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Clinical Pharmacology II > GI Disorders > Flashcards

GI Disorders Flashcards

1
Q

What receptors are in the vomiting center?

A

H1
M1
5HT3
NK1

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2
Q

What emesis receptors are in the chemotrigger zone (CTZ)?

A

D2
5HT3
NK1
CB1

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3
Q

What emesis receptors are in the vestibular system and what does activation of these cause?

A

H1
M1

Motion sickness

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4
Q

What receptors are in the GI tract that can also modulate emesis?

A

Smell; rotten food

Mu
5HT3
D2
CB1/2
NK1
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5
Q

What does agonizing the corpus striatum D1 and D2 receptors do?

A

Control of movement and posture

Treats Parkinson’s disease

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6
Q

What does agonizing the limbic systems D1, D2, D3, and D4 receptors do?

A

Causes aggression, agitation, hallucinations, and hypervigilance

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7
Q

What does agonizing the pituitary glands D2 receptors do?

A

Increases GH release and decreases prolactin release causing decreased breast milk and treatment of amenorrhea

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8
Q

What does antagonizing the corpus striatum D1 and D2 receptors do?

A

Slowed and abnormal movements

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9
Q

What does antagonizing the limbic systems D1, D2, D3, and D4 receptors do?

A

Reduces aggression, agitation, and vigilance = Antipsychotics

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10
Q

What does antagonizing the Pituitary glands D2 receptors do?

A

Increases prolaction release

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11
Q

Where is are the target receptors of D2 receptor antagonists in order to treat vomiting?

A

CTZ D2 receptors

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12
Q

Are D2 receptor antagonists selective to their target receptors?

A

No, they will also antagonize other D2 receptors throughout the body and will cause ADRs

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13
Q

What are the ADRs of D2 Receptor antagonists?

A

Movement disorders
Prolactin release
Sedation
Hypotension

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14
Q

What other receptors does D2 receptor antagonists act on?

A

GIT = improving GI motility and LES

block H1 receptors to treat motion sickness

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15
Q

What are the effects of 5HT3 Receptor antagonists?

A

The target receptors are found in the GI tract

Antagonism reduces vomiting

Most effective to treat CINV

Not effective against motion sickness

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16
Q

What is Metoclopramide?

A

D2 and 5HT3 receptor antagonist

Less effective than agents for the individual receptors

Has prokinetic effect and can be used to treat GERD by causing the stomach acid to keep moving and not sit in the LES

4X/day dosing

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17
Q

What is Aprepitant/Fosaprepitant?

A

Neurokinin-1 Receptor antagonist

Workson substance P receptors found in CTZ and GIT

No analgesic effect; only used to prevent CINV

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18
Q

What are the ADRs for Metoclopramide?

A

BBW for tardive dyskinesia

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19
Q

What are cannabinoid Receptor Agonists?

A

Act on CB1 receptor in CTZ and CB1/2 receptors in periphery

Used for CINV, anorexia, and AIDs related wasting

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20
Q

What are the ADRs of cannabinoid receptor agonists?

A 
Tachycardia
Palpitations
Euphoria
Altered sense of reality
Xerostomia
Hunger
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21
Q

What can occur in withdrawal of cannabinoid receptor agonist?

A

Insomnia

Irritability

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22
Q

What drugs do we use to treat constipation?

A

Stimulant laxative and stool softener

23
Q

What are the treatments used to treat diarrhea?

A

Bismuth Subsalicylate
Peripheral Mu-agonists
Bile acid sequestrants in refractory cases

24
Q

What are the side effects of Bismuth subsalicylate?

A

Salicylate toxicity

Darkened stool and tongue

25
Q

How is acid produced in the stomach?

A

Parietal cells make acid (H) after ACh, histamine, and/or gastrin receptors are activated

Acid is secreted out of the parietal cells by H/K Proton pumps into gastric lumen

26
Q

What causes acid production in the stomach to turn off?

A

Somatostatin which causes less gastrin release/activation

27
Q

What disease states involve acid production in the stomach?

A

Peptic Ulcer Disease (PUD)
Gastro-esophageal Reflux disease (GERD)
Stress ulcer prophylaxis

28
Q

What are the underlying causes of PUD?

A 
H. pylori
NSAID
Smoking
Liver cirrhosis
Stress
29
Q

What are the goals of treatment for PUD?

A

Reduce symptoms

Heal lesions

30
Q

What are the approaches to treating PUD?

A

Get rid of any offending agent = if H. Pylori, patient must be treated with antibiotics for 10-14 days first

Protect stomach lining
Reduce/neutralize acid production

31
Q

What drugs will Protect the stomach lining?

A

Misoprostol

Sucralfate

32
Q

What drugs will reduce/neutralize acid production?

A

H2RAs

PPIs

33
Q

What is Misoprostol?

A

Prostaglandin E analog

Increases mucus production and is a cytoprotective

Used in ulcer treatment/prophylaxis from NSAID use; Promotes labor and induces cervical ripening

34
Q

What is a cytoprotective agent?

A

Works really good at treating the ulcers but doesn’t have any acid issues

35
Q

What are the ADRs of Misoprostol?

A

DIARRHEA

Uterine contractions (abortification)

36
Q

What is Sucralfate?

A

Aluminum sucrose sulfate that is activated in the presence of stomach acid

This drug forms a viscous adhesive coating over an ulcer by binding charged proteins in the ulcer

37
Q

What are the ADRs of Sucralfate?

A

Constipation

Many DDIs

Accumulates in renal insufficiency

38
Q

What are Histamine 2 Receptor Antagonists (H2RAs)?

A

-Tidines

Reversible binding of receptors

Have potential for tolerance to build up

Reduce nocturnal and post-prandial acid secretion

Must be renally dose adjusted

Fairly well tolerated

39
Q

What are PPIs?

A

-prazole

Irreversibly inhibit H+/K+ ATPase pump

Has delayed onset because it requires activation by acid in parietal cells (its a prodrug) = NOT for immediate symptom release

40
Q

What are ADRs of PPIs?

A 
Rebound acidity upon d/c (taper with chronic use)
Osteoporosis/fractures
C. diff
Low Mg/B12
Pneumonia
Dementia
CKD
CAD
Death
41
Q

What is GERD?

A

Occurs when the amount of gastric juice that refluxes into the esophagus exceeds the normal limit, causing symptoms with or without associated esophageal mucosal injury

42
Q

What are the goals of GERD treatment?

A

Reduce symptoms

Heal esophagitis

43
Q

What are the symptoms of GERD?

A

heartburn (pyrosis)
Regurgitation
Dysphagia

44
Q

What are the therapeutic approaches to GERD?

A

Inhibit retrograde movement = improve LES function/tone; Prokinetic action

Reduce/neutralize acid production =

Get rid of any offending agent/consider lifestyle modifications

45
Q

What drugs are used to treat GERD?

A

all the same ones as PUD

Also includes Antacids

46
Q

What are antacids?

A

Neutralize acid and raise gastric pH

Calcium, Magnesium, and Aluminum

Used for intermittent symptomatic relief because of rapid onset and short duration

47
Q

What are ADRs of antacids?

A

Constipation (Ca/Al)
Diarrhea (Mg)
Accumulation of Mg/Al in renal insufficiency

48
Q

What are the DDIs of antacids?

A

Chelation (fluoroquinolones, tetracyclines, and levothyroxine)

Reduced absorption caused by increases in pH = azole antifungals, bisphosphonates, iron

49
Q

What should you avoid using H2RAs with?

A

Cimetidine

50
Q

What are the clinical pearls of H2RAs?

A

Can be taken with or without foodL
Heartburn/GERD = take 30-60 min. before food
PUD course = 4-8 weeks

Inexpensive

Less effective than PPIs for erosive esophagitis

DDIs with pH dependent absorption

51
Q

What are the PPI clinical pearls?

A

Commonly overprescribed and unnecessarily continued

Different course for different disease:
Heartburn = 2 weeks
GERD = 4 weeks
PUD = 4-8 weeks

Need to be taken 30-60 minutes before a meal for symptomatic heartburn

Not for as needed use

DDI’s with pH dependent absorption

52
Q

Which two PPIs do not need to be taken 30-60 minutes before a meal?

A

Rabeprazole

Dexlansoprazole

53
Q

OMeprazole and Esomepazole have DDI’s with what?

A

Moderate 2C19 inhibitors like clopidogrel

Clinical Pharmacology II (25 decks)

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