Drugs Acting On Gastrointestinal Tract Gastrointestinal Tract Professor Kassim Al-Saudi,...
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Transcript of Drugs Acting On Gastrointestinal Tract Gastrointestinal Tract Professor Kassim Al-Saudi,...
Drugs Acting OnDrugs Acting On
Gastrointestinal TractGastrointestinal Tract
Professor Kassim Al-Saudi,
M.B.,Ch.B.,Ph.D.
OBJECTIVESOBJECTIVES Identify classes of drugs used to improve GI
function. Identify uses and varying actions of these
drugs. Identify how these drugs are absorbed,
distributed, metabolized, and excreted. Identify drug interactions and adverse
reactions to these drugs. Be familiar with drug-induced hepatotoxicity
DRUGS AND THE GI DRUGS AND THE GI SYSTEMSYSTEM Classes of drugs used to improve GI
function include:
Peptic ulcer drugs Antiemetic and emetic drugs Antidiarrheal drugs Laxative drugs
Peptic Ulcer•The term “peptic ulcer” refers to an ulcer in the lower Oesophagus, stomach, duodenum (commonly), jujenum and ileum (rarely)
• Gastric and duodenal ulcers may be acute
or chronic
• Acute ulcer shows no evidence of fibrosis
• Both penetrate the muscularis mucosae
• Erosions do not penetrate the muscularis
mucosae
AetiologyAetiology::
1- Infection – Helicobacter pylori (Gm –ve)
- 50% Industrialized
- 90% Developing (Childhood)
- Majority symptoms free
- 90% of DU patients and 70% of GU
patients are infected with H. pylori
2- Acid and Pepsin secretion
3- Mucosal defensive mechanism
Pathogenesis of UlcersPathogenesis of Ulcers
Aggressive Aggressive FactorsFactors
Acid, pepsinAcid, pepsin Bile saltsBile salts Drugs (NSAIDs)Drugs (NSAIDs) H. pyloriH. pylori
Defensive FactorsDefensive Factors Mucus, bicarbonate Mucus, bicarbonate
layerlayer Blood flow, cell renewalBlood flow, cell renewal ProstaglandinsProstaglandins PhospholipidPhospholipid Free radical scavengersFree radical scavengers
Therapy is directed at enhancing host defense or eliminating aggressive factors; i.e., H. pylori.
Aim of TreatmentAim of Treatment
Relief Symptoms Heal Ulcer Prevent recurrence Prevent complications
Lifestyle measuresLifestyle measures
Raise the head of the bed Decrease fat intake Avoid certain foods Avoid lying down for 3 hours after eating Stop smoking Lose weight if appropriate
PEPTIC ULCER DRUGSPEPTIC ULCER DRUGS
Aimed at either eradicating H. pylori or Aimed at either eradicating H. pylori or restoring balance between acid and restoring balance between acid and pepsin secretions and the GI mucosal pepsin secretions and the GI mucosal defense.defense.
These drugs include: systemic antibiotics, These drugs include: systemic antibiotics, antacids, Histamine-2 (H2)-receptor antacids, Histamine-2 (H2)-receptor antagonists, proton pump inhibitors, and antagonists, proton pump inhibitors, and other peptic drugs such as misoprostol other peptic drugs such as misoprostol and sucralfate.and sucralfate.
Eradication of H. pylori
Tests For Initial Diagnosis of Tests For Initial Diagnosis of InfectionInfection
Urea Breath Test and Stool AssayUrea Breath Test and Stool AssayNon-invasive, sensitive and specificNon-invasive, sensitive and specific
SerologySerologyO.K. for initial diagnosisO.K. for initial diagnosisFair sensitivity and specificityFair sensitivity and specificity
Endoscopy Not necessary for diagnosisEndoscopy Not necessary for diagnosis
Who Should Be Treated For Who Should Be Treated For H. pyloriH. pylori Infection Infection??
Patients who have documented Patients who have documented H. pylori H. pylori infection infection and:and:Definitely had or has a duodenal or stomach ulcerHave had stomach lymphoma or family hx of stomach
cancer Consider treatment if:
Presence of “severe histologic” gastritis and H. pylori infection
Ulcer-like dyspepsia in the absence of an ulcer or prior to endoscopy in a young patient
FDA-Approved Treatment FDA-Approved Treatment Regimes for Regimes for H. pyloriH. pylori Infection Infection
Omeprazole 20 mg BID + Clarithromycin 500 mg BID + Amoxicillin 1 g BID for 10 days
Lansoprazole 30 mg BID +Clarithromycin 500 mg BID + Amoxicillin 1 g BID for 10 days
Bismuth subsalicylate (Pepto Bismol) 525 mg QID + Metronidazole 250 mg QID + Tetracycline 500 mg QID X 14 days + H2 receptor antagonist x 4 wks
Known Factors Which Determine Success of H. pylori Therapy
Patient compliance or non-complianceMedicine complications or side effects
Antimicrobial resistance of infecting H. pylori strains Duration of Therapy Correct dosing
Clearance of H. pylori infection is not equivalent to eradication.
Drugs Affecting Gastric Acid Drugs Affecting Gastric Acid SecretionSecretion
PROTON PUMP PROTON PUMP INHIBITORSINHIBITORS
Disrupt chemical binding in stomach cells to reduce acid production, lessening irritation and allowing peptic ulcers to heal.
These drugs include: Omeprazole (Prilosec) Rabeprazole (Aciphex) Pantoprazole (Protonix) Lansoprazole (Previcid) Esomaprazole (Nexium)
PROTON PUMP INHIBITORSPROTON PUMP INHIBITORS
Pharmacokinetics:Pharmacokinetics: Given orally in enteric-coated form to Given orally in enteric-coated form to
bypass the stomach and are dissolved and bypass the stomach and are dissolved and absorbed in the small intestine.absorbed in the small intestine.
Highly protein-bound and are extensively Highly protein-bound and are extensively metabolized by the liver; eliminated in the metabolized by the liver; eliminated in the urine.urine.
PROTON PUMP INHIBITORSPROTON PUMP INHIBITORS
Pharmacodynamics:Pharmacodynamics: Block the last step in the secretion of Block the last step in the secretion of
gastric acid by combining with hydrogen, gastric acid by combining with hydrogen, potassium, and adenosine triphosphate in potassium, and adenosine triphosphate in the parietal cells of the stomach.the parietal cells of the stomach.
PROTON PUMP INHIBITORSPROTON PUMP INHIBITORS
PharmacotherapeuticsPharmacotherapeutics:: Indicated for:Indicated for: Short term treatment of gastric ulcersShort term treatment of gastric ulcers Active duodenal ulcers and peptic ulcers Active duodenal ulcers and peptic ulcers
(H. pylori)(H. pylori) Erosive esophagitisErosive esophagitis GERDGERD Hypersecretory statesHypersecretory states
PROTON PUMP INHIBITORSPROTON PUMP INHIBITORS
Drug interactions:Drug interactions: May interfere with the metabolism of May interfere with the metabolism of
diazepam, phenytoin, and warfarin.diazepam, phenytoin, and warfarin. May also interfere with drugs that depend May also interfere with drugs that depend
on gastric pH for absorption.on gastric pH for absorption.
Adverse reactions:Adverse reactions: Abdominal pain, diarrhea, nausea, and Abdominal pain, diarrhea, nausea, and
vomitingvomiting
Pharmacological therapy – Pharmacological therapy – PPIsPPIs
Significantly more effective than H2RAs for Significantly more effective than H2RAs for both symptom resolution and healing of both symptom resolution and healing of erosive esophagitiserosive esophagitis
Also effective in more severe cases of Also effective in more severe cases of GERDGERD
Most patients respond well to standard Most patients respond well to standard therapy, but some require prolonged and/or therapy, but some require prolonged and/or high-dose treatmenthigh-dose treatment
% e
sop
hag
itis
case
s h
eal
ed
0
20
40
60
80
100
2 4 6 8 10Weeks of treatment
12
PPIs
H2RAs
Placebo
p < 0.0005
PPIs are the most effective PPIs are the most effective drugs for the initial drugs for the initial treatment of GERDtreatment of GERD
H2-RECEPTOR H2-RECEPTOR ANTAGONISTSANTAGONISTS
Commonly prescribed anti-ulcer drugs Commonly prescribed anti-ulcer drugs include:include:
Cimetidine (Tagamet)Cimetidine (Tagamet) Ranitidine (Zantac)Ranitidine (Zantac) Famotidine (Pepcid)Famotidine (Pepcid) Nizatidine (Axid)Nizatidine (Axid)
H2-RECEPTOR H2-RECEPTOR ANTAGONISTSANTAGONISTS
Pharmacokinetics: Absorbed rapidly and completely except for
famotidine; food and antiacids may reduce absorption; distributed widely throughout the body; metabolized by the liver; excreted primarily in the urine.
Pharmacodynamics: Block histamine from stimulating the acid-
secreting parietal cells of the stomach.
H2-RECEPTOR ANTAGONISTS
Pharmacotherapeutics: Used therapeutically to: Promote healing of duodenal and gastric
ulcers. Provide long-term treatment of
pathological GI hypersecretory conditions. Reduce gastric acid production and
prevent stress ulcers.
H2-RECEPTOR H2-RECEPTOR ANTAGONISTSANTAGONISTS
Drug interactions:Drug interactions: Cimetidine inhibits metabolism of ethyl Cimetidine inhibits metabolism of ethyl
alcohol in the stomach resulting in higher alcohol in the stomach resulting in higher blood alcohol levels.blood alcohol levels.
Adverse reactions:Adverse reactions: Headache, diarrhea, and rashHeadache, diarrhea, and rash
Prevention of ulcers in NSAID Prevention of ulcers in NSAID UsersUsers
16.3
5.2 5.7
0.5
0
10
20
30
Ulc
er R
ecur
renc
e (%
)
Gastric Ulcer Duodenal Ulcer
Ranitidine 150 mg bidn = 215Omeprazole 20 mg qdn = 210
*
** p< 0.05
Antimuscarinic drugsAntimuscarinic drugsPirenzepine, telenzepinePirenzepine, telenzepine
• • M1 receptors antagonists :M1 receptors antagonists :Pirenzepine, telenzepine (a more potent analog), reduce gastric acid secretion with fewer adverse effects than atropine and others.
• • Contraindicated in some gastric ulcers as theyContraindicated in some gastric ulcers as they may slow gastric emptying and prolong themay slow gastric emptying and prolong the exposure of the ulcer bed to acid.exposure of the ulcer bed to acid.
ANTACIDS
Over-the-counter medications that include: Magnesium hydroxide and aluminum
hydroxide Sodium bicarbonate Calcium carbonate Simethicone
ANTACIDSANTACIDS
Pharmacokinetics:Pharmacokinetics: Work locally in the stomach by neutralizing Work locally in the stomach by neutralizing
gastric acid.gastric acid. Distributed throughout the GI tract; eliminated Distributed throughout the GI tract; eliminated
primarily in the feces.primarily in the feces.
Pharmacodynamics:Pharmacodynamics: Reduce the total amount of acid in the GI tract.Reduce the total amount of acid in the GI tract.
ANTACIDS
Pharmacotherapeutics: Prescribed to relieve pain and promote
healing in peptic ulcer disease. Also used to relieve symptoms of acid
indigestion, heart-burn, dyspepsia, or GERD. Also used to prevent stress ulcers, GI
bleeding, and hyperphosphatemia in kidney failure.
ANTACIDSANTACIDS
Drug interactions: All antacids can interfere with the All antacids can interfere with the
absorption of oral drugs given at the same absorption of oral drugs given at the same time.time.
Adverse reactions: Diarrhea, constipation, electrolyte Diarrhea, constipation, electrolyte
imbalances imbalances
Antacids
Mucosal Protective AgentsMucosal Protective Agents
Tripotassium dicitratobismuthate is a bismuth chelate effective in healing gastric & duodenal ulcers.
Low absorption has been reported
Colloidal Bismuth Subcitrate (CBS) is used in the management of gastric and duodenal ulcers, and in combination with two antibacterials for the eradication of H. pylori.
Bismuth Compounds:
Sucralfate
• It is a complex of aluminium hydroxide and sulphated sucrose but has minimal antacid properties.
• May act by protecting the mucosa from acid-pepsin attack in gastric and duodenal ulcers.
OTHER PEPTIC ULCER OTHER PEPTIC ULCER DRUGSDRUGS
MisoprostolMisoprostol (Cytotec) - Protects (Cytotec) - Protects against peptic ulcers caused by against peptic ulcers caused by NSAIDs by reducing the secretion of NSAIDs by reducing the secretion of gastric acid and by boosting the gastric acid and by boosting the production of gastric mucus.production of gastric mucus.
NSAID Use in the Arthritis NSAID Use in the Arthritis Patient with a History of Patient with a History of
Bleeding UlcerBleeding Ulcer
Treating H. pylori is likely to be of benefit if there was a duodenal ulcer;
test and treat for H. pylori is recommended. Use COX2 Inhibitor Add a PPI or Misoprostol