Upper GIT Module 3rd Year 2012

7/28/2019 Upper GIT Module 3rd Year 2012

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Learning objectives

drugs used in management of peptic ulcer withrespect to their

important kinetic properties, therapeutic uses and

adverse effects of these drugs.

Recommend the appropriate management of

Determine the of peptic ulcer and factors

affecting therapeutic approach.

Recommend the appropriate management of

List of HP eradication.


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Peptic ulcer disease

It differs from

erosions and gastritis

.

One of


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.

Zollinger

Ellison Radiation

Chemo-

therapy

Vascular

insufficiency


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.

Protective

Aggressive

H. Pylori

Smoking

Others

NSAIDs

Smoking


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.

Protective Aggressive

H. Pylori

Smoking

Others

Eradication of HP

Decrease acidityCytoprotective


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.

Misoprostol


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.

Protective Aggressive

Decrease acidity

Proton pump inhibitors

H2 receptor blockers

Antimuscarinic drugs

Cytoprotective

PG analogue

Sucralfate

Bismuth

Antacids

PG Analogue

Eradication of HP


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.

Omeprazole

Lansoprazole

Inhibit 90% of basal and

stimulated secretion

Enteric coated

Absorbed from

duodenum

Activated incanaliculi

30 min. before

meals+

+

Hepaticmetabolism

Irreversible

Inhibit only active pumps


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.

Peptic ulcer

Zollinger Ellison syndrome

Omeprazole

Lansoprazole

Erosive oesphagitis

Conventional therapy

Prophylaxis with NSAIDs

Eradication of HP

Prevention of stress related mucosalbleeding (ICU)


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.

Prolonged achlorhydria, 2ndry

hypergastrinemia. In aniamls

Headache, diarrhea, rashIncrease concentration of viable

bacteria

Omeprazole

Lansoprazole


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.

Dose

adjustment

Microsomal enzyme inhibition

Alter the bioavailability of

orally administered drugssuch as ketoconazole

orpH-dependent dosage

forms.

Omeprazole

Lansoprazole


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.

Mainly

Equal efficacy in equipotentdoses

800, 300, 40, 300

Single dose after dinner or at

bed time


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.

Zollinger Ellison syndrome

&Other hypersecreteroy states

Peptic ulcer

Gastro-duodenal reflux esophagitis

Prevention of stress related mucosalbleeding (ICU)

Before anesthesia to prevent gastric

aspiration

Conventional therapy


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.


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Dose adjustment in renal disease

.

Microsomal enzyme inhibition

(Theophylline, phenytoin,

lidocaine , warfarin)

Alter the bioavailability of

orally administered drugssuch as ketoconazole

orpH-dependent dosage

forms.


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.

Selective M1 blocker (minimal effect on

heart, eye , bladder)

Used as adjuncts to H2 blockers, in refractorycases or patients with nocturnal pain

Adverse effects: dry mouth, blurring of

vision


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existing stomach

acid (HCL).

neutralizing

pH

Basic substances

gastric acidity

BY

Decrease pepsinactivity

Increase PG


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metallic ion

Trisilicate

Hydroxide or Oxide

Carbonate or bicarbonate

Al+++

Ca++

Na+

Mg++

Base ion

Potenc

y

Diarrhea

Constipations

Fluid

retentionCO2

physical


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NaHCO3 + HCI NaCI+ H2O + CO2

NaHCO3

DisadvantagesAdvantages

Rapid onset

Short duration

Systemic alkalosis

Fluid retention

CO2


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MgCO3 + 2HCI MgCI2 + H2O + CO2

MgCO3


Rapid onset

Long duration

No systemic alkalosis

No fluid retention

CO2

Laxative effect

Hypermagnesemia


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MgO + 2HCI MgCI2 + H2O

MgO


Rapid onset

Long duration


No fluid retention

Laxative effect

Hypermagnesemia


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Mg trisilicate + 2HCI MgCI2 + Silicon dioxide

MgTrisilicate


Slow onset

Long duration


No fluid retention

Laxative effect

hypermagnesemia

Physical & chemical


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Al (OH)3+3HCI AlCI3 +H2O

Al (OH)3


Slow onsetLong duration


No fluid retention

Constipation

Drug interaction

Physical& chemical

Hypophosphatemia


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Systemic absorption Na HCO3

Relive


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Rapid onset Long duration

Disturbance of acid base balance

Disturbance in bowel habits

CO2

Drug interactions

palatableCheap

No


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.

Short

duration

Delayed

onset

Co2

rebound

Bowel

habits

Systemic

alkalosis

Fluid

retention

Should be

used in

mixtures

1 hour aftermeals

Hyperm

agense

miain

renal

impai

rment

hypophosphatemia


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.

Fluid retention Na HCO3

Renal impairment 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)


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Sulphatedsucrose

+++

strong

- ve

Complex

gel with

mucus

Prevent back diffusion of H+

Stimulate mucus, PGs, HCO3


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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

Peptic ulcer (conventional therapy)


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HCL

Pepsin

mucus HCO3

Blood flow


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Protective actionAntimicrobial action

Adsorb pepsin

Coats ulcer base

HCO3 PG

N, V, black tongue& stool

Encephalopathy in renal

impairment

Eradication of HP

HP Eradication regimen

Traveller's diarrhea


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Desired outcome


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.


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Pathogenic

mechanisms

Toxins

Direct mucosal injury Enzymes

Adherence

Alterations of the host immune/inflammatory response

Hypergastrinemia

Carcinogenic conversions of susceptible gastric

mucosal cells
http://www.clinsci.org/cs/110/0305/cs1100305f01.htm


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.
http://www.clinsci.org/cs/110/0305/cs1100305f01.htmhttp://www.clinsci.org/cs/110/0305/cs1100305f01.htm


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Eradication of HP

7 days 10-14 days

Effective

80-90% cure

Well tolerated

Cost effective

Minimize

resistance

PPI Clarithromycin AmoxicillinPPI Clarithromycin Metronidazole

PPI Amoxicillin Metronidazole

1st

Allergy

Compliance


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.

Proton

Pump

Inhibitor

PPI

Clarithromycin Amoxicillin

Clarithromycin Metronidazole

Amoxicillin Metronidazole

Omeprazole 20mg twice

Lansoprazole 30mg twice

500 mg twice

500 mg twice

1 gtwice


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.

Bismuth Metronidazole Tetracycline PPI

Similar

efficacy

adverseeffects

Poor

compliance

Amoxicillin,Clarithromycin

H2 blockers


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Increase resistance of other organisms

Metallic taste Headache

N, V, abdominal cramps Diarrhea: 30-50% of patients

Rash


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.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.

2nd line empiric treatment should

utilize

In case of Metronidazole resistance

(100 mg four times a day) can be used.


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Inhibition of systemic endogenous PGs

Increase Leukotrienes

Neutrophil adherence

Pathogenic

mechanisms

Damage endothelium

Reduce mucosal blood flow

ROS

Drugs of acidic nature have topical irritant effect


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Stop NSAIDs Continue NSAIDs

PPI

H2 receptor

blockers

Sucralfate

Prophylaxis

NSAIDs + PPI

NSAIDs

+

Misoprostol


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Ulcer related complications Healed refractoryulcer

Failed HP eradication Heavy smokers

Chronic NSAIDs users

Single

agent

4

weeks


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Learning objectives

drugs according to their ofaction.

the appropriate for prevention or treatment

of different cases of N & V.

, discuss their of action and list

their

the clinical usefulness of the different classes as

antiemetics.

the important adverse effects of the studied antiemeticdrug classes

the antiemetic combination in common clinical use


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Excitability of labyrinthine receptors

Conduction from labyrinth to vomiting

center

Motion

sickness Preoperative

Dry mouthBlurring of

vision

Reduce Adverse effects

Relief for 72 hours

Adverse effects


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Diphenhydramine Dimenhydrinate

Cyclizine Meclizine

Promethazine

Motionsickness

PregnancyVertigo

Adverse effects: dry mouth, sedation

Doxylamine

Inhibit cholinergicpathway of

vestibular

apparatus


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Block dopamine

receptors in CTZ

MetoclopramidePhenothiazine &

ButyrophenonesBlock 5HT3 inhigh dose Domperidone

(Prokinetic)

Adverse effects

Prokinetic

Adverse effects

Extrapyramidal manifestations,prolactin

DiarrheaAnticholinergic

-blocking

Chemotherapy,,, radiation induced vomiting

Narcotic induced,,,, Postoperative nausea


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Ondansetron Granisetron

Longer acting

More potent

More potent thanmetoclopramide

Chemotherapy induced, Radiation induced,postoperative vomiting

Given oral and IV

Headache, flushing, GIT upsets


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Inhibit VC Chemo. induced

Sedation, psychoactive effects, dry mouth, orth.

hypotention

Dexamethsone Methylprednisone

Usually in

combinations Oral or IV


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Lorazepam Diazepam

Anxiolytic effect Anticipatoryvomiting

Amnesia (4-6 hs)

Vertigo, menieres disease


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Aprepitant

Delayed phase ofCINV

Acute phase ofCINV

Used in combination

(Aprepitant + Dexamethasone+ Ondansetron)

Drug interactions


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Anti-emetic activity

Toxicity

Dexamethasone

Any group

Diphenhydramine

Metoclopramide

Metoclopramide

Corticosteroids


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Pyridoxine

Other

antihistaminics

Phentothiazine

Corticosteroids

Pyridoxine Doxylamine

Metoclopramide


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Prokinetic


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Prokinetic

Tone of lower

esophageal

sphincter

emptying ofthe upper GIT

Relax pyloric antrum and

duodenal cap

Enhance the action of Ach


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Therapeutic uses

Disorders of

Gastric emptying

e.g

Diabetes

Reflux

esophagitis

Gastric emptying

before anesthesia

and labor

MetoclopramideExtrapyramidal

Domperidone

NO Extrapyramidal

Motilin and its analogue

Erythromycin

D2 antagonists

Anti-emetic, prokinetic

5HT4 receptor agonist

Tegaserod

Small intest, colon

Restricted use now


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Upper GIT Module 3rd Year 2012

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