GI Perspective Flashcards
Effects of the ANS (PSNS vs SNS) on GI motility?
Parasympathetics stimulate GI motility (rest and digest) while Sympathetics inhibit GI motility (fight or flight)
Predominant tone of GI tract smooth muscle?
Parasympathetic (muscarinic CHOLINERGIC)
What parasympathetic receptors are found in the GI tract?
M3
What is the effect of parasympathetic stimulation on the walls, sphincters, and secretions w/in the GI tract?
- Walls: contracts
- Sphincter: relaxes
- Secretions: increase
=Overall an increase in GI motility via M3’s (rest and digest)
What are the effects of sympathetic stimulation on the walls, sphincters, and secretions of the GI tract? What receptors are involved?
- Walls: relax via alpha-2 and beta-2 (beta-2 works thru presynaptic inhibition of parasympathetic activity)
- Sphincters: contract via alpha-1
- No significant effect on secretions
=Overall a decrease in GI motility (fight or flight)
Effect of ganglionic blockade in the GI system?
B/c PSNS is predominant tone:
- Reduced GI tone and motility
- Constipation
- Decreased gastric and pancreatic secretions
Effects of Cholinergic agonists or AchE inhibitors (cholinergic excess)?
DUMBBELS
Diarrhea, Urination, Miosis/muscle weakness, Bronchorrhea, Bradycardia, Emesis, Lacrimation, Salivation/Sweating
Effects of muscarinic antagonists (cholinergic deficit)?
Opposite of DUMBBELS + Central Effects
Constipation, Urinary retention, Mydriasis/Blurred Vision, Large Bronchiole Dilation, Tachycardia, Antiemesis, Decreased glandular secretions, Hypo/anhidrosis, Restlessness/confusion/delirium/hallucinations
Some medications taken for non-GI conditions have ___________ activity that can lead to _________ as an ADE?
Anticholinergic activity that can lead to constipation as an ADE. But, usually, not every drug w/in a given class has this ADE, or another drug class w/out this ADE can be used to provide the same clinical effect.
What are the 4 most significant substances involved in neuronal transmission in the Enteric Nervous System? Why?
These are the 5 that are subject to direct modulation by drug therapy:
- Ach
- Dopamine
- Enkephalin and related opioids
- Serotonin
Role of Ach in ENS?
- Excitatory to smooth muscle and secretory cells
2. Major neuron-to-neuron (ganglionic) nt in ENS
Role of Dopamine in ENS?
It’s a modulatory nt in the ENS
Role of enkephalin and related opioid peptides in ENS?
Present in some secretomotor and interneurons in ENS.
- Inhibits Ach release and peristalsis
- May stimulate secretion
Role of Serotonin in ENS?
Important transmitter or co-transmitter at excitatory neuron-to-neuron junctions in the ENS
What is the overall effect of dopamine and by what two mechanisms is this accomplished?
Overall effect= GI relaxant
Mechanisms:
1. Activates D2-R (in LES, stomach)→direct relaxant
2. Activates pre-junctional D2-R→inhibition of Ach release from cholinergic neurons→indirect inhibition of muscular contraction
T/F: Anti-dopaminergics are prokinetic?
True
Subtypes of Irritable Bowel Syndrome?
- D-IBS=diarrhea predominant
- C-IBS=constipation predominant
- Mixed IBS
What is implicated in some cases of IBS? How would this be treated?
Serotonin disequilibrium: Rx with drugs that modify serotonergic signaling
a. Excess 5-HT (hyperactivity)→D-IBS (Tx w/ 5HT3 antagonist)
b. Insufficient 5-HT release (hypoactivity)→C-IBS (Tx w/ 5HT4 agonist)
c. A partial agonist/antagonist would be better for Tx of IBS as antagonists and agonists completelely block/stimulate causing a pt with diarrhea/constipation to develop the opposite
Agonisms of 5-HT4 receptors results in what?
Ach release via activation of pre-junctional excitatory 5-HT4-R’s→motility/propulsion
Where are 5HT4-R’s located in the GI system?
- Enteric neurons
2. Smooth muscle
Basis for differences in serotonin receptor modulating drug pharmacology?
Selectivity for the type of 5-HT receptor it binds to
How do probiotics work in the treatment of IBS? (4)
- Improve epithelial barrier function
- Inhibit pathogenic bacteria
- Acidify colon
- Improve dysmotility
What are 2 types of probiotics?
a. Nonpathogenic strains of Lactobacillus and Bifidobacterium
b. Fermented dairy products, meats, and vegetables
Overall success rate of probiotics in the Rx of IBS?
Generally more effective than placebo but not very successful
What is a drug target in the treatment of Inflammatory bowel disease (IBD)? Why?
TNF-alpha: b/c it plays a pivotal role in the inflammation associated with IBD
Rx of IBD?
Anti-inflammatory agents and, in certain circumstances, TNF-alpha inhibitors
What are three opioid receptors in the GI tract? What are there ligands?
- Delta-R’s→Enkephalin
- Kappa-R’s→Dynorphin
- Mu-R’s→Beta-endorphin
Where in the GI tract are these 3 opioid receptors located?
In the ENS
a. All are located in the Myenteric plexus
b. Mu-R’s are also found in the Submucosal plexus
Effects of GI opioid receptor activation?
a. All 3→Delayed transit time (gastroparesis)
b. Kappa and Mu also cause visceral antinocioception
What is the main ADE in the GI system associated with prescription opioids?
CONSTIPATION and incomplete evacuation (hard dry stools)
What are two options for opiod antagonists that could be prescribed with opiod analgesics and how do they work?
- Naloxone - opiod antagonist with low oral bioavailability, so concentration is highest before metabolism - in the GI
- Methylnaltrexone: quat. ammonium unable to cross BBB, will only act in other parts of the body
What is the mc type of preventable ADE in older ambulatory persons?
GI tract events
6 types of drug-induced diarrhea?
- Osmotic diarrhea: drug draws water out
- Secretory diarrhea: impaired Na+ absorption and Cl and HCO3 are secreted
- Disordered motility: drugs affecting cholinergic tone
- Inflammatory diarrhea: direct damage to gastric mucosa or disruption of colonic flora followed by C dif colitis
- C dif diarrhea: disruption of acid/base environment or epithelial homeostasis
- Fatty diarrhea: maldigestion/malabsorption (ie weight loss products)
Describe pill-induced esophagitis?
A feeling that pill is stuck in throat from esophageal damage; can lead to perforation/hemorrhage if unhealed
Risk factors for pill esophagitis?
a. Patient: old age (decreased saliva production), institutionalized, esoph/swallowing disorder, recumbent, neurologic condition, pre-existing GERD or stricture, hiatal hernia
b. Drug: gelatin capsules and extended/sustained-release products, concurrent anticholinergics (decrease saliva production)
Rate of oral drug absorption depends on what? (2)
a. Drug factors (formulation/physiochemical properties→mucosal permeability)
b. Host factors (intestinal villous blood flow, pH)
Where are oral drugs absorbed?
Absorption may occur in the oral cavity, esophagus, stomach, or small intestines, depending on the formulation/phyiochemical properties of the drug and the local pH.
