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120 Cards in this Set

  • Front
  • Back
Propulsion in the bowel is controlled by both…..
Intrinsic and extrinsic nerves
The extrinsic nerves consist of…
Sympathetic and parasympathetic fibers

1. Increase in parasymp activity relaxes the GI sphincters and increases motility and tone – thus anterograde movement through the gut

2. Efferent vagal activity (ACh) releases 5-HT from the myenteric plexus via stim of the prejxnal M2-muscarinic receptors, and the released 5-HT stims the 5-HT2 receptors causing contraction of GI smooth muscle and anterograde movement

3. NE released by sympth fibers stims prejxnal α2-adrenoceptors located on parasympth fibers: ACh release is partially inhibited, so antegrade propulsion is inhibited
Opiate receptors in the GI are found where?
1. Smooth muscle cells – Mu receptor stim causes tonic contraction, but at same time, decreases motility and secretion. Antegrade movement stops

2. Prejxnal receptors on parasymp fibers – my receptor stim partially inhib ACh release to cause further suppression of anterograde mvmt
The intrinsic nerves of the GI…
Operate independently of the autonomic NS

1. control lower GI fxn via afferent sensory fibers, interneurons and local NTs such as 5-HT and peptides (VIP, CGRP)

2. 5-HT contracts longidutinal/circular GI muscle via 5-HT2 receptors

3. 5-HT ampilifies ACh release via prejxnal 5-HT4 receptors

4. Increased release of ACh and 5-HT causes antegrade mvmt of food/feces
What are the indications for use of emetic agents?
1. Oral ingestion of toxic
-- cleaning products
-- other chemicals
-- pesticides
-- plants
-- cosmetics
-- drugs

2. Poisoning w/ acetaminophen, aspirin or iron supplements in children
Contraindications for emesis?
1. petroleum distillates can cause chemical “pneumonia”
2. corrosive chemicals such as acids and bases can cause further damage to the stomach and esophagus
3. CNS depressants can obtund the pt who then aspirates vomitus
4. Can precipitate seizures in pts poisoned w/ CNS stimulants
Ipecac derivation?
From the roots and rhizomes (underground stems) of the plant Cephalis ipecacuanha
Ipecac MOA?
Stimulates the CTZ and causes local irritation of the stomach and upper portion of the duodenum
Ipecac use?
-- clears contents of stomach and upper dupdenum
-- may also induce reflexly-mediated diarrhea

Effective after overdose w/ antiemetic drugs (antihistamines and phenothiazines)

Although safe for use at home, most recent guidelines for unwanted oral ingestion in children favors visit to ER
Ipecac S/Es?
Temporary drowsiness
Chronic use (bulimia) can cause emetine-induced cardiomyopathy
Name the antiemetic drugs.
Which antiemetic agents are anticholinergic?
Scopolamine MOA?
Blocks muscarinic receptors in the vestibular nuclei and reticular formation
Major S/Es of scopolamine?
Inability to concentrate
Which antiemetic drugs are antihistamine/anticholinergic?
How do the antihistamine/anticholinergic drugs work?
They have to block central muscarinic receptors to stop emesis
Which antiemetic drugs are serotonin/dopa receptor antagonists?
Metaclopramide MOA?
Blocks 5-HT3 receptors (vagal afferents and CTZ)
Blocks D2-dopa receptors (CTZ)
Which antiemetic drugs are Dopa receptor antagonists
Prochlorperazine MOA?
Blocks D2-dopa receptors in CTZ
Which antiemetic drugs are 5-HT3 receptor antagonists?
Ondansetron, dolasetron MOA?
Ondansetron, dolasetron MOA?
Block 5-HT3 receptors at vagal afferent nerve endings and/or the CTZ
Which antiemetics are steroids?
Dexamethasone – MOA unknown
Which antiemetics are based on THC?
Dronabinol – MOA unknown
Which antiemetics are used to treat motion sickness prophylactically?
Which antiemetics are used to treat motion sickness?
Which antiemetics are used as prophylaxis during pregnancy?
Which antiemetics are used to treat vertigo of vestibular origin?
Which drugs are used as prokinetic agents
Prokinetic agent = increase GI motility = gastric emptying

Prokinetic agents’ MOA?
Enhance release of ACh by stim prejxnal 5-HT4 receptors on cholinergic fibers

TEGOSEROD also stims release of calcitonin gene-related peptide (CGRP) from sensory neurons in the GI tract
What are the net GI effects of prokinetic agents?
1. increased LES pressure

2. gastric emptying

3. antegrade mvmt of food through the GI tract
Indications for use of prokinetic agents?
1. Clear stomach prior to GI endoscopy or GI surgery – METOCLOPRAMIDE

2. Diabetic gastroparesis = charact by nausea, vomiting, heartburn, anorexia, and persistent feeling of fullness after meals – METOCLOPRAMIDE

3. Treatment of IBS primarily assoc w/ constipation – TEGASEROD
Explain the pathophys of constipation
1. can be caused by inhibition of natural defecation reflexes, poor eating habits, costive (constipating) drugs

2. DOES NOT depend on the frequency of bowel movements! Pts vary greatly in the frequency of defecation.

3. Constipation is correctly defined as having the urge to defecate but being unable to defecate

**Some pts (espec older) are convinced they must defecate daily to remain healthy
-- leads to the abuse of cathartic agents
-- self-med w/ OTC products causes long periods free of bowel movements
-- pts often tempted to dose again in attempt to cause defecation daily for “regularity”
-- situation should be avoided b/c causes chronic water loss and leads to laxative dependence
Name the bulk laxatives
Calcium polycarbophil

**These DO NOT cause laxative dependence
What is methylcellulose?
It consists of the indigestible components of cereal bran, fruits and vegetables
Methylcellulose MOA?
Attracts water to form a hydrogel w/ feces in the large bowel

-- hydration increases the bulk by 30-fold

-- bowel distension activates stretch receptors which increases peristalsis by locsl reflexes

-- After 1-3 days ingestion, methylcellulose softens the stool and increases volume of feces, water content of feces, colonic transit rate, and frequency of defecation
What is psyllium?
A hydrophilic mucilloid refined from the indigestible seed coat of the “flea” seed or plantago
Psyllium MOA?
Attracts water to form a hydrogel w/ feces in the large bowel (increases bulk 30-fold)
What is calcium polycarbophil?
A hydrophilic, polyacrylic resin that can absorb 60 times its weight in water
Calcium polycarbophil MOA?
Draws water into bowel to expand the bulk of the feces and thus activate local peristaltic reflexes
What is lactulose?
It is a synthetic disaccharide
Lactulose MOA?
It is not absorbed by the GI tract

-- bacteria in the bowel degrade lactulose into lactic, acetic and organic acids which exert an osmotic effect drawing water into the colon and thus increase the bulk of feces

-- increased peristalsis via local reflexes (bowel distension)

-- Acidification of the colonic contents causes ammonia in the blood to be trapped and excreted as ammonium ions
Name the stool softeners
Docusate sodium

Mineral oil (don’t want patients taking!)
Docusate sodium MOA?
An anionic surfactant:
-- detergent action lowers the surface tension of feces to allow the penetration of water
-- emulsifying action softens the stool
Name the irritant purgative agent selective for the colon
Bisacodyl MOA?
Irritant action increases the accum of water and electrolytes in the lumen of the colon and enhances colonic peristalsis by activation of local reflexes

Produces soft semifluid stool w/in 6-12h of p.o. dosing

Suppositories exert a purgative effect within 15-60 min
Bisacodyl side effects?
Can cause GI colic, laxative dependence, dehydration and electrolyte imbalance
Name the osmotic (saline) purgative agents.
Magnesium hydroxide
Magnesium citrate
Magnesium sulfate
Polyethylene glycols
MOA of the osmotic (saline) purgative agents?
These hypertonic solutions create osmotic forces which draw water into the large bowel

Bowel distension activates stretch receptors which increase peristalsis via local reflexes

Produce soft semifluid stool 6-12h after p.o. dosing
Adverse effects of the osmotic (saline) purgative agents?
Can cause GI colic, laxative dependence, dehydration and electrolyte imbalance
How do we treat constipation?
1. Bulk laxatives
2. Stool softeners
sodium docusate
3. Cathartic agents
magnesium hydroxide/citrate/sulfate
Why is it important to use the stool softeners?
1. want to ensure soft stool in pts who have undergone various types of abdominal, anal or rectal surgery
-- decreases likelihood of producing mechanical damage since straining is not required for defecation

2. used to maintain soft stool in pts who should avoid straining during defecation
-- pts w/ hemorrhoids, hernia, anal lesions, rectal prolapse, CAD, HTN, or prior MI or CVA

3. Fecal softeners (docusate) also added to iron supplements to prevent the constipating effects of iron
Drugs used for GI examination?
Magnesium hydroxide/citrate/sulfate
Polyethylene glycol

All used to evacuate bowel prior to radiological or sigmoidoscopic exam

Evacuation prior to exam or x-ray eliminates shadows caused by feces and gas in the large bowel
Pathyphys of Irritable Bowel Syndrome?
-- Alternating periods of constipation and diarrhea

-- Etiology unknown

-- Constipation results from alternating segmental contractions which cause bidirectional “shuttling” of feces in the large bowel

-- “shuttling” hardens the stool b/c it allows more time for the reabsorption of water from feces
Treatment of IBS?
-- expand large bowel and thus prevent alternating segmental contractions of smooth muscle
-- antegrade peristalsis is restored

2. MUSCARINIC RECEPTOR ANTAGONISTS may prevent bowel spasm which is sometimes assoc w/ IBS
-- dicyclomine

3. PROKINETIC agents to relieve constipation
-- tegoserod
Pathophys of diarrhea?
1. Etiology is diverse and can range from poor or irregular eating habits to serious infections such as Shigella or C. diff

2. Diarrhea assoc w/ viral infections (flu) is probably the most common GI illness seen by physicians

3. Severe/chronic diarrhea can cause dehydration and electrolyte imbalance (loss of K and Cl leads to alkalosis)
Which drugs can we use to treat diarrhea?
-- diphenoxylate
-- loperamide

-- kaopectate

-- calcium polycarbophil (note it treats constipation AND diarrhea)

-- bismuth subsalicylate

-- octreotide
MOA of diphenoxylate?
Slows the colonic transit rate by direct/indirect inhibition of GI motility despite the fact that GI muscle tone in increased

Bowel stasis allows absorption of fluids and consolidation of the feces

**contains subtherapeutic dose of atropine sulfate to prevent abuse of this opiate
What is kaopectate?
It is a hydrated aluminum silicate clay (attapulgite) combined w/ a complex CHO (pectin)
Kaopectate MOA?
Large surface area of the finely powdered clay, which bears a negative charge, absorbs bacterial toxins

Pectin becomes hydrated to form a viscous colloidal solution which helps to consolidate the stool
Calcium polycarbophil MOA?
This resin absorbs excess water in the bowel to form a gel which helps consolidate the stool
Bismuth subsalicylate antiulcer action MOA?
1. Astringent action protects the irritated GI mucosa by contracting the surface layer of the mucus

2. Demulcent action coats the irritated mucosa

3. Increases PG synth and alkali secretion

4. Antiproteolytic action counteracts breakdown of mucus coat by pepsin and H. pylori protease

5. Antibacterial effects
Bismuth subsalicylate antibac effect MOA?
1. binds to –SH groups of microbial proteins to destroy their tertiary structure

2. prevents binding of microorg to epith by reducing their adherent properties

** exerts a synergistic antibac effect when combined w/ other antibiotic drugs
Bismuth subsalicylate S/Es?
Salicylate toxicity

Decreased absorption of tetracyclines

**Stool becomes radioopaque (interferes w/ X-ray exam) and turns gray-black (don’t confuse w/ melena)
Octreotide MOA?
Stimulates somatostatin receptors in the GI tract
Therapeutic use of octreotide?
1. Reduces the diarrhea/flushing assoc w/ metastatic carcinoid syndrome and VIPomas, but the dose must be increased w/ time

2. Used to stop GI bleeding in pts w/ esophageal varices
-- fewer adverse effects than AVP (does not cause angina or MI)
-- constricts splanchnic arterioles to decrease splanchnic blood flow and thus portal venous pressure
Steps in treating diarrhea?
1. Establish primary cause and treat

2. If results from bacterial infection, treat w/ approp antibiotic agent and take care NOT to stop the bowel w/ DIPHENOXYLATE or LOPERAMIDE if the organism is invasive (ex. Shigella)

3. KAOPECTATE absorbs excess fluids and bacterial toxins and increases consistency of stool

4. BISMUTH SUBSALICYLATE exerts antibac effects and absorbs bacterial toxins

5. Because of direct and indirect inhibitory effects of opiates of GI motility, these drugs can be used to produce bowel stasis in diarrhea – LOPERAMIDE and DIPHENOXYLATE

6. Use PROMETHAZINE to treat any assoc nausea and vomiting
Pathophys of duodenal ulcers?
1. H. pylori infection of the GI tract is the cause of recurrent ulceration
-- produces urease which breaks urea down into ammonia (base) to neutralize acidic environment of stomach (also damages epith cells of glycolyx)

2. Normal or excess secretion of gastric acid which enhances ulceration
Aim of duodenal ulcer therapy?
1. eradicate H. pylori

2. neutralize gastric acids
-- antacids

3. decrease secretion of gastric acid
-- H2 receptor blockers
-- proton pump inhibitors
-- PGE1 analogs (misoprostol)

4. Construct protective barrier over the ulcer to protect the damaged tissue from further damage as it heals
-- sucralfate
Explain antibiotic triple therapy.
1. combined therapy with CLARITHROMYCIN, AMOXACILLIN, and OMEPRAZOLE (proton pump inhib) produces a cure rate of 95%

2. Cure rate depends on eradication of H. pylori from GI tract
Name the antacids.
Aluminum hydroxide
Magnesium hydroxide
Al/Mg hydroxides
Antacid MOA?
These chemically neutralize stomach acid
-- weak bases which are slowly soluble in water
-- onset of acid neutralizing action is 10-15min
-- pH of gastric contents temporarily rises to 3-4

Products vary as much as 6-7fold in their acid neutralizing capacity

Liquids are more potent and effective than tablets
S/Es of antacids
1. Aluminum cmpds cause constipation whereas Magnesium cmpds cause diarrhea
-- laxative effect of the Mg cmpds predominates in Al/Mg mixtures

2. Al and/or Mg toxicity can occur in pts w. renal insufficiency

3. Prevent GI absorp of tetracyclines, iron, and isoniazid
What are the H2-histamine receptor antagonists used to treat duodenal ulcers?
MOA of the H2-histamine receptor antagonists?
Block H2-histamine receptors on gastric parietal cells
-- decrease basal and nocturnal acid secretion
-- block acid secretion elicited by histamine, food, coffee, insulin, and increased vagal nerve activity
Pharm effects of cimetidine?
1. gastric pH rises to 3-4

2. Does NOT alter LES pressure, gastric motility or emptying, or pancreatic and biliary secretion

3. Reoccurrence of ulcer disease is common after cessation of therapy
Adverse effects of cimetidine?
1. Increases half-life of other drugs by inhib CYP450:
-- B-blockers
-- warfarin
-- diazepam

2. Antiandrogenic effects in males result from decreased estrogen metabolism (estrogen degraded by CYP450)

3. CNS effects ranging from mental confusion to frank psychosis can occur in older pts, pts w/ hx of psych diseases, and pts receiving large doses for a prolonged period
What about ranitidine and famotidine adverse effects?
NO CNS effects
NO inhibition of drug metabolism
NO antiandrogenic effects
Name the proton pump inhibitors (PPI) used for treatment of duodenal ulcers
Inhibits gastric H-K ATPase: blocks acid secretion for 24-72h
Pharm effects of the PPIs?
1. inhibits basal and nocturnal acid secretion as well as the acid secretion caused by all other stimuli
-- gastric pH rises to 4-5

2. NO effect on LES pressure, gastric emptying, or GI motility

3. Cause a reactive increase in plasma gastric conc in 5-10% of pts, but gastric enterochromaffin cell hyperplasia and carcinoid tumors have NOT been reported w/ prolonged use

4. Does NOT inhibit release of intrinsic factor from gastric parietal cells, but increase in gastric pH partially inhibits absorption of protein bound vitamin B12 – does NOT cause megaloblastic anemia
Name the PGE1 analog.
Misoprostol MOA?
1. stim of PGE1 receptors on gastric parietal cells inhibits acid secretion

2. NO effect on basal acid secretion

3. BLOCKS increase in acid secretion caused by histamine, pentagastrin, aspirin, food, and coffee

4. Also exerts a protective effect on the gastric mucosa

5. NO effect on LES pressure, plasma gastrin, or gastric emptying
Adverse effects of misoprostol?
1. diarrhea occurs in 5-15% of pts

If a patient begins experiencing ulcers after treatment with a corticosteroid, which drug should you use to treat the patient?

Corticosteroids inhibit PGs, causing stomach ulcers  has NOTHING to do w/ H.pylori so triple antibiotic therapy not necessary
Name the coating agent used in the treatment of ulcers.
Sucralfate MOA?
-- water insol cmplx of AlOH and sucrose sulfate which polymerizes (when pH<4) wo form a sticky viscous gel which forms a protective layer on the ulcer

-- binds tightly to ulcerated gastric mucosa, and gel refluxed into lower esoph aids in treatment of GERD

-- polymerized gel does not dissolve in the duodenum (pH>7)

-- polymerized gel is poorly permeable to HCl, pepsin, trypsin, and bile salts

-- DOES NOT neutralize stomach acid or inhib acid secretion
Efficacy of sucralfate?
-- more effective on duodenal ulcers than gastric ulcers

-- healing rate NOT affected by smoking cigarettes

-- prevents relapse

-- since an acidic pH is required for activation, do NOT use in combo w/ H2-histamine receptor antagonists, omeprazole (PPI), or antacids
S/Es of sucralfate?
1. Al toxicity in pts w/ renal failure

2. hypophosphatemia in pts w/ chronic alcoholism
What is Zollinger-Ellison syndrome?
-- occurs in 0.1% of pts w/ duodenal ulcers

-- hypersecretion of gastrin from a malignant pancreatic gastrinoma causes hypersecretion of gastric acid w/ ulceration and diarrhea
How do we treat Zollinger-Ellison?
1. Omeprazole (PPI)
-- drug tolerance does not develop
-- after healing, suppressive therapy ay be req’d
-- often effective in healing ulcers in 30% of Z-E pts whose symptoms are not controlled by treatment w/ H2-histamine receptor antagonist

2. H2-histamine receptor antagonist
-- drug tolerance develops
-- failure rate of therapy is 25-50%
Pathophys of a gastric ulcer?
**occurs later in life than the duodenal and is more difficult to heal w/ drugs
Tx of gastric ulcer?
Same as for duodenal ulcers:

1. Antibiotics – clarithromycin, omeprazole, amoxacillin

2. H2-histamine receptor antagonist

3. Omeprazole

4. Sucralfate

5. Antacids
Pathophys of stress ulcers?
-- erosion of GI tissue develops w/in 24h in pts w/ birns, shock, sepsis, or severe trauma

-- incidence is 90% in pts w/ burns and severe trauma

-- thought to result from mucosal ischemia w/ normal acid secretion exacerbating the erosion and ulceration

-- ulceration is superficial – blood loss is minimal but may become substantial w/ time
Treatment of stress ulcers?
-- Adjunctive therapy w/ H2-histamine antagonists for treatment and prophylaxis
-- Antacids given by NG-tube w/ monitoring of gastric pH

-- give i.v. infusion to maintain gastric pH at 4+

-- elevated gastric pH may increase risk of nosocomial pneumonia in ventilated pts since antibiotic action of low gastric pH normally guards against colonization of G(-) bacilli
-- sucralfate prevents ulcer formation WITHOUT affecting the gastric pH and therefore may be the preferred drug in ventilated pts
Pathyphys of gastropathy?
1. ASA and other NSAIDs can produce a gastropathy by inhibiting the formation of cytoprotective PGEs

2. Many older pts w/ ASA induced ulcers are asymptomatic (no pain or dyspepsia) which leads to higher mortality since these pts present in the ER w/ sudden and severe GI bleeds
Treament of gastropathy?
-- prevents GI ulceration and bleeding
-- does not affect pharmacokinetics/pharmacodynamics of the NSAIDs
-- use only in high risk pts such as those aged 60+, smokers or pts w/ prior hx of ulcers or GI bleeding

-- decreases heartburn and epigastric burning/pain
Prophylaxis of corticosteroid-induced gastropathy?
MISOPROSTOL – prevents GI ulceration from chronic use of corticosteroids (PG inhibitor)
Pathophys of heartburn?
Substernal burning sensation is caused by the reflux of gastric acid into the esophagus
Treatment of heartburn?
Self medication w/ OTC antacids and H2-receptor antagonists (cimetidine and famotidine) are used for symptomatic relief of heartburn, acid stomach, and indigestion caused by ingestion of too much food or spicy food
Pathophys of GERD?
1. Under normal circumstances, contents of the stomach do not move retrograde into lower esoph b/c of tonic constriction of the LES

2. When LES becomes weakened or LES pressure is overcome by increased gastric pressure, reflux of acidic contents (pH of 1.5-2.5) causes tissue erosion, ulceration, and hemorrhage

3. As the tissue of the lower esoph becomes damaged, the ability of the lower esoph to clear gastric reflux is progressively decreased b/c the smooth muscle is damage
Tx of GERD?
Use agents that decrease acidity of the stomach contents , coat the ulcerated tissue, or increase LES pressure

1. Inhibitors of gastric acid secretion
-- proton pump inhibitor (omeprazole)
-- H2-histamine antagonist (cimetidine, famotidine)

2. Sucralfate
-- protects irritated tissue and prevents further damage
-- healing occurs in 90% of pts and is assoc w/ restoration of motor fxn in the lower esoph

3. Antacids
-- only symptomatic relief

4. Cisapride – increases LES pressure (off the market)

5. Tegoserod – off label use that has been shown effective in one study
Pathophys of Inflammatory Bowel Disease (IBD)
ULCERATIVE COLITIS – continuous lesion that involves rectum
1. thought to be organ specific auto-immune disease or psychosomatic illness
-- can also involve secondary bacterial infection
-- diet also affects symptoms
2. Inflamm of mucosa and submucosa
3. Charact by constant or intermittent diarrhea (can cause metabolic alkalosis), mucosal hemorrhage w/ rectal bleeding (can cause anemia) and pain

CROHN’S DISEASE – transmural, discontinuous “skip” lesions, spares rectum
1. IBD w/ symptoms similar to ulcerative colitis
2. inflamm of all layers of the intestinal wall of the small and large bowel, the mesentery, and regional lymph nodes
Which drugs can be used in the treatment of IBD?
1. Corticosteroids
-- methylprednisone

2. Non-steroidal anti-inflamm agents
-- sulfasalazine
-- mesalamine
-- olsalazine

Also (but not on drug list) – infliximab (monoclonal Ab) and metronidazole
Explain corticosteroid use in treatment of IBD.
1. Acts by inhibiting the synth of PGs and leukotrienes (LTs) and locally altering immune fxn
-- given p.o. for extensive colonic disease or disease involving the small bowel
-- also available as enema, foam, and suppositories
What is sulfasalazine, and what is its MOA?
It is a conjugate of the sulfonamine dulfapyridine and 5-ASA

1. about 65% of a dose reaches the distal ileum and large bowel where bacterial degrade sulfasalazine to sulfapuridine and 5-ASA
2. 5-ASA blocks both PG and LT synth by inhibiting COX and lipooxygenase, respectively
-- 5-ASA is a more potent inhib of LT synth than PG synth
Adverse effects of sulfasalazine?
Hepatic damage
Bone marrow depression
**both espec in pts who are slow acetylators

Can interfere w/ folate absorption (causing anemia), so must give folate supplements
Mesalamine MOA
-- Pentasa capsule slowly releases 5-ASA as it moves through the bowel
Olsalazine MOA?
Consists of two 5-ASA molecules joined by an azo bond that is cleaved by bacterial enzymes in the large bowel
What drug do we use in the treatment of gallstones?
General properties of ursodiol?
-- trace constituent of normal bile acids excreted by the liver

-- undergoes enterohepatic recirculation
MOA of ursodiol?
Increases ratio of bile acids and phospholipids:cholesterol by:
1. decreasing cholesterol synth (inhibits HMG CoA reductase)
2. reducing GI absorption of cholesterol
3. decreases biliary secretion of cholesterol

Promotes formation of a liquid crystalline phase at the surface of gallstones which increases solubility of cholesterol

Gallstones no longer form, and existing stones are dissolved
How effective is gallstone treatment?
-- success rate is 50-80% in pts w/ radioluscent cholesterol stones

-- since reoccurrence rate is 50% w/in 5 years, pts can be maintained on prophylactic therapy indefinitely

-- do not use in pts w/ sever or recurrent biliary colic or cholecystitis: surgery is indicated
Pathophys of primary biliary cirrhosis?
-- an autoimmune disease in which T-cells and eosinophils cause the gradual destruction of the bile ducts

-- diagnosed via elevated plasma alkaline phosphatase and gammaglytamyltransferase and a positive antimitochondrial antibody (AMA) titer. ANA may be positive or negative

-- may become part of a larger autoimmune disease which affects the salivary glands and thyroid (ANA usually positive)

**Also want to look at:
-- plasma bilirubin (↑)
-- PT time (↑)
-- albumin levels (↓)
Treatment of primary biliary cirrhosis?
1. Immunosuppressive therapy w/ corticosteroids has NOT been effective in preventing disease progression

2. Continuous daily therapy w/ ursodiol appears to slow the progression of the disease and increase the time before hepatic transplant is required
Pathophys of hyperlipoproteinemia?
Primarily genetic
Treatment of hyperlipoproteinemia?
1. Chronic ingestion of psyllium lowers total cholesterol by 5-15% and LDL by 10-20%
MOA of psyllium?
The same as bile acid sequestrants cholestyramine and cholestipol and the cmpds which inhibit the GI absorption of cholesterol (EZE and stanols)

1. fecal excretion of bile acids increases due to psyllium binding
2. loss of bile acids decreases intrahepatic conc of the “sterol” pool leading to upregulation of hepatic LDL receptors via the “sterolstat”
3. The increase in hepatic LDL receptors causes a decrease in plasma LDL cholesterol
Pathophys of portal-systemic encephalopathy assoc w/ chronic hepatic disease?
1. Ammonia is probably the neurotoxic substance

2. Exact cause unknown, but severe hepatocellular dysfxn and/or shunting blood away from the liver prevents the liver from detoxifying substances absorbed by the intestine (liver cannot convert ammonia to urea)

In pts w/ stable cirrhosis, encephalopathy us usually precipitated by:
-- increased dietary protein
-- GI bleeding
-- hypokalemic alkalosis secondary to overuse of diuretic agents (directly stims renal ammonia production)
-- severe diarrhea w/ K loss = hypokalemia
Treatment of portal-systemic encephalopathy assoc w/ chronic hepatic disease?
LACTULOSE is used for both acute and chronic therapy
-- acidification of colonic contents causes ammonia in blood to be trapped inside the bowel as ammonium ions which are then excreted in the feces
-- therapy w/ lactulose decreases plasma ammonia by 25-50% and improves mental state and EEG in 75% of pts

**As effective as neomycin (decreases colonic ammonia by killing colonic bacteria)
-- cotreatment w/ lactulose and neomycin have additive effect in lowering plasma ammonia

**AVOID use of antacids during lactulose therapy since they oppose acidification of bowel contents