gastroesophagial reflux disease seminar

7/30/2019 Gastroesophagial Reflux Disease Seminar

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Introduction Gastrointestinal tract and wall

Clinical relevance

Gastric motility and Gastric glands Gastroesophageal reflux disease (GERD)

Acid secretion and regulation

Pharmacological targets for (GERD)

Recent drugs

Conclusion


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NEURONAL PLEXUSESdiabetes mellitus

connective tissue disorders


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ALTERED PERISTALSISPregnancy

Obstruction

IMPROPER MIXING OFFOOD


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JUICES VOLUME PH

SALIVA 1000ml 6-7

GASTRIC 1500ml 1-3.5

PANCREATIC 1000ml 8-8.3

BILE,BRUNNERS 1200ml 7-8

INTESTINES 2000ml 7.5-8

TOTAL 6700ml


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QUANTITY OF SECRETION

PHASES OF SECRETION


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MUCOUS NECK CELLS

PARIETAL CELL


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Chronic relapsing condition

Significant morbidity

Estimated lifetime prevalence of 25-35 %

44% have heartburn once a month

14% have weekly symptoms

7 % have daily symptoms


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Caffeine

Peppermint

Fatty foods

Chocolate

Spicy foods

Citrus fruits

Tomato

Alcohol


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History

Response to a PPI

Radiologic findings Endoscopy

Ambulatory pH monitoring


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Pyrosis (Heartburn) regurgitation

or both.

High specificity, low sensitivity


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Atypical chestpain

Hoarseness

Nausea

Cough

Odynophagia

Globus sensation

Onset after age 45

Recurrent

laryngitis Subglottic stenosis


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Omeprazole 40 mg BID X 14 days as

specific and sensitive for diagnosis as

24 hour ph monitoring

Failure to respond warrants further

investigation of patients symptoms


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Diagnostic gold standard


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Esophagitis Strictures

Ulcerations

Barretts esophagus

Adenocarcinoma


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Dysphagia Odynophagia

Early satiety

GI bleeding

Iron deficiency anemia

Vomiting

Weight loss


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Head of bed elevated by six inches

Decreased fat intake Smoking cessation

Weight loss

Avoidance of recumbency for 3 hourspost-prandially

Avoidance of large meals


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OMEPRAZOLE RABEPRAZOLE


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OMEPRAZOLE

ESOMEPRAZOLE

LANSOPRAZOLE

RABEPRAZOLE

PANTOPRAZOLE

TENATOPRAZOLE


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PRODRUG


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ABSORBED INTO SYSTEMIC CIRCULATION

DIFFUSES INTO PARIETAL CELLS

ACCUMULATES IN SECRETORY CANALICULI

ACTIVATED TO TETRACYCLIC SULFENAMIDE


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BINDS COVALENTLY TO ACID - PUMP

IRREVERSIBLY INHIBITS THE PUMP

ACID SECRETION IS SUPPRESSED

BOTH BASAL AND STIMULATED


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Provides acid suppression for 24-48 hours Acid secretion resumes after new enzyme

synthesis

Block final step in acid secretion Metabolized by CYP2C19, CYP3A4

Dose reduction is recommended for

esomeprazole and lansoprazole in hepaticdisease


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PHARMACOKINETICS


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Prodrugs

Administered 30 minutes before food

Are highly plasma bound

Maximal acid secretion suppressionrequires several doses

Single daily dosing may need 2-5 days

Lansoprazole is preferred in pregnancy


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Nausea

Abdominal pain

Constipation Flatulence

Diarrhea


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Hypergastrinemias

Gastrointestinal tumors

Carcinoid tumors Vitamin B12 malabsorption

Campylobacter infection


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Decrease clearance of


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Disulfiram

Phenytoin

Imipramine

Tacrine

Theophylline

Ketoconazole

Ampicillin Esters

Iron salts


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CIMETIDINE FAMOTIDINE


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CIMETIDINE

RANITIDINE

FAMOTIDINE

NIZATIDINE


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PHARMACOKINETICS


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Rapid oral absorption

Peak concentration achieved in 1-3 hours

Absorption enhanced by food

Small % are protein bound Major site for excretion is kidney

Hemodialysis nor peritoneal dialysis clears

significant amount of drug


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Head ache

Diarrhea

Drowsiness

Fatigue

Muscular pain

Constipation


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Galactorrhea

Gynacomastia

Impotence Reduced sperm

count

Thrombocytopenia


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Cimetidine inhibits CYP1A2,P2C9,P2D6

Ranitidine inhibits CYP hepatic

Famotidine and Nizatidine have no significant

drug intractions

Slight increase in blood alcohol


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Decreased therapeutic effect

Tolerance can develop within 3 days

Resistant to increased doses ofmedication

May be due to secondary

hypergastrenemia

PPI H2RA


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-MORE POTENT

-IRREVERSIBLE

INHIBITOR

-GIVEN BEFORE FOOD

-METABOLISED IN LIVER

-REDUCES BOTH

SECRETION

-LESS POTENT

-REVERSIBLE

INHIBITORS

-GIVEN WITH FOOD

-HEPATIC 10% -35%

-REDUCES BASAL

SECRETION

PPI H2RA

A


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-EXTENSIVELY PROTEIN

BOUND

-TOLERANCE NOT SEEN

-HEALING RATES AT

4 WEEKS IS 80%

-STRICTURES RESPOND

BETTER

-SMALL % PROTEIN BOUND

-TOLERANCE SEEN

-HEALING RATES AT

4 WEEKS IS 50%

-STRICTURES RESPOND

POORLY

A


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Metoclopramide

Domperidone

Cisapride


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Increases gastric motility

Action is independent of vagal

innervations

LES tone is increased

No effect on gastric secretion


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D2 selective antagonist

5HT4 receptor agonist

5HT3 antagonist Sensitization of muscarinic

receptors on smooth muscle


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PHARMACOKINETICS


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Rapidly absorbed orally

Crosses blood brain barrier

Half life is 4-6 hours

Secreted in milk

Partly conjugated in liver

Excreted in urine


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Sedation Dizziness

Diarrhea

Muscle dystonias Galactorrhoea

Gynacomastia


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Hastens absorption of Aspirin

Hastens absorption of Diazepam

Decreases absorption of Digoxin

Bioavailability of Cimetidine is reduced

Abolishes the therapeutic effect ofLevodopa


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Chemically related to haloperidol

Pharmacologically related to

Metaclopramide

Crosses BBB poorly

EPS are rare

Oral bioavailability is 15%

Plasma t is 7.5 hours

Cardiac arrhythmias can develop onrapid iv injection


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SODIUM BICARBONATE SODIUM CITRATE

MAGNESIUM SALTS

ALUMINIUM HYDROXIDE GEL MEGALDRATE

CALCIUM CARBONATE

SIMETHICONE


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Water soluble Acts instantaneously

Short duration

Absorbed systemically May produce alkalosis

Produce CO2 in stomach

Rebound acid production can occur


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Very potent Rapidly acting

Releases CO2 and causes discomfort

Can cause hypercalcaemia,calciumstones,calciuria,alkalosis

Can cause milk alkali syndrome with

milk


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Fast (mag salts) slow (alum salts) Laxative (mag salts) constipation

(alum salts)

Gastric emptying is hastened (magsalts) delayed (alum salts)

Toxicity is counteracted


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Is a surfactant

Decreases foaming

Is indicated in many antacid preparations


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Cholecystokinin A receptor antagonist

Improves gastric emptying

Suppresses transient relaxation of LES Investigations in Europe are suggestive

of its use in GERD


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Amino guanidine indole


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Partial 5-HT4 agonist

Negligible affinity for receptor subtypes Stimulates motility in GI tract

Should be taken on empty stomach

98% plasma bound t is 11hours

Diarrhea and headache are side effects

No significant cardio-toxicity reported

No clinically relevant drug interactions


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1)THE PHARMACOLOGICAL BASIS OF


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THERAPEUTICS

2)CLINICAL PHARMACOLOGYBENNETTAND BROWN

3)MATINDALE 33rd EDITION

4)LIPPINCOTS ILLUSTRATEDPHARMACOLOGY

5)BERTRAM KATZUNG 10 EDITION

6)GENERAL PHARMACOLOGICAL PRINCIPALSKD TRIPATHI

7) HARRISONS TEXT BOOK OF INTERNALMEDICINE


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8) DAVIDSONS PRINCIPLES AND PRACTICE

OF MEDICINE9) API TEXT BOOK OF INTERNAL MEDICINE

10)TEXT BOOK OF PREVENTIVE MEDICINE

PARK

11)CURRENT MEDICAL DIGNOSIS AND

TREATMENT

12)BASICS OF PHYSIOLOGYGYTON

13)TEXT BOOK OF PHYSIOLOGY-GANONG

14)GASTROENTROLOGY AND HEPATICDISEASES VOLUME 1-NORMAN DAVID


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15)GRAYS ANATOMY

16)BIOLOGICAL HEALTH DEPARTMENTCALIFORNIA STATE UNIVERSITY

17)CASE STUDIESAIIMS NEW DELHI

18)DEPARTMENT OF GASTROENTROLOGYUMC MANGALORE

gastroesophagial reflux disease seminar

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