Flashcards in Bowel Motility Pharm Deck (72):
What drug classes stimulate GI motility?
Dopamine receptor antagonists
5-HT4 receptor agonists
What classes of drugs act as laxatives?
Luminally active agents
Nonspecific stimulants or irritants
Chloride channel activators
What classes of drugs act as antidiarrheal agents?
Octreotide and somatostatin
What does the esophagus do for motility of the GI system?
Propulsive peristalsis to move stuff to stomach
What do the fundus and corpus of the stomach do in response to eating?
Relax to store food
Then slowly increase in tension to move food into antrum
What does the Antrum in the stomach do in response to food?
Mixes and grinds to break up food by alternating contractions with pylorus in order to grinding food by shooting it back and forward
What does the small intestine do in the GI system to process food?
Occasional peristalsis (slow mixing of contents)
Describe GI motility in the colon
Tonic contractions = segmental propulsion
Describe an enteric circuit including the names and general locations of the neurons
EPANs = extrinsic primary afferent neurons
Sense stretch but are not entirely contained in enteric nervous system
IPANs = intrinsic primary afferent neurons
Located in GI wall
Describe the extrinsic innervation of the GIT including the name of the afferent neuron and 3 types of efferent neurons that modulate the enteric circuit
EPAN = afferent => CNS
From CNS, the efferent neurons =
SANS = sympathetic nervous system
PANS = parasympathetic nervous system
NANC = no adrenergic-noncholinergic
Describe the location of the D2 and 5HT-4 receptors within the ENS and the effect of dopamine and serotonin on GI motility
Receptors are located in the GI wall
Dopamine = inhibitory
Serotonin = stimulatory
Why can't mAChR agonists or AChE inhibitors be used as pro-kinetic agents?
Stimulate uncoordinated increased GI motility
= minimal net propulsion
What is the effect of dopamine on GI motility?
Dopamine = inhibitory
What do dopamine antagonists do?
Increase esophageal peristaltic amplitude
Inc. LES pressure (useful for GERD!!!)
🗑Enhance gastric emptying
What is the MOA of metoclopramide?
Effects confined to UPPER digestive tract:
+ stimulates antral/small intestinal contractions
+ inc. LES tone
What is the clinical use for metoclopramide?
Impaired gastric emptying
(post- surgery, diabetic gastroparesis)
Prevention of vomiting
What AEs are associated with metoclopramide?
CNS: restlessness, drowsiness, insomnia, anxiety
Movement problems, Tardive dyskinesia
Inc. prolactin = galactorrhea, gynecomastia, ED, menses issues
Where is serotonin produced and what does it trigger?
Produced by EC cells in response to chemical and mechanical stimulation
Triggers peristaltic reflex
What is the MOA of cisapride?
Weak 5HT3 antagonist
What is the clinical use of cisapride?
Impaired gastric emptying
What AEs are associated with Cisapride?
Fatal cardiac arrhythmias, TdP
What DDIs are associated with Cisapride?
Agents that interfere with CYP3A4 metabolism - that's the CYP that metabolizes cisapride!
How is erythromycin considered a motilide?
Mimics the effects of motilin (peptide hormone found in GI M cells and EC cells = potent contractile agent of the upper GI tract)
What is the clinical use of erythromycin?
What problems are associated with erythromycin use for stimulating GI motility?
Tolerance (downregulation of motilin receptor)
Describe the sequence of treatment for constipation
1. Treat specific cause
2. No diagnosis => symptomatic therapy
+ inc. fluid intake
+ dietary modifications
+ alter lifestyle (exercise)
+ pharmacological therapy (if necessary)
What is meant by laxative habituation?
Longer interval of time needed to refill rectum before defecation after use of laxatives because they will completely evacuate the rectum
What are indications for laxative use?
☠️Acute evacuation of entire intestine for oral poisoning
✅acute cleaning of bowel PRIOR to diagnostic/surgerical procedures
reduce straining in presence of illness
chronic use for anal disorders
💊compensate for drugs with constipating action
What is the general MOA of laxatives?
Stimulation of peristalsis by intraluminal filling
Name 3 types of luminally active agents:
Name two types of nonspecific stimulants or irritants
Name a chloride channel activator
What is the MOA of bulk-forming agents?
Indigestible, hydrophilic substances absorb water to form a bulky, emollient gel
= inc. peristalsis
Softens feces in 1-3 days
What drugs are bulk-forming agents?
What is the MOA of osmotic agents?
Nonabsorbable osmotic agents will increase secretion of water into colon to soften stool and promote defecation
Watery evacuation in 1-3 hours
What drugs are osmotic agents?
Saline laxatives (Mg citrate, Mg(OH)2, sodium phosphate)
Nondigestible sugars and alcohols (lactulose, sorbitol)
What caution is associated with saline laxatives ?
Mg containing products should be avoided in patients with renal insufficiency because they can end up with hypermagnesemia
What is the MOA of stool wetting agents and emollient?
Soften fecal material and allow water to penetrate
What drugs are stool wetting agents and emollients?
(Soften feces in 1-3 days)
(Softening in 6-8 hours)
What are side effects associated with mineral oil?
Interference with absorption of fat soluble substances
Aspiration can result in severe lipid-pneumonia
What is the general MOA of nonspecific stimulants or irritants?
Direct effect on enterocytes, enteric neurons and GI SM
Probably induce low-grade inflammation in small and large bowel to stimulate secretory cells = accumulate water and electrolytes to increase motility
How long until Bisacodyl takes effect?
PO = 6 - 12 hrs
Supp = 30 - 60 min
What AEs are associated with bisacodyl?
What is the MOA of antraquinone laxatives?
Monoanthrones irritate oral mucosa and induce BM in 6-12 hours
What AEs are associated with antraquinone laxatives?
Melanotic pigmentation of colon
How long until castor oil takes effect?
What AEs are associated with castor oil?
What is the MOA of lubiprostone?
Stimulates EP4 receptors on GI epithelial cells
= activation of chloride channels
= Cl rich fluid secretion increases => increased motility
Induce BM in 24 hrs
What is the clinical use of lubiprostone?
Chronic constipation and IBS-C
What AEs and contraindications are associated with lubiprostone?
Contraindicated in pregnancy
Define diarrhea and briefly explain the different types of diarrhea and their underlying mechanisms
Excessively fast passage of bowel contents
1) SECRETORY = inc. fluid transport out of cells into GIT lumen
2) OSMOTIC = inc. luminal osmolarity
3) EXUDATIVE = injury to intestinal epithelial lining
4) DYSMOTILITY = changes in intestinal motility
What are specific causes of the different types of diarrhea?
Secretory = tumors, cholera
Osmotic = malabsorption syndromes (lactose intolerance), antacids, lactulose therapy
Exudative = inflammatory disorders of GIT
Dysmotility = post-surgical
What are 4 classes of anti-diarrheal agents?
Bile acid sequestrants
Octreotide and somatostatin
What are examples of opioid agonists?
What are examples of bile acid sequestrants?
What is the MOA of loperamide?
Opioid receptor activity:
Decrease peristaltic contractions
Inc. segmental contractions (more mixing = more absorbing = dry out!)
What is the clinical use of loperamide?
Acute and chronic diarrhea
What AEs are associated with loperamide?
Provide a rationale for the inclusion of atropine in the commercial preparations of diphenoxylate
Higher doses of diphenoxylate/difenoxin have CNS effects
Inclusion of atropine will prevent abuse by using bothersome anti-cholinergic AEs to deter potential users
What is the clinical use of diphenoxylate/difenoxin?
What AEs are associated with diphenoxylate and difenoxin?
CNS effects (@ high dose) = depression, headache, dizziness
Anti cholinergic effects = dry mouth, blurred vision,, urinary retention
What is the MOA of bile-acid sequestrants?
Bind bile salts and some bacteria
= dec. unbound bile acids
= dec. fluid/electrolyte secretion
What is the clinical use of bile acid sequestrants?
Diarrhea caused by excess fecal bile acids
(In patients with resection of distal ileum or Crohn's Disease)
What AEs are associated with bile acid sequestrants?
What interactions are associated with bile-acid sequestrants?
Should not be given within 2 hours of other drugs
What is the MOA of bismuth compounds?
Direct antimicrobial effects
What is the clinical use of bismuth compounds?
Nonspecific treatment of dyspepsia
Peptic ulcers caused by H.pylori
Acute and travelers diarrhea
What AEs are associated with bismuth compounds?
Black stools and tongue
Absorption of salicylate = Reye's syndrome
What are the physiologic effects of somatostatin?
Inhibits hormone secretion of gastrin, cholecystokinin (CCK), VIP, 5-HT
Dec. intestinal fluid and pancreatic secretion
Dec. GI motility
What is octreotide?
Analog of SST
What is the clinical use of octreotide?
Diarrhea caused by hormone secreting tumors