Learning objectives

drugs used in management of peptic ulcer with respect to their important kinetic properties, therapeutic uses and adverse effects of these drugs. Determine the of peptic ulcer and factors affecting therapeutic approach. Recommend the appropriate management of List of HP eradication.

Recommend the appropriate management of

Peptic ulcer disease

One of
It differs from erosions and gastritis

Zollinger Ellison

Radiation

Chemotherapy

Vascular insufficiency

H. Pylori Smoking Others

.

Protective

NSAIDs
Smoking

Aggressive

Eradication of HP

H. Pylori
Smoking Others

Cytoprotective

Decrease acidity

Protective

Aggressive

Misoprostol

Eradication of HP

Decrease acidity
Cytoprotective
. Sucralfate

Proton pump inhibitors

H2 receptor blockers Antimuscarinic drugs PG Analogue Antacids

PG analogue Bismuth

Protective

Aggressive

Omeprazole Lansoprazole

InhibitIrreversible 90% of basal and stimulated secretion Inhibit only active pumps
.

Enteric coated Absorbed from duodenum Activated in canaliculi

30 min. before meals Hepatic metabolism

+ +

Omeprazole Lansoprazole

Peptic ulcer
.

Conventional therapy
Prophylaxis with NSAIDs Eradication of HP Prevention of stress related mucosal bleeding (ICU) Zollinger Ellison syndrome Erosive oesphagitis

Omeprazole Lansoprazole

Headache, diarrhea, rash Increase concentration of viable bacteria Prolonged achlorhydria, 2ndry hypergastrinemia. In aniamls

Omeprazole Lansoprazole

Dose adjustment
.

Microsomal enzyme inhibition Alter the bioavailability of orally administered drugs such as ketoconazole or pH-dependent dosage forms.

Mainly

Equal efficacy in equipotent doses 800, 300, 40, 300 Single dose after dinner or at bed time

Peptic ulcer Conventional therapy

.

Gastro-duodenal reflux esophagitis Zollinger Ellison syndrome &Other hypersecreteroy states Prevention of stress related mucosal bleeding (ICU) Before anesthesia to prevent gastric aspiration

Microsomal enzyme inhibition (Theophylline, phenytoin, lidocaine , warfarin) Alter the bioavailability of orally administered drugs Dose adjustment in renal disease such as ketoconazole or pH-dependent dosage forms.

Selective M1 blocker (minimal effect on heart, eye , bladder)

. Used as adjuncts to H2 blockers, in refractory

cases or patients with nocturnal pain

Adverse effects: dry mouth, blurring of vision

Basic substances

pH gastric acidity

existing stomach acid (HCL). Decrease pepsin activity

neutralizing BY

Increase PG

Base ion
physical

metallic ion

Al+++
Trisilicate

Constipations

Mg++
Hydroxide or Oxide

Diarrhea

Ca++
Carbonate or bicarbonate CO2

Na+

Fluid retention

Potency

NaHCO3 NaHCO3 + HCI NaCI + H2O + CO2 Disadvantages

Short duration Systemic alkalosis Fluid retention CO2

Advantages
Rapid onset

MgCO3 MgCO3 + 2HCI

Advantages

MgCI2 + H2O + CO2

Disadvantages
CO2 Laxative effect Hypermagnesemia

Rapid onset
Long duration No systemic alkalosis

No fluid retention

MgO MgO + 2HCI

Advantages

MgCI2 + H2O
Disadvantages
Laxative effect

Rapid onset
Long duration No systemic alkalosis

Hypermagnesemia

No fluid retention

MgTrisilicate
Mg trisilicate + 2HCI
Advantages Long duration Physical & chemical

MgCI2 + Silicon dioxide

Disadvantages
Slow onset Laxative effect hypermagnesemia

No systemic alkalosis
No fluid retention

Al (OH)3

Al (OH)3+ 3HCI
Advantages
Long duration
Physical& chemical No systemic alkalosis

AlCI3 +H2O
Disadvantages

Slow onset
Constipation Drug interaction

No fluid retention

Hypophosphatemia

Systemic absorption

Na HCO3

Relive

Rapid onset Cheap

Long duration

palatable

Disturbance of acid base balance Disturbance in bowel habits

No

CO2 Drug interactions

Short duration

Delayed onset

Co2 rebound

Bowel habits

Systemic alkalosis

Fluid retention

Should be in used mixtures 1 hour after meals

Hypermagense mia in renal impairment

hypophosphatemia

Fluid retention Renal impairment

.

Na HCO3 Mg antacids

Decrease absorption of acidic drugs, increase absorption of basic ones Increase excretion of acidic drugs

Al ion can chelate some drugs (digoxin and tetracyclin)

strong - ve
+++

Sulphated sucrose

Complex gel with mucus

Prevent back diffusion of H+

Stimulate mucus, PGs, HCO3

Peptic ulcer (conventional therapy) Constipation, dry mouth, N,V

Reduce absorption of many drugs (digoxin, tetracyclin, quinolones...

Antacids, PPIs or H2 blockers should NOT with or prior to its administration

HCL Pepsin

mucus

HCO3

Blood flow

Antimicrobial action

Protective action Coats ulcer base Adsorb pepsin

Eradication of HP HCO3 PG

N, V,Eradication black tongue& stool HP regimen

Encephalopathy in renal Traveller's diarrhea impairment

Desired outcome

Pathogenic mechanisms

Toxins
Direct mucosal injury
.

Enzymes
Adherence

Alterations of the host immune/inflammatory response Hypergastrinemia Carcinogenic conversions of susceptible gastric mucosal cells

Eradication of HP

Effective 80-90% cure Well tolerated Cost effective Compliance Minimize resistance

PPI

Clarithromycin Amoxicillin

1st
Allergy

PPI PPI

Clarithromycin Metronidazole Amoxicillin Metronidazole

7 days 10-14 days

500 mg twice Proton Pump Inhibitor . PPI Clarithromycin Amoxicillin Clarithromycin Metronidazole

1g twice

Amoxicillin

Metronidazole

500 mg twice Omeprazole 20mg twice Lansoprazole 30mg twice

Similar efficacy adverse effects Poor compliance

.

Bismuth

Metronidazole

Amoxicillin, Tetracycline
Clarithromycin

H2 PPI blockers

Increase resistance of other organisms

.

N, V, abdominal cramps Metallic taste

Diarrhea: 30-50% of patients

Headache

Rash

2nd line empiric treatment should utilize

Antibiotics not previously used.
.

Antibiotics not having resistance problems. Drug that has a topical effect such as bismuth. The duration of treatment should extend (10-14 ) days.

In case of Metronidazole resistance (100 mg four times a day) can be used.

Pathogenic mechanisms
Inhibition of systemic endogenous PGs
Drugs of acidic nature have topical irritant effect
.

Increase Leukotrienes Neutrophil adherence

Damage endothelium Reduce mucosal blood flow ROS

Stop NSAIDs
.

Continue NSAIDs

PPI H2 receptor blockers Sucralfate

Prophylaxis

NSAIDs + PPI
NSAIDs + Misoprostol

4 weeks
Single agent

Ulcer related complications Failed HP eradication

Healed refractory ulcer Heavy smokers

Chronic NSAIDs users

Learning objectives
drugs according to their action. the clinical usefulness of the different classes as antiemetics. the important adverse effects of the studied antiemetic drug classes the appropriate of different cases of N & V. for prevention or treatment of

the antiemetic combination in common clinical use , discuss their their of action and list

Adverse effects

Excitability of labyrinthine receptors

Dry mouth Blurring of vision

Conduction from labyrinth to vomiting center Reduce Adverse effects

Motion Reliefsickness for 72 hours Preoperative

Diphenhydramine Cyclizine Promethazine

Dimenhydrinate Meclizine

Doxylamine

Inhibit cholinergic Motion Pregnancy pathway of Vertigo sickness vestibular Adverse effects: dry mouth, sedation apparatus

Metoclopramide Block dopamine receptors in3CTZ Block 5HT in high dose Prokinetic Adverse effects

Phenothiazine & Butyrophenones Domperidone (Prokinetic) Adverse effects

Extrapyramidal manifestations,prolactin Chemotherapy,,, radiation induced vomiting Anticholinergic Diarrhea Narcotic induced,,,, Postoperative nausea -blocking

Ondansetron More potent than metoclopramide

Granisetron Longer acting More potent

Chemotherapy induced, Radiation induced, postoperative vomiting Given oral and IV Headache, flushing, GIT upsets

Inhibit VC

Chemo. induced

Sedation, psychoactive effects, dry mouth, orth. hypotention

Dexamethsone
Usually in combinations

Methylprednisone
Oral or IV

Lorazepam
Anxiolytic effect

Diazepam Anticipatory vomiting

Amnesia (4-6 hs) Vertigo, menieres disease

Aprepitant Acute phase of CINV Delayed phase of CINV

Used in combination (Aprepitant + Dexamethasone+ Ondansetron) Drug interactions

Toxicity Anti-emetic activity Dexamethasone Diphenhydramine

Metoclopramide
Corticosteroids Metoclopramide

Any group

Pyridoxine Pyridoxine Doxylamine

Phentothiazine

Metoclopramide

Other antihistaminics

Corticosteroids

Prokinetic

Enhance the action of Ach

Tone of lower esophageal sphincter

Prokinetic

emptying of the upper GIT Relax pyloric antrum and duodenal cap

Therapeutic uses Metoclopramide

Domperidone

Extrapyramidal NO Extrapyramidal Gastric emptying Reflux before anesthesia esophagitis D2 antagonists and labor Anti-emetic, prokinetic

Disorders of Motilin and its analogue Gastric emptying e.g Erythromycin Diabetes

5HT4 receptor agonist Tegaserod

Small intest, colon Restricted use now