Gastrointestinal Drugs II

Question 1

Causes of gastroesophageal reflux

Answer 1

• Lower esophageal sphincter - inappropriate relaxation, low resting tone, anatomical alteration
• Acid hypersecretion
• Decreased acid clearance due to impaired peristalsis or abnormal saliva production
• Delayed gastric emptying and/or duodenogastric reflux of bilee salts and pancreatic enzymes

Question 2

GERD lifestyle Tx

Answer 2

• Elevate head of bed
• Avoid food/liquid 2-3 hrs before bedtime
• Avoidance of fatty or spicy food
• Avoidance of cigs/alcohol
• Weight loss
• Liquid antacid
• Pregnancy

Question 3

Tx of GERD in patients w/o Esophagitis

Answer 3

• Alginic acid antacids
• Promotility drugs - cisapride, metoclopramide
• H2 blockers - cimetidine, ranitidine, famotidine, nizatidine

Question 4

Tx of GERD of patients w/ esophagitis

Answer 4

• H2 blockers
• OR
• H2 recceptor blockers + promotility agent
• OR
• PPI
• OR
• Anti-reflux surgery

Question 5

MOA of promotility drugs to treat GERD?

Answer 5

Promotility drugs prevent acid from sitting in stomach too long

Question 6

What are the promotility drugs?

Answer 6

Metochlopramide, cisapride

Question 7

SE of promotility drugs?

Answer 7

Tremor

Question 8

What is vomiting mediated by?

Answer 8

Chemoreceptor Trigger Zone and Vomiting Center in the Medulla

Question 9

What is vomiting stimulated by?

Answer 9

Local irritation or CNS stimulation

Question 10

Metabolic consequences of vomiting?

Answer 10

• Dehydration
• Hypochloremic metabolic alkalosis
• Hypokalemia (Kidney reuptake of acid results in K+ loss)

Question 11

What are the classes of antiemetics?

Answer 11

• Phenothiazines
• Benzamide
• Tetrahydrocannabinol
• Serotonin (5HT3) receptor antagonists

Question 12

What are the phenothiazines?

Answer 12

The neuroleptic class

• Prochlorperazine
• Promethazine

Question 13

MOA of Phenothiazine? Promethazine?

Answer 13

• Prochlorperazine - Dopaminergic receptor antagonist
• Promethazine - H1 anticholinergic

Question 14

SE of prochlorazine and promethazine?

Answer 14

1. Prochlorperazine - Torticollis
2. Promethazine - Somnolence

Question 15

Adverse effects of Benzamide derivatives?

Answer 15

Extrapyramidal Syx (but ont as severe phenothiazines)

Question 16

What are the Benzamide derivatives?

Answer 16

• Trimethobenzamide
• Metochlopramide

Question 17

MOA of Trimethobenzamide and Metochlopramide?

Answer 17

• Trimethobenzamide - unknown effects on CRTZ
• Metochlopramide - CNS and peripheral dopaminergic receptor antagonism

Question 18

MOA of THC?

Answer 18

Suppress the CRTZ by probable anticholinergic mechanism

Question 19

What are the 5HT3 blockers?

Answer 19

Ondansetron, Granesitron, Dolasetron

Question 20

Adverse SE of 5HT3 antagonists?

Answer 20

Headache, dizziness, somnolence

Question 21

Tx strategy for gastroparesis?

Answer 21

Metochlopramide, cisapride, domperidone

Question 22

5 Types of diarrhea?

Answer 22

1. Secretory - Na and Cl secretion/decreased reabs
2. Osmotic - Nonabs molecules in gut lumen
3. Inflammatory absorptive surface - Destruction of mucosa, impaired abs, outpouring of blood, mucus
4. Decreased abs - impaired reabs of electrolytes
5. Motility disorder - Increased motility/decreasd motility with bacterial growth

Question 23

What are the goals to treat diarrhea?

Answer 23

Decrease GI secretion and decrease GI motility

Question 24

What are the classes for diarrhea Tx?

Answer 24

• Anticholinergics
• Opioid Agonists
• Colloids
• Pectins

Question 25

Anticholinergic drugs to treat diarrhea?

Answer 25

Atropine sulfate

Question 26

MOA of loperamide?

Answer 26

Immodium! increase rectal tone and disrupt peristalsis via mu receptor

Question 27

MOA of diphenoxylate and codeine sulfate?

Answer 27

Mu-R agonist causing contraction of circular muscle "segmentation"

Question 28

What are the colloids and pectins and what is their MOA?

Answer 28

* Colloid - Metamucil * Pectin - Kaopectate Bulk up stool

Question 29

What is the treatment for constipation?

Answer 29

Laxatives or cathartics

Question 30

What are the classes of treatments for constipation?

Answer 30

* Irritants/Stimulants * Osmotic cathartics * Bluk-forming (hydrophilic colloids) * Lubricants and fecal softeners

Question 31

What are the irritants/stimulants?

Answer 31

Castor oil, cascara sagrada/aromatic fluid extract, senne extract, bisacodyl, phenolphthalein

Question 32

What are the osmotic cathartics?

Answer 32

Magnesium citrate solution, magnesium sulfate, sodium sulfate, milk of magnesia, sodium phosphate, lactulose

Question 33

What are the bulk forming colloids?

Answer 33

psyllium seed (metamucil), methycellulose, sodium carboxymethylcellulose

Question 34

What are the lubricant and fecal softeners?

Answer 34

Mineral oil, dioctyl sodium sulfo-succinate, poloxalkol

Question 35

What is the likely the etiology of the inflammatory bowel diseases?

Answer 35

Likely autoimmune

Question 36

What are the **acute** treatments for inflammatory bowel diseases?

Answer 36

1. Anti-inflammatories 2. Cortiocsteroids 3. Antibiotics

Question 37

What are the antiinflammatory drugs, and what do they target?

Answer 37

1. Mesalamine - delayed release for terminal ileum, colon 2. Sulfasalazine - ulcerative colitis (colon) 3. Olsalazine - ulcerative colitis

Question 38

What is the mechanism of sulfasalazine? What causes its SEs?

Answer 38

Sulfasalazine is hydrolyzed into 5-ASA (mesalamine - active drug) and sulfapyridine. Sulfapyridine causes side effects

Question 39

What makes olsalazine so special?

Answer 39

It is a dimer of mesalamine and has few side effects!

Question 40

What are the drugs used to treat ulcerative colitis and chron's disease (**chronic** Tx)?

Answer 40

Immunosuppressive agents: 1. Azathiprine - purine antimetabolite that interferes with DNA synth 2. Corticosteroids 3. Infliximab - binds to and neutralizes TNFalpha 4. Cyclosporine - suppresses T helper and T suppressor lymphocytes

Question 41

What are the drugs used to treat Irritable Bowel syndrome?

Answer 41

1. Bulking agents (metamucil) 2. Opioids - loperamide 3. Anticholinergics - **antispasmodics** - Dicyclomine hydrochloride, hyoscyamine sulfate 4. Antidepressants

Question 42

What antidepressant is used for diarrhea predominant irritable bowel syndrome? Constipation predominant?

Answer 42

* Alosetron for diarrhea predominant (**5HT3 antagonist**) * Tegaserod maleate for constipation predominant (**5HT4 agonist**)

Question 43

What conditions affect the large bowel? Small bowel?

Answer 43

* Large - Ulcerative colitis, granulomatous (Chron's) colitis * Small - Chron's disease