6. Gastric Mucosal Barrier
•Surface mucosa cells in the pyloric region secrete a thick, alkaline-rich mucus that protects the
epithelium of the stomach and duodenum from harsh acid conditions of the lumen.
•This is known as the gastric mucosal barrier.
•These cells are stimulated by mechanical and chemical irritation and parasympathetic inputs.
•This protective mucus barrier can be damaged by bacterial and viral infection, certain drugs,
and aspirin.
11. Serotonin (5-
Hydroxytryptamine)
• Key neurotransmitter in the intestine
• Present in abundance within the gut
• Most is stored in enterochromaffin cell granules
• Released by many stimuli - most potently by mucosal stroking
• Serotonin stimulates enteric nerves to initiate secretion and
propulsive motility
14. Gastroesophageal Reflux Disease (GERD)
-Backflow of stomach acid into the esophagus
-Esophagus is not equipped to handle stomach acid => scaring
-Usual symptom is heartburn, an uncomfortable burning sensation behind the
breastbone (MI often mistaken for GERD !)
-More severe symptoms: difficulty swallowing, chest pain
-Reflux into the throat can cause sore throat
-Complications include esophageal erosions, esophageal ulcer and narrowing of the
esophagus (esophageal stricture)
-In some patients (~10%), the normal esophageal lining or epithelium may be
replaced with abnormal (Barrett's) epithelium. This condition (Barrett's esophagus)
has been linked to cancer of the esophagus.
17. Peptic Ulcer Disease
Benign PUD: Normal gastric acid pro-
duction however the mucosal barrier is weak.
Malignant PUD: Excessive secretion of gastric
Acid that overwhelms the mucosal barrier.
22. Treatment of peptic ulcer
Antimicrobial agents (tetracycline, bismuth subsalicylate, and metronidazole) to eradicate H. pylori
infection
Misoprostol (a prostaglandin analog) to inhibit gastric acid secretion and increase carbonate and mucus
production, to protect the stomach lining
Antacids to neutralize acid gastric contents by elevating the gastric pH, thus protecting the mucosa and
relieving pain
Avoidance of caffeine and alcohol to avoid stimulation of gastric acid secretion
Anticholinergic drugs to inhibit the effect of the vagal nerve on acid-secreting cells
H2 blockers to reduce acid secretion
Sucralfate, mucosal protectant to form an acid-impermeable membrane that adheres to the mucous
membrane and also accelerates mucus production
Dietary therapy with small infrequent meals and avoidance of eating before bedtime to neutralize gastric
contents
Insertion of a nasogastric tube (in instances of gastrointestinal bleeding) for gastric decompression and
rest, and also to permit iced saline lavage that may also contain norepinephrine
Gastroscopy to allow visualization of the bleeding site and coagulation by laser or cautery to control
bleeding
Surgery to repair perforation or treat unresponsiveness to conservative treatment, and suspected
malignancy.
23. H/K
P
H/K
P
histamine-
secreting cell
Acetylcholine
neural input
neurocrine
Gastrin
hormonal input
endocrine
PARIETAL cell
paracrine
release of
histamine
histamine
receptor
ACh
receptor
gastrin
receptor
transduction-
activation events
HCl
secretion
Combined neurocrine, endocrine and paracrine
events in the activation of gastric HCl secretion
ECL cell
G cell
ECL cell =
enterochromaffin-like cell
G cell =
gastrin-secreting cell
HOW IT WORKS AT THE RECEPTOR LEVEL
24. H/K
P
H/K
P
histamine-
secreting cell
Acetylcholine
neural input
neurocrine
Gastrin
hormonal input
endocrine
PARIETAL cell
paracrine
release of
histamine
histamine
receptor
ACh
receptor
gastrin
receptor
transduction-
activation events
HCl
secretion
Combined neurocrine, endocrine and paracrine
events in the activation of gastric HCl secretion
ECL cell
G cell
ECL cell =
enterochromaffin-like cell
G cell =
gastrin-secreting cell
HOW IT WORKS AT THE RECEPTOR
LEVEL
H-2 receptor blockers
H/K ATPase pump inhibitors
Tagamet
Zantac
Pepcid
Prilosec
Nexium
Aciphex
25. RECOMMENDATIONS OF HELICOBACTER
PYLORI ERADICATION
omeprazole 20mg
amoxicillin 1000mg
clarithromycin 500mg, all twice daily for 7 days.
An alternative regimen with a similar eradication
rate of around 90% is:
omeprazole 20mg
clarithromycin 250mg
metronidazole 400mg, again all twice daily for 7
days.
26. A typical quadruple therapy
a PPI twice a day
bismuth 120 mg four times a day
metronidazole 400 mg three times a day
oxytetracycline 500 mg four times a day, all for 7 days.
27. Antacids
Systemic Antacid: Sodium Bicarbonate
Nonsystemic Antacid:
Aluminum Hydroxide + Magnesium Hydroxide Combinations (Maalox and Mylanta)
Contraindicated in patients with impaired renal function
Magnesium may cause diarrhea
Calcium Carbonate (Tums)
Calcium may cause constipation
28.
29.
30.
31.
32.
33.
34.
35.
36.
37. ANTACID NEUTRALIZING CAPACITY (ANC)
Amount of 1N HCl(meq) brought to pH 3.5 by an antacid solution within
15 min.
FDA requires a Min=5 meq/dose
As the ANC number increases the neutralizing capacity of an antacid
increases.
Maalox TC=28
Mylanta DS=23
Tums EX=15
38. Histamine H2 Receptor Blockers
Cimetidine
• Inhibit secretion of gastric acid through competitive inhibition of Histamine H2
receptors
• Prevention & tx of PUD, Esophagitis, GI bleeding, stress ulcers, and Zollinger-
Ellison Syndrome
• May alter the effects of other drugs through interactions with CYP450 (especially
cimetidine)
• Very few side effects (except for cimetidine - inhibits metabolism of estrogen)
• Suppresses 24 hour gastric secretion by 70%
Famotidine Ranitidine Nizatidine
39.
40.
41. Proton Pump Inhibitors
• Strong inhibitors of gastric acid secretion through irreversible inhibition of proton pump,
preventing “pumping” or release of gastric acid (24 hr action)
• Indicated in PUD, Gastritis, GERD, & Zollinger-Ellison syndrome
• Faster relief and healing than H2 receptor blockers
• Decreases acid secretion by up to 95% for up to 48 hours
• 4-8 week course of treatment
Omeprazole
Esomeprazole
Lansoprazole
Pantoprazole
Rebeprazole
42.
43.
44.
45.
46.
47. Prostaglandins
Misoprostol
• Misoprostol
• PGE1 analog
• Stimulates Gi pathway, leading to decrease in gastric
acid release
• For treatment of NSAID induced injury
• Side effects include diarrhea, pain, and cramps (30%)
• Do not give to women of childbearing years unless a reliable
method of birth control can be DOCUMENTED
• Can cause birth defects, and premature birth
48.
49. Anticholinergics
• Pirenzipine
• Muscarinic M1 acetylcholine receptor antagonist
• Blocks gastric acid secretions
• About as effective as H2 blockers
• Rarely used, primarily as adjunct therapy
• Anticholinergic side effects (anorexia, blurry vision,
constipation, dry mouth, sedation)
52. Mucosal Protective Agents
• Sucralfate (carafate)
• Can be used to prevent & treat PUD
• It requires an acid Ph to activate
• Forms sticky polymer in acidic environment and adheres
to the ulcer site, forming a barrier
• May bind with other drugs and interfere with absorption
• Give approximately 2 hours before or after other drugs
• Take on an empty stomach before meals
• Chelated Bismuth
• Protects the ulcer crater and allows healing
• Some activity against H. pylori
• Should not be used repeatedly or for more than
2 months at a time
• Can cause black stools, constipation
53.
54.
55. Helicobacter pylori
H. pylori are bacteria able to attach to the epithelial cells of the stomach
and duodenum which stops them from being washed out of the stomach.
Once attached, the bacteria start to cause damage to the cells by secreting
degradative enzymes, toxins and initiating a self-destructive immune
response.
www.science.org.au/ nobel/2005/images/invasion.jpg
56.
57.
58. Anti-H.pylori Therapy
Triple Therapy - 7 day treatment - Effective 80-85%
Proton pump inhibitor + amoxicillin/tetracycline + metronidazone/clarithomycin
Quadruple Therapy - 3 day treatment, as efficacious as triple therapy
- Add Bismuth to triple therapy
• >85% PUD caused by H. pylori
• Antibiotic Ulcer Therapy - Used in Combinations
• Bismuth - Disrupts bacterial cell wall
• Clarithromycin - Inhibits protein systhesis
• Amoxicillin - Disrupts cell wall
• Tetracycline - Inhibits protein synthesis
• Metronidazone - Used often due to bacterial resistance to
amoxicillin and tetracycline, or due to intolerance
59. Ulcers associated with NSAIDs
omeprazole 20mg daily is preferable to ranitidine
150mg twice daily as the respective rates of
healing are 80% and 63%.
H2RAs are slow to heal the ulcers if the offending
drug is not stopped and so, under these
conditions, a PPI is preferred.
H pylori eradication is no more effective than
omeprazole alone to heal ulcers, but if the infection
is present, then eradication will reduce the rate of
relapse.
H pylori is not associated with an increased risk of
ulcer with NSAIDs in the elderly but there is an
increased risk of bleeding.
60.
61. Inflammatory Bowel Disease
• Ulcerative colitis
• Diffuse mucosal inflammation limited to the
colon
• Bloody diarrhea, colicky pain,
urgency,tenesmus
• Crohn’s Disease
• Patchy transmural inflammation
• May affect any part of GI tract
• Abdominal pain, diarrhea, weight loss,
intestinal obstruction
62. Inflammatory Bowel Disease
Therapeutics:
• Aminosalicylates - for mild symptoms
• Corticosteroids - for moderate symptoms
• Thiopurines - for active and chronic symptoms
• Methotrexate - for active and chronic symptoms
• Cyclosporin - for active and chronic symptoms refractory to
corticorsteroids- (significant side effects)
• Infliximab - antibody infusion
Treatment = Resolve acute episodes and prolong remission
63. Aminosalicylates
Sulfasalazine (5-aminosalicylic acid and sulfapyridine as carrier substance)
Mesalazine (5-ASA), eg Asacol, Pentasa
Balsalazide (prodrug of 5-ASA)
Olsalazine (5-ASA dimer cleaves in colon)
MOA: Remove toxic free radicals; Remission in 3-6 month
Oral, rectal preparation
Use
Maintaining remission
Active disease
May reduce risk of colorectal cancer
Adverse effects
10-45%
Nausea, headache, epigastric pain, diarrhoea, hypersensitivity, pancreatitis,
blood disorders, lung disorders, myo/pericarditis
Caution in renal impairment, pregnancy, breast feeding
65. Corticosteroids
Anti-inflammatory agents for moderate to severe relapses
Inhibition of inflammatory pathways (↓IL transcription,
suppression of arachidonic acid metabolism, lymphocyte
apoptosis)
Side effects
• Acne, moon face
• Sleep, mode disturbance
• Dyspepsia, glucose intolerance
• Cataracts, osteoporosis, myopathy…
66. Are apolar steroid hormones with broad biological effects. Able to penetrate
the cell membrane and bind glucocorticoid receptors (GRs) in the
cytosol. The newly formed receptor-ligand complex translocates to the
nucleus where it binds glucocorticoid response elements (GRE) in the
promoter region of different target genes.
Transactivation Up-regulating the expression of anti-inflammatory
cytokines.
Transrepression Preventing translocation of pro-inflammatory
transcription factors and cytokines repressing their expression (Ex. NF-κB,
AP-1, IL-1β, IL-2, IL-4, IL-8, TNF-α etc. ).
Corticosteroids I
Inhibiting leukocyte adhesion, migration, chemotaxis,
phagocytosis and cytokine secretion
67. Mechanism of action
Decrease production of inflammatory mediators as
prostaglandins, leukotrienes, histamine, PAF, bradykinin.
Decrease production of cytokines IL-1, IL-2, interferon,
TNF.
Stabilize lysosomal membranes.
Decrease generation of IgG, nitric oxide and histamine.
Inhibit antigen processing by macrophages.
Suppress T-cell helper function
decrease T lymphocyte proliferation.
68. Very important anti-inflammatory mechanisms of corticosteroids are the inhibition
of phospholipase A2 directly and indirectly (by synthesizing lipocortin-1; a PA2
inhibitor) and, the inhibition of cyclooxygenases (like NSAIDs).
Inhibition of the arachidonic acid pathway decreases the pro-
inflammation mediators prostaglandins (PGE2 for example) and
leukotrienes (LTs).
CORTICOSTEROIDS
In addition as does endogenous cortisol:
↓ proliferation and differentiation of mast
cells
↓ platelet activating factor
↓ NO production
↓ number of circulating T cells
↓ interleukin production
↓ IFN-γ production
69. Kinetics
Can be given orally or parenterally.
Dynamics
1. Suppression of response to infection
2. anti-inflammatory and immunosuppresant.
3. Metabolic effects.
70. Corticosteroids
reliable effects & reliable side effects
- Central obesity
- Growth reatardation in childhood
- Susceptibility to infections
- Increased risk of thrombosis, coronary
heart disease
- Lengthened wound healing, ulcers
- Gastric ulcer
- Osteoporosis, aseptic bone necrosis
- Hypertension
- Hirsutism (excessive hairiness), atrophy of skin
- Glaucoma, cataract
Strict dose limitations, alternating dosage, gradual dose decreasing!
Local administration: fewer (not as significant) side effects!
71. Thiopurines
Azathioprine, mercaptopurine
Inhibit ribonucleotide synthesis
Inducing T cell apoptosis by modulating cell signalling
Azathioprine metabolised to mercaptopurine and 6-thioguanine nucleotides
Use
• Active and chronic disease
• Steroid sparing
Side effects
• Leucopaenia (myelotoxic)
• Monitor for signs of infection, sore throat
• Flu like symptoms after 2 to 3 weeks, liver, pancreas toxicity
72. AZATHIOPRINE
CHEMISTRY:
Derivative of mercaptopurine.
Prodrug.
Cleaved to 6-mercaptopurine then to
6-mercaptopurine nucleotide, thioinosinic
acid (nucleotide analog).
Inhibits de novo synthesis of purines required
for lymphocytes proliferation.
Prevents clonal expansion of both B and T
lymphocytes.
73.
74. Pharmacokinetics
orally or intravenously.
Widely distributed but does not cross BBB.
Metabolized in the liver to 6-mercaptopurine
or to thiouric acid (inactive metabolite) by
xanthine oxidase.
excreted primarily in urine.
Drug Interactions:
Co-administration of allopurinol with
azathioprine may lead to toxicity due to
inhibition of xanthine oxidase by allopurinol.
75. Cyclosporin
Inhibitor of calcineurin
Chemistry
Cyclosporine is a fungal polypeptide composed of 11 amino acids.
Use
Active and chronic disease
Steroid sparing
Bridging therapy
Mechanism of action:
Acts by blocking activation of T cells by inhibiting interleukin-2 production
(IL-2).
Decreases proliferation and differentiation of T cells.
76. Cyclosporine binds to cyclophilin
(immunophilin) intracellular protein
receptors .
Cyclosporine- immunophilin complex
inhibits calcineurin, a phosphatase necessary
for dephosphorylation of transcription factor
(NFATc) required for interleukins synthesis
(IL-2).
NFATc (Nuclear Fcator of Activated Tcells).
Suppresses cell-mediated immunity.
77.
78. Pharmacokinetics:
Can be given orally or i.v. infusion
orally (25 or 100 mg) soft gelatin capsules, microemulsion.
Orally, it is slowly and incompletely absorbed.
Peak levels is reached after 1– 4 hours, elimination half life
24 h.
Oral absorption is delayed by fatty meal (gelatin capsule
formulation)
50 – 60% of cyclosporine accumulates in blood
(erythrocytes – lymphocytes).
metabolized by CYT-P450 system (CYP3A4).
excreted mainly through bile into faeces, about 6% is
excreted in urine.
Microemulsion
( has higher bioavailability-is not affected by food).
79. Adverse Effects (Dose-dependent)
Therapeutic monitoring is essential (Blood pressure, FBC, renal
function)
Nephrotoxicity
(increased by NSAIDs and aminoglycosides).
Liver dysfunction.
Hypertension, hyperkalemia.
(K-sparing diuretics should not be used).
Hyperglycemia.
Viral infections (Herpes - cytomegalovirus).
Lymphoma (Predispose recipients to cancer).
Hirsutism
Neurotoxicity (tremor).
Gum hyperplasia.
Anaphylaxis after I.V.
80. Drug Interactions
Clearance of cyclosporine is enhanced by co-administration of
CYT p 450 inducers (Phenobarbitone, Phenytoin & Rifampin )
rejection of transplant.
Clearance of cyclosporine is decreased when it is co-
administered with erythromycin or Ketoconazole, Grapefruit
juice cyclosporine toxicity.
81. Methotrexate
Inhibits dihydrofolate reductase
Probably inhibition of cytokine and eicosanoid synthesis
a folic acid antagonist
Orally, parenterally (I.V., I.M).
Excreted in urine.
Inhibits dihydrofolate reductase required for folic acid activation
(tetrahydrofolic)
Inhibition of DNA, RNA &protein synthesis
Iterferes with T cell replication.
Use
Relapsing or active CD refractory or intolerant to AZA or thiopurine
85. Infliximab
Anti TNF-α monoclonal antibody
Potent anti inflammatory effects
Use
Fistulizing CD
Severe active CD refractory/intolerant of steroids or
immunosuppression
iv infusion
Side effects
Infusion reactions
Sepsis
Reactivation of Tb, increased risk of Tb
86.
87.
88. Chronic pancreatitis
There is no cure for chronic pancreatitis. Once the pancreas is
damaged, then it is not able to return to normal function and there is
always the potential for further attacks. Treatment is, therefore,
directed towards preventing attacks, controlling the pain and treating
the complications.
Preventing symptoms worsening
Patients with chronic pancreatitis should avoid alcohol altogether. If
the pancreatitis is due to excess alcohol consumption, then this is
essential. If it is due to other causes, then it seems sensible to avoid
a substance which is capable of damaging the pancreas.
If an underlying cause has been identified then this should be
treated. Disorders of calcium metabolism and of fat metabolism will
be treated appropriately. recommend removal of the gall bladder if
pancreatitis is thought to be caused by gall stones.
89. Chronic pancreatitis
Preventing attacks
The long-standing principle has been to try and rest the
pancreas. This involves giving pancreatic supplements such as
Creon (which contain pancreatic enzymes in high
concentration) together withdrugs which reduce secretion
drugs which reduce acid secretion by the stomach. Patients
should also follow a low-fat diet.
These measures reduce the presence of fat in the duodenum,
reduce acid in the duodenum and reduce the need for
pancreatic enzyme secretion. These measures are very
successful in about a third of patients, moderately successful in
a third and unhelpful in a third.
the use of antioxidants in the treatment of chronic pancreatitis.
These antioxidants include selenium and vitamin C.
90. Chronic pancreatitis
Control of pain
This is a very important aspect of the treatment of chronic
pancreatitis. Pancreatic pain varies in severity from mild
(controllable with simple analgesics such as paracetamol to severe
(requiring morphine-like drugs for control).
In addition to the preventive measures listed above, the basic
principle is to use the drug lowest down the analgesic ladder which
controls the pain. Since the pain is often worse at night and since
both body and mind are at their lowest ebb in the early hours of the
morning, the lowest rung of the analgesic ladder may be pethidine
or morphine (eg MST.) Since the pain is chronic and severe, there is
a fine line between adequate analgesia and addiction.
91. Constipation
•Usually effectively treated with dietary modification.
•Only if this fails should laxatives be used.
•The #1 cause of constipation in laxative abuse!
Therapy:
1. Bulking agents
2. Osmotic laxatives
3. Stimulant drugs
4. Stool softners
93. Indications for Use
1. To relieve constipation in pregnant women, elderly clients whose
abdominal and perineal muscles have become weak and atrophied,
children with megacolon, and clients receiving drugs that decrease
intestinal motility (eg, opioid analgesics, drugs with anticholinergic
effects)
2. To prevent straining at stool in clients with coronary artery disease
(eg, postmyocardial infarction), hypertension, cerebrovascular disease,
and hemorrhoids and other rectal conditions
3. To empty the bowel in preparation for bowel surgery or diagnostic
procedures (eg, colonoscopy, barium enema)
4. To accelerate elimination of potentially toxic substances from the GI
tract (eg, orally ingested drugs or toxic compounds)
5. To prevent absorption of intestinal ammonia in clients with hepatic
encephalopathy
6. To obtain a stool specimen for parasitologic examination
7. To accelerate excretion of parasites after anthelmintic drugs have
been administered
8. To reduce serum cholesterol levels (psyllium products)
94. Bulk Laxatives
Psyllium
Bran
Methylcellulose
•Insoluble and non-absorbable
•Non digestible
•Must be taken with lots of water!
(or it will make constipation worse)
-Increase in bowel content volume triggers stretch receptors in the intestinal wall
-Causes reflex contraction (peristalsis) that propels the bowel content forward
95.
96. Saline and Osmotic Laxatives
•Nondigestible sugars and alcohols
•Lactulose (broken down by bacteria to acetic and lactic acid, which
causes the osmotic effect)
•Salts
•Milk of Magnesia (Mg(OH)2)
•Epsom Salt (MgSO4)
•Glauber’s Salt (Na2SO4)
•Sodium Phosphates (used as enema)
•Sodium Citrate (used as enema)
•Polyethylene glycol
-Effective in 1-3 hours
-Used to purge intestine (e.g. surgery, poisoning)
-Fluid is drawn into the bowel by osmotic force, increasing volume and triggering peristalsis
99. Irratant/Stimulant Laxatives-Cathartics
Castor Oil - From the Castor Bean
Senna - Plant derivative
Bisacodyl
Lubiprostone -PGE1 derivative that stimulates chloride channels,
producing chloride rich secretions
-Increases intestinal motility
-Irritate the GI mucosa and pull water into the lumen
-Indicated for severe constipation where more rapid effect is required (6-8 hours)
Bisacodyl Senna Lubiprostone
100.
101. Laxative Abuse
•Most common cause of constipation!
•Longer interval needed to refill colon is misinterpreted as constipation
=> repeated use
•Enteral loss of water and salts causes release of aldosterone
=> stimulates reabsorption in intestine, but increases renal excretion of K+
=> double loss of K+ causes hypokalemia, which in turn reduces peristalsis.
=>This is then often misinterpreted as constipation
=> repeated laxative use
102.
103. Contraindications to Use
Laxatives and cathartics should not be used in the
presence of undiagnosed abdominal pain. The danger is that
the drugs may cause an inflamed organ (eg, the appendix) to
rupture and spill GI contents into the abdominal cavity with
subsequent peritonitis, a life-threatening condition. Oral
drugs also are contraindicated with intestinal obstruction and
fecal impaction.
105. Antidiarrheal drugs are indicated in the following circumstances:
1. Severe or prolonged diarrhea (>2 to 3 days), to prevent severe fluid
and electrolyte loss
2. Relatively severe diarrhea in young children and older adults. These
groups are less able to adapt to fluid and electrolyte losses.
3. In chronic inflammatory diseases of the bowel (ulcerative colitis and
Crohn’s disease), to allow a more nearly normal lifestyle
4. In ileostomies or surgical excision of portions of the ileum, to
decrease fluidity and volume of stool
5. HIV/AIDS-associated diarrhea
6. When specific causes of diarrhea have been determined
106. Diarrhea
•Caused by:
•Toxins
•Microorganims (shigella, salmonella, E.coli, campylobacter, clostridium difficile)
•Antibiotic associated colitis
•Indications for treatment
•>2-3 days
•Severe diarrhea in the elderly or small children
•Chronic inflammatory disease
•When the specific cause has been determined
107. Anti-Diarrheal Agents
•Anti-motility Agents
•Reduce peristalsis by stimulating opioid receptors in the bowel
•Allow time for more water to be absorbed by the gut
•Morphine
•Codeine
•Diphenoxylate
•Loperamide
40-50x more potent than morphine
Poor CNS penetration
Increases transit time and sphincter tone
Antisecretory against cholera toxin and some E.coli toxin
T½ 11 hours, dose: 4 mg followed by 2mg doses (16mg/d max)
Overdose: paralytic ileus, CNS depression
Caution in IBD (toxic megacolon)
•Contraindications for antidiarrheals
•Toxic Materials
•Microorganisms (salmonella, E.coli)
•Antibiotic associated
Loperamide
108. Contraindications to Use
Contraindications to the use of antidiarrheal
drugs include diarrhea caused by toxic materials,
microorganisms that penetrate intestinal mucosa
(eg, pathogenic E. coli, Salmonella, Shigella), or
antibiotic-associated colitis. In these
circumstances, antidiarrheal agents that slow
peristalsis may aggravate and prolong diarrhea.
Opiates (morphine, codeine) usually are
contraindicated in chronic diarrhea because of
possible opiate dependence. Difenoxin,
diphenoxylate, and loperamide are
contraindicated in children younger than 2 years
of age.
109. Clostridium Difficile
•The major cause of diarrhea and colitis in patients exposed to antibiotics (~20%).
•Fecal - oral route of transmission
•Three steps to infection
•Alteration of normal fecal flora
•Colonic colonization of C. difficile
•Growth and production of toxins
•Infection can lead to formation of colitis and toxic megacolon
•Pharmacological Treatment
• Discontinue offending antibiotic
• Metronidazole (contraindicated in patients with liver or renal impairment)
• Vancomycin (contraindicated in patients with renal impairment)
110. Antiflatulants
•Used to relieve the painful symptoms associated with gas
•Simethicone (a detergent)
•Alters elasticity of mucus-coated bubbles, causing them to break
•Large bubbles -> smaller bubbles, and less pain
•Used often, but limited data regarding effectiveness
Simethicone
112. Syrup of Ipecac Emetic
Prepared from the root of the ipecacuanha plant
Induces emesis
Side effects include drowsiness, diarrhea, and stomach ache
Acceptable for use when:
• There is no contraindication to the use of ipecac
• There is substantial risk of serious toxicity to the victim
• There is no alternative therapy available or effective to decrease
gastrointestinal absorption (e.g., activated charcoal)
• There will be a delay of greater than 1 hour before the patient will
arrive at an emergency medical facility and ipecac syrup can be
administered within 30-90 minutes of the ingestion
• Ipecac syrup administration will not adversely affect more definitive
treatment that might be provided at a hospital
113. Antiemetic Therapuetics
•Muscarinic M1 receptor antagonist
•Scopolamine
•Side Effects:
•Dry Mouth
•Dizziness
•Restlessness
•Dilated Pupils
•Delirium at high doses
•Allergic Reaction
•Contraindications
•Kidney or liver disease
•Enlarged prostate
•Difficulty in urination / bladder problems
•Heart Disease
•Glaucoma
115. Antiemetic Therapuetics
•Serotonin 5-HT3 receptor antagonist
•Ondansetron (Zofran)
•Granisetron
•Excellent for chemotherapy induced nausea and vomiting
•Side Effects
•Very few common side effects - usually well tolerated
•Headache
•Constipation
•Rarely
•Hiccups
•Itchiness
•Transient blindness
116. Sites - Summary
Cancer Chemotherapy Drugs
Dopamine agonists
Ondansetron
Phenothiazines
Scopolamine
H1 Antihistamines
Ondansetron
All
Chemoreceptor
Trigger Zone
(CTZ)
