Pharmacology. Peptic Ulcer Disease Imbalance between mucosal defensive factors and aggressive...
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Transcript of Pharmacology. Peptic Ulcer Disease Imbalance between mucosal defensive factors and aggressive...
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Pharmacology
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Peptic Ulcer Disease Imbalance between mucosal defensive
factors and aggressive factors Major defensive – mucus and bicarbonate Major aggressive – gastric acid, H. pylori,
nonsteroidal anti-inflammatory drugs, pepsin
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Defensive factors Prevent the stomach and duodenum from being
harmed (self-digestion). Mucus – continually secreted, protective effect Bicarb – secreted from endothelial cells, neutralized
hydrogen ions Blood flow – good blood flow helps to maintain
mucosal integrity Prostaglandins – stimulate secretion of bicarb and
mucus and help promote blood flow, suppress secretion of gastric acid
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Aggressive factors Helicobacter pylori – gram negative
bacteria, can live in stomach and duodenum
May breakdown mucus layer, inflammatory response to presence of the bacteria may breakdown defenses, also produces urease – forms CO2 and ammonia which are toxic to mucosa
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NSAIDS – inhibit the production of prostaglandins
Decrease blood flow, decrease mucus production and bicarb synthesis, promote gastric acid secretion
Gastric Acid – also needs to be present for ulcer to form – activates pepsin and injures mucosa
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Pepsin Smoking
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Classes of drugs Antibiotics Antisecretory agents Mucosal protectants Antisecretory agents that enhance mucosal
defenses Antacids
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Nondrug therapy Diet – change in eating pattern, 5-6 small
meals a day Smoking cessation, NSAID and ASA
should be avoided whenever possible, avoid alcohol
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Antibacterial drugs Combinations must be used Bismuth – disrupts cell wall of H. pylori,
pepto-bismol Clarithromycin – inhibits protein synthesis Amoxicillin – disrupts cell wall, good
when given with omeprazole Tetracyclin – inhibits protein synthesis Metronidazole – resistance,
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Histamine 2-receptor antagonists Suppress secretion of gastric acid (activation of
H2 receptors promotes secretion of gastric acid) Cimetidine - first available, oral, IV, IM May take up to twelve weeks for ulcer to be
healed Therapeutic uses – ulcers, GERD, Zollinger-
ellison syndrome, aspiration pneumonitis, heartburn, indigestion
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Ranitidine (Zantac) More potent – than cimetidine Fewer side effects Fewer drug interactions PO, IM, IV Famotidine, Nizatidine
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Proton Pump Inhibitors Suppress secretion of gastric acid Omeprazole – prilosec – prodrug that
converts to active form in parietal cells of stomach – inhibits enzyme that generates gastric acid
Ulcers, GERD, Zollinger-Ellison syndrome May contribute to development of gastric
tumors?
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Other PPIs Lansoprazole Rabeprazole Pantoprazole – protonix – usually given 40
mg per day
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Sucralfate Creates a protective barrier against acid
and pepsin Form sticky gel that coats ulcer portion Given every 6 hours Very few side effects – minimal systemic
absorption
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misoprostol Cytotec – prevention of gastric ulcers
caused by long-term NSAID therapy Replacement for endogenous
prostaglandins
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Antacids Peptic ulcers and GERD Neutralize acid Dosing – 7 times per day
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Laxatives Laxative effect – production of a soft
formed stool over a period of 1 or more days
Catharsis – prompt, fluid evacuation of the bowel, more intense
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Function of the colon – water and electrolyte absorption
Bowel evacuation – individual
Dietary fiber
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Constipation Consistency vs. frequency Causes – diet and fluid, medications,
activity
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Indications for laxative use Pain associated with bowel movements To decrease amount of strain under certain
conditions Evacuate bowel prior to procedures or
examinations Remove poisons To relieve constipation caused by
pregnancy or drugs
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Laxative contraindications Inflammatory bowel diseases Acute surgical abdomen Chronic use and abuse
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Classifications I – osmotic (high doses) II – osmotic (low doses), stimulant except
castor oil – most frequently abused III – bulk-forming, surfactant
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Bulk-forming Identical to fiber – soften fecal mass,
increasing bulk Temporary treatment of constipation,
preferred for patients with inflammatory bowel diseases
May help with diarrhea
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Adverse reactions Not absorbed – no systemic effects Must take with sufficient water Intestinal, esophageal obstruction Metamucil, citrucel
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Surfactant laxatives Bisacodyl, castor oil Stimulate intestinal motility Increase water and electrolytes in intestinal
lumen Produce stool within 6-12 hours
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types Bisacodyl – dulcolax – suppository, orally Anthraquinones – cascara and senna Castor oil – works in small intestine
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Osmotic laxatives Draws water into intestinal lumen Time of action is dose-dependent Magnesium, sodium and potassium salts Can cause dehydration Electrolyte imbalances
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Miscellaneous laxatives Mineral oil Lactulose Glycerin suppository Polyethylene glycol-electrolyte solutions
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Laxative abuse Most common cause of constipation Teaching
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Prokinetic agents Reglan – suppresses emesis and increases
upper GI motility Given for nausea related to chemotherapy GERD Diabetic gastroparesis Adverse effects – diarrhea, sedation, EPS,
(dopamine antagonist)
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propulsid GERD and nocturnal heartburn Taken off the market Causes potentially lethal dysrhythmias
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Antiemetic drugs Serotonin receptor antagonists –
Ondansetron (Zofran) – most effective with chemo-type drugs, very effective – works well with dexamethasone
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Phenothiazines Blocks dopamine2 receptors in the
chemoreceptor trigger zone Side effects include EPS, anticholinergic
effects, hypotension and sedation Prochlorperzine, phenergan,
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butyrophenones Haloperidol and droperidol (Inapsine) Block dopamine 2 receptors in
chemoreceptor trigger zone
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Additional drugs Glucocorticoids Cannaboids Benzodiazepines Antihistamines
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Antidiarrheals Symptom – excessive volume and fluidity
of stools Infection, digestion problems, bowel
disorder, inflammation
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Complication and goal of treatment Electrolyte imbalances and dehydration Goal of treatment – treat underlying cause,
replace water and salts (electrolytes), relief of pain, cramping and reducing passage of unformed stools
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Nonspecific – treat symptoms Opioids – slow intestinal motility, decrease
fluid in small intestine – stool goes into large intestine with less fluid
Lomotil and imodium Bulk-forming agents Anticholinergics antispasmodics - atropine
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Infectious diarrhea Infections – bacteria and virus Salmonella, shigella, campylobacter,
clostridium Traveler’s diarrhea – e coli
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Crohn’s disease and ulcerative colitis Aminosalicylates – sulfasalazine –
metabolized producing component which reduces inflammation
Mild to moderate ulcerative colitis
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Glucocorticoids – suppress inflammation Primarily used for an exacerbation
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immunomodulators Azathioprine and mercaptopurine Cyclosporine Infliximab methotrexate
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END