GI II - Motility and Water Efflux Flashcards Preview

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Flashcards in GI II - Motility and Water Efflux Deck (52):
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?

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

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 _____.

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

3

2 types of cholinergic agents?

Cholinergic agents:

a. Choline derivatives

b. Acetylcholinesterase inhibitors

4

Choline derivatives:

1. ___ receptors mediate _____ induced increases intracellular ___ and GI smooth muscle ____

2. Drug? However?

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)

5

Acetylcholinesterase Inhibitors:

1. How do they accelerate GI transit times?

2. Drug? Use? 

3. Side effects of drug? How to reverse?

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

6

Dopamine receptor antagonists:

1. Dopamine acts at ____ receptors to _____ GI motility by ______ ACh release from ____ motor neurons.

2. Effectiveness? Also relieve?

3. Drug?

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

7

Metoclopramide:

1. Drug class?

2. Administration?

3. Creates coordinated contractions that enhance ____ primarily by acting on?

4. Increases ____ tone and stimulates ____ and _____ _____ contractions

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

8

Metoclopramide:

1. Therapeutic uses? (3)

2. Greatest use?

3. Adverse effects?

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)

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

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

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?

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

11

Serotonin Receptor Modulators:

2 drugs?

Serotonin Receptor Modulators:

a. Tegaserod

b. Cisapride

12

Tegaserod:

1. Receptor?

2. Stimulates ___ and accelerates transit where?

3. Stimulates ___ secretion

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

13

Tegaserod:

Uses:

1. Females with?

2. Mild to modest improvement of stool _____

3. Reduced ____ and pain

Tegaserod:

Uses

1. Females with constipation IBS**** 

2. Improvement of stool frequency

3. Reduced bloating and pain

14

Tegaserod:

1. Adverse effects?

2. Drug interactions?

Tegaserod:

1. SE: diarrhea and HA

2. Interactions: NONE

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?

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

16

Motilin mimetic drugs?

Motilin mimetic drugs:

a. Erythromycin and other macrolide abx like:

b. oleandomycin

c. azithromycin

d. clarithromycin

17

Erythromycin:

1. What is a motilin mimetic?

2. Action? No effect on?

3. Therapeutic uses? (2)

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

18

Agents that suppress motility:

1. Smooth muscle ____ treat ____ in which the ___ fails to relax causing severe difficulty in ____

2. Agents?

3. Mostly for?

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

19

Laxatives act by:

1. Enhancing ___ of intraluminal ____

2. Decreasing net absorption of ___ by effects on?

3. Altering ____ inhibiting segmenting (______) contractions or stimulating ______ contractions

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

20

Classification of laxatives:

3 classes?

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)

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 ____.

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

22

Dietary fiber and supplements:

6 agents?

Dietary fiber and supplements:

a. Bran

b. Pectins and hemicelluloses

c. Psyllium husk

d. Methylcellulose

e. Calcium polycarbophil

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.

Dietary fiber and supplements:

1. Bran40% 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

24

Dietary fiber and supplements:

1. Methylcellulose: a __________ cellulose; _____ fermented; absorbs ____ and _____ fecal ___

2. Ca++ polycarbophil: Hydrophilic resin; ______ fermented. Absorbs _____ and _____ fecal _____

 

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

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 _____

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

26

types of laxative drugs?

Laxative drugs:

a. Saline laxatives

b. Nondigestable/nonabsorbable sugars and alcohols

c. Polyethylene Glycol-electrolyte solutions

d. Stool-wetting agents

 

27

Saline laxatives:

1. 4 drugs?

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

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

28

Nondigestible sugars and alcohols:

3 drugs?

Nondigestible sugars and alcohols:

a. Lactulose

b. Sorbitol

c. Mannitol

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?

Nondigestible sugars and alcohols:

1. Lactulose: resists intestinal disaccharidase activity and osmotically draws H2O into the lumen

2. Sorbitol and Mannitolhydrolyzed 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

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?

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

31

Stool-Wetting Agents:

2 agents?

Stool-Wetting Agents:

a. Docusate sodium

b. Mineral oil

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?

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

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

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

34

Stimulant laxatives:

1. Direct effect on?

2. Induce a low grade ____ response that promotes? and stimulates?

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

35

Stimulant laxatives:

3 classes/types?

Stimulant laxatives:

a. Diphenylmethane derivatives

b. Anthraquinone laxatives

c. caster oil

36

Diphenylmethane derivatives:

1. Drug?

2. Requires ____ by endogenous ____ in the ____.

3. Adverse effects?

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

37

Anthraquinone Laxatives:

1. Derivatives of what plants? Only one used?

2. Produce what?

3. Induce what?

Anthraquinone Laxatives:

1. Derivatives of aloe, cascara, and senna; only senna used

2. Produce giant migrating colonic contractions

3. Induce water and electrolyte secretion

38

Caster oil

1. Contains what 2 noxious ingredients?

2. Both a ____ and _____ agent

Caster oil

1. Noxious agents: ricin and ricinoleic acid

2. Both a laxative and cathartic agent

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 ____

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

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 _____

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

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?

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 

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?

Diarrheal agents and treatment:

1. Oral rehydration: balanced mixture of glucose and electrolytes in volumes matched to loss

2. Bulk/hydroscopic agentsCarboxymethylcellulose, Kaolin, and Attapulgite; useful for mild chronic diarrhea; thought to create a gel that increases stool viscosity

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

Diarrheal agents and treatment:

1. BA sequesterantsCholestyramine; 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

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 _____

Diarrheal agents and treatment:

Bismuth:

1. Bismuth subsalicylate + MgAl clay

2. Bismuth has antisecretoryantiinflammatory, and antimicrobial effects while also relieving nausea

3. Prevention of traveler's diarrhea, episodic diarrhea, and acute gastroenteritis

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.

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

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?

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

4. Over the counter = loperamide

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?

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"

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

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

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 _____ ____.

Vomitting phases:

1. Pre-ejectiongastric 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

50

6 antiemetic classes?

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

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?

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)

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?

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