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Flashcards in Bowel Motility Pharm Deck (72):
1

What drug classes stimulate GI motility?

Dopamine receptor antagonists

5-HT4 receptor agonists

Motilides

2

What classes of drugs act as laxatives?

Luminally active agents

Nonspecific stimulants or irritants

Chloride channel activators

3

What classes of drugs act as antidiarrheal agents?

Opioid agonists

Bile-acids sequestrants

Bismuth

Octreotide and somatostatin

4

What does the esophagus do for motility of the GI system?

Propulsive peristalsis to move stuff to stomach

5

What do the fundus and corpus of the stomach do in response to eating?

Relax to store food

Then slowly increase in tension to move food into antrum

6

What does the Antrum in the stomach do in response to food?

Mixes and grinds to break up food by alternating contractions with pylorus in order to grinding food by shooting it back and forward

7

What does the small intestine do in the GI system to process food?

Segmentation

Occasional peristalsis (slow mixing of contents)

8

Describe GI motility in the colon

Tonic contractions = segmental propulsion

9

Describe an enteric circuit including the names and general locations of the neurons

EPANs = extrinsic primary afferent neurons
Sense stretch but are not entirely contained in enteric nervous system

IPANs = intrinsic primary afferent neurons
Located in GI wall

10

Describe the extrinsic innervation of the GIT including the name of the afferent neuron and 3 types of efferent neurons that modulate the enteric circuit

EPAN = afferent => CNS

From CNS, the efferent neurons =
SANS = sympathetic nervous system
PANS = parasympathetic nervous system
NANC = no adrenergic-noncholinergic

11

Describe the location of the D2 and 5HT-4 receptors within the ENS and the effect of dopamine and serotonin on GI motility

Receptors are located in the GI wall

Dopamine = inhibitory
Serotonin = stimulatory

12

Why can't mAChR agonists or AChE inhibitors be used as pro-kinetic agents?

Stimulate uncoordinated increased GI motility

= minimal net propulsion

13

What is the effect of dopamine on GI motility?

Dopamine = inhibitory

14

What do dopamine antagonists do?

Increase esophageal peristaltic amplitude

Inc. LES pressure (useful for GERD!!!)

🗑Enhance gastric emptying

👅Antiemetic function

15

What is the MOA of metoclopramide?

D2 antagonist

5HT3 antagonist

5HT4 agonist

Effects confined to UPPER digestive tract:
+ stimulates antral/small intestinal contractions
+ inc. LES tone

16

What is the clinical use for metoclopramide?

Impaired gastric emptying
(post- surgery, diabetic gastroparesis)

Prevention of vomiting

GERD

17

What AEs are associated with metoclopramide?

CNS: restlessness, drowsiness, insomnia, anxiety

Movement problems, Tardive dyskinesia

Inc. prolactin = galactorrhea, gynecomastia, ED, menses issues

18

Where is serotonin produced and what does it trigger?

Produced by EC cells in response to chemical and mechanical stimulation

Triggers peristaltic reflex

19

What is the MOA of cisapride?

5HT4 agonist

Weak 5HT3 antagonist

20

What is the clinical use of cisapride?

Impaired gastric emptying

GERD

21

What AEs are associated with Cisapride?

Fatal cardiac arrhythmias, TdP

22

What DDIs are associated with Cisapride?

Agents that interfere with CYP3A4 metabolism - that's the CYP that metabolizes cisapride!

23

How is erythromycin considered a motilide?

Mimics the effects of motilin (peptide hormone found in GI M cells and EC cells = potent contractile agent of the upper GI tract)

24

What is the clinical use of erythromycin?

Diabetic gastroparesis

25

What problems are associated with erythromycin use for stimulating GI motility?

Tolerance (downregulation of motilin receptor)

Antibiotic effect

26

Describe the sequence of treatment for constipation

1. Treat specific cause

2. No diagnosis => symptomatic therapy
+ inc. fluid intake
+ dietary modifications
+ alter lifestyle (exercise)
+ pharmacological therapy (if necessary)

27

What is meant by laxative habituation?

Longer interval of time needed to refill rectum before defecation after use of laxatives because they will completely evacuate the rectum

28

What are indications for laxative use?

☠️Acute evacuation of entire intestine for oral poisoning

✅acute cleaning of bowel PRIOR to diagnostic/surgerical procedures

reduce straining in presence of illness

chronic use for anal disorders

💊compensate for drugs with constipating action

29

What is the general MOA of laxatives?

Stimulation of peristalsis by intraluminal filling

30

Name 3 types of luminally active agents:

Bulk-forming

Osmotic laxatives

Stool surfactants

31

Name two types of nonspecific stimulants or irritants

Bisacodyl

Anthraquinone dervivatives

Castor oil

32

Name a chloride channel activator

Lubiprostone

33

What is the MOA of bulk-forming agents?

Indigestible, hydrophilic substances absorb water to form a bulky, emollient gel

= inc. peristalsis

Softens feces in 1-3 days

34

What drugs are bulk-forming agents?

Psyllium preparations

Methylcelullose

Calcium polycarbophil

35

What is the MOA of osmotic agents?

Nonabsorbable osmotic agents will increase secretion of water into colon to soften stool and promote defecation

Watery evacuation in 1-3 hours

36

What drugs are osmotic agents?

Saline laxatives (Mg citrate, Mg(OH)2, sodium phosphate)

Nondigestible sugars and alcohols (lactulose, sorbitol)

PEG solutions

37

What caution is associated with saline laxatives ?

Mg containing products should be avoided in patients with renal insufficiency because they can end up with hypermagnesemia

38

What is the MOA of stool wetting agents and emollient?

Soften fecal material and allow water to penetrate

39

What drugs are stool wetting agents and emollients?

Docusate salts
(Soften feces in 1-3 days)

Mineral oil
(Softening in 6-8 hours)

40

What are side effects associated with mineral oil?

Interference with absorption of fat soluble substances

Aspiration can result in severe lipid-pneumonia

41

What is the general MOA of nonspecific stimulants or irritants?

Direct effect on enterocytes, enteric neurons and GI SM

Probably induce low-grade inflammation in small and large bowel to stimulate secretory cells = accumulate water and electrolytes to increase motility

42

How long until Bisacodyl takes effect?

PO = 6 - 12 hrs

Supp = 30 - 60 min

43

What AEs are associated with bisacodyl?

Abdominal pain

44

What is the MOA of antraquinone laxatives?

Monoanthrones irritate oral mucosa and induce BM in 6-12 hours

45

What AEs are associated with antraquinone laxatives?

Melanotic pigmentation of colon

46

How long until castor oil takes effect?

1-3 hours

47

What AEs are associated with castor oil?

Unpleasant taste

Abdominal pain

48

What is the MOA of lubiprostone?

Stimulates EP4 receptors on GI epithelial cells

= activation of chloride channels
= Cl rich fluid secretion increases => increased motility

Induce BM in 24 hrs

49

What is the clinical use of lubiprostone?

Chronic constipation and IBS-C

50

What AEs and contraindications are associated with lubiprostone?

Nausea

Contraindicated in pregnancy

51

Define diarrhea and briefly explain the different types of diarrhea and their underlying mechanisms

Excessively fast passage of bowel contents

1) SECRETORY = inc. fluid transport out of cells into GIT lumen

2) OSMOTIC = inc. luminal osmolarity

3) EXUDATIVE = injury to intestinal epithelial lining

4) DYSMOTILITY = changes in intestinal motility

52

What are specific causes of the different types of diarrhea?

Secretory = tumors, cholera

Osmotic = malabsorption syndromes (lactose intolerance), antacids, lactulose therapy

Exudative = inflammatory disorders of GIT

Dysmotility = post-surgical

53

What are 4 classes of anti-diarrheal agents?

Opioid agonists

Bile acid sequestrants

Bismuth compounds

Octreotide and somatostatin

54

What are examples of opioid agonists?

Loperamide

Diphenoxylate

55

What are examples of bile acid sequestrants?

Cholestyramine

Colestipol

Colesevalam

56

What is the MOA of loperamide?

Opioid receptor activity:

Decrease peristaltic contractions

Inc. segmental contractions (more mixing = more absorbing = dry out!)

57

What is the clinical use of loperamide?

Travelers diarrhea

Acute and chronic diarrhea

58

What AEs are associated with loperamide?

Constipation

Abdominal pain

59

Provide a rationale for the inclusion of atropine in the commercial preparations of diphenoxylate

Higher doses of diphenoxylate/difenoxin have CNS effects

Inclusion of atropine will prevent abuse by using bothersome anti-cholinergic AEs to deter potential users

60

What is the clinical use of diphenoxylate/difenoxin?

Diarrhea

61

What AEs are associated with diphenoxylate and difenoxin?

CNS effects (@ high dose) = depression, headache, dizziness

Anti cholinergic effects = dry mouth, blurred vision,, urinary retention

62

What is the MOA of bile-acid sequestrants?

Bind bile salts and some bacteria

= dec. unbound bile acids

= dec. fluid/electrolyte secretion

63

What is the clinical use of bile acid sequestrants?

Diarrhea caused by excess fecal bile acids
(In patients with resection of distal ileum or Crohn's Disease)

64

What AEs are associated with bile acid sequestrants?

Constipation

Bloating

65

What interactions are associated with bile-acid sequestrants?

Binds drugs

Should not be given within 2 hours of other drugs

66

What is the MOA of bismuth compounds?

Direct antimicrobial effects

67

What is the clinical use of bismuth compounds?

Nonspecific treatment of dyspepsia

Peptic ulcers caused by H.pylori

Acute and travelers diarrhea

68

What AEs are associated with bismuth compounds?

Black stools and tongue

Absorption of salicylate = Reye's syndrome

69

What are the physiologic effects of somatostatin?

Inhibits hormone secretion of gastrin, cholecystokinin (CCK), VIP, 5-HT

Dec. intestinal fluid and pancreatic secretion

Dec. GI motility

70

What is octreotide?

Analog of SST

71

What is the clinical use of octreotide?

Diarrhea caused by hormone secreting tumors

72

What AEs are associated with Octreotide?

Short - term
N, bloating or pain @ injection sites

Long-term:
Gallstone formation and hypo/hyper-glycemic