The GI system, from pharmacology’s perspective Flashcards
Gastrointestinal Tract Smooth Muscle
Sympathetic Effect/Receptor
Walls
Relaxes
alpha-2 & Beta-2
Gastrointestinal Tract Smooth Muscle
Sympathetic Effect/Receptor
Sphincters
Contracts
alpha-1
Gastrointestinal Tract Smooth Muscle
Parasympathetic Effect/Receptor
Walls
Contracts
M3
Gastrointestinal Tract Smooth Muscle
Parasympathetic Effect/Receptor
Sphincters
Relaxes
M3
Gastrointestinal Tract Smooth Muscle
Parasympathetic Effect/Receptor
Secretions
Increases
M3
Gastrointestinal Tract
Predominate Tone:
Parasympathetic (cholinergic)
Gastrointestinal Tract
Effect of Ganglionic Blockade
Reduced tone & motility; constipation; decreased gastric & pancreatic secretions.
DUMBBBELS
Cholinergic Agonists or AchE Inhibitors
Diarrhea/Defecation: relaxation internal anal sphinc Urination: Miosis: pupil constriction Bronchorrhea Bronchospasm Bradycardia Emesis: Vomiting Lacrimation: Salivation:
Some medications that are taken for non-‐G.I. conditions have anticholinergic activity that can lead
to?
Constipation as an ADE.
The processes of mixing, propulsion, & absorption of nutrients in the GI tract are controlled locally through a restricted part of the peripheral nervous system called?
The enteric nervous system (ENS).
The ENS is involved in sensorimotor control & thus consists of both afferent sensory neurons & a number of motor nerves & interneurons that are organized principally into two nerve plexuses:
The myenteric (Auerbach’s) plexus & the submucosal (Meissner’s) plexus.
The myenteric plexus, located between the
Longitudinal & circular muscle layers, plays an important role in the contraction & relaxation of GI smooth muscle.
The submucosal plexus is involved with
Secretory & absorptive functions of the GI epithelium, local blood flow, & neuroimmune activities.
Within the enteric nervous system a large number of neuromodulators play a role in
Regulating autonomic control over the semi-‐autonomous functioning of the G.I. smooth muscle & secretory glands
The enteric nervous system lining with G.I. tract has as its principal neurotransmitter
acetylcholine
Co-‐transmicers & modulators that serve to provide local control over prevailing central neural tone?
Dopaminergic & opiate receptors (Enkephalin) can be modulated by drug therapy.
Metoclopramide is an older drug that is used to treat
N/V & is also used for its gastrokinetic actions, in other words it is used to treat gastroparesis.
The mechanisms of action of metoclopramide are complex & involve
5‐HT4 receptor agonism, vagal & central 5-HT3 antagonism, & possible sensitization of muscarinic receptors on smooth muscle, in addition to DA receptor antagonism.
Metoclopramide administration results in
Coordinated contractions that enhance transit. Its effects are confined largely to the upper digestive tract, where it increases lower esophageal sphincter tone & stimulates antral & small intestinal
contractions.
Irritable Bowel Syndrome (IBS) is multifactorial condition involving episodes of both constipation & diarrhea, has been attributed,
in part, to dysfunction in serotonergic signaling in the G.I. tract.
In IBS it would appear that the use of partial agonists or antagonists, rather than full agonist/antagonist would be
The most appropriate option for treatment.
The chronic debilitating illness known as irritable bowel syndrome is characterized by
Recurring pain & discomfort in the lower abdomen, & by functional impairment of G.I. motility.
Studies indicate that defense mechanism in IBS is
Compromised
Inflammatory Bowel Disease (IBD) most common components are
Ulcerative colitis & Crohn’s disease.
In IBD the intestinal microflora is implicated in the
Genesis of this condition, & TNF alpha has been identified as playing a pivotal role in the inflammatory response.
TNF alpha inhibitors, are the drugs of choice for both
Crohn’s disease & ulcerative colitis.
One of the most significant & persistent adverse effects of chronic opiate therapy is
Constipation.
Opiate receptors are found in the enteric nervous system where their activation leads to
Gastroparesis.
The opiate receptors are found throughout the G.I. tract & their activation by the narcotic analgesics not only promotes (blank) but also (blank).
Nausea & Vomiting,
Constipation & Incomplete Evacuation.
Drug-‐induced diarrhea can occur through any one of a number of mechanisms, such as
Attracting or retaining excess water, modification to normal motility signaling, & disruption of the microflora.
Disruption of the microflora can be due to the use of
Antimicrobial agents, or simply through effects on the microbes micro-environment, such as drug-induced changes in pH, epithelial integrity, or immune system function.
The weight-loss product orlistat&cholestyramine used for hypercholesterolemia produce
diarrhea
Octreotide, a drug that blocks the affects of many GI hormones is useful in controlling many types of
secretory diarrhea including patients with GI carcinoid tumors & in HIV‐associated diarrhea.
The common antidiabetic drug metormin produces diarrhea in almost 50% of patients taking the drug; this is thought due to
Inhibition of glucose in the GI tract, thus producing large quantities of unabsorbed material that produces osmotic diarrhea. Diarrhea is also a symptom of lactic acidosis, the major adverse effect of this drug.
Pill‐induced esophagitis:
A problem primarily experienced by older patients & one that can lead to esophageal perforation & hemorrhage in extreme situations.
Pill‐induced esophagitis most commonly it is seen with
sustained or extended release products or gelatin capsules which catch in the throat of older patients who by virtue of their age, are producing less saliva to aid in swallowing.
Most commonly in regards to G.I. bleed, we think about
nonsteroidal anti‐inflammatory drugs.
Recall that both CYP3A & P‐GP are to be found in the intestinal wall where they modulate
bioavailability & participate in 1st‐pass metabolism.
The 3 ways in which gastric acidity can be modulated:
Antacids, proton pump inhibitors, & H2 histamine blockers.
Some drugs rely on gastric acidity to be
Absorbed, so a simple change in pH can reduce their bioavailability.
Antacids have the capacity to
chelate, that is to bind up & prevent absorption of a number of drugs.
Most commonly chelated drugs we think about
Doxycycline, tetracycline, & fluoroquinolones.
For the H2‐blockers & proton pump inhibitors the change in pH can also impact
bioavailability of concurrent medications.
