs
Since it requires acid for activation - given 1 hr before meals
Other acid suppressing agents not coadministered
P.P.I. - Side effects & Interactions
Extremely safe drugs
Causes hypergastrinemia but no evidence of tumors in man
Inhibit CYP 450 & hence metabolsim of warfarin, phenytoin, etc
Pantoprazole & Rabeprazole have no significant interactions
Omeparazole: Action, requirements, absorption, protein binding %, metabolization and halflife
Most potent inhibitor of gastric acid secretion
Needs an acidic environment (pH <3) to show effects
95% bound to plasma proteins
Mainly metabolized in liver
T ½ 1 hourly
Omeparazole: Uses and side effects
Uses: Ulcerative reflux esophagitis, peptic ulcer, NSAID ulcers, H2RA resistant ulcers, Zollinger Ellison syndrome
Side effects: Headache, nausea, diarrhoea, weakness
Increased gastrin blood levels
Prolonged increased gastrin - bacteria in stomach - increased nitrates and carcinogenic nitrosoamines
Selective antimuscarinic: MoA and halflife
Selective against gastric secretory function
Hydrophilic because limited passage across BBB
Decreased volume of gastric acid secretion in response to vagal, histamine and gastrin stimulation
Decreased pepsin secretion
T ½ 11 hours
Selective antimuscarinic: side effects and contraindications
Dry mouth, blurred vision ,tachycardia, dry mouth, blurred vision , difficulty in near vision, photophobia, decreased tone of lower oesophageal sphincter
Glaucoma , obstructive uropathy & GIT disease. Paralytic ileus, arrhythmia , severe ulcerative colitis , myasthenia gravis
Inhibit acid secretion by preventing gastrin release from antrum
Inhibit pepsin secretion
Prevent luminal H+ from back diffusion
Increased rate of cell replication in mucosa
Stimulate mucus & HCO3 secretion
Increased mucosal blood flow
Act by binding to prostaglandin E on parietal cell (inhibit adenyl cyclase)
Decreased acid secretion due to histamine, gastrin and meals
Prostaglandins: Side effects and uses and effects
Side effects: Diarrhea, vomiting, abdominal pain, nausea, headache, increase uterine contractions
Misoprostol: Uses and MoE
PGE1 synthetic analog
Uses: Chronic gastric ulcer, duodenal ulcers from NSAIDs
Strengthen mucosal barrier and protect against ulceration caused by NSAIDs, bile, alcohol
mucosal protective agent - complex aluminium salt of sucrose with sulphate GPS
No effect on acid secretion; needs acid environment
Sulphate GP polymerize - Paste (very sticky, viscid, yellowish white gel) form - Adheres to mucous membrane
Binds to pepsin and bile acids
Increased release of PGE2 in lumen and increased mucus secretion
How does Sucralfate act?
Sucrose salt, insoluble in water, becomes viscous paste within stomach & duodenum, binding to site of ulceration.
Serves as barrier, promotes trophic action by binding growth factors such as EGF, enhancing prostaglandin synthesis, stimulating mucus and bicarbonate secretion, and enhancing mucosal defense and repair.
Sucralfate: uses, side effects and contraindications
In acidic pH polymerizes to viscous gel that adheres to ulcer crater
Taken on empty stomach 1 hr. before meals
Uses: Chronic gastritis, duodenal ulcer, gastric ulcer
Side effects: Constipation, dry mouth, skin rash, nausea, dizziness
Concurrent antacids, H2 antagonist avoided as it needs acid for activation
Colloidal Bismuth Compounds
mucosal protective agent
No effect on acid secretion - Precipitate in acid medium (pH < 5)
Form protective film over ulcerative mucosa= mucosal resistance & Increased prostaglandin synthesis
Inhibit pepsin activity
Causes changes in mucus composition and production
Bactericidal against Helicobacter pylori
Colloidal Bismuth Compounds: uses, side effects and contraindications
Coats ulcer, stimulates mucus & bicarbonate secretion
Not used for long periods - bismuth toxicity
Uses: Gastric ulcer, duodenal ulcer, gastritis.
Side effects: Unpleasant taste, constipation, blackens mouth and stools, encephalopathy.
What are the traditional mono, dual and triple therapies used against H pylori?
Monotherapy: Bismuth compounds
Dual therapy: Bismuth compounds + Amoxicillin/Metronidazole
Triple therapy: Bismuth compounds + amoxicillin + Metronidazole
What is the current therapy against H pylori?
Omeprazole + clarithromycin/amoxicillin+ Metronidazole (12 days)
What is the best triple therapy for Hpylori?
Omeprazole / Lansoprazole
Amoxycillin / Metronidazole
Given for 14 days followed by P.P.I for 4 - 6 weeks
Short regimens for 7 - 10 days not very effective
When is quadruple therapy for H pylori given and what drugs are used?
Given when Triple Therapy fails
Omeprazole/Lansoprazole, Bismuth subsalycilate, Metronidazole, Tetracycline
Once an ulcer is documented and H pylori is found to be present, what treatment is recommended?
triple therapy 14 days, followed by continued acid-suppressing drugs (H2 receptor antagonist or PPIs) for 4-6 weeks
H. pylori eradication means?
What is the test of choice?
organisms gone at least 4 weeks after completing antibiotics
Urea breath test (UBT).
Summary of ulcer+ H pylori treatment
Stop smoking, alcohol, NSAID'S
Alternatively sucralfate , bismuth, pirenzepine
Is it rational to combine aluminium hydroxide and magnesium hydroxide in antacid preparations ?
yes. Combination provides balance and preserves normal bowel function:
Magnesium Hydroxide - Rapidly acting
Aluminium Hydroxide - Slowly acting
Aluminium Hydroxide - constipation
Magnesium hydroxide - diarrhoea
Your friend wants to take a H2 antagonist before he takes alcohol to avoid gastric irritation .He consults you .Which H2 antagonist will you ask him to take ?
All H2 antagonist except famotidine inhibit gastric first pass metabolism of ethanol and increase its bioavailability .
The half life of proton pump inhibitors is 1.5 hours only and these drugs are generally given once daily. How this can be justified ?
P.P.I - Irreversible inhibitors of H+K+ATPase
(Hit and run drugs)
A patient comes to your clinic at midnight complaining of heart burn. You want to relieve his pain immediately. What drug will you choose?
Antacids neutralise the already secreted acid in the stomach. All other drugs act by stopping acid secretion and so may not relieve symptoms atleast for 45 min.
A pregnant lady (first trimester) comes to you with peptic ulcer disease. Which drug will you prescribe for her ?
Antacids or Sucralfate
H2 antagonists cross placenta and are also secreted in breast milk. Safety of Proton pump inhibitors not established in pregnancy. Misoprostol causes abortion .
What drugs can cause a peptic ulcer?
Non Steroidal Anti Inflammatory Drugs (NSAIDs)
What are Cushing's and Curling's ulcers?
Cushing's ulcer - Stress induced ulceration after head trauma
Curling's ulcer - Stress induced ulceration after severe burns