Lower GI Drugs - Fitz Flashcards
One of your patients has improved a lot since the last time you saw him. His depression is less severe and his IBS constipation has basically resolved. You did this with just one medication.
What was it?
How did it work?
SSRI - Selective Serotonin re-uptake inhibitor
- By decreasing reuptake of 5HT into EC cells, the afferent synapse in the myenteric plexus is stimulated more.
- The interneurons on both sides of the reflex arch stimulate increased peristalsis
(hooray!)
Name the three SSRI’s used for constipation-prominent IBS:
Fluoxetine, Paroxetine, Sertaline
How do bulk laxatives increase peristalsis?
They attract H2O in the lumen to increase stool mass.
This luminal distention then increases afferent stimulation in the Myenteric plexus and stimulates peristalsis
What two factors limit the usage of a bulk laxative?
1) Neurons generating the peristaltic reflex must be intact
2) Cause of constipation must be KNOWN
Besides dietary fiber, name 3 bulk laxatives:
Methylcellulose, Polycarbophil, Psyllium
Contact Cathartics stimulate cause gut irritation, which stimualtes peristalsis. From which cathartic might you expect side ffects like dehydration, electrolyte imbalance, and uterine contractions?
Castor oil
All cathartics have remote possibility of creating dependency or destroying the myenteric plexus long-term
What is the difference between Bisacodyl/Antraquinones and Castor Oil???
Bisa/Anthro:
- Act on large intestine only
- not as potent
Castor Oil
- Small and large intestine
- more potent, more side effects
What drug targets 5HT-3 receptors? Why is this drug only available for compassionate use?
Alosetron
Decreases peristalsis by decreasing afferent stimulation
This drug works well, but often works too well and pts can get severe constipation.
.3% can actually develop ischemic colitis (fatal)
Name 3 anthraquinones:
Cascara Sagrada, Danthron, Senna
If you had to choose a drug that you though worked exactly opposite to Alosetron, what would it be?
Tegaserod! or Cisapride
5HT-4 Agonists
Do Tegaserod/Cisapride have any important side effects?
Yes!
They have cardio toxicity
Can cause arrythmias - Long QT!
What are the most effective andi-diarrheal drugs?
Explain their mechanism:
Opiates are the most effective anti-diarrheals
Loperamide and Diphenoxylate
- They stimulate mu receptors on both ends of the afferent neuron in the peristaltic reflex
- Enkephalin neurons usually stop peristalsis using these mu receptors, and these drugs act in the same spot to do the same
Shortly after beginning prescription therapy for his diarrhea, your roommate begins to notice a lower appetite, blurry vision, and dry mouth. “That’s weird,” he says, “I thought I was on an opiate, I don’t know how people could ever get addicted to these.”
What should you explain to your friend?
It sounds like your roommate is on Dephenoxylate, which is an opiate like he said. This drug is prescription because some can cross the BBB and cause euphoria.
To ameliorate these risks, the drug is combined with atropine, which can have unpleasant side effects
"know the abcd's of anticholinergic side effects": anorexia blurry vision constipation/ confusion dry mouth sedation/ stasis of urine
You have a patient on opiates for chronic back pain after a car accident. Their back pain seems to be handled okay, but now they are having terrible constipation. She tells you she would rather go back to the back pain because she just can’t live with the bowel problems.
What do you do?
Explain that using a medication like Alvimopan or Methylnaltrexone will offset her constipation problems while still providing her the pain maintenance she needs.
These drugs are Mu-receptor antagonists. This means that they will get rid of the GI symptoms, but the CNS will be unaffected because they don’t cross the BBB
Why is Alvimopam usually given in the setting of short-term hospital visits whereas Methylnaltrexone is used in long-term care?
Alvimopan can increase the risk of MI’s, which you’d rather have happen in a hospital
What class of drug is metoclopramide?
What is it’s mechanism?
D2 receptor antagonist
Basically it increases the action of ACh in the gut by decreasing it’s inhibition
Its an overall gut PROKINETIC
What are TCA’s used for?
Decreasing motility, anti-diarrhea
What kind of drug stimulates motilin receptors on smooth muscle?
What is the result?
Macrolide antibiotics like Erythromycin
This activates the migrating moto complex –> anti-constipation
Best drugs used for overall impaired gut motility?
Ex: gastroparesis, vagotomy
Metoclopramide (D2 receptor antagonist)
Erythromycin (Macrolide Antibiotic)
Cisapride - (5HT Agonist)
Which drug activates guanylyl-cylcase? What effect does it have?
Linactolide
BY activating guanylyl cyclase, CFTR is activated to secrete Cl into the lumen
H2O then follows
Which medication is often used specifically for diarrhea following HIV drug treatment?
Crofelemer
What serious side effects can come from metoclopramide?
Dystonia, Parkinsonism, tardive dyskinesia
Increased Prolactin release (causing impotence, menstrual problems, galactorrhea)
Mechanism of action for Lubiprostone?
activates CIC2 to increase Cl secretion
Bam! Constipation cured.
What are the side effects of the drug used specifically to prevent traveler’s diarrhea?
Bismuth Subsalicylate
Side effects: Black tongue and stool
High dose: salicylate tox can cause tonnitus, acid-base disturbance, etc.
