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GI Week 3 > Lecture 26: Pharmacology for Treatment of Motility Disorders > Flashcards

Lecture 26: Pharmacology for Treatment of Motility Disorders Flashcards

1
Q

How many neurons are in the Enteric Nervous System?

A

The same number as the spinal cord (400-600 million)

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2
Q

What is achalasia?

A

The inability of lower esophageal sphincter to relax

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3
Q

What are the neurons that are present in the enteric nervous system?

A

iPANs
intrinsic primary afferent nerves
receive input from cholinergic, adrenergic and dopaminergic neurons
Located in Meissner’s plexus

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4
Q

What is the predominant neurotransmitter in the ENS?

A

Serotonin

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5
Q

What is the plexus in submucosa?

A

Meissner’s plexus

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6
Q

What is the plexus in between the circular and longitudinal muscle?

A

Auerbach’s plexus

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7
Q

At the level of the esophagus, what is the excitatory neurotransmitter? Inhibitory?

A

Acetylcholine = excitatory
NO = inhibitory
You have both cholinergic myenteric plexus neurons and nitric oxide myenteric plexus neurons
More inhibitory neurons as you move distally from esophagus

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8
Q

What is the aim of esophageal motility therapy?

A
  1. reduce lower esophageal sphincter pressure
    OR
  2. Reduce vigor of distal esophageal smooth muscle contractions
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9
Q

What is the etiology of achalasia?

A
  1. degeneragion of inhibitory myenteric plexus neurons (NO)
  2. damage to vagal branches
  3. damage to dorsal vagal nucleus (DMX)
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10
Q

What is the only medication for achalasia?

A

Botulinum toxin

Blocks the vesicular release of acetylcholine at the synapse

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11
Q

What is the treatment for achalasia that does not require medication?

A
  1. Heller myotomy
  2. Pneumatic dilation
  3. peroral endoscopy myotomy (POEM)
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12
Q

What is a Heller myotomy?

A

A surgical procedure in which the muscles of the lower esophageal sphincter are cut

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13
Q

What medications reduce muscular vigor?

A

5 phosphodiesterase inhibitors
Blocks NO degradation, so prolong smooth muscle relaxation
Same shit used in sildenafil
Muscular vigor syndromes are DIFFERENT from achalasia (because the muscular contractions are very strong, and there is some relaxation)

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14
Q

What are the components of gastric motility?

A
  1. Fundus = accommodation
    • increases volume without increasing pressure
  2. Body/Antrum = Trituration
    • when you squeeze the food in antrum
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15
Q

What is trituration?

A

The processing of materials done in antrum

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16
Q

What must you do if you have a vagotomy?

A

Must do a pyloroplasty (cut the pyloric sphincter) to allow shit to pass through

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17
Q

What are the characteristics of the interstitial cells of Cajal (ICC)?

A

Joined by gap junctions and are responsible for organized contraction

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18
Q

Where is most of the serotonin in our body located?

A

In the GI tract not in the brain
95% in GI tract
5% in brain…

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19
Q

What are the two types of neurons in the GI tract?

A
  1. Excitatory cholinergic motor neurons
    • 5HT3 receptor
    • 5HT4 receptor
  2. Inhibitory nitrergic motor neuron
    • 5HT1D receptor
    • 5HT7 receptor
    • 5HT1A recptor
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20
Q

How does the GI tract know when to move?

A
  1. A bolus of food applies PRESSURE to the Enterochrommafin (EC) cells in the stomach
  2. EC cells when activated by pressure release serotonin
  3. Serotonin transmit signal to intrinsic primary afferent neurons (IPANs)
  4. IPANs transmit signal to circular and longitudinal muscles
  5. also transmitted to interneurons that comminucate with excitatory/inhibitory neurons in Auerbach’s plexus
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21
Q

What is the difference between EC cells and ECL cells?

A

Enterochromaffin cells are found THROUGHOUT GI tract

Enterochromaffin-like cells are found only in the stomach and secrete histamine

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22
Q

What are the targets for gastric motility?

A
  1. Accelerate emptying
  2. Delay emptying
  3. Improve fundic accommodation
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23
Q

What are examples of Prokinetic drugs?

A

Drugs that accelerate emptying

Metoclopramide

24
Q

What is the MoA of metoclopramide?

A

Serotonin 5HT4 receptor agonist (excitatory neuron)
D2 antagonist (dopamine inhibits smooth muscle contraction)
Antiemetic effects

25
Q

What is Metoclopramide used for?

A

A prokinetic
Approved for diabetic gastroparesis
Prevention of postop and chemo induced nausea/vomiting

26
Q

What are the types of drugs that delay emptying?

A
  1. Anticholinergics

2. Somatostatin analogs

27
Q

What are types of anticholinergics?

A
  1. Dicyclomine

2. Hyoscyamine

28
Q

What are types of somatostatin analog?

A
  1. Octreotide

- inhibits release of serotonin, motilin

29
Q

What is dycyclomine?

A

An anticholinergic

Delays gastric emptying

30
Q

What is hyoscamine?

A

An anticholinergic

Delays gastric emptying (because Ach is what the excitatory neurons use)

31
Q

What is octreotide?

A

A somatostatin analog
Used to delay gastric emptying
Acts by inhibiting serotonin and motilin release (both of which can act on excitatory neurons)

32
Q

What are the drugs used to improve accommodation?

A
  1. Busiprone
    Improves fundic an pyloric relaxation
    Dependent on inhibitory impulses from neuronal NO
33
Q

What is the MoA of Busiprone?

A 
ACCOMODATION
A 5HT1A receptor agonist
5HT1A is a receptor on the INHIBITORY neuron present in the Auerbach’s plexus
Inhibits Ach release
Promotes NO release
Effective in functional dyspepsia
34
Q

How many layers of ICC do you have in the colon?

A

You have 3 layers of ICC cells in the colon

35
Q

Why does colon have both forward and backward contractions?

A

To promote mixing and absorption of water

36
Q

Do patients with constipation always have less motility in their colon?

A

No, not always. Sometimes the constipated patients have more motility, specifically during sleep and after lunch

37
Q

What is the treatment of constipation?

A
  1. Drinking more water
  2. Increase fiber to facilitate water absorption
  3. Laxatives
  4. medications
38
Q

What are types of laxatives?

A
  1. Magnesium, sulfate, phosphate
    • creates a hyperosmolar intraluminal environment
  2. PEG
    • isoosmotic and binds water molecules
  3. Anthraquinones/diphenylmethanes
    • mucosal afferent nerve fiber irritants
39
Q

What are anthraquinones and diphenylmethanes?

A

Types of laxatives

40
Q

What is PEG?

A

Pyloethylene glycol
Isosmotic
Binds water molecules

41
Q

What are types of medication (aside from laxatives) that are used for constipation?

A
  1. Lubiprostone
    -increases intestinal fluid secretion and transit by activating chloride channel
  2. Tegaserod
    -5HT4 partial agonist
    Restricted due to CV issues
42
Q

What is Lubiprostone used for?

A

A medication that acts to treat constipation

43
Q

What is Tegaserod used for?

A

A medication used to treat constipation

44
Q

What treatments should you avoid?

A
  1. tap water enemas (water intoxication)

2. soap suds enemas (colitis/necrosis)

45
Q

How is emesis controlled?

A

An emetic center in the medulla oblongata (brainstem)

Emetic center is regulated by the Chemoreceptor trigger zone (CTZ)

46
Q

Where is the CTZ located?

A

In the area postrema

47
Q

Where is the emetic center located?

A

Medulla

48
Q

What are characteristics of the vomiting center?

A 
No blood brain barrier to monitor blood and CSF easily
High receptor concentration in CTZ for 
	i. histamine
	ii. 5HT3
	iii. dopamine
	iv. Neurokinin
49
Q

What are potential emetic stimuli?

A
  1. sensory input
  2. cerebellar/inner ear input
  3. memory/fear
  4. solitary tract nucleus (gaggin) input
  5. blood-borne pathogens
  6. local iritants like drugs and copper
50
Q

What is the most common cause of emesis?

A

5HT3 (so you want to block the 5HT3 receptor)

51
Q

What is the most common anti-emetic class of drugs?

A

5HT3 receptor antagonists

52
Q

What is an example of a 5HT3 receptor antagonist?

A

Ondansetron

53
Q

What is Ondansetron?

A

A 5HT3 receptor antagonist

Used to treat emesis, nausea and vomiting

54
Q

What is an example of a cannabinoid receptor agonist?

A

This works because CTZ has cannabinoids that it can use to activate emetic center
Dronabinol

55
Q

What is Dronabinol?

A

An example of a Cannabinoid receptor AGONIST anti-emetic drug

56
Q

What is an example of Muscurainic receptor antagonists?

A

Scopolamine

57
Q

What is scopolamine?

A

A muscarinic receptor antagonist anti-emetic drug

GI Week 3 (11 decks)

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