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How do the basic cell functions protect the gut mucosa.
The mucus and tight cellular junctions protect the stomach from pepsin and HCl acid and there is a rapid epithelial cell turnover cell turnover. Anything that interfere with the normal process will precipitate irritation/ulcers.
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How does PGE and NO
- Increases mucus production
- increase HCO3 production
- Decreases HCl productions
- Vasodilation causes rapid blood flow
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What are the defense mechanisms in GI tract
- mucus
- blood flow
- PGE
- HCO3
- rapid cell turnover
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What factors irritate the GI tract
- H. pylori
- smoking, alcohol
- stress --> HCl, pepsin, bile salts, pancreatic
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What is included in Peptic Ulcer Disease
- Gastritis
- Gastric ulcer from decreased protective factors and pyloric reflux
- Duodenal Ulcer from increased HCl
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What causes stress ulcers
- Hypoperfusion of the stomach
- Increased HCl production
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What can cause hypoperfusion of the stomach
- Hypovolemia
- Shock
- Burns and trauma
- ischemia, anoxia/hypoxia
- severe and/or prolonged stress
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What causes an increase in HCl production
- Neuro injury
- vagal nerve stimulation
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How is gastric acid secreted
Gastric acid exhibits circadian rhythm and its peak is highest in the evening and lowest in the morning
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What are the basic management strategies for increased HCl
Suppress nocturnal acid secretion which is unbuffered by food and causes prolonged duonenal acidification
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What the basic goals of managing HCl
Keep the pH>4 because if it is >4 pepsinogen does not break down into pepsin, this prevents pepsin-acid complex which is proteolytic
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What is the side effect of low HCl?
You don't absorb Vit B12 as well which results in anemia
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What are the overall goals of pharmacotherapy for ulcers
- Relieve pain
- Treat symptoms
- Heal ulcer
- Prevent complications
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What are the pharmacological options for ulcers
- Antacids
- H2 receptor antahonists
- Sulcrafates
- Prostaglandins
- Proton pump inhibitors
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What are the heal times periods for the major medicines for ulcers
- In general it takes 4-6 wks
- Proton pump take 4 and the others take 4-6
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What is the MOA of antacids
Neutralize
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Which antacid neutralizes more acid
Liquid(150-180) compared to tablets (12meq)
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What is the goal of antacids
Treat the symptoms they arent a cure
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What is the MOA of H2 blockers(H2 receptor antagonists)
They competitively and reversibly bind H2 receptors on parietal cells decreasing cAMP production and secretion H2 stimulated gastric acid (which contains HCl)
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What is the strongest to weakest H2 blockers
- "CRNF"
- WEAK
- cimetidine
- ranitidine
- nizatidine
- famotidine
- STRONG
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When treating duodenal ulcers with H2 blockers what is the best dosing schedule
Nighttime dosing is more effective than bid dosing
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When treating refractory ulcers with H2 blockers what is the best dosing
Use a high dose
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What is important to remember about drug interactions and H2 blockers
Cimtidine, nizatidine, famotidine inhibit the cytochrome p450 system (remember that this will cause other drugs to accumulate in the body)
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What is the MOA of sucralfate
- It is a sucrose sulfate aluminum salt complex that binds to the HCl and acts like a buffer and it binds to the inflamed tissue and creates a protective barrier for up to 6 hours
- Inhibits pepsin activity
- Stimulates PG synthesis in the mucus
- Forms a physical barrier to prevent back diffusion of acid and pepsin
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What are the main side effects of sucralfate
- Constipation
- Aluminum tox in patients with renal failure
- Hypophos because it binds to the gut and prevents absorption of phos
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What are the major drug interactions of sucralfates
- May reduce absorption of other drugs that are typically absorbed in the stomach
- Ex quinolones, dig, warfarin, phenytoin
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How should you administer multiple drugs when a pt is receiving sucralfates
Administer 2 hours AFTER other drugs
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What is the MOA of action prostaglandins
Inhibits histamine mediated cAMP production in parietel cells inhibiting HCl release
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What is cytotec(misoprostol)
A prostaglandin analog used to treat gastric ulcers
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Why are GI problem are prostaglandins used for
Prevention of NSAID induced gastric ulcers
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Who should NEVER use cytotec (misoprostol)
Pregnant women bc it contains PG
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What should you avoid when taking cytotec (misoprostol)
Mag containing antacids bc it may increase diarrhra and this is always a side effect
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What are the side effects of misoprostol
- Abd cramping
- Diarrhea
- GYN issues
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What are the most commonly used proton pump inhibitors
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The most powerful acid inhibiting and ulcer healing drugs available
Proton pump inhibitors
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What is the MOA of proton pump inhibitors
- Inhibits the last step in HCl secretiom by altering the activity of H+/K+ ATPase (proton pump) within the parietal cells
- Result: reduced transport of H+ out of the cell
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What are side effects of proton pump inhibitors
Sustained hypochlohydria results in chronic hypergastrinemia which leafs to gastric carcinoid tumors
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A side effect of proton pump inhibitors is carcinoid tumors what is the FDA recommendations
Limit treatment to 4-6 weeks
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What is the most common cause of ulcers
- h. pylori
- It accounts for 80% of stomach ulcers and 90% of duodenal ulcers
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Do all people with h pylori have ulcers
No most dont develop ulcers
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How does h pylori interfere with normal gastric function
It survives in stomach bc it secretes enzymes that neutralize the acid This weakens the protective mucus coating of the stomach and duodenum
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How is h pylori spread
- Food and water
- It is in infected peoples saliva and can be spread from mouth the mouth cobtact
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What ate the goals of h pylori tx
- Kill bact - antibs
- Reduce stomach acid - H2 blockets or PPI
- Protect stomach lining - bismuth subsalicylate
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What is the FDA approved tx regime for h pylori in patients with PUD
- "Triple therapy"- administer each therapy for 10-14 days
- OAC- omprazole amoxicillin chlarithomycin for 10 days
- BMT - bismuth subsalicylate, metrodiazole and tetracycline for 14 days
- LAC- lansoprazole, amoxicillin, chlarithromycin for 10 or 14 days
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What is GERD
Gadtric contents back flow into the esophagus
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What are the symptoms of dysphagia
- Dyapepsia
- Regurgitation
- Dysphagia
- Odynophagia
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How does GERD effect the infant
- Failure to thrive
- Pulmonary aspiration
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How does GERD effect the child/adolescent
- Esophagitis
- Stricture formation
- Barrets esophagus- adenocarcinoma
- Esopghageal perforation
- Asthma/wheezing
- Bleeding/anemia
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What are the goals of GERD tx
- Alleviate symptoms
- Decrease frequency/duration of reflux
- Promote healing
- Prevent complications
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GERD therapy is directed at
- Increasing LES tone- bethanechol,reglan
- Increase esophageal clearance- bethanochol
- Improve gastric emptying- reglan
- Protect mucosa - sucralfate
- Decrease acidity in reflux- antacids, H2antagonists,PPI
- Decrease the volume available to reflux- reglan
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What are the phases of GERD therapy
- I - lifestyle changes, antacids
- IIa-H2, antagonists, prokinetic agents(reglan),bethanachol, sucralfate
- IIb- high doses of H2 antagonists and PPI
- III Nissen
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What is the MOA of Bethanochol (urecholine)
Increases GI tone & motility and increases LES tone
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What type of medication is bethanechol
Cholinergic - parasympathetic
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What the contraindications of bethanachol
PUD or obstruction
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What are adverse effects of bethanechol
Abdominal cramping & blurred vision
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What is the MOA of anticholinergics
Inhibits gastric acid secretions by blocking acetylcholine receptors on the parietal cells
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When should anticholinergics be given
1 hour after meals � it is not that effective
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What are the contraindications of anticholinergics
- Remember it stops the cholinergics which is a parasympathetic (feed and breath)
- Bleeding, tachycardia, glaucoma, achalsia, obstruction, or a suspected megacolon
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What are the adverse effects of anticholinergics
Blurred vision, urinary hesitancy or retention, dry mouth, nose, throat, constipation
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Uneasiness of the stomach that often accompanies the urge to vomit
Nausea
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contraction of the diaphragm & abdominal muscles with opening of the LES and forceful expulsion of gastric contents
Vomitting
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Similar to vomiting but without gastric contents
Retching
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Spontaneous vomiting without nausea and vomiting
Projectile vomiting
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What triggers vomiting that is controlled by the brain
- Chemoreceptor trigger zone (CTZ)-nerve fibers in the brainstem (medulla) sense changes in the chemical composition of the blood; this is an evolutionary protective mechanism
- Increased ICP from trauma, infection, tumors, AVM, aneurysm
- Cortex - unpleasant memory (anticipatory) sight, odor
- Migraine HA
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What controls vomiting
- Brain
- Vesitubular nuclei in the brainstem
- Sensors in the stomach and bowel
- Protective mechanisms
- Responses to inflammation or irritation of the gut
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What triggers vomiting that is controlled by the vestibular nuclei (brainstem)
- The brainstem interprets signals from the inner ear or eye and uncoordinating signals cause N & V
- Ex: Dizziness, motion sickness
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Why do protective mechanisms cause vomiting
- Prevents the ingestion of harmful substances and irritating foods/drugs
- Ex: opiods, dig, anesthetics, ETOH, Chemo
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What causes vomiting as a result of a response to inflammation or irritation
- Ulcers, reflux, severe constipation, GI obstruction/gastric outlet obstruction
- Infection: viral or bacterial
- Tumor growth and invasion of the gut
- Radiation
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What is the most common antiemetics
Phenothiazines
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What is the MOA of the antiemetic drugs phenothiazines
- Blocks dopamine receptors in the CTZ
- Effective in most case of N & V
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When are phenothiazines NOT effective
Motion sickness
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Compazine, Phenergen, Torecan, Tigan
Phenothiazines
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What is the MOA of butyrophenones
Block dopamine receptors in the CTZ
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What are the adverse effects of butyrophenomes
- QT prolongation, torsades de pointes, EPS
- They are generally less sedating than phenothiazines
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Droperidol and Haldol
Butyrophenones
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What medication is usually used for motion sickness
Antihistamines and anticholinergics
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meclizine, diphenhydramine, Dramamine
antihistamines used to tx motion sickness
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This antiemetic for motion sickness is applied behind the ear
Scopolamine
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What is the MOA of substituted bezamine
Blocks dopamine receptors in the CTZ
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How does the dose of benzamine change the with different condition
- 10-20 mg.kg po QID for gastroparesis, low dose chemo
- 1-2 mg/kg for high dose chemo
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Reglan
Substituted Reglan
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What is the MOA serotonin antagonists
Selectively blocks serotonin (5HT3) receptors in the GI tract & CTZ
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Zofran, Kytril, Anzemet, Aloxi
Serotonin antagonists
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Cortocosteroids are used for antiemetics, what are the adverse effects
- Insomnia
- Hyperglycemia
- Inc appetite
- Euphoria
- Agitation
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What is the MOA of cannabinoids
Unknown but likely causes depression of the higher cortical pathways leading to the emetic center
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What are some adverse effects of cannabinoids
Sedation, euphoris, dysphoria, mood changes, hallucinations
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What is the MOA of benzodiazopines
Amnesic, anxiolytic and sedative properties
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What are common side effects of benzodiazopines
Sedation, hypotension, disinhibition, motor incoordination
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Valium, versed, ativan
- Benzodiazopines
- Ativan is primarily used for nausea
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What are the cheapest benzodiazopines used for nausea and vomittting
Dexamethasone, haldol, raglan
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What is large volume diarrhea
Increased water content in stools, usually painless
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What causes large volume diarrhea
- Osmotic problems r/t drugs
- Malabsorption problems d/t pancreratic or bile defieciency, short gut, lactose disease, celiac disease
- Deranged gut flora d/t antib�s, viruses,bacteria (salmonella, shingles, )- the bac�t attach to the bowel wall and make toxins, they invade and damage the brush border
- Secretory problems from enteric organisms or laxatives- Ecoli secretes toxins that stimulates fluid secretions, S.aureus invades and destroys epithelial cells and alters fluid transport; parasites also cause secretory problems
- Deranged motility � short gut, IBS
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What is the difference between opiods and opiates
- Opiate � natural
- opium � synthetic
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How doe opiods and opiates work to decrease diarrhea
Inhibits intestinal motility
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Morphine, methylmorphine, camphorated tincture of opium
Opium alkaloids (opiates) for diarrhea
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Lomotil and Imodium
Synthetic opiums alkaloids for diarrhea
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How does kaopectate treat diarrhea
Decreases the fluid in the stools
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How does pepto bismol decrease diarrhea
Decreases intestinal secretions
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What other jobs do antidiarrheals do
- May also absorb toxins and provide a protective coating for the mucosa
- What are some negatives r/t antidiarrheals
- May delay intestinal clearing of pathogens
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What are the contrindications of antidiarrheals
- Not recommended for those with a fever, bloody diarrhea or < 2 years old
- Not recommended for long term use
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What are causes of constipation?
- Infrequent passage of stools and increased transit time
- Failure to respond to the urge to defecate from pain, discomfort, hemorrhoids, sexual abuse, and toileting issues
- Inadequate fiber, decreased fluid intake, abdominal wall weakness, inactivity and bedrest, pregnancy
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What occurs with chronic constipation
- Dilation of the rectum or colon
- Allows for large amounts of stool to build up with little or no sensation
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What is fecal impaction
- Retention of hardened stool in rectum and colon
- Can cause partial or complete bowel obstruction
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How does hyperosmotic colonic lavages work (preps)
Increases intraluminal pressure and stimulates peristalsis
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Polyethylene glycol
hyperosmotic colonic lavages
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What should you remember about hyperosmotic colonic lavages
Has a lot of sodium and kids can become dehydrated
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When is miralax used
Used for slow transit constipation and encopresis (leaking of stool) in children
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How do stimulants treat constipation
Produces local irritation which increases intestinal motility
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When are bowel stimulants contraindicated
Obstruction, peritonitis or recent abdominal surgery
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What type of drug is Dulcolax
A stimulant for tx of constipation
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How do bulk forming cathartics work for constipation
They are natural or synthetic polysaccharides/cellulose derivatives that aren�t absorbed therefore they
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Metamucil and citracel
Bulk forming cathartics, used to treat constipation
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How do lubricant cathartics treat constipation
Softens stool by acting as a wetting agent
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Mineral oil, glycerin chips
Lubricant cathartics
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How do emollient laxatives work
Act as surfactants that soften the fecal mass by facilitating the mixture of aqueous and fatty substances
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Colace
Emollient laxative
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