Flashcards in EXAM #1: GI PHARMACOLOGY II Deck (83):
What is the role of 5-HT in GI motility?
1) 5-HT stimulates gastric motility by inducing the release of ACh from neurons on the gastric smooth muscle
2) Plays a role in relaying sensory information from the gut to CNS
What is the role of ACh in GI motility?
ACh binds muscarininc receptors to INCREASE GI motility
How is ACh metabolized?
What is the role of DA-2 in GI motility?
- Dopamine activates pre-synatic receptors in ENS neurons to decrease neuronal firing
- This leads to a decrease in GI motility
Specifically, pre-synaptic DA-2 agonism negatively regulates release of ACh on gastric smooth muscle
What is the physiologic outcome of DA-2 agonism?
What is the physiologic outcome of DA-2 antagonism?
What is the role of Motilin in GI motility?
Promotion of GI motility in the UPPER GI tract
What are "prokinetic agents?"
Agents that increase GI motility
List the Prokinetic agents.
What is the mechanism of action of Metoclopramide?
What are the indications for Metoclopramide?
2) Impaired gastric emptying
What are the adverse effects of Metoclopramide?
Altered Motor Function
- PD-like symptoms
This drug crosses the BBB; thus, as a DA-antagonist, it can cause PD-like symptoms.
What is the mechanism of action of Bethanecol?
What are the indications for Bethanecol?
What are the adverse effects of Bethanecol?
Cholinergic side effects
What is the mechanism of action of Neostigmine?
What are the indications for Neostigmine?
1) Urinary retention
2) Abdominal distension
What are the adverse effects of Neostigmine?
Cholinergic side effects
What is the mechanism of Erythromycin?
Motilin receptor agonist
This is an antibiotic. One of the side effects of many abx is diarrhea. Here the reason that this drug causes diarrhea is b/c it is a motilin receptor agonist.
What is the indication for Erythromycin?
What are non-pharmacologic methods to treat constipation?
1) Increase water intake
2) Increase fiber intake
What is a "bulk-forming" laxative?
- Ingestion of fiber that CANNOT be digested and absorbed
- Fiber retains water in the lumen of the GI tract
Bulk-forming agents will form a large clump/bolus that will induce a mass peristaltic contraction. Water retention with fiber will make the movement easier.
What does a bulk-forming laxative need to be taken with?
WATER--things can be made worse without water
What is the prototypical bulk forming agent?
What is the mechanism of action of a stool-softener?
1) May literally soften stool
2) May "coat" and cause stool to "fall out"
What is the prototypical stool softener?
What is an osmotic laxative?
Drugs that induce changes in osmotic pressure with non-absorb-able sugars and salt
What are the prototypical osmotic laxative agents?
What are the mechanisms of "stimulant" laxatives?
These are laxatives that generally stimulate the ENS, and may also:
1) Induce "leaky" mucosa
2) Inhibiting Na+ uptake by the gut
What is the prototypical stimulant laxatives?
Anthraquinone derivatives such as aloe and SENNA
What are the indications for laxatives?
2) Minimize straining post operatively
3) Prior to surgical/ endoscopic procedure
What is the adverse effect of bulk forming agents?
Gas and bloating that can lead to abdominal discomfort
What is the adverse effect seen with surfactants/ stool softeners?
Coating of the GI tract and absorptive surface on a chronic basis will lead to malabsorption.
What is the adverse effect of stimulant laxatives?
General GI irritation
What are the adverse effects of the osmotic laxatives?
- Gas/ bloating
- Electrolyte flux
How can 5-HT receptors be targeted for therapeutic action as a laxative? What is the secondary advantage of this mechanism?
1) Activation of 5-HT4 receptors will promote NT release in ENS, resulting in motility
2) Activation will also decrease firing of extrinsic sensory neurons to the CNS i.e. block pain
Some of the NTs include ACh
What is the prototypical 5-HT4 receptor agonist?
What is a CIC-2 channel?
Chloride Ion Channel 2
Describe how activation of CIC-2 channels can function as laxatives.
- Cl- channel
- Cl- into the lumen, Na+ and water follow
As a result, stool will soften and motility will be stimulated
What type of laxative can be used to treat opoid induced constipation?
Mu-opoid receptor ANTAGONIST
These drugs do NOT cross the BBB; thus, there is antagonism of mu-opoid receptors in the gut to prevent constipation, but opoid analgeisa will NOT be affected.
What is the prototypical CIC-2 agonist?
What are the prototypical mu-opoid receptor antagnoist?
What is the indication for Tegaserod?
Chronic idiopathic constipation
What is the inidication for Lubiprostone?
What are the adverse effects of Lubiprostone?
What is the indication for Methylnaltrexone?
Opoid-induced constipation during palliative care
What are the adverse effects of Methylnaltrexone?
What are the indications for Alvimopan?
Post-operative ileus in hospitalized patients with bowel resection
What is the adverse effect associated with Alvimopan? What are the treatment indications?
Myocardial infarction; thus, only use on a SHORT TERM bases i.e. less than 7 days
What is the general pharmacological strategy to treat diarrhea?
1) Treat the underlying cause
2) Anti-diarrheal agent
What type of opoid durg is used as an anti-diarrheal?
How do opoids alter GI smooth muscle?
Activation of opoid receptors in the GI system generally SLOW motility by:
1) Decreasing peristalsis
2) Increasing segmental (mixing) contractions
3) Increasing internal anal sphincter tone
4) Decreasing perception of GI distension
Describe Bismuth Subsalicylate's mechanism of action as an anti-diarrheal.
1) Thick substance that can absorb GI toxins
2) Salicylate DECREASES intestinal PG secretion
- This leads to a decrease in smooth muscle contraction and secretion of water
Note that this is in CONTRAST to what is seen in the STOMACH, where Bismuth Subsalicylate INCREASES PG synthesis
What is the mechanism of action of bile salt binding resins as antidiarrheals?
1) Bind bile salt
2) Excreted into the feces
Bile is reabsorbed in the ileum. Chorn's disease or ileal resection can prevent proper absorption of bile salts. Excess bile salts in the lumen cause osmotic diarrhea. Thus, excretion of bile salts by binding to resins prevents diarrhea.
What is Octreotide?
- SOMATOSTATIN agonist
- Peptide that is similar in structure to SOMATOSTATIN that:
1) Decreases GI motility
2) Increases fluid absorption
What are the prototypical opoid agonists used as anti-diarrheals?
What are the adverse effects of Loperamide?
What are the adverse effects of Diphenoxylate?
Note that this drug has more CNS effects compared to Loperamide. Thus, it is given in conjunction with atropine to deter abuse.
What is the mechanism of action of Cholestyramine?
This is a bile acid resin that binds bile salts and facilitates their fecal elimination
What is the indication for Cholestyramine?
Impaired bile salt-absorption mediated diarrhea, which can be seen in:
1) Chron's Disease
2) Ileal resection
What are the adverse effects of Cholestyramine?
- Fecal impaction
- Impaired fat absorption/ fat-soluble vitamin absorption
What is the mechanism of action of Octreotide?
Somatostatin receptor agonist that:
1) Increases fluid absorption
2) Decreases GI motility
What are the indications for Octreotide?
What are the adverse effects of Octreotide?
1) Impaired pancreatic secretion
2) Decreased GI motility causes nausea and pain
3) Decreased gallbladder contraction
4) Impaired glucose homeostasis
What are the receptors that regulate the emetic response?
What is the general strategy of antiemetic drugs?
Antagonism of the various receptors involved in the emetic response
List the antiemetic drugs.
What emetic receptor is antagonised by Ondansetron?
What emetic receptor is antagonised by Scopolamine?
What emetic receptor is antagonised by Metoclopramide?
What emetic receptor is antagonised by Dimenhydrinate?
What emetic receptor is antagonised by Aprepitant?
What emetic receptors are antagonised by Prochlorperazine?
Which two antiemetics are used specifically for motion sickness? What receptors do they antagnoize?
What antiemetic is used for emesis caused by: 1) chemotherapy, 2) postoperative, 3) post-radiation?
What antiemetic is indicated for chemo and radiation induced nausea and vomiting?
What anti-emetic is used for nausea and vomiting associated with chemotherapy?
What anti-emetic is used for severe nausea and vomiting, when other anti-emetic have not worked? Why?
Prochlorperazine b/c it blocks M1, D1, and H1 receptors (the most)
What are the indirect antiemetic agents?
These are agents that will increase NT release to have a decrease in the emetic response
What are the three general mechanisms of indirect antiemesis?
1) GABA agonist
2) Cannabinoid agonist
3) Clucocorticoid agonist
What is the GABA agonist used as an antiemetic?
What is the Cannabinoid agonist used as an antiemetic?