GI II - Motility and Water Efflux

Question 1

Typical motility disorders include:

1. ____ of the esophagus. What is this? Result? Can cause?
2. ______ = delayed gastric _______
3. ___ and neuropathic forms of intestinal _____. Example?

Answer 1

Typical motility disorders include:

1. Achalasia of the esophagus. This is impaired relaxation of the LES associated with defective esophageal peristalsis. Results in dysphagia and regurgitation (can cause aspiration and pneumonia)
2. Gastroparesis = delayed gastric emptying
3. Myopathic and neruopathic forms of intestinal dysmotility; IBS or chrons disease

Question 2

Prokinetic Agents and Stimulants of Motility:

1. Overall goal?
2. Prokinetic agents enchance ______ motility and promote _____.
3. Agents enhance the release of _______ neurotransmitters at the _______ without interfering with normal _____ pattern and _____.

Answer 2

Prokinetic Agents and Stimulants of Motility:

1. Goal = stimulate propulsion
2. Enhance coordinated motility and promote transit
3. Agents enhance release of excitatory NTs at the NMJ without interfering with normal motility pattern and rhythm

Question 3

2 types of cholinergic agents?

Answer 3

Cholinergic agents:

a. Choline derivatives
b. Acetylcholinesterase inhibitors

Question 4

Choline derivatives:

1. ___ receptors mediate _____ induced increases intracellular ___ and GI smooth muscle ____
2. Drug? However?

Answer 4

Choline derivatives:

1. M3 receptor mediate ACh induced increases intracellular Ca++ and GI smooth muscle contraction
2. Bethanechol; however, lack real efficacy and have broad side effects (bradycardia, flushing, diarrhea, cramps, salivation, and blurred vision)

Question 5

Acetylcholinesterase Inhibitors:

1. How do they accelerate GI transit times?
2. Drug? Use?
3. Side effects of drug? How to reverse?

Answer 5

Acetylcholinesterase Inhibitors:

1. Accelerate transit times by enhancing contractile effect of ACh released at synaptic and NMJs
2. Neostigmine methylsulfate; for acute colonic pseudo-obstruction (ogilvie’s syndrome) and paralytic ileus
3. SE = serious bradycardia; make sure atropine is around to reverse

Question 6

Dopamine receptor antagonists:

1. Dopamine acts at ____ receptors to _____ GI motility by ______ ACh release from ____ motor neurons.
2. Effectiveness? Also relieve?
3. Drug?

Answer 6

DA receptor antagonists:

1. DA acts at D2 receptors to inhibit GI motility by suppressing ACh release from myenteric motor neurons
2. Highly effective prokinetic agents and also relieve N/V
3. Drug = metoclopramide

Question 7

Metoclopramide:

1. Drug class?
2. Administration?
3. Creates coordinated contractions that enhance ____ primarily by acting on?
4. Increases ____ tone and stimulates ____ and _____ _____ contractions

Answer 7

Metoclopramide:

1. DA D2 antagonist
2. Oral, IM, or IV
3. Enhance transit by acting on upper digestive tract
4. Increases LES tone and stimulates antral and small intestinal contractions

Question 8

Metoclopramide:

1. Therapeutic uses? (3)
2. Greatest use?
3. Adverse effects?

Answer 8

Metoclopramide:

1. GERD (doesnt heal but relieves symptoms), gastroparesis, and for chemo induced vomitting
2. Primary is to ameliorate N/V associated with GI dysmotility syndromes
3. Adverse: EPS (dystonia, parkinsonian like symptoms, and tardive dyskinesia) and galactorrhea (rare)

Question 9

Serotonin Receptor Modulators:

1. Most of 5-HT is where?
2. 5HT released from EC stimulates ____, ____, and _____ ___ through ____ receptors in the extrinsic ___ and _____ sensory afferent neurons and the ____ reflex by stimulating ____ receptors in intrinsic ____ neurons in the _______ plexus

Answer 9

Serotonin Receptor Modulators:

1. Most in the enterochromaffin cells of GI tract
2. 5HT released from EC stimulates N/V and ab pain through 5HT3 receptors in the extrinsic vagal and spinal sensory aferent neurons and the peristaltic reflex by stimulating 5HT1p receptors in intrinsic seonsory neurons in the myenteric plexus

Question 10

Serotonin Receptor Modulators:

1. ___ receptors facilitate the release of ACh and ____ at the terminals which activate _____ nerve pathways. It also stimulates submucosal intrinsic ____ neurons to activate ____ reflexes resulting in _____ secretion.
2. Current agents act at what receptors?

Answer 10

Serotonin Receptor Modulators:

1. 5HT4 facilitate release of ACh and CGRP at the terminals which activate peristaltic nerve pathways. It also stimulates submucosal intrinsic afferent neurons to activate secretomotor reflexes resulting in epithelial secretion.
2. Agents act at 5HT3 and 5HT4

Question 11

Serotonin Receptor Modulators:

2 drugs?

Answer 11

Serotonin Receptor Modulators:

a. Tegaserod
b. Cisapride

Question 12

Tegaserod:

1. Receptor?
2. Stimulates ___ and accelerates transit where?
3. Stimulates ___ secretion

Answer 12

Tegaserod:

1. Partial 5HT agonist
2. Stimulates motility and accelerates transit everywhere up to the ascending colon (no trans colon/descending colon)
3. Stimulates chloride secretion

Question 13

Tegaserod:

Uses:

1. Females with?
2. Mild to modest improvement of stool _____
3. Reduced ____ and pain

Answer 13

Tegaserod:

Uses

1. Females with constipation IBS****
2. Improvement of stool frequency
3. Reduced bloating and pain

Question 14

Tegaserod:

1. Adverse effects?
2. Drug interactions?

Answer 14

Tegaserod:

1. SE: diarrhea and HA
2. Interactions: NONE

Question 15

Cisapride:

1. A ______ agonist and ____ ____ antagonist. Increases _____ _____ activity within neurons and may directly stimulate smooth muscle
2. Why no longer available?
3. ONLY used when?

Answer 15

Cisapride:

1. A 5HT4 agonist and weak 5HT3 antagonist. Increases adenylyl cyclase activity
2. No longer available due to serious and fatal arrhythmias
3. Used only in a limited access program for patients who fail ALL standard regimens and undergo a thorough eval and ECG

Question 16

Motilin mimetic drugs?

Answer 16

Motilin mimetic drugs:

a. Erythromycin and other macrolide abx like:
b. oleandomycin
c. azithromycin
d. clarithromycin

Question 17

Erythromycin:

1. What is a motilin mimetic?
2. Action? No effect on?
3. Therapeutic uses? (2)

Answer 17

Erythromycin:

1. Motilin is the hormone that sweeps through the small bowel to “clear”
2. Action: increase LES pressure and stimulates gastric and SI contractility; NO effect on colon
3. Use: diabetic gastroparesis and “dumping effect” to clear stomach of undigestable residue

Question 18

Agents that suppress motility:

1. Smooth muscle ____ treat ____ in which the ___ fails to relax causing severe difficulty in ____
2. Agents?
3. Mostly for?

Answer 18

Agents that suppress motility:

1. Smooth muscle relaxants treat achalasia in which the LES fails to relax causing severe difficulty in swallowing
2. Agents: organic nitrates, Ca+ antagonists, and Botulinum toxin
3. Mostly for esophageal spasm

Question 19

Laxatives act by:

1. Enhancing ___ of intraluminal ____
2. Decreasing net absorption of ___ by effects on?
3. Altering ____ inhibiting segmenting (______) contractions or stimulating ______ contractions

Answer 19

Laxatives act by:

1. Enhancing retention of intraluminal fluid
2. Decreasing net absorption of fluid by effects on SI and LI fluid and electrolyte transport
3. Altering motility inhibiting segmenting (nonpropulsive) contractions or stimulating propulsive contractions

Question 20

Classification of laxatives:

3 classes?

Answer 20

3 classes of laxatives:

a. Luminally active agents
b. Nonspecific stimulant or irritants (effects on fluid secretion and motility)
c. Prokinetic agents (act on motility)

Question 21

Dietary Fiber and Supplements:

Colonic bacteria variably _____ fiber to (1) produce short chain ____ ____ that are trophic for ____ epithelium and may be _____, and (2) increase ____ mass. Fiber that is not _____ (such as ____) attracts water, increases stool ____, and increases stool ____.

Answer 21

Dietary fiber and supplements:

Colonic bacteria ferment fiber to (1) produce short chain fatty acids that are trophic for colonic epithelium and may be prokinetic, and (2) increase bacterial mass. Fiber that is not fermented (lignin) attracts water, increases stool bulk and increases stool transit

Question 22

Dietary fiber and supplements:

6 agents?

Answer 22

Dietary fiber and supplements:

a. Bran
b. Pectins and hemicelluloses
c. Psyllium husk
d. Methylcellulose
e. Calcium polycarbophil

Question 23

Dietary fiber and supplements:

1. Bran: ____ % dietary fiber with high ____ content and therefore is the most effective at?
2. Pectins and hemicelluloses: from ___ and ________. More _____ fiber and produces less effect on stool ____.
3. Psyllium husk: contains hydrophilic _____ that undergoes significant _____ in the ___ which increases _____ _____ masses.

Answer 23

Dietary fiber and supplements:

1. Bran: 40% dietary fiber with high lignin content; most effective at increasing stool weight
2. Pectins and hemicelluloses: from fruits and veggies. More fermentable fiber, less effect on stool transit
3. Psyllium husk: contains hydrophilic mucilloid that undergoes significatn fermentation in the colon which increases colonic bacterial masses

Question 24

Dietary fiber and supplements:

1. Methylcellulose: a __________ cellulose; _____ fermented; absorbs ____ and _____ fecal ___
2. Ca++ polycarbophil: Hydrophilic resin; ______ fermented. Absorbs _____ and _____ fecal _____

Answer 24

Dietary fiber and supplements:

1. Methylcellulose: a semisynthetic cellulose; poorly fermented; absorbs water and increases fecal bulk
2. Ca++ polycarbophil: hydrophilic resin; poorly fermented; absorbs water and increases fecal bulk

Question 25

Dietary fiber and supplements:

1. Single adverse effect?
2. General contraindications?
3. Ca++ polycarbophil preparations release ____ that are contraindicated in patients on _____ restriction or those taking _____

Answer 25

Dietary fiber and supplements:

1. Adverse effect = bloating
2. Contraindication: megacolon, megarectum, or obstruction
3. Ca++ polycarbophil releases Ca++ that are contraindicated in patients on Ca++ restriction or those taking tetracycline

Question 26

4 types of laxative drugs?

Answer 26

Laxative drugs:

a. Saline laxatives
b. Nondigestable/nonabsorbable sugars and alcohols
c. Polyethylene Glycol-electrolyte solutions
d. Stool-wetting agents

Question 27

Saline laxatives:

1. 4 drugs?
2. These are ___ rather than laxative - results from _____ mediated water retention which then stimulates ____

Answer 27

Saline laxatives:

1. Mg sulfate, Mg hydroxide, Mg citrate, Na phosphate
2. These are cathartic rather than laxative - results from osmotically mediated water retention which then stimulates peristalsis

Question 28

Nondigestible sugars and alcohols:

3 drugs?

Answer 28

Nondigestible sugars and alcohols:

a. Lactulose
b. Sorbitol
c. Mannitol

Question 29

Nondigestible sugars and alcohols:

1. Lactulose: resists intestinal ______ activity and _____ draws water into the lumen.
2. Sorbitol and Mannitol: _____ in the colon to ____-____ ____ ____ which osmotically draws water into the lumen and stimulates?
3. Common side effects?

Answer 29

Nondigestible sugars and alcohols:

1. Lactulose: resists intestinal disaccharidase activity and osmotically draws H2O into the lumen
2. Sorbitol and Mannitol: hydrolyzed in the colon to short-chain fatty acids which osmotically draw water into the lumen and stimulates colonic propulsive activity
3. SE: discomfort, distention, and flatulence

Question 30

Polyethylene glycol electrolyte solutions:

1. ____ solutions of long chain polyethylene glycols with ____ to prevent net transfer of ____ across the intestine.
2. Absorption?
3. Highly ____ and used in high volume for ____ as colonic cleansing for?

Answer 30

Polyethylene glycol electrolyte solutions:

1. Aqueous solution of LC PEglycols with salts to prevent net transfer of ions across the intestine
2. Poor absorption
3. Highly osmotic used in high volume for catharsis as colonic cleansing for radiological, surgical and endoscopic procedures

Question 31

Stool-Wetting Agents:

2 agents?

Answer 31

Stool-Wetting Agents:

a. Docusate sodium
b. Mineral oil

Question 32

Stool-Wetting Agents:

Docusate sodium:

1. These are _____ ____ that lower the ____ ___ of the stool to allow mixing of ___ and ___ substances, softening the stool and permitting easier defecation. Stimulate secretion of?
2. Alter intestinal mucosal ______.
3. Effectiveness?

Answer 32

Stool-Wetting Agents:

Docusate sodium:

1. These are anionic surfactants that lower surface tension of the stool to allow mixing of aqueous and fatty substances. Stimulate secretion of fluid and electrolytes
2. Alter intestinal mucosal permeability
3. Limited effectiveness

Question 33

Stool-Wetting Agents:

Minteral Oil:

1. ____ and ____ stool and may interfere with?
2. SE: interference with absorption of ____-____ substances (such as _____); elicitation of ____-____ reaction in the mucosa; leakage of oil past the _____ ____.
3. _____ _____ limit the usefulness

Answer 33

Stool-Wetting Agents:

Minteral Oil:

1. Penetrates and softens stool; interefere w/ H2O resorption
2. SE: interference with absorp. of fat-soluble substance (vitamins); elicitation of foreign-body reaction; anal leakage
3. Side effects limit usefullness

Question 34

Stimulant laxatives:

1. Direct effect on?
2. Induce a low grade ____ response that promotes? and stimulates?

Answer 34

Stimulant laxatives:

1. Direct effect on enterocytes, enteric neurons, and GI smooth muscle
2. Induces a low grade inflammatory response that promotes water and electrolyte accumulation and stimulates motility in the small and large intestine

Question 35

Stimulant laxatives:

3 classes/types?

Answer 35

Stimulant laxatives:

a. Diphenylmethane derivatives
b. Anthraquinone laxatives
c. caster oil

Question 36

Diphenylmethane derivatives:

1. Drug?
2. Requires ____ by endogenous ____ in the ____.
3. Adverse effects?

Answer 36

Diphenylmethane derivatives

1. Bisacodyl
2. Requires activation by endogenous esterases in the colon
3. Adverse effect: OD can lead to catharsis and fluid/electrolyte deficit and mucosal inflammation in small bowel and colon

Question 37

Anthraquinone Laxatives:

1. Derivatives of what plants? Only one used?
2. Produce what?
3. Induce what?

Answer 37

Anthraquinone Laxatives:

1. Derivatives of aloe, cascara, and senna; only senna used
2. Produce giant migrating colonic contractions
3. Induce water and electrolyte secretion

Question 38

Caster oil

1. Contains what 2 noxious ingredients?
2. Both a ____ and _____ agent

Answer 38

Caster oil

1. Noxious agents: ricin and ricinoleic acid
2. Both a laxative and cathartic agent

Question 39

Other:

1. 5HT4 receptor agonists such as ____ and ____ may alleviate chronic _____
2. Lubiprostone: useful in treating ______. It is a ____ channel activator in the ___ membrane of intestinal _____ epithelium. Activation of ____ secretion results in production of a ____ rich fluid into the lumen which stimulates ____ and relieves ____

Answer 39

Other:

1. 5HT receptor agonists such as tegaserod and misoprosotol may alleviate chronic constipation by stimulating GI motility
2. Lubiprostone: useful in treating IBS-C. It is a Cl- channel activator in the apical membrane of intestinal mucosal epithelium. Activation of Cl- secretion results in production of a chloride rich fluid into the lumen which stimulates motility and relieves constipation

Question 40

Diarrhea can be caused by:

1. _________ ______ load within the intestine.
2. Excessive _____ of ____ and water into the lumen
3. _____ of _____ and fluid from the mucosa
4. Altered motility resulting in _____ transit and ____ fluid _____

Answer 40

Diarrhea can be caused by:

1. Increased osmotic load
2. Excessive secretion of electrolytes and water into the lumen
3. Exudation of protein and fluid from the mucosa
4. Altered motility resulting in rapid transit and decreased fluid absorption

Question 41

Agents and treatments for diarrhea:

1. Oral ______ therapy
2. _____ Forming and ______ agents
3. ____ ____ sequestrants
4. _____
5. Anti-_____ and Anti-______ agents
6. What other two drugs?

Answer 41

Agents and treatments for diarrhea:

1. Oral rehydration therapy
2. Bulk forming and hydroscopic agents
3. Bile acid sequestrants
4. Bismuth
5. Anti-_motility_ and Anti-_secretory_ agents
6. Octreotide and Somatostatin

Question 42

Diarrheal agents and treatment:

1. Oral rehydration therapy: balanced mixture of ____ and ____ in volumes matched to?
2. Bulk forming and hydroscopic agents: 3 drugs? Useful for? Thought to create a ___ that increases?

Answer 42

Diarrheal agents and treatment:

1. Oral rehydration: balanced mixture of glucose and electrolytes in volumes matched to loss
2. Bulk/hydroscopic agents: Carboxymethylcellulose, Kaolin, and Attapulgite; useful for mild chronic diarrhea; thought to create a gel that increases stool viscosity

Question 43

Diarrheal agents and treatment:

Bile acid sequesterants: drug? Binds bile acids and some? Used to treat bile ____ induced ____ (eg: pt with ____ of distal ____) and mild _____ diarrhea

Answer 43

Diarrheal agents and treatment:

1. BA sequesterants: Cholestyramine; binds bile acids and some bacterial toxins; used to treat bile salt induced diarrhea (eg: pt with resection of distal ileum) and mild antibiotic diarrhea

Question 44

Diarrheal agents and treatment:

Bismuth:

1. Drug?
2. Bismuth has _____, ____, and ____ effects while also relieving ____ and abdominal cramps
3. Used for the prevention of _______ diarrhea, _____ diarrhea, and acute _____

Answer 44

Diarrheal agents and treatment:

Bismuth:

1. Bismuth subsalicylate + MgAl clay
2. Bismuth has antisecretory, antiinflammatory, and antimicrobial effects while also relieving nausea
3. Prevention of traveler’s diarrhea, episodic diarrhea, and acute gastroenteritis

Question 45

Diarrheal agents and treatment:

Antimotility and Antisecretory Agents:

1. 4 drugs?
2. Action mediated through either m- or d- _____ receptors on ____ nerves, _____ cells, and muscle.

Answer 45

Diarrheal agents and treatment:

Antimotility and Antisecretory Agents:

1. Opioids, Diphenoxylate, Difenoxin, and Loperamide
2. Action mediated through either m- or d- opioid receptors on enteric nerves, epithelial cells, and muscle

Question 46

Diarrheal agents and treatment:

Antimotility and Antisecretory Agents:

1. Loperamide is 40/50X more potent than ____ as an _____ agent and penetrates the ____ poorly
2. Loperamide has _____ activity against _____ ____ and some forms of _______.
3. What of the 4 drugs is over the counter?

Answer 46

Diarrheal agents and treatment:

Antimotility and Antisecretory Agents:

1. Loperamide is 40/50X more potent than morphine as an antidiarrheal agent and penetrates the CNS poorly
2. Loperamide has antisecretory activity against cholera toxin and some forms of E. coli
3. Over the counter = loperamide

Question 47

Diarrheal agents and treatment:

Octreotide and Somatostatin:

1. Effective in inhibiting severe secretory diarrhea brought about by?
2. Has some effectiveness in secretory diarrhea associated with ____ and ____ infection
3. Very effective in treating?

Answer 47

Diarrheal agents and treatment:

Octreotide and Somatostatin:

1. Effective in inhibiting diarrhea from hormone-secreting tumors of the pancreas and GI tract
2. Some effectiveness in diarrhea of chemo and HIV
3. Very effective in treating post gastric surgical “dumping syndrome”

Question 48

Nausea and vomiting:

1. Three phases of vomitting?
2. This is accompanied by mutiple autonomic phenomena including _____, _____, and _____ changes.
3. Receptors for ____, ____, and ____ participate in these phenomena as do receptors for ____, histamine, and ____ in the _____ ____ nucleus

Answer 48

Nausea and vomitting:

1. Phases: pre-ejection phase, retching, and ejection
2. This is accompanied by mutiple autonomic phenomena including salivation, shivering, and vasomotor changes
3. Receptors for serotonin (5HT3), dopamine (D2), and opioids participate as do receptors for enkaphalin, histamine, and ACh in the solitary tract nucleus

Question 49

Vomitting phases:

1. Pre-ejection: _____ relaxation and retro_____
2. Retching: rhythmic action of ____ muscles preceeding vomitting and consisting of contraction of ____ and ____ muscles and the ____ against?
3. Ejection: intense contraction of the ____ muscles and ____ of the upper _____ ____.

Answer 49

Vomitting phases:

1. Pre-ejection: gastric relaxation and retroperistalsis
2. Retching: rhythmic action of respiratory muscles consisting of contraction of abdominal and intercostal muscles and the diaphragm against a closed glottis
3. Ejection: intense contraction of the abdominal muscles and relaxation of the upper esophageal sphincter

Question 50

6 antiemetic classes?

Answer 50

Antiemetic classes:

a. 5HT3 receptor antagonists
b. Centrally acting DA receptor antagonists
c. H1 receptor antagonists
d. Muscarinic receptor antagonists
e. Neurokinin receptor antagonists
f. Cannabinoid receptor agonists

Question 51

Antiemetics:

1. 5HT3 receptor antagonists: drug? most effective against?
2. DA receptor antagonists: drugs? most effective against?
3. Histamine H1 receptor antagonists: drug? Most effective against?

Answer 51

Antiemetics:

1. 5HT3: Ondansetron for cytotoxic drug induced emesis (like chemo)
2. DA: Metochlopramide and Promethazine for cytotoxic drug induced emesis
3. H1: cyclizine for vestibular emesis (motion sickness)

Question 52

Antiemetics:

1. Muscarinic receptor antagonists: drug? most effective against?
2. Neurokinin receptor antagonists: drug? Most effective against?
3. Cannabinoid receptor antagonists: drug? most effective against?

Answer 52

Antiemetics:

1. Muscarinic: Hyoscine (scopolamine) for motion sickness
2. Neurokinin: Aprepitant for cytotoxic drug induced emesis (delayed vomiting (cisplatin?))
3. Cannabinoid: dronabinol for cytotoxic drug induced emesis