Chapter 161- Gastrointestinal Protectants

Question 1

Gastric Ulceration and Erosion (GUE) is a result of which 2 most common causes in the dog? and what other conditions cause GUE?

Answer 1

1) Stress- i.e. an event causing substantial hypoperfusion or anoxia of the gastric mucosa
2) Drug therapy- especially NSAID and dexamethasone (prednisolone at common dosages is rarely ulcer inducing unless there is a concurrent cause)

Also

3) Hyperacidity (gastrinoma, MCT)
4) Hepatic Failure
5) Tumors
6) FB

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Question 2

Prevention of GUE…

Answer 2

• GI protectors are poor at preventing ulcers when the cause persists.
• PPI and H2RA prevent GI ulceration caused by certain forms of stress in dogs.
• No drug is shown to prevent GUE caused by steroids.

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Question 3

Gastric acid reduction and nausea

Answer 3

• Drugs that decrease gastric acid secretion are not antiemetics (no effec on medullary vomiting center or CRTZ), however they can have antidyspeptic (or anti-indigestion) effects which may lesson nausea

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Question 4

H₂RA

Answer 4

• Block histamine receptor on the gastric parietal cell
• Competative inhibitors of gastric acid secretion (which means they do not decrease gastric acid secretion as well as PPIs)
• Maximal effect of decreasing gastric acid secretion occurs almost immediately
• Some prokinetic activity via antiacetylcholinesterase activity (Nizatidine and ranitidine)

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Question 5

Potency order of H₂RA

Answer 5

Most potent- famotidine (9x more potent then ranitidine and 32x more potent then cimetidine)

Intermediate potency- nizatidine

Least potent- Cimetidine < ranitidine (5-12x cimetidine)

S/H, Booth

Question 6

Which two H2RAs have prokinetic effects?

Answer 6

Ranitidine

Nizatidine

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Question 7

Cimetidine

Answer 7

• Gastric acid reducer
• MOA: H2RA
• Absorption delayed with food adminstration (unlike others)
• Metabolized extensively by the liver with extensive first-pass metabolism
• Marked inhibition of hepatic P-450 enzymes and has been used to decrease severity of acetaminophen toxicity
• Cimetidine decrease hepatic blood flow by 20%

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Question 8

Famotidine

Answer 8

• Gastric acid reducer
• MOA: H2RA
• Most potent H2RA
• Longest duration of action of H2RA
• Gan be given with food (does not effect absorption)
• Sunstantial first-pass hepatic metabolism
• Least bioavailable orally (of the H2RAs)
• Not metabolized by liver (excreted unchanged in urine)

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Question 9

Ranitidine

Answer 9

• Gastric acid reducer
• MOA: H2RA
• Has prokinetic effect
• Gan be given with food (does not effect absorption)
• Sunstantial first-pass hepatic metabolism
• Metabolized by the liver
• Has much less effect on hepatic P-450 then cimetidine

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Question 10

Nizatidine

Answer 10

Gastric acid reducer

• MOA: H2RA
• Has prokinetic effect
• Gan be given with food (does not effect absorption)
• NO first-pass hepatic metabolism
• Not metabolized by the liver (excreted unchanged in urine)
• No effect on hepatic P-450

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Question 11

New H2RA- Lafutidine

Answer 11

• additional MOA (NO mediated and histamine independent mechanism)
• Mucus protective action via capsaicin-sensative sensory nerves

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Question 12

PPI MAO (specifically omeprazole)

Answer 12

• Irreversibly inhibit hydrogen-potasssium ATP on the luminal side of the parietal cell, thus stopping secretion of hydrogen ions into the gastric lumen
• Omeprazole (a prodrug) susceptible to destruction by gastric acid (so adminsitered in enteric-coated granules which are absorbed in the duodenum)
• Absorption decreased by food (best to give 1 hour before meal because there is maximal acidity in the parietal cells and thus increase the amount of omeprazole sequestered there).
• First pass hepatic metabolism and the rest is selectively sequestered in the acidic environment of the parietal cells where it is transformed into the active drug.
• Takes 2-5 days before maximal acid suppression
• More effective than H2RAs
• Inhibit hepatic P-450 enzymes

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Question 13

Sucralfate

Answer 13

• The octasulfate of sucrose combined with aluminum hydroxide
• Locally acting drug
• Binds tightly to epithelial cells in the acidic environment of the stomach (especially to the base of erosions or ulcers) and remains for 6 hours (give before antiacid therapy for maximal effect) [greater in duodenum then gastric ulceration- Boothe}
• Protects and stimulates local production of prostaglandins and binding to epidermal growth factor (favors mucosal repair)
• SE- consitpation
• Absorbs other drugs
• Do not give with enteral feeding because it may bind the fat soluable vitamins

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Question 14

Misoprostol

Answer 14

• Prostoglandin E1 analog
• Antiacid (>)and mucosal protective properties (stimulates secretion of the mucus and bicarbonate and increases gastric mucosal blood flow)
• Acts directly on parietal cells to inhibit both nocturnal acid secreation and secretion in response to food, pentagastrin and histamine.
• Rapidly absorbed, first-pass metabolism (liver becomes active form)
• Short half live, dose frequenty (q8-12hr)
• SE: diarrhea (due to increased colonic motility), uterine contraction (abortion in pregnant females)

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Question 15

Antiacids

Answer 15

• Numerous durgs PO to neutralize gastric acid
• Dont prevent or treat GUE due to short half life compared to H2RA and PPI
• Can delay or prevent absorption of other drugs
• An effective antiacid should raise pH to 3-4 (boothe)
• Cl, water, carbon dioxide (why you burp)- boothe

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Question 16

Complications of increased gastric pH?

Answer 16

• May increase infectious agents gaining access to the intestinal tract
• Increased risk of pneumonia following an aspiration event
• Increases C. difficile in humans, not a major problem in vetmed

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Question 17

GI protects drug chart

Answer 17