drug-induced gastrointestinal diseases (adrs)
DESCRIPTION
Drug-Induced Diseases/Adverse Drug Reactions on the Gastrointestinal Tract, with references included.TRANSCRIPT
![Page 1: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/1.jpg)
GASTROiNTESTINAL DISEASES
ADVERSE DRUG REACTIONS
![Page 2: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/2.jpg)
OUTLINE
I. DysgeusiaII. Upper GIT UlcerationIII. Dyspepsia IV. GIT HemorrhageV. Antibiotic-induced diarrhea and
antibiotic-associated (pseudomembranous) colitis (AAC)
![Page 3: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/3.jpg)
I. DYSGEUSIA
![Page 4: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/4.jpg)
DYSGEUSIA
• Distortion in the perception of a correct taste
• Altered taste sensation• It may manifest as an unusual,
bitter, metallic taste or distaste for food
• Hypogeusia - blunting or decreased sense of taste
• Ageusia – total loss of taste
![Page 5: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/5.jpg)
Dysgeusia
• The mechanism of drug-related taste disturbance appears to involve:- interference with the chemical composition or flow of saliva- direct effects on taste receptor function or signal transduction
![Page 6: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/6.jpg)
Dysgeusia
• Changes in taste are a frequently reported side effect of a wide range of medications, including macrolide antibiotics, antifungals, ACE inhibitors.
![Page 7: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/7.jpg)
Medications known to cause Dysgeusia
• Captopril and Zofenopril (sulfhydryl compounds)Impaired or salty taste is common
complaint, common cause of taste disturbances
• Systemic GriseofulvinRenders particular foods tasteless,
with worsening symptoms corresponding to duration of drug administration
![Page 8: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/8.jpg)
Medications known to cause Dysgeusia
• Penicillamine Has been known to cause a partial or total loss of taste
• Lithium carbonate & Tetracycline–Saliva can have traces of the drug, giving rise to a metallic flavor in the mouth
![Page 9: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/9.jpg)
Medications known to cause Dysgeusia
• Metronidazole & Chlorhexidine have been found to interact with metal ions that associate with the cell membrane.
![Page 10: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/10.jpg)
Consequences• Poor compliance with medications• Nutritional deficiencies and weight loss
![Page 11: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/11.jpg)
Dysgeusia • For many drugs where taste disturbance is a side effect, it appears to be dose-related, and resolves within weeks of discontinuation of the offending agent.• Type of ADR: Augmented
![Page 12: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/12.jpg)
II. UPPER GASTROINTESTINAL ULCERATION
![Page 13: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/13.jpg)
UPPER GASTROINTESTINAL ULCERATION
• Ulcer – a break in the skin extending to all its layers, or in the mucous membrane lining the alimentary tract, that fails to heal and is often accompanied by inflammation.
• Parts included in upper GI–Esophagus–Stomach –Duodenum
The Bantam Medical Dictionary
![Page 14: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/14.jpg)
UPPER GASTROINTESTINAL ULCERATION
• Drug-induced ulceration of the upper GIT can be a significant problem resulting in perforation, obstruction or bleeding.
![Page 15: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/15.jpg)
Medications causing upper GIT ulceration
• Aspirin and Non-steroidal anti-inflammatory agents –most frequent causative agents
• Wax matrix potassium chloride preparations
• Corticosteroids• Doxycycline • Ferrous sulfate• Bisphosphonates
![Page 16: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/16.jpg)
Mechanism • Aspirin and Non-steroidal
anti-inflammatory agents–Inhibit gastric mucosal prostaglandin synthesis by inhibiting the COX enzyme system altering prostaglandin-associated GI defense mechanisms
![Page 17: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/17.jpg)
Mechanism• Aspirin and Non-steroidal anti-
inflammatory agents –Both COX-1(produces prostaglandins
known to protect the GI mucosa) and COX-2 (primarily present at sites of inflammation) enzymes are inhibited.
![Page 18: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/18.jpg)
Mechanism• Aspirin and Non-steroidal anti-
inflammatory agents – inhibition of COX-2 by traditional
NSAIDs accounts for the anti-inflammatory effect of the drugs while the inhibition of COX-1 can lead to NSAID toxicity and associated side effects
–Type of ADR: Continuous
![Page 19: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/19.jpg)
Cox-1 and Cox-2 Activity of Selected NSAIDs
NSAID COX-1 COX-2
In Vitro Inhibitory Activity
Ketorolac +++++ +
Indomethacin ++++ +
Naproxen +++ +
Ibuprofen +++ +
Piroxicam ++ ++
Sulindac ++ ++
Diclofenac ++ +++
Celecoxib + +++
Meloxicam + +++
Etodolac + +++
+ Minimal Activity; ++ Some activity; +++ Significant activity; ++++ High activity; +++++ Very High activity
![Page 20: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/20.jpg)
Mechanism• Bisphosphonates–Only nitrogen-containing
bisphosphonates (i.e. Alendronate, risedronate & pamidronate) have been implicated–Several mechanisms have been
suggested, but the most probable mechanism is direct topical irritation–Ulcers are not seen during IV
administration
![Page 21: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/21.jpg)
Mechanism
• Bisphosphonates–Prolonged contact of the tablet with the esophageal tissue may occur when the patient takes a tablet in the supine position or without sufficient water.–Type of ADR: Augmented
![Page 22: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/22.jpg)
Mechanism
• Potassium Chloride preparations–May induce GI damage caused by direct irritation from the high concentrations of KCl in the GI mucosa–Type of ADR: Augmented
![Page 23: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/23.jpg)
Mechanism
• Doxycycline and Ferrous Sulfate • Drug-induced ulceration
associated with these drugs may be the result of a low pH when the drug is dissolved, causing erosions and inflammation of the esophageal mucosa
• Type of ADR: Augmented
![Page 24: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/24.jpg)
Drugs That May Cause Upper GI Ulceration
Drug Most common site of ulceration
Incidence
ASA Stomach 10-15
Bisphosphonates
Esophagus 0.2-0.4
Corticosteroids
Stomach 0.4
COX-1 NSAIDs
Stomach 10-15
COX-2 NSAIDs
Stomach 5-8
Doxycycline Esophagus Unknown
Ferrous Sulfate
Esophagus, Stomach
Unknown
KCl Esophagus, Stomach
8-19
Drug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
![Page 25: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/25.jpg)
Mechanisms of Drug-Induced Upper GI Ulceration
Drug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
Medication Mechanism
ASA COX-1 inhibition
NSAIDs COX-1 inhibition
KCl Direct irritant
Corticosteroids Controversial
Doxycycline Direct irritant
Ferrous Sulfate Direct irritant
Bisphosphonates Direct irritant
![Page 26: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/26.jpg)
II. Treatment options for Management of Drug-Induced
Upper GI Ulceration
Drug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
Medication Action
All Discontinue medication if possible
ASA, NSAIDs Eradicate HPHeal ulcer with PPI, misoprostolConsider maintenance for prevention of recurrence with PPI, misoprostol, or an NSAID with a lower risk of ulceration
Bisphosphonates, KCl, Tetracyclines
Consider other medications, administer medication with sufficient water
Bisphosphonates
Avoid taking medication with mealsAvoid a recumbent position for at least 1 hour after medication, medication with sufficient water
![Page 27: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/27.jpg)
III.DYSPEPSIA
![Page 28: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/28.jpg)
DYSPEPSIA• Indigestion (dyspepsia) is a vague
feeling of discomfort in the upper belly or abdomen during or right after eating. This may include:–A feeling of heat, burning, or pain in
the area between the navel and the lower part of the breastbone–A feeling of fullness that is bothersome
and occurs soon after the meal begins or when it is over
![Page 29: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/29.jpg)
Dyspepsia• It is important to recognize that
dyspepsia/uninvestigated dyspepsia relates to a symptom complex rather than a true diagnosis or single medical disease/condition. In fact, dyspepsia may be indicative of a variety of possible conditions that may be the cause of the patient's dyspeptic symptoms.
![Page 30: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/30.jpg)
Medications causing Dyspepsia
• Non-steroidal anti-inflammatory drugs (NSAID) e.g. aspirin, ibuprofen, naproxen, diclofenac.
• Corticosteroids e.g. prednisolone, prednisone.
• Estrogens• Bisphosphonates • Certain antibiotics (Rifampin)
![Page 31: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/31.jpg)
Drug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
DYSPEPSIA & DIU
• The presence of dyspepsia in a patient taking medications that produce DIU does not always indicate that an ulcer is present but should raise suspicion.
![Page 32: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/32.jpg)
IV. GIT HEMORRHAGE
![Page 33: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/33.jpg)
GIT HEMORRHAGE• Gastrointestinal (GI) bleeding refers to
any bleeding that starts in the gastrointestinal tract.
• Bleeding may come from any site along the GI tract, but is often divided into:–Upper GI bleeding: The upper GI tract
includes the esophagus, stomach, and first part of the small intestine.–Lower GI bleeding: The lower GI tract
includes much of the small intestine, large intestine or bowels, rectum, and anus.
![Page 34: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/34.jpg)
Medications causing GIT Hemorrhage
• NSAIDs–Ketorolac has the highest COX-1 activity and has the highest risk of GI bleeding of all the NSAIDs–Indomethacin & Ibuprofen also have significant proportion of COX-1 activity compared to COX-2–Type of ADR: Continuous
![Page 35: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/35.jpg)
Medications causing GIT Hemorrhage
• Corticosteroids–Have long been implicated as a
cause of GI hemorrhage but the exact mechanism is not clear.–However, it has been proposed that
these agents impair mucosal healing through reduction of epithelial regeneration.–Research suggests that the
incidence is small
![Page 36: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/36.jpg)
V. ANTIBIOTIC-INDUCED DIARRHEA AND
ANTIBIOTIC-ASSOCIATED
(PSEUDOMEMBRANOUS) COLITIS
![Page 37: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/37.jpg)
ANTIBIOTIC-INDUCED DIARRHEA AND ANTIBIOTIC-ASSOCIATED
(PSEUDOMEMBRANOUS) COLITIS
• Patients with either of these diseases present with profuse diarrhea (rarely with blood) consisting of mucoid, greenish, foul-smelling, watery stools; abdominal pain; low-grade fever.
![Page 38: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/38.jpg)
DIARRHEA
• Diarrhea – increased frequency of bowel movements (≥3/d), decreased stool consistency, and/or increased stool weight (>200g/d)
![Page 39: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/39.jpg)
DIARRHEA• Arises from two basic
mechanisms:–Decreased absorption of water and electrolytes–Increased active secretion of water and electrolytes in GIT
• Result in a net secretion that causes an increase in stool volume & weight
![Page 40: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/40.jpg)
DIARRHEA• Drugs increasing active
secretion alter intestinal motility–Drug-altered intestinal motility is attributed to 3 different mechanisms:1. Reduction of contact time in the
small intestine2. Premature emptying of the colon3. Bacterial overgrowth
![Page 41: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/41.jpg)
Antibiotic-induced diarrhea • Drug-induced diarrhea
associated with chemotherapeutic agents is well recognized, particularly with Fluorouracil (10-80%) and Irinotecan (50-80%).
Drug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
![Page 42: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/42.jpg)
Mechanism • Antineoplastics increase active
secretion and destroy the intestinal mucosa of the small & large intestines, causing exudative mechanisms.
• Additionally, they may affect the absorptive, secretory, or motility functions of the gut
• Type of ADR: Type ADrug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
![Page 43: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/43.jpg)
Other Antibiotics causing DIARRHEA
• Antibiotics–Clindamycin –Macrolides (erythromycin)–Penicillins –Quinolones –Sulfonamides –Tetracycline
![Page 44: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/44.jpg)
ANTIBIOTIC-ASSOCIATED (PSEUDOMEMBRANOUS)
COLITIS• Pseudomembranous colitis is
infection of the large intestine (colon) with an overgrowth of Clostridium difficile bacteria.• a cause of antibiotic-associated
diarrhea (AAD), • It is an inflammation of
the colon
![Page 45: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/45.jpg)
Mechanism• The mechanism for diarrhea resulting
from pseudomembranous colitis is bacterial proliferation. (Clostridium difficile)
• The bacteria secretes: enterotoxin A – adheres to the brush-
border membrane of enterocytes, inducing lesions and an inflammatory response, and;
cytotoxin B – may also cause GI mucosal damage
![Page 46: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/46.jpg)
Mechanism • The use of clindamycin, broad-
spectrum antibiotics such as cephalosporin, or any penicillin-based antibiotic such as amoxicillin causes the normal bacterial flora of the bowel to be altered. In particular, when the antibiotic kills off other competing bacteria in the intestine, any bacteria remaining will have less competition for space and nutrients.
![Page 47: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/47.jpg)
Other Antibiotics that cause AAC
• Ciprofloxacin (<1%)• Chloramphenicol • Cloxacillin • Erythromycin • Gentamicin • Rifampin (1-10%)
![Page 48: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/48.jpg)
Management of AAD & AACManagement of antibiotic-induced diarrhea
Discontinue offending drug/change to another drug if possible
Lower (adjust dose) if possible
Implement low residual diet
Provide rehydration and maintenance of fluid electrolytes
Clostridium difficile must be eliminated as the cause of diarrhea before implementation of antiperistaltic drugs
For Clostridium difficile and pseudomembranous colitis, initiate metronidazole (first line) or oral vancomycin
![Page 49: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/49.jpg)
References:
• Remington: The Science & Practice of Pharmacy, 19th Edition• Drug-Induced Diseases: Prevention, Detection and
Managemet; Drug-Induced Diseases by Tisdale, J.E.; Miller, D.A.
• McGraw-Hill Drug Handbook; Schull, P.D.• http://www.nlm.nih.gov/medlineplus/ency/article/
003133.htm• http://www.dwp.gov.uk/publications/specialist-guides/
medical-conditions/a-z-of-medical-conditions/dyspeptic-disorders/
• http://www.nlm.nih.gov/medlineplus/ency/article/003260.htm
![Page 50: Drug-Induced Gastrointestinal Diseases (ADRs)](https://reader033.vdocuments.net/reader033/viewer/2022061305/5499d97db479597e6a8b45a2/html5/thumbnails/50.jpg)
Thank You for Being
Attentive!!!