The post Peptic ulcer, Classification of Antiulcer Drugs, Mechanism of action, Pharmacokinetics, Side effects, Drug interactions and Uses, MCQs for GPAT, NEET PG,NIPER, Drug inspector exam and pharmacist exam. appeared first on Gpatindia: Pharmacy Jobs, Admissions, Scholarships, Conference,Grants, Exam Alerts.
]]>Types of peptic ulcer: There are two types of peptic ulcer.
Risk factors of peptic ulcer:
Sign and symptoms:
Classification of drugs:
A. Gastric acid secretion inhibitors:
a. Cimetidine
b. Ranitidine
c. Famotidine
d. Roxatidine
e. Lafutidine
2. Anticholinergics:
a. Pirenzepine
b. Propantheline
c. Oxyphenonium
3. Proton pump inhibitors:
a. Omeprazole (Prototype)
b. Pantoprazole
c. Esomeprazole
d. Lansoprazole
e. Rabeprazole
f. Dexrabeprazole
g. Ilaprazole
4. Prostaglandin analogue:
a. Misoprostol
B. Gastric acid neutralizers (Antacid):
1. Systemic:
a. Sodium bicarbonate
b. Sodium citrate
2. Non systemic:
a. Mag. hydroxide
b. Mag. trisilicate
c. Alumin. hydroxide
d. Magaldrate
e. Calcium carbonate
C. Ulcer protectives:
a. Sucralfate
b. Colloidal bismuth subcitrate (CBS)
D. Anti H,pylori drugs:
a. Amoxicillin
b. Clarithromycin
c. Metronidazole
d. Tinidazole
e. Tetracycline
f. CBS
A. Gastric acid secretions inhibitors:
1.H2- Antihistamines:
a. Cimetidine:
First H2 blocker to be introduced clinically, described as ‘protoype’ drug. All clinically used H2 blockers are competitive antagonist of histamine except famotidine. These drugs block histamine- induced gastric acid secretions. Inhibit acid production by reversible competing with histamine for binding with H2 receptor on the basolateral membrane of parietal cells. Suppress acid production by 70%. Inhibit basal acid secretions and nocturnal secretion also.
Pharmacokinetis: Absorbed orally, bioavailability is 60-80% due to first pass hepatic metabolism. It crosses placenta and reaches milk, but poorer blood brain barrier. About 2/3rd drug is excreted unchanged in urine and bile. The t1/2 is of 2-3hr, but duration of action is longer.
Side effects: 1. Diarrohea, headache, drowsiness, fatigue, constipation.
2.Confusion, delirium, hallucinations, and slurred speech.
3. Rebound hyperacidity.
4. Thrombocytopenia.
5. Pancytopenia, neutropenia, anaemia.
Uses: Peptic ulcer, non ulcer dyspepsia, urticaria, GERD(gastroesophageal reflux disease), bleeding from stress ulcers and erosive gastritis.
Drug interactions: Inhibit the metabolism of many drugs:
b. Ranitidine: Non-imidazole H2 blocker. 5 times more potent than cimetidine. Longer duration of action, with greater 24hr acid suppression is obtained. Less penetration in brain, less inhibition of hepatic metabolism of other drugs.
Side effects: Headache, diarrhea, constipation.
Uses: Used in peptic ulcer, GERD and urticaria.
c. Famotidine: Thiazole ring containing H2 blockers which bind tightly with H2 receptors and exhibit longer duration of action. Some inverse agonistic action has been demonstrated. 5-8 times more potent than cimetidine. Oral bioavailability is 40-50 %. it is excreted trough kidney 70% in unchanged form.
Side effects: Dizziness, bowel upset, headache, rashes
Uses: Peptic ulcer, GERD.
d. Roxatidine: Same mechanism of action, pharmacokinetics and side effects to that of rantidine. It is twice more potent and longer acting.
e. Lafutidine: This is second generation H2 blocker. It acts by preventing gastric acid secretions. It also activates calcitonin gene related peptide, resulting in the stimulation of nitric oxide (NO) and regulation of gastric mucosal blood flow, increases somatostatin levels also resulting in less gastric acid secretion.
Side effects: Constipation, diarrhea, drug rash, nausea, vomiting and dizziness.
Uses: Exact uses are not known but it can be use for gastric ulcers and duodenal ulcers, gastritis and chronic gastritis.
2. Proton pump inhibitors (PPIs): This the most commonly used class of acid suppressants.
a. Omeprazole: It is prototype member of benzimidazoles which inhibit the final step of gastric acid secretions. It is a powerful inhibitor of gastric acid. It has dose dependent suppression of gastric acid secretion without blocking any receptor. After absorption of prodrug it gets activate tetracyclic sulfonamide cation. This activated form then binds to sulfhydryl groups of cysteine in the H+ k+ ATPase, irreversibly inactivating the pump molecule. Especially when two molecule of omeprazole reacts with one molecule of the enzyme. It also inhibit gastric mucosal carbonic anhydrase.
Pharmacokinetics: All PPIs are enteric coated to protect the drug from molecular transformation in the acidic gastric juice. it as administered orally. Oral bioavailability is about 50% due to acid lability. Bioavailability of all PPI are reduced by food. So they should be taken in empty stomach, because 10% of proton pumps are active. Omeprazole is highly plasma protein bound drug. Rapidly metabolized in liver by CYP2C19 and CYP3A4. Plasma t1/2 is of 1hr. Metabolites are excreted in urine.
Side effects: These are very safer drugs. Some side effects are nausea, loose stools, headache, and dizziness.
Interactions: Inhibits oxidation of certain drugs:
Reduced gastric acidity decreases absorption of:
Clarithromycin inhibits omeprazole metabolism.
Uses:
b. Pantoprazole: It has same potency like omeprazole. It is more stable and has higher oral bioavailability. Affinity for CYP450 is lower than omeprazole. It is use as i.v for bleeding peptic ulcer, and for prophylaxis of acute stress ulcers. also used foe peptic ulcer, stress ulcer, Zollinger- Ellison syndrome.
c. Esomeprazole: It is S-enantiomer of Omeprazole. Have higher bioavailability and better control of intra-gastric pH than omeprazole in GERD patients because of slower elimination and longer t1/2. It is provide healing effects in erosive gastritis and symptomatic relief in GERD. Side effects and drug interactions are similar to of omeprazole.
d. Lansoprazole: It has similar action like omeprazole. More potent then omeprazole. Reversible inhibition of H+K+ ATPase. It has higher oral bioavailability. Fastest onset of action and slightly longer t1/2 than omeprazole. Dose should be reduced in case of liver disease. Side effects are similar but less drug interactions, diazepam and phenytoin metabolism may be reduced.
e. Rabeprazole: It is the fastest acid suppressant drug. Due toe it’s higher pKa, it is more rapidly converted into active species. Potency and efficacy are exactly similar to omeprazole. No drug interaction have been observed.
f. Dexrabeprazole: It is active dextro-isomer of rabeprazole, produces similar acid suppression at half the dose.
g. Ilaprazole: Ulcer healing efficacy and tolerability is similar to omeprazole. It is excreted in urine both as unchanged drug and as sulphone metabolite.
3. Anticholinergics:
a. Pirenzepine: It is M1 selective antagonist, is used in the treatment of peptic ulcer, as it reduces gastric acid secretion and reduces muscle spasm.
b. Propantheline: It is used with other medicine to treat ulcer. It works by slowing the movement of food through the stomach and intestines and decreasing the amount of acid made by the stomach. It has a direct effect on smooth muscles. About 70% drug is excreted in the urine mostly as metabolites.
4. Prostaglandin analogue:
a. Misoprostol: PGE2 and PGI2 are produced in the gastric mucosa and appear to serve a protective role by inhibiting acid secretions and inhibits gastrin release, increase mucosal blood flow and have cytoprotective action. Misoprostol is PGE1 analogue.
Pharmacokinetics: Misoprostol is a longer acting synthetic PGE1 derivative which inhibits acid output. Shorter duration of action having very short t1/2. Ulcer healing rates comparable to cimetidine have been obtained in 4-8 weeks, but misoprostol is poorer in releiving ulcer pain.
Side effects: Diarrhea, abdominal cramps, uterine bleeding, abortion.
Uses: Prevention and treatment of NSAID associated gastrointestinal injury and blood loss.
B. Antacids: Antacids are basic substances which neutralise gastric acid and raise pH of gastric contents. Peptic acidity is reduced if pH rises above 4.
a. Sodium bicarbonate: It is a potent neutralizer pH may rise above 7. Duration of action is short.
Side effects: Large dose induces alkalosis, ulcer perforation, CHF, edema, acid rebound occurs(due to higher pH more acid is secreted in patients with hyperacidity and duodenal ulcers cause acid rebound).
Uses: Heartburn, to treat acidosis.
b. Sodium citrate: Similar properties to sodium bicarbonate.
2. Non-systemic Antacids: These are insoluble poorly absorbed basic compounds.
a. Magnesium hydroxide: It reacts with HCL promptly and is an efficacious antacid. It has lower water solubility.
b. Magnesium trisilicate: It has low solubility and reactivity. About 5% of Mg is absorbed systemically. All Mg salts have laxative property.
c. Aluminium hydroxide gel: It is weak and slowly acting antacid. Its 5ml suspension neutralize only 1mEq HCL. The Al3+ ions relax smooth muscle, it delays gastric emptying. It frequently causes constipation due to its smooth muscle relaxant property.
d. Calcium carbonate: It is potent and rapidly acting acid neutralizer . Ca ions are partly absorbed . It may cause acid rebound. Milk alkali syndrome is a major side effect. Large quantity of milk was prescribed with CaCO3 for peptic ulcer, such regimen may cause syndrome like headache, anorexia, weakness abdominal discomfort.
Antacid combination: A combination of two or more antacids is frequently used:
Uses: Healing peptic ulcer, GERD, dyspepsia.
C. Ulcer protectives:
1. Sucralfate: It is basic aluminium salt of sulfated sucrose. It is strongly adheres to the ulcer base, remain there for 6hrs especially in duodenal ulcer. Surface proteins present at ulcer base starts precipitated together with which it acts as a physical barrier, it prevents acid, pepsin and bile coming in contact with ulcer base.
Pharmacokinetics: Absorbed orally. Healing efficacy is exactly similar to cimetidine.
Side effects: Constipation is recorded in 2%patients. Dry mouth and nausea are infrequent.
Interactions: It Interferes with the absorption of tetracyclines, fluoroquinolones, cimetidine, phenytoin and digoxin.
Uses: Bile reflex, gastritis, prophylaxis of stress ulcers.
b. Colloidal bismuth Subcitrate (CBS): It is a colloidal bismuth compound, water soluble. It heals 60% of ulcers at 4weeks and 80-90% at 8 weeks. It is also use for gastritis and non ulcer dyspepsia associated with H. pylori.
4. Anti H. pylori drugs: H.pylori is gram negative bacteria survive in hostile enviornment of stomach.
“Rescue therapy” regimen: Combination of ” Omeprazole+ Amoxicillin+ Levofloxacin”
“Quadruple therapy” regimen: Combination of “Omeprazole+ Tetracycline+ Metronidazole”
MCQS:
1. Which of the following receptor is closed by drugs of peptic ulcer?
a. H1
b. H2
c. Proton pump
d. none
2. Which of the following drugs are anti histaminics?
a. Cimetidine
b. Omeprazole
c. Pirenzepine
d. Misoprostol
3. Which of the following drugs are anticholinergics?
a. Cimetidine
b. Omeprazole
c. Mg. hydroxide
d. Pirenzepine
4. Which drug cause acid rebound?
a. Sodium bicarbonate
b. Omeprazole
c. Cimetidine
d. Misoprostol
5. What are the Risk factor of peptic ulcer?
a. Helicobacter pylori
b. Zollinger-Ellison syndrome
c. a&b
d. None
6. Which ulcers develop sores in the inside lining of the upper portion of small intestine?
a. Gastric ulcers
b. Duodenal ulcers
c. a&b
d. None
7. Drugs of choice for Zollinger-Ellison syndrome?
a. Antacid
b. H2 antihistamines
c. Proton pump inhibitor
d. Ulcer protectives
8. In antacid preparation aluminium hydroxide is added with magnesium salts because:
a. Magnesium caused constipation
b. Aluminium caused diarrhea
c. To counteract the laxative effect of alum
d To counteract the constipating effect of aluminium.
9. Select the correct combination of H2 antihistamines, proton pump inhibitors, and anticholinergic drugs.
a. Ranitidine, Pirenzepine, Omeprazole
b. Misoprostol, Pirenzepine, Ranitidine
c. Roxatidine, Esomeprazole, Propanthlene
d. Misoprostol, Famotidine, Rantidine
10. Which of the following has been associated with peptic ulcer.
a. H. pylori. a gram negative bacteria
b. H. pylori. a gram positive bacteria
c. H. pylori. a gram negative fungi
d. H. pylori. a gram positive fungi
11. Which of the following correctly defines a peptic ulcer?
a. When lower esophagus gets lined be red colored tissue.
b. A benign lesion of gastric mucosa.
c. When upper esophagus gets lined be red colored tissue.
d. When esophagus starts getting thinner.
12. Which drugs are used in “rescue therapy” regimen?
a. Omeprazole+ Rantidine+ Ampicillin
b. Tetracycline+ Misoprostol+ Cimetidine
c. Pirenzepine+ Cimetidine+ Misoprostol
d. Omeprazole+ Amoxicillin+ Levofloxacin
13. Which drugs are used in ” quadruple therapy” regimen?
a. Omeprazole+ Amoxicillin+ Levofloxacin
b. Omeprazole+ Tetracycline+ Metronidazole
c. Pirenzepine+ Cimetidine+ Misoprostol
d. Tetracycline+ Misoprostol+ Cimetidine
14. Which of the following drug are ulcer protectives?
a. Sucralfate
b. Omeprazole
c. Misoprostol
d. Cimetidine
15. Which drug posses ” first pass metabolism”?
a. Pantoprazole
b. Roxatidine
c. Cimetidine
d. Tetracycline
Answers:
References:
2. “Khyber medical university” Pharmacology of peptic ulcer, ” Health and medicine”, Jan 18, 2018
3.”Vincezo De Francesco” World Journal of Gastrointestinal pathophysiology.
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The post Peptic ulcer, Classification of Antiulcer Drugs, Mechanism of action, Pharmacokinetics, Side effects, Drug interactions and Uses, MCQs for GPAT, NEET PG,NIPER, Drug inspector exam and pharmacist exam. appeared first on Gpatindia: Pharmacy Jobs, Admissions, Scholarships, Conference,Grants, Exam Alerts.
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