GI II - Motility and Water Efflux Flashcards
1
Q
Typical motility disorders include:
- ____ of the esophagus. What is this? Result? Can cause?
- ______ = delayed gastric _______
- ___ and neuropathic forms of intestinal _____. Example?
A
Typical motility disorders include:
- 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)
- Gastroparesis = delayed gastric emptying
- Myopathic and neruopathic forms of intestinal dysmotility; IBS or chrons disease
2
Q
Prokinetic Agents and Stimulants of Motility:
- Overall goal?
- Prokinetic agents enchance ______ motility and promote _____.
- Agents enhance the release of _______ neurotransmitters at the _______ without interfering with normal _____ pattern and _____.
A
Prokinetic Agents and Stimulants of Motility:
- Goal = stimulate propulsion
- Enhance coordinated motility and promote transit
- Agents enhance release of excitatory NTs at the NMJ without interfering with normal motility pattern and rhythm
3
Q
2 types of cholinergic agents?
A
Cholinergic agents:
a. Choline derivatives
b. Acetylcholinesterase inhibitors
4
Q
Choline derivatives:
- ___ receptors mediate _____ induced increases intracellular ___ and GI smooth muscle ____
- Drug? However?
A
Choline derivatives:
- M3 receptor mediate ACh induced increases intracellular Ca++ and GI smooth muscle contraction
- Bethanechol; however, lack real efficacy and have broad side effects (bradycardia, flushing, diarrhea, cramps, salivation, and blurred vision)
5
Q
Acetylcholinesterase Inhibitors:
- How do they accelerate GI transit times?
- Drug? Use?
- Side effects of drug? How to reverse?
A
Acetylcholinesterase Inhibitors:
- Accelerate transit times by enhancing contractile effect of ACh released at synaptic and NMJs
- Neostigmine methylsulfate; for acute colonic pseudo-obstruction (ogilvie’s syndrome) and paralytic ileus
- SE = serious bradycardia; make sure atropine is around to reverse
6
Q
Dopamine receptor antagonists:
- Dopamine acts at ____ receptors to _____ GI motility by ______ ACh release from ____ motor neurons.
- Effectiveness? Also relieve?
- Drug?
A
DA receptor antagonists:
- DA acts at D2 receptors to inhibit GI motility by suppressing ACh release from myenteric motor neurons
- Highly effective prokinetic agents and also relieve N/V
- Drug = metoclopramide
7
Q
Metoclopramide:
- Drug class?
- Administration?
- Creates coordinated contractions that enhance ____ primarily by acting on?
- Increases ____ tone and stimulates ____ and _____ _____ contractions
A
Metoclopramide:
- DA D2 antagonist
- Oral, IM, or IV
- Enhance transit by acting on upper digestive tract
- Increases LES tone and stimulates antral and small intestinal contractions
8
Q
Metoclopramide:
- Therapeutic uses? (3)
- Greatest use?
- Adverse effects?
A
Metoclopramide:
- GERD (doesnt heal but relieves symptoms), gastroparesis, and for chemo induced vomitting
- Primary is to ameliorate N/V associated with GI dysmotility syndromes
- Adverse: EPS (dystonia, parkinsonian like symptoms, and tardive dyskinesia) and galactorrhea (rare)
9
Q
Serotonin Receptor Modulators:
- Most of 5-HT is where?
- 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
A
Serotonin Receptor Modulators:
- Most in the enterochromaffin cells of GI tract
- 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
Q
Serotonin Receptor Modulators:
- ___ 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.
- Current agents act at what receptors?
A
Serotonin Receptor Modulators:
- 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.
- Agents act at 5HT3 and 5HT4
11
Q
Serotonin Receptor Modulators:
2 drugs?
A
Serotonin Receptor Modulators:
a. Tegaserod
b. Cisapride
12
Q
Tegaserod:
- Receptor?
- Stimulates ___ and accelerates transit where?
- Stimulates ___ secretion
A
Tegaserod:
- Partial 5HT agonist
- Stimulates motility and accelerates transit everywhere up to the ascending colon (no trans colon/descending colon)
- Stimulates chloride secretion
13
Q
Tegaserod:
Uses:
- Females with?
- Mild to modest improvement of stool _____
- Reduced ____ and pain
A
Tegaserod:
Uses
- Females with constipation IBS****
- Improvement of stool frequency
- Reduced bloating and pain
14
Q
Tegaserod:
- Adverse effects?
- Drug interactions?
A
Tegaserod:
- SE: diarrhea and HA
- Interactions: NONE
15
Q
Cisapride:
- A ______ agonist and ____ ____ antagonist. Increases _____ _____ activity within neurons and may directly stimulate smooth muscle
- Why no longer available?
- ONLY used when?
A
Cisapride:
- A 5HT4 agonist and weak 5HT3 antagonist. Increases adenylyl cyclase activity
- No longer available due to serious and fatal arrhythmias
- Used only in a limited access program for patients who fail ALL standard regimens and undergo a thorough eval and ECG
16
Q
Motilin mimetic drugs?
A
Motilin mimetic drugs:
a. Erythromycin and other macrolide abx like:
b. oleandomycin
c. azithromycin
d. clarithromycin
17
Q
Erythromycin:
- What is a motilin mimetic?
- Action? No effect on?
- Therapeutic uses? (2)
A
Erythromycin:
- Motilin is the hormone that sweeps through the small bowel to “clear”
- Action: increase LES pressure and stimulates gastric and SI contractility; NO effect on colon
- Use: diabetic gastroparesis and “dumping effect” to clear stomach of undigestable residue
18
Q
Agents that suppress motility:
- Smooth muscle ____ treat ____ in which the ___ fails to relax causing severe difficulty in ____
- Agents?
- Mostly for?
A
Agents that suppress motility:
- Smooth muscle relaxants treat achalasia in which the LES fails to relax causing severe difficulty in swallowing
- Agents: organic nitrates, Ca+ antagonists, and Botulinum toxin
- Mostly for esophageal spasm
19
Q
Laxatives act by:
- Enhancing ___ of intraluminal ____
- Decreasing net absorption of ___ by effects on?
- Altering ____ inhibiting segmenting (______) contractions or stimulating ______ contractions
A
Laxatives act by:
- Enhancing retention of intraluminal fluid
- Decreasing net absorption of fluid by effects on SI and LI fluid and electrolyte transport
- Altering motility inhibiting segmenting (nonpropulsive) contractions or stimulating propulsive contractions
20
Q
Classification of laxatives:
3 classes?
A
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
Q
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 ____.
A
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
Q
Dietary fiber and supplements:
6 agents?
A
Dietary fiber and supplements:
a. Bran
b. Pectins and hemicelluloses
c. Psyllium husk
d. Methylcellulose
e. Calcium polycarbophil
23
Q
Dietary fiber and supplements:
- Bran: ____ % dietary fiber with high ____ content and therefore is the most effective at?
- Pectins and hemicelluloses: from ___ and ________. More _____ fiber and produces less effect on stool ____.
- Psyllium husk: contains hydrophilic _____ that undergoes significant _____ in the ___ which increases _____ _____ masses.
A
Dietary fiber and supplements:
- Bran: 40% dietary fiber with high lignin content; most effective at increasing stool weight
- Pectins and hemicelluloses: from fruits and veggies. More fermentable fiber, less effect on stool transit
- Psyllium husk: contains hydrophilic mucilloid that undergoes significatn fermentation in the colon which increases colonic bacterial masses
24
Q
Dietary fiber and supplements:
- Methylcellulose: a __________ cellulose; _____ fermented; absorbs ____ and _____ fecal ___
- Ca++ polycarbophil: Hydrophilic resin; ______ fermented. Absorbs _____ and _____ fecal _____
A
Dietary fiber and supplements:
- Methylcellulose: a semisynthetic cellulose; poorly fermented; absorbs water and increases fecal bulk
- 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
4 _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 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
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 agents_: _Carboxymethylcellulose, 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 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
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 _antisecretory_, _antiinflammatory_, 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-ejection_: _gastric_ relaxation and retro**_peristalsis_**
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
