Pharmacology Flashcards
What are the pharmacokinetic properties and mechanisms of action of drugs used in bowel motility disorders?
They vary by class and subclass but share a common thread in their clinical applications.
What should students be able to do after completing the preparation materials?
Describe pharmacokinetic properties, relate clinical applications, and correlate adverse effects of bowel motility drugs.
Name the types of disorders related to gut motility.
- Impaired gastric emptying / Ileus
- Diarrhea
- Constipation
- Irritable bowel syndrome (IBS)
- IBS-C
- IBS-D
What are the classes of drugs for disorders of gut motility?
- Prokinetic agents
- Antidiarrheals
- Laxatives
- Antispasmodics
- Antibiotics
What is the mechanism of action of prokinetic agents like Metoclopramide?
Antagonism of dopamine’s inhibitory effect on myenteric motor neurons.
List some uses of Metoclopramide.
- Diabetic gastroparesis
- Post-pyloric enteral tube placement
- Radiologic exam of stomach
- Chronic intestinal pseudo-obstruction
What are the adverse effects of Metoclopramide?
- Depression
- Dizziness
- Sedation
- Extrapyramidal side effects
- Tardive dyskinesia
True or False: Domperidone crosses the blood-brain barrier.
False
What are the effects of Erythromycin as a motilin receptor agonist?
- Stimulates motilin receptors
- Induces high amplitude propulsive contractions
- Effective in gastroparesis
What are the possible adverse effects of Erythromycin?
- Small bowel spasms
- Vomiting
- QT interval prolongation
Fill in the blank: _______ is a cholinesterase inhibitor that enhances contractile effects of ACh.
Neostigmine
What is the mechanism of action of mu Opioid Receptor (MOR) agonists in treating diarrhea?
Stimulate peripheral MORs on enteric nerves and GI epithelial cells.
List the therapeutic uses of Bismuth subsalicylate.
- Nausea and vomiting
- Mild, nonspecific diarrhea
- Traveler’s diarrhea
- H. pylori eradication
What are some risk factors for serious adverse drug effects in bowel motility treatments?
Specific risk factors vary by drug class and mechanism of action.
What are the main dopaminergic pathways of the brain?
- Mesocortical pathway
- Mesolimbic pathway
- Nigrostriatal pathway
- Tuberoinfundibular pathway
What is a potential adverse effect of high doses of Loperamide?
QTc prolongation leading to ventricular arrhythmia.
What is the role of serotonin in the mechanism of bowel motility?
Mucosal stimulation leads to release of serotonin which excites intrinsic primary afferent neurons.
Fill in the blank: The chemoreceptor trigger zone is located at the caudal end of the _______.
fourth ventricle
What is the primary action of bismuth subsalicylate?
Antisecretory effects, anti-inflammatory effects, antimicrobial action, coats and protects intestinal mucosa, adsorbs intestinal toxins or microorganisms
List the therapeutic uses of bismuth subsalicylate.
- Nausea and vomiting
- Mild, nonspecific diarrhea
- Traveler’s diarrhea
- H. pylori eradication
What are common side effects of bismuth subsalicylate?
- Impaction
- Dark stools (harmless)
- Black tongue (harmless)
True or False: Bile acid sequestrants form a nonabsorbable complex that is excreted in the urine.
False
What conditions are treated with bile acid sequestrants?
- Bile salt-induced diarrhea
- Inflammatory bowel disease
- Irritable bowel syndrome-diarrhea
- Post-colectomy
- Radiation therapy of abdomen
What are the potential adverse effects of bile acid sequestrants?
- Bloating
- Flatulence
- Constipation
- Fecal impaction
What is the mechanism of action of octreotide?
Inhibits secretion of GI hormones such as serotonin, gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide
What are the therapeutic uses of octreotide?
- Severe secretory diarrhea caused by carcinoid tumors
- Gastroenteropancreatic tumors
- VIP-secreting tumors (VIPomas)
- Acromegaly
- Variceal and upper GI bleeding
What is the onset time for bulk-forming laxatives?
12-72 hours
Fill in the blank: Docusate salts are classified as _______.
Stool softeners
What is the primary action of osmotic agents like PEG 3350?
Osmotically draws water into the lumen
What is the mechanism of lactulose in the management of hepatic encephalopathy?
Acidifies pH in colon, shifts NH3 to NH4+, inhibits diffusion of NH3 from colon to circulation
What are the cautions associated with saline laxatives?
- Magnesium toxicity
- Renal impairment
- Neuromuscular disease (Myasthenia gravis)
- Acute phosphate nephropathy
What are the main classes of laxatives?
- Bulk-forming laxatives
- Stool softeners
- Osmotic laxatives
- Stimulant laxatives
- Peripherally acting mu-opioid receptor antagonists
What are the primary uses of peripherally acting mu-opioid receptor antagonists?
- Opioid-induced constipation in cancer pain
- Chronic non-cancer pain
- Post-operative ileus
What are the adverse effects of linaclotide and plecanatide?
- Diarrhea
- Dehydration
True or False: Guanylate cyclase 2C agonists increase intestinal fluid and motility.
True
What is Tenapanor’s mechanism of action?
Inhibits NHE3 on enterocytes, reduces dietary Na+ and water absorption
What is the primary action of lubiprostone?
Activates chloride channel type 2 (ClC-2) to increase chloride-rich fluid secretions
What are common adverse effects of lubiprostone?
- Nausea
- Abdominal pain
- Diarrhea
- Flatulence
- Headache
- Dyspnea
What is the mechanism of action for Chloride channel activators?
Activates chloride channel type 2 (ClC-2) on apical aspect of GI epithelial cells
This activation leads to increased chloride-rich fluid secretions, softening stool, increasing motility, and promoting spontaneous bowel movements.
List two adverse effects of Chloride channel activators.
- Nausea
- Abdominal pain
What is Prucalopride classified as?
5-HT4 Receptor Agonist
It is indicated for severe, refractory cases.
What is the elimination route for Prucalopride?
Excretion: Urine (unchanged mainly)
It has a half-life of approximately 24 hours.
What conditions is Prucalopride used to treat?
- Chronic Idiopathic Constipation (CIC)
- Opioid-induced chronic constipation
True or False: Tegaserod is currently available on the market.
False
Tegaserod was withdrawn from the market due to safety concerns.
What neurotransmitter release is enhanced by the activation of 5-HT4 receptors?
- Acetylcholine (ACh)
- Calcitonin gene-related peptide (CGRP)
What are the indications for Alosetron?
Used in adult females only with severe diarrhea and chronic IBS symptoms
Generally for patients who have failed to respond to other therapies.
Fill in the blank: The mechanism of Eluxadoline involves mixed ______ receptor actions.
opioid
List two key therapeutic uses of Octreotide.
- Inhibit severe secretory diarrhea
- Treatment of acromegaly
What is the mechanism of action for Loperamide?
Activates mu opioid receptors in the enteric nervous system
This action slows motility.
What type of laxative is PEG 3350 classified as?
Osmotic agent
It increases water content of stool.
What is the primary action of bulk-forming laxatives?
Absorb water to increase volume and stimulate evacuation.
What is the mechanism of action for Methylnaltrexone?
Blocks intestinal mu opioid receptors but does not enter CNS.
What are the adverse effects of Eluxadoline?
- Constipation
- Nausea
What is the role of serotonin (5-HT) in gastrointestinal function?
Stimulates submucosal intrinsic primary afferent neurons (IPANs) via 5-HT1P receptors.
List two adverse effects associated with Alosetron.
- Ischemic colitis
- Complications of constipation
What is the therapeutic use of Lubiprostone?
- IBS-C
- Chronic Idiopathic Constipation
- Opioid-induced constipation
What is the mechanism of action for Stimulant laxatives like bisacodyl?
Direct action on intestinal mucosa and nerve plexus to stimulate peristalsis.
True or False: Octreotide is only administered orally.
False
It can be administered via I.V., subcutaneous, intramuscular long-acting release suspension, and oral delayed-release capsules.
What is the primary use of Alosetron?
Severe diarrhea with chronic IBS symptoms in adult women who have failed to respond to other therapies
Alosetron is a 5-HT3 receptor antagonist that is potent and reduces gastrointestinal transit, secretions, and visceral pain.
What are the serious adverse effects of Alosetron?
Ischemic colitis and complications of constipation
These serious adverse effects are rare but significant.
What condition does the drug that reduces diarrhea and pain primarily treat?
IBS-D with severe diarrhea refractory to all other therapies
This indicates a specific type of Irritable Bowel Syndrome characterized by diarrhea.
What are some adverse effects associated with the use of the drug that reduces diarrhea and pain?
Sphincter of Oddi spasm; pancreatitis; several contraindications
These adverse effects highlight the potential risks involved in using the medication.
According to Sydney Smith, what contributes significantly to unhappiness in the world?
Little stoppages, a duct choked up, food pressing in the wrong place
This quote emphasizes the importance of gastrointestinal health in overall well-being.
Who is AT Stills and what was his contribution to health?
Founder of osteopathy; believed correcting structural imbalances can alleviate health problems
His views highlight the interconnection between physical structure and health outcomes.
Fill in the blank: Alosetron is a _______ receptor antagonist.
5-HT3
True or False: Alosetron is indicated for use in adult men with IBS-D.
False
Alosetron is specifically indicated for adult women.
