Pharm - S2B2 - 14 Gastrointestinal Drugs

Front 1

What 2 things do GI drugs usually correct disorders of?

Back 1

1. Secretion

2. Motility

Front 2

What is the most common secretory disorder of the GI?

Back 2

Acid-peptic disease:
1. Peptic ulcer disease
2. GERD
3. other hypersecretory states (Z-E syndrome)

Front 3

What are the 3 aims of drug treatment for Acid-peptic disease?

Back 3

1. releive pain

2. promote healing

3. prevent recurrence

Front 4

What do motility disorders include?

Back 4

Vomiting

Diarrhea

Constipation

Front 5

Neural pathway regulating Gastric Acid secretion: Neural
1. Mediator
2. Receptors
3. Antagonist

Back 5

1. Acetycholine
2. Muscarinic
3. Anti-muscarinic

Front 6

Neural pathway regulating Gastric Acid secretion: Endocrine
1. Mediator
2. Receptors
3. Antagonist

Back 6

1. Gastrin
2. Gastrin / CCK-B
3. H2 blocker

Front 7

Neural pathway regulating Gastric Acid secretion: Paracrine
1. Mediator
2. Receptors
3. Antagonist

Back 7

1. Histamine
2. H2
3. H2 blocker

Front 8

What 3 things does Gastrin stimulate?

Back 8

1. Gastric motility
2. HCl secretion
3. Pepsin secretion

Front 9

T or F: there are no Gastrin antagonists?

Back 9

True

Front 10

What are the actions of Histamine on the GI?

Back 10

1. H2 receptors -> activate Adenylyl Cyclase -> increased cAMP -> activates proton pump -> increased Gastric Acid secretion

2. enhances Parietal Cell affinity for both Gastrin and ACh

Front 11

Why are Anti-muscarinic drugs relatively weak inhibitors of acid secretion?

Back 11

b/c they act at only one receptor site

**Acid secretion can therefore be stimulated by Gastrin & Histamine

Front 12

When & how are Anti-muscarinic drugs used to treat Gastric Acid treatment?

Back 12

Used as adjuncts to H2 blockers especially in patients that respond poorly to H2 blockers

Front 13

Describe Gastric Acid secretion in terms of Enterchromaffin-like cells, Parietal cells, their mediators, and their receptors

Back 13

1. ECL cells are stimulated by Gastrin & ACh to secrete Histamine

2. Parietal Cells have Gastrin, Muscarinic, & H2 receptors -> activate AC -> increased cAMP

3. cAMP -> activates Protein Kinases -> stimulate Acid secretion by ATPase proton pump (which is final common pathway)

Front 14

What are the most poweful drugs for inhibiting gastric acid secretion?

Back 14

Proton pump inhibitors = "-prazoles"

**blocks the final common pathway for acid secretion

Front 15

Therapeutic goal of Drug treatment for Acid-peptic disease:
1. Proton pump inhibitors
2. H2-antagonists
3. Antacids
4. Mucosal protective agents
5. Antimicrobial

Back 15

1. inhibit gastric acid secretion
2. inhibit gastric acid secretion
3. Neutralize gastric acid
4. Acid barrier in necrotic tissue
5. eradicate H. pylori

Front 16

What is the common ending for the Proton Pump Inhibitors?

Back 16

-PRAZOLE

**Ome-prazole

Front 17

What does a single daily dose of PPI's provide?

Back 17

-inhibits Gastric acid secretion by 95-100%

-does NOT affect Pepsin secretion or Gastric Motility

Front 18

How long does Gastric Acid inhibition persist after PPI withdrawal? Why

Back 18

4-5 days b/c that is the amount of time need to synthesize new proton pumps (H+/K+ ATPase)

Front 19

List 3 most common side effects of PPI's

Back 19

1. GI effects = nausea, colic, flatulence, constipation, diarrhea

2. CNS effects = headache, dizziness, somnolence

3. Skin rashes

Front 20

What are 2 side effects that may occur with prolonged use of PPI's

Back 20

1. Diarrhea due to GI bacterial overgrowth from removal of natural acid barrier

2. Hyper-gastrin-emia

Front 21

How are PPI's cleared from the body?

Back 21

Hepatic metabolism w/ neglible renal clearance

Front 22

What type of compounds are PPI's?

What is their mechanism of action?

Back 22

Benz-imi-dazole

IRREVERSIBLE inhibit the Parietal Cell proton pump, H+/K+ ATPase

Front 23

PPI's are __1__ that are inactive at __2__ pH

Back 23

1. prodrugs

2. neutral

Front 24

Activation of PPI's requires what type of environment? What should they be taken with...why?

Back 24

Acidic environment

Meals so that food can stimulate acid secretion

Front 25

B/c PPI's are unstable at a low pH, what is done to avoid degradation by acid in the esophagus and stomach?

Back 25

Dosage forms are supplied as Enteric Coated Granules that dissove only at Alkaline pH

Front 26

After PPI's pass through the stomach, the __1__ dissolve and the PRODRUG is absorbed in the __2__

Progdrug is then carried by the __3__ to the Parietal cells where it accumulates in the secretory canaliculi to be activated at __4__ pH and form __5__ which then binds to __6__ groups on the H+/K+ ATPase

Back 26

1. enteric coating
2. Intestines
3. circulation
4. acid
5. Sulfonamide or Sulfenic acid
6. Sulfhydryl

Front 27

Intestinal absorption of PPI's is rapid, but what does the bioavailability of the absorbed form depend on?

Back 27

activation at Gastric Acid pH

Front 28

What 2 things do PPI's promote?

PPI's are often effective in patients unresponsive to _____

PPI's are more effective than H2-antagonists for ______ & _____

Back 28

Peptic ulcer healing & prevent ulcer recurrence

H2-antagonists

GERD or NSAID-induced peptic ulcers

Front 29

What is the common ending for the H2-receptor Antagonists?

Back 29

-TIDINE

Cime-tidine
Famo-tidine
Niza-tidine
Rani-tidine

Front 30

H2-receptor antagonists are all __1__ preparations that inhibit acid secretion for < __2__ hours

Back 30

1. OTC

2. 6

Front 31

H2-antagonists are structural analogs of __1__ that block H2 receptors selective to reduce __2__ & __3__ secretion without affecting H+/K+ ATPase, H1 or any other receptors

Back 31

1. Histamine

2. Gastric acid
3. Pepsin

Front 32

GI drug that is especially effective against NOCTURNAL secretion of Gastric Acid

Back 32

H2-antagonists (-tidine's)

**nocturnal secretion is largely due to Histamine
**Acid is reduced by 90% at night as compared with 60-80% during day

Front 33

List the relative potentcy of the 4 H2-antagonists

Back 33

Famo > Niza = Rani > Cime

**all end in -tidine
**are all equally effective, rapidly and well absorbed orally, and generally well tolerated with few side effects

Front 34

To what people should H2-antagonists not be given to?

Back 34

Pregnant or nursing women b/c they cross the placenta and are secreted into Breast milk

Front 35

What are the most common side effects of the -tidine's?

Back 35

Diarrhea
Headache
Fatigue
Myalgias
Constipation
Bradycardia

Front 36

Mental changes like confusion, hallucination, and agitation may occur with __1__ administration of "-tidine's" in patients who are __2__ or who have __3__

Back 36

1. IV

2. Elderly
3. Renal or Hepatic dysfunction

Front 37

GI drug that may cause Gynecomastia or Impotence in men; Galactorrhea in women

Why does it do this?

Back 37

Cime-tidine

inhibits binding of Dihydrotestosterone to androgen receptors, inhibits estradiol metabolism, and increases serum prolactin

Front 38

GI drug that interferes with Cytochrome P450 pathways for Hepatic metabolism of many drugs including warfarin, theophylline, phenytoin, lidocaine, quinidine, propranolol, labetalol, metoprolol, tricyclic antidepressants, benzodiazepines, calcium channel antagonists, sulfonylureas, metronidazole, and ethanol

Back 38

Cimetidine

**listed drugs will not be metabolized if Cimetidine is co-taken

Front 39

All H2-antagonists (-tidine's) are equally effective for these 2 things

Back 39

Healing & preventing recurrence of Peptic Ulcer Disease

Front 40

GI drug given once daily at bedtime to suppress nocturnal acid secretion & will produce ulcer healing rates of > 80-90% after 6-8 wks of treatment

Back 40

-tidine's = H2 antagonists

Front 41

For what 2 reasons has the use of H2-antagonists markedly declined?

Back 41

Discovery of PPI's

Discovery of role of H. pylori in PUD

Front 42

H2-antagonists have a 20% failure rate in these 2 groups of ulcer patients

Back 42

1. Smokers

2. Elderly

Front 43

Why should H2-antagonists not be used in conjunction with PPI's?

Back 43

H2-antagonists reduce the efficacy of PPI's by reducing their acid activation

Front 44

H2-antagonists are combined with these 2 things for treatment of patients with H. pylori infection

Back 44

1. Antibiotics

2. Bismuth

Front 45

List the 3 preparations of Antacids

Back 45

1. Aluminum hydroxide

2. Calcium carbonate

3. Aluminum hydroxide + Magnesium hydroxide

Front 46

What is the most common side effect of Aluminum hydroxide?

Back 46

Constipation

**aluMINIMUM amount of feces

Front 47

What is the most common side effect of Magnesium hydroxide?

Back 47

Diarrhea

**Mg = Must Go to the bathroom

Front 48

What is the general use of Antacids?

Back 48

PRN ("as the situation arises") to relieve pain in Esophagitis, Peptic ulcer, and GERD

Front 49

What is the mechanism of action of Antacids?

Back 49

Are weak bases that neutralize Gastric HCl to form salt & water

**may interfere with the absorption of other drugs

Front 50

Aside from neutralizing Gastric HCl, what other function may Antacids provide?

Back 50

Mucosal protection by stimulating PG synthesis

Front 51

Binds selectively to necrotic ulcer tissue and acts as a barrier

Back 51

Sucral-fate

**"Sucks" to the ulcer site

Front 52

Mucosal protective agent that requires acid pH for activation and should not be given together with Antacids, H2-antagonists, or PPI's

Back 52

Sucral-fate

Front 53

What is the mechanism of action of Sucralfate

Back 53

1. Polymerizes to produce a viscous, sticky gell that adheres strongly to epithelial cells and ulcer craters in acid environment

2. effective in healing Duodenal ulcers

Front 54

What is the most common adverse effect of Sucralfate?

Back 54

Constipation

Front 55

Methyl analog of PGE1 that binds to PG receptors on Parietal cells to inhibit acid secretion

Back 55

Misoprostol

Front 56

What is Misoprostol used specifically to prevent? Why?

Back 56

NSAID-induced ulcers

b/c NSAID's inhibit PG formation; Misoprostol is a PG analog

Front 57

What are the 2 most frequent side-effects of Misoprostol?

Back 57

Diarrhea

Abdominal pain

Front 58

2 mechanisms of Misoprostol

Back 58

1. PGE1 analog thtat increases production and secretion of Gastric MUCUS BARRIER

2. Decreases acid production by inhibiting Histamine-stimulated gastric secretion

Front 59

Binds selectively to ulcers and provides protective coating; may also be antibacterial against H. pylori

Back 59

Bismuth subsalicylate = Pepto-Bismol

Front 60

What are the adverse effects of Bismuth?

Back 60

Darken the tongue and stools b/c the Bismuth Sulfide formed is a black solid

Front 61

What is the best regimen of treatment for H. pylori infection?

Back 61

10-14 day "triple therapy" treatment:

1. Clarithromycin
2. Amoxicillin
3. PPI

**pts allergic to Penicillin, use Metronidazole instead of Amoxicillin

Front 62

What should a normal stool frequency be in Western culture?

Back 62

at least 3 times per week

Front 63

What people most commonly suffer from constipation?

Back 63

Women & Elderly

Front 64

Drugs used to promote defecation & treat constipation are reffered to as:

Back 64

laxative = cathartic = purgative = aperient =evacuant

Front 65

Why are Laxatives usually unnecessary?

Back 65

Constipation can usually be resolved by:
1. increasing water and fiber content of diet
2. appropriate bowel habits and training
3. improved physical activity & exercise
4. attention to psychosocial & emotional factors

Front 66

List the 3 Osmotically Active Laxatives

Back 66

1. Saline laxatives

2. Nondigestible sugars and alcohols

3. Polyethylene Glycol (PEG)-electrolyte solutions

Front 67

Nonabsorbable salts containing Magnesium cations or Phosphate anions

Back 67

Saline laxatives

Front 68

Mechanism of action of Saline Laxatives

Back 68

Salts act by osmotic force to hold water inside intestines ➡ distened intestines ➡ stimulate peristalsis

Front 69

Laxatives that have an extremely bitter taste that is masked by adding citrus juices

Back 69

Saline Laxatives

Front 70

Under what conditions should Saline Laxatives be avoided?

Back 70

1. Renal insufficiency

2. Heart Disease

3. Electrolyte imbalance

4. being treated with Diuretic drugs

Front 71

Trihydroxy alcohol that when given rectally acts as a lubricant and hygroscopic agent ➡ water retention ➡ stimulate peristalsis

Back 71

Glycerin

Front 72

3 nonabsorbable sugars ➡ hydrolyzed to organic acids ➡ acidify luminal contents ➡ draw water into lumen ➡ increase colonic propulsive motility

Back 72

Lactulose

Sorbitol

Mannitol

Front 73

What is in a Polyethylene glycol (PEG)-electrolyte solution?

Back 73

1. Sodium sulfate
2. Sodium bicarbonate
3. Sodium chloride
4. Potassium chloride
5. Isotonic solution containing 60 g of Polyethylene glycol per L

Front 74

Laxative used to prepare for colonoscopy: drink 3-4 liters over 3-4 hrs to produce water diarrhea and remove solid wastes

Back 74

Polyethylene glycol (PEG)-electrolyte solution

Front 75

Describe the mechanism of action of Stimulant or Irritant Laxatives

Back 75

1. act directly on Enterocytes, Enteric neurons, and muscle
2. induce low-grade intestinal inflammation
3. water and electrolytes accumulate
4. increased intestinal motility

Front 76

Diphenylmethane derivative that is available as enteric coated tablets taken at bedtime to take effect the next morning (causes you to poop)

Back 76

Bisa-codyl

**to avoid activation in the stomach (causes gastric irritation & cramping) tablets should be swallowed w/out chewing or crushing

**"B is a code" that you take at night & you wake up to go poop

Front 77

3 Anthraquinones that are poorly absorbed in the small intestine and require activation in the colon with laxative effect 6-12 hrs later

Back 77

Aloe

Cascara sagrada

Senna

Front 78

Longterm usage of this Laxative causes Melanomic pigmentation of colon mucosa and "cathartic colon" (colon becomes dilated and ahaustral)

Back 78

Anthraquinones
-Aloe
-Cascara sagrada
-Senna

Front 79

Castor oil that is a local irritant that increases intestinal secretion and motility; now seldom used due to unpleasant taste and toxic potential

Back 79

Rici-noleic acid

**Rice crispies with Castor Oil will run right thru you

Front 80

List 3 stool softners

Back 80

1. Mineral oil

2. Glycerin suppositories

3. Docusate

Front 81

Stool softner that is often prescribed to prevent straining in hospitalized patients

Back 81

Docusate

Front 82

Dietary supplements that add bulk & hold water to intestinal contents

Back 82

Bulk-forming Laxatives

Front 83

List 3 Bulk-forming Laxatives

Back 83

1. Methyl-cellulose

2. Lactulose

3. Poly-carbo-phil

**My Large Poop

Front 84

2 anti-diarrheal drugs that act on intestinal opioid receptors to decrease GI motility

Back 84

Loper-amide

Di-phenoxyl-ate

Front 85

Antidiarrheal that is 40-50 times more effective than morphine

Back 85

Loperamide

Front 86

Loperamide:
-increases __1__ time and __2__ tone
-acts quickly on oral administration with peak levels at __3__
-effective against __4__, but should be discontinued if clinical improvement does not occur within 48 hours

Back 86

1. intestinal transit
2. anal sphincter
3. 3-5 hours
4. Traveler's Diarrhea

Front 87

2 Anti-diarrheal drugs that act by absorbing compounds and presumably binding potential intestinal toxins

Back 87

Kaolin

Pectin

Front 88

List 5 of the most widely used Anti-diarrheal drugs

Back 88

1. Loper-amide
2. Di-phenoxyl-ate
3. Di-fenoxin
4. Bismuth subsalicylate
5. Kaolin/Pectin

Front 89

Vomiting is a complex process coordinated by a __1__ vomiting center that activates __2__ pathways in the __3__(3) nerves of the __4__ muscles

Back 89

1. Medullary (medulla)
2. efferent
3. Vagus, Phrenic, and Spinal innervation
4. Abdominal

Front 90

4 classes of Antiemetic drugs (anti-vomiting)

Back 90

1. Histamine H1 antagonists
2. Dopamine D2 & Serotonin 5-HT3 antagonists
3. Pheno-thiazines & Benzo-diazepines
4. Marijuana derivatives

Front 91

How do the Histamine H1 Antagonists provide anti-emetic activity?

Back 91

Produce sedation & anti-muscarinic activity which prevent Motion Sickness

Front 92

List the 4 Histamine H1 Antagonists used as Anti-emetic drugs

Back 92

1. Di-men-hydrinate

2. Di-phen-hydramine

3. Cyclizine

4. Me-clizine

Front 93

List the Dopamine D2 antagonists used as Anti-emetic drugs

Back 93

1. Meto-clopramide

2. Tri-metho-benzamide

***"3 Meth dealers in a Benz-amide" take exit D2 to METOCLOPRAMIDE street

Front 94

List the 3 HT3 antagonists that are currently used for nausea and vomiting during Cancer Chemotherapy

Back 94

Ondan-setron

Grani-setron

Dola-setron

Front 95

List the 2 Phenothiazines used as Anti-emetics

Back 95

Chlor-proma-zine

Pro-chlor-perazine

*the "Color Pro's" do not like to puke

Front 96

List the 2 Benzodiazepines used as Anti-emetics

Back 96

Lor-azepam

Alpra-zolam

Front 97

Marijuana derivative used as a prophylactic antiemetic in patients receiving cancer chemotherapy

Back 97

Dron-abinol

**"Drawn Abs" on a Cancer patient will make them LAUGH (marijuana) instead of puke

Front 98

What are the side effects of Dron-abinol?

Back 98

Increased sympathomimetic activity in the form of marijuana-like highs
-mood changes
-laughing
-paranoid rxns
-thinking abnormalities

Front 99

2 Marijuana derivative used as Anti-emetics

Back 99

1. Tetra-hydro-cannabinol (THC)

2. Dron-abinol