Pharmacology of the G.I.T

7/30/2019 Pharmacology of the G.I.T

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Drugs used in

Gastro-intestinal system


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Treatment of peptic ulcer

Anti emetics

Laxatives Anti diarrhea


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Pharmacology of the GIT

The mouth

a proper flow of saliva is necessary to keep the mouthfresh & free from infection.

Salivary flow will be diminished in fever, dehydration ,&

by certain drugs.

Several oral infection may supervene if salivary flow ismarkedly decreased.


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DISEASES OF THE MOUTH

CANDIDIASIS :The yeast Candidaalbicansis a normal mouth commensalbut it may proliferate to cause thrush.

White patches are seen on the tongueand buccal mucosa. A clinical diagnosis issufficient to instigate therapy, althoughbrushings or biopsies can be obtainedfor mycological examination.


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Oral thrush is treated using nystatin oramphotericin suspensions or lozenges.Resistant cases or immunosuppressedpatients may require oral fluconazole.


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Parotitis is due to viral or bacterial

infection

Bacterial parotitis usually occurs as a

complication of major surgery. It is a

consequence of dehydration and poor oral

hygiene and can be avoided by good post-

operative care

Broad-spectrum antibiotics are required,


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Prevention of oral infection

1. Avoid oral infection during surgery

2. Avoid dehydration

3. Use mouthwashes


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The major components of mouthrinses:

1. Water: the major vehicle to solubilize theingredients.

2. Flavoring: is designed to make mouthrinsepleasant to use.

3. Humectant: to prevent crystallization around

the opening of the container.


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4.Surfactant: to solubilize the flavoring agent &provide foaming action.

5. Alcohol is also helps solubilize some of theingredients present in the formulation.

6. Active ingredients vary within the productcategory antimicrobial agents, fluoride, &chlorophyllins


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Chlorophyllins can serve as topicaldeodorizers to mask halitosis.

Fluoride rinses will reduce cariouslesions.


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chlorhexidine broad spectrumantibacterialagent

Depending on the dose, it can interfere withbacterial cell wall transport or disrupt thecell wall.

Is used in 0.2% solution , the mouth is rinsed2 to 3 times daily with about 10 ml for 1minute.

The tongue & teeth may be stained brown butthis can be avoided by brushing the teethbefore use.


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General dosing information:

The usual adult dose is 10-20 ml. the duration

of rinsing varies depending on the type ofagent used.

The maximal dose for each patient must beindividualized depending on factors as age,physical status, ability to effectively rinse &expectorate, oral health & sensitivity.

Mouthwashes are often not prescribed foryoung pediatrics.


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Patient advise

To receive the greatest antiplaque oranticaries benefit, the patient should rinsebefore retiring to bed

After using the mouthwash , the patientshould not rinse with water or drink anythingfor at least 30 minutes, immediately drinkingor rinsing with water will increase the drug

clearance from the mouth & reduce itseffectiveness.


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P l D


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Peptic Ulcer Disease

Definition

Break & discontinuity of the mucosa of thestomach or duodenum, penetrating into muscularismucosa

Factors

1. Infection with Helicobacter Pylori (H.Pylori)

2. Increased HCL secretion

3. Inadequate mucosal defense against gastricacid

4. Other factors: smoking, NSAIDs, alcohol


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Peptic Ulcer Disease

In peptic ulcer (PU) thereis imbalance between:

The damaging factors:

gastric acid, pepsin, H.pylori& NSAIDs.

The protective factors:prostaglandins, mucus,bicarbonate & mucosalblood flow.

Protective

factors

Aggressive

factors


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Treatment:

Aim

1. Symptomatic relief

2. Prevent relapse

3. Prevent complication

Non pharmacological approaches

1. Stop smoking

2. Avoid alcohol3. Stop the use of ulcerogenic drugs (NSAIDs)


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Pharmacological

1. Eradicate H.Pylori

2. Reduce or neutralize the acid3. Protect the gastric mucosa from damage


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Drugs used in the treatment of PU

Drugs that neutralize gastric acidityAntacids

Drugs that decrease gastric acid secretionH2 blockers

PPIAntimuscarinic

Mucosal protective agents

SucralfateMisoprostol

Colloidal Bismuth compounds

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Eradication of Infection

H.Pylori adapted to live in the mucus thatoverlies gastric epithelial cells & mucosa inthe duodenum

This Gram -ve bacteria may cause pepticulcer by impairing mucosal defense viaelaboration of toxins & enzymes, by

provoking local inflammatory response.


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H. pylori


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Optimal therapy of patient with peptic ulcer(duodenal & gastric ulcers) who are infected with

H. Pylori requires antimicrobial treatment

Various drug combination which are effective:

Omeprazole (antisecretory)

Antibiotic like Clarithromycin, Amoxicillin, Tetracycline& Metronidazole

Triple therapy

RegimenOmeprazole or Lanzoprazole + Amoxicillin +

Clarithromycin.


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Eradication of H.Pylori results in rapid healing of active pepticulcer & low recurrence rates (less than 15% compared to 60 to100% per year for patients used traditional antisecretory

agents)

2. Reduction of Acidity

This can be done by inhibit H+ secretion or

neutralize H+ Gastric acid secretion by parietal cells of the

gastric mucosa is controlled by:

1. Acetylcholine2. Histamine they stimulate H+

3.Gastrin


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4. Prostaglandins (PGs) E2 & I2 inhibit acid secretion,stimulate mucus & bicarbonate secretion.

A. Drugs Used to Inhibit H+ Secretion

1.Histamine antagonists (H2-receptorantagonists)

MOA: blocks histamine receptors

inhibit H+secretion

Examples: Cimetidine, Ranitidine

Indications:

1. Peptic ulcer

2. Gastroesophageal reflux disease


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Unwanted effects are rare.

Cimetidine sometimes gynaecomastia in men &rarely, a decrease in sexual function.

Cimetidine also inhibits cytochrome P450 andretard metabolism of a range of drugs.


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2.Proton Pump Inhibitors (PPIs)

MOA: bind to H+/K+ -ATPase enzyme system,

suppressing secretion of H+ ions into gastriclumen

Examples: Omeprazole, Lanzoprazole

Indications:

1.As one component of therapy for eradication ofH.Pylori.

2.Treatment of NSAIDs induced ulcer.


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3. Anti-muscarinic DrugsSpecific muscarinic M1-receptor antagonists:

Pirenzepine

Antacids They are weak bases, they reduce gastric acidity by

neutralization

Antacid + HCl salt + water

Commonly used antacids are salts of Aluminum &Magnesium as Al(OH)3, Mg(OH)2 either alone or incombination; NaHCO3, CaCO3 also used


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Therapeutic uses:

For symptomatic relief of peptic ulcer disease & GRED

S/Es:

1. Mg-containing antacids cause diarrhea

2. Al-containing antacids cause constipation

3.NaHCO3 librates CO2 causing belching & flatulence.

Should not be given to patients who are on a sodium-

restricted diet.


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B. Mucosal Protective Agents1.Sucralfate

It is combination of Al salts & sulfated sucrose

MOA:In acidic medium, it forms complex gel with mucus, so

creates a physical barrier that impairs diffusion ofHCL

Sucralfate should not be administered with antacids,H2-antagonists or PPIs

S/Es: Constipation


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2.Misoprostol

MOA

Stable analogue of PGE1, it inhibit gastric acid secretion

It is used to prevent gastric damage that canoccur with chronic use of NSAIDs

S/Es: Diarrhea, Uterine contraction may occur


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emetic Agents-Anti

Nausea & vomiting may occur in variety of

conditions, for examples:

1. Motion sickness

2. Hepatitis

3. Chemotherapeutic agents4. Pregnancy

Uncontrolled vomiting can produce dehydration,metabolic imbalance & nutrients depletion


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Receptors mediate emesis:

1. Histamine receptors [H1]2. Dopamine receptors [D2]

3. 5-HT3 (serotonin) receptors

4. Muscarinic receptors

Anti-emetic classified as antihistamine,anticholinergic, anti-dopaminergic, anti-5-HT3drugs


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exampleDrug class

MetoclopramideD2-receptor antagonists

CyclizineHistamine [H1] Receptor

AntagonistsOndansetron5-HT3 Receptor Antagonists

HyoscineAntimuscarinic Agents

DexamethasoneCorticosteroids


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Metoclopramide

MOA:1. Centrally block D2 receptors / in CTZ

2. Peripherally it is prokinetic agent, it

accelerates gastric emptying [cholinergic effect]

Given orally or by injection

S/Es

Peripheral: Abdominal cramps


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Disorders of the Lower GI Tract

Constipation

Diarrhea


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GI Motility

http://img.tfd.com/vet/thumbs/gr294.jpg

increased transit time

- Increased waterabsorption constipation

decreased transit time

-Decreased water and

nutrient absorption diarrhea


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Antidiarrheal Agents

Diarrhea: frequent passage of liquid feces

Pathophysiology of diarrhea1. motility of GIT

2. secretion of fluid into GIT lumen

3. fluid absorption in the intestine

Causes of diarrhea

1. Infections

2.Toxins

3.Drugs


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Treatment

1.Maintenance of fluid & electrolyte balanceOral rehydration is the 1st priority

2. Use of Anti-infective agents

3. Use of Non-antimicrobial Antidiarrheal agents(Antimotility)

a. Antimuscarinic agents


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b. Opiates1. Codeine

2. Loperamide

S/Es of antimotility agents: constipation.

P (l )


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Purgatives (laxatives)

Constipation: refers to bowel movements

that are infrequent and/or hard to pass Causes:

1. Pregnancy2. Drugs

3. Elderly patients4. Diet contents

Treatment:1. Remove the cause2. Accelerate the movement of food through

GIT by several methods:

is discouragedlaxativesThe routine use of
http://en.wikipedia.org/wiki/Bowel_movementhttp://en.wikipedia.org/wiki/Bowel_movement


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is discouraged,laxativesThe routine use ofas having bowel movements may come to be

dependent upon their use.

Examples

Classes

MethylcelluloseBulk laxatives

LactuloseOsmotic laxatives

GlycerinsuppositoriesFecal softener

BisacodylStimulantPurgatives

Pharmacology of the G.I.T

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