Pharm: GI disorders II

Question 1

What is the major control network for the GI tract (contraction, secretion, absorption control)?

Answer 1

enteric nervous system

Question 2

What are the two networks for the enetric system?

Answer 2

myenteric/auerbach plexus: responsible for motor control; found btw muscle layer of GI
submucosal/meisner’s plexus: secretory, transport, vascular control

Question 3

What neurotransmitter is seen in excitatory motor neurons of the GI tract? What neurotransmitter is seen in inhibitory neurons of the GI tract?

Answer 3

excitatory: ACh
inhibitory: NO

Question 4

What chemical factors contribute to the development of GERD?

Answer 4

content/pH of refluxed fluid

epidermal growth factor activity: can be a cancer risk

Question 5

What four physical factors contribute to the development of GERD?

Answer 5

1. decr. lower esophageal sphincter pressure
2. anatomical factors like a hiatal hernia
3. decreased esophageal clearance
4. delayed gastric emptying (gastroparesis)

Question 6

Metoclopramide/reglan. What is the class and gemical structure

Answer 6

dopamine D2 receptor antagonist (substituted benzamine); 5-HT4 agonist

Question 7

What does dopamine do in the GI tract?

Answer 7

inhibits cholinergic neurons

lowers lower desophageal sphincter pressure

Question 8

MEtoclopramide/reglan: What is its action? What does it NOT do?

Answer 8

1. incr. lower esophageal tone
2. incr. small intestines contraction
3. some anti-emetic effects
   Provides symptomatic relief of GERD symptoms but does NOT heal the esophagus.

Question 9

What are some side effects of metoclopramide?

Answer 9

sedation, diarrhea, tardive dyskinesia

Question 10

What is cisapride/propulsid? (chemical structure, type/class, action)

Answer 10

substituted benzamide: serotonin agonist (serotonin incr. movement in GI)
prokinetic treatment for GERD through action on myenteric/auerbach plexus.

Question 11

What are side effects of cisapride/propulsid?

Answer 11

cardiac arrhythmia, sudden death, long QT syndrome. esp. seen in pts taking other drugs metabolized by CYP3A4 or with certain polymorphisms
not used here except as a very last experimental resort; must monitor with EKG

Question 12

What are the 4 types of laxatives?

Answer 12

luminally active bulking agents
irritants
stool softeners
prokinetic agents

Question 13

How do different kinds of luminally active bulking agents work (3)?

Answer 13

1. hydrophilic colloids: absorb water to incr. stool bulk and stimulate GI motitily
2. saline cathartics: indcue osmotically mediated water retention
3. lactulose: disaccharide- aslo acts as an osmotic laxative

Question 14

What is loperamide? How does it work (simple)?

Answer 14

trade name imodium
inhibit ACh release through mu opiod receptors
treats diarrhea

Question 15

3 phases of emesis

Answer 15

1. pre-ejection phase (gastric relzxation)
2. retching phase (rhythmic contractions)
3. ejection phase (intesne contractions and relaxed upper esophageal sphincter)

Question 16

From what 4 areas does the emesis center receive input?

Answer 16

1. chemoreceptor trigger zone, which monitors blood and CSF for toxic substances
2. cerebral cortex, which mediates vomiting associated with emotional disturbances
3. cerebellum/vestibular system, which mediates motion sickness
4. solitary tract nucleus (STN)/vagus nerve and splanchnic afferents, which mediates vomiting due to GI irritations

Question 17

What is ondasetron (Zofran)?
(drugs in this class end in -etron)

Answer 17

5-HT3 receptor antagonist (serotonin receptor antagonist)
interfere with input from the chemoreceptor trigger zone and solitary tract nucleus into the emesis center
treat many causes of vomiting, but not vomiting due to motion sickness.

Question 18

What 5-HT3 (serotonin) receptor antagonist that works as an anti-emetic should I know?

Answer 18

ondasetron/zofran

Question 19

What is chlorpromazine (thorazine)? uses? sides?

Answer 19

dopamine receptor antagonist; phenothiazines structure.
helps a little with chemo-induced vomiting
sides: hypotension, extrapyramidal symptoms

Question 20

What drugs should be used to treat vomiting caused by motion sickness?

Answer 20

antihistamines (H1 receptor antagonists)
promethazine (phenegran) is the one we need to know
also diphenhydramine (benadryl) and diphenhydrinate (dramamine)