Gi - Pharm I

Front 1

What is the most common GI complaint in the US?

Back 1

Constipation

Front 2

How often does the average adult have diarrhea?

Back 2

4 bouts per year

Front 3

What is one of the seven warning signs of cancer that has to do with GI?

Back 3

changes in bowel habits

Front 4

What is a "normal bowel pattern"?
Constipation?
Diarrhea?

Back 4

Normal = defined by the individual

Constipation = decrease in freq of BMs; difficult passage of hard, dry stool

Diarrhea = increase in freq of BMs; soft, watery stools
- acute
OR
- chronic

Front 5

Explain the physiology behind the GI fluid balance??

Back 5

9 liters fluid into small intestines per day:
- 2 liters ingested
- 7 liters secreted

Small intestine absorbs 80%
Ileum and Colon absorb rest (19%)
0.1 L passed into stool (1%)

****Drugs/events that affect balance between uptake, absorption, osmotic gradients for water flux/intestinal secretions OR alter GI motlity --> CONSTIPATION or DIARRHEA!

Front 6

NSAIDs
- cause what GI efffect?
- mechanism?

Back 6

Constipation
- inhibit PG synthesis --> slows GI tract

Front 7

Antacids
- ex??
- cause what GI efffect?
- mechanism?

Back 7

Ex: CaCO3, Al(OH)2

Constipation
- local astringent (contraction of tissue) effects

Front 8

Iron Supplements
- cause what GI efffect?
- mechanism?

Back 8

Constipation
- local astringent effects???

Front 9

Anticholinergic Agents
- cause what GI efffect?
- mechanism?
- what else works by this mech?

Back 9

Constipation
- decrease GI motility

... also other drugs with AntiCh effects - e.g., Tricyclic Antidepressants; Antihistamines

Front 10

What is the result of CHRONIC laxative use??

Back 10

Constipation!
- due to chronic colonic distention

Front 11

Muscle Relaxants
- cause what GI efffect?
- mechanism?

Back 11

Constipation
- due to smooth muscle relaxation in GI tract

Front 12

Opioids
- cause what GI efffect?
- mechanism?

Back 12

Constipation
- slow GI motility

Front 13

Calcium Channel Blockers
- cause what GI efffect?
- ex?

Back 13

Constipation
**especially Verapamil

Front 14

Antihistamines
- cause what GI efffect?
- mechanism?

Back 14

Constipation
- antagonist of cholinergic receptors

Front 15

What are the causes of constipation?

Back 15

- drugs
- metabolic and endocrine disorders (e.g., diabetes)
- neurogenic
- structural; (e.g., obstruction secondary to cancer, polyp)
- miscellaneous

Front 16

What are the symptoms of constipation that might be complained of?

Back 16

- anorexia
- headache
- low back pain
- feelings of abd distention

Front 17

What is NON-pharm treatment for constipation?

Back 17

- increased fiber in diet
- increased fluid intake
- increased activity level?

Front 18

What is the IDEAL laxative??

Back 18

- non-irritating
- non-toxic
- acts only on descending and sigmoid colon
- produces normally formed stool within a few hours
- after BM, normal bowel activity would resume

Front 19

What are the classes of laxatives?

Back 19

1. bulk-forming
2. osmotic/saline/hyperosmotic
3. surfactants
4. lubricants
5. irritant/stimulant/contact
5. other

Front 20

Bulk-forming laxatives
- names?
- MOA
- indications

Back 20

= Psyllium (metamucil)
= carboxymethylcellulose

MOA:
- these are hydrophilic colloids made from indigestible parts of fruits, vegetables, seeds
- absorb water in intests
- form gels that expand within LG intestines --> distends tract --> stimulates peristalsis
(same effect as bran, fiber)

Indications: chronic constipation (and diarrhea)

Front 21

Bulk-forming laxatives
- contraindications?

Back 21

***pts with swallowing difficulties, severely slow colon - won't get thru
***diverticulitis - can get stuck in out-pouchings and worsen problem
- GI obstruction/perforation
- gastric retention
- undiagnosed abd pain
- vomiting - or other signs of appendicitis
- toxic colitis, ileus, megacolon

Front 22

Bulk-forming laxatives
- adverse effects?

Back 22

- bloating
- flatulence
(diminish with time)

Front 23

Bulk-forming laxatives
- drug interactions?

Back 23

*May absorb other oral meds on their surfaces -- separate admin by 1 hour

Front 24

Osmotic Laxatives
- aka?
- names?

Back 24

aka: saline; hyperosmotic

= magnesium citrate
= magnesium hydroxide (milk of magnesia)

Front 25

Osmotic Laxatives
- MOA?
- indications?

Back 25

MOA:
- these are non-absorbable/non-digestible salts or sugars
- hold water in intestine by osmotic force
--> distends intestine and stimulates peristalsis

Indications:
- (chronic) constipation
- evacuation of colon prior to radiology, endoscopy
- removal of ingested toxins
- sugars - hepatic encephalopathy

Front 26

Osmotic Laxatives
- adverse effects?
- contraindications?

Back 26

AE: **electrolyte abnormality

Contraindications
- same as bulk-forming agents
- renal insufficiency - risk of electrolyte abnormalities!!

Front 27

Osmotic Laxatives
- drug interactions?

Back 27

Mg(OH)2 may decrease absorption of some antibiotics
- oral meds given within 1 hour before start may be flushed out and not absorbed

Front 28

Surfactants
- names?
- indication?
- MOA?

Back 28

= docusate
= stool softeners! (detergents)

MOA:
- these are anionic surfactants
- become emulsified with stool, thus softening it --> makes passage easier
- (also is a weak laxative)

***NOT USEFUL ONCE CONSTIPATION HAS ALREADY OCCURRED

Front 29

Surfactants
- adverse effects?
- contraindications?
- drug interactions?

Back 29

AE: mild cramping

Contra:
- same as for bulk-forming agents
- fecal impaction/intestinal obstruction (i.e., already constipated - won't work)
- acute abdominal pain

Drug InterX:
- MINERAL OIL!! may increase absorption --> toxicity

Front 30

Lubricants
- name?
- MOA?
- indication?

Back 30

= Mineral Oil

MOA:
- penetrates and lubricates feces --> easier passage
- coats inside of GI tract --> prevents water absorption (some abs when given orally; no absorption when enema)

Indications:
- fecal impaction
- post-MI, post-surgery, post-partum to avoid straining

Front 31

Lubricants
- adverse effects?
- contraindications?
- drug interx?

Back 31

AE:
- risk of aspirating the mineral oil --> lipoid pneumonia (occurs in debilitated patients or in sleep - don't give within 2 hours of sleep)
- anal leakage

Contraindications:
- appendicitis
- diverticulitis
- ulcerative colitis

Interactions:
- Docusate (surfactant)
- Decreases fat-sol vitamin absorption

Front 32

Irritants
- aka?
- names?
- most common?

Back 32

aka: stimulants, contact laxatives

= Cascara Sagrada (anthraquinones)
= Castor Oil
= Bisacodyl -- most common

Front 33

Irritants
- MOA?

Back 33

- PRODRUGS - must be converted to active form within ACIDIC stomach!

- contact irritant effects on enterocytes, enteric neurons, and muscles
- causes accum of water and electrolytes
- causes production of NO, PGs, etc. --> stimulate peristalsis!!!

Front 34

Irritants
- indications?

Back 34

- constipation
- prep for delivery, surgery, GI exam

Front 35

Irritants
- adverse effects?
- interactions?

Back 35

AE:
- melanosis coli - black staining of GI tract (benign)
- cathartic colon - motility of GI tract fails after too much use
- cramps
- severe diarrhea
- dependency
- tachyphylaxis
- castor oil - can damage microvilli

*****NOT FOR CHRONIC USE!!!!!

Interactions:
- milk, antacids - neutralize acid in stomach

Front 36

What is Tachyphylaxis?

Back 36

rapidly decreasing response to a drug after initial dosing

Front 37

What is the common theme for the "other" anti-constipation drugs?

Back 37

not related, but all use RECEPTOR MECHANISMS (opioid receptors and chloride channels)

Front 38

Methylnaltrexone
- mode of admin?
- MOA?

Back 38

- subcutaneous injetion

MOA
= peripheral mu opioid receptor antagonist --> block
opioids from binding to these receptors in the gut and slowing down GI motility

***DO NOT CROSS BBB (quaternary amine), so does not affect opioid receptors in CNS, thus does not inhibit pain management

Front 39

Methylnaltrexone
- indications?
- contraindications?
- adverse effects?
- drug interactions?

Back 39

Indications: opioid-induced constipation, post-operative ileus

Contraindications:
- mechanical GI obstruction

Adverse Effects:
- diarrhea
- abdom pain
- nausea
- dizziness

PREG CATEGORY B

Interactions: none known

Front 40

Methylnaltrexone
- pharmacokinetics?

Back 40

85% eliminated unchanged - thus, little metabolism, so FINE for liver dysfunction

Front 41

What are the causes of diarrhea?

Back 41

- drugs
- infections
- organic
- malabsorption

Front 42

What are the drugs that can cause diarrhea?

Back 42

- antibiotics!!!
- adrenergic neuron blockers
- cholinergic agonists/cholinesterase inhibitors
- laxatives
- prokinetic agents
- PGs
- quinidine (anti-arrhythmia)

Front 43

What is the warning regarding diarrhea and children?!

Back 43

children under the age of 3 or over 3 with high fever and vomiting should be seen by a physician --> could be a serious illness and could lead to dehydration quickly

Front 44

What are non-pharm means to treat diarrhea?

Back 44

dietary measures - e.g., crackers, etc that will absorb GI contents

Front 45

What are the types of drugs used to treat diarrhea?

Back 45

- bulk-forming agents
- narcotic analogs
- non-specific
- bile acid binders
- anti-secretory agents
- other

Front 46

Bulk-forming anti-diarrheal drugs
- MOA?
- indications?

Back 46

MOA:
- hydrophilic colloids that absorb water (more from stool) --> in the case of diarrhea, they SLOW the passage through the GI tract

Indications:
- chronic diarrhea
- diarrhea with incontinence
- diarrhea with IBS

Front 47

Bulk-forming anti-diarrheal drugs
- contraindications?
- adverse effects?
- interactions?

Back 47

Contra:
- GI obstruction/perforation
- gastric retention
- undiagnosed abd pain, vomiting and other signs of appendicitis
**avoid in swallowing difficulties, severely slow colon

AE:
- may increase K+ losses
- constipation

Interactions:
May absorb oral meds - separate by 1 hour!!!

Front 48

Bismuth Subsalicylate
- trade name?
- indication?
- MOA?

Back 48

= Pepto Bismol

Indication: diarrhea, Traveller's diarrhea

MOA:
- (not totally sure)
- may bind bacterial toxins, which irritate gut and cause diarrhea
- anti-secretory effects
- non-specific anti-inflamm effects

Front 49

Bismuth Subsalicylate
- Contraindications?
- Adverse Effects?
- Interactions?

Back 49

Contraindications:
- HYPERSENSITIVITY to ASA (salicylates)
- children <16 with viral inf - risk of Reye's Syndrome
- avoid chronic use in patients with renal failure

AE:
- temporary black tongue, stools
- high doses can cause toxicity - salicylate tox is ringing in ears

InterX:
- tetracycline (impaired absorption)
- additive with other subsalicylates

Front 50

Bile Acid Binders
- names?
- MOA?
- indication?

Back 50

= Cholestryamine

MOA
- anion exchange resin --> binds bile acids, which cause secretory diarrhea

Indications:
- secretory diarrhea
- post-op diarrhea

Front 51

Bile Acid Binders
- AEs?
- Contraindications?
- Interactions?

Back 51

AE:
- bloating, constipation, gritty texture

Contraindications:
- use cautiously in patients sensitive to constipation

InterX:
- BIND TO OTHER DRUGS -- dosage of ANY other oral med may require adjustment (give 1 hour before or 4-6 hours after)
- may interfere with diagnostic tests

Front 52

Anti-Secretory Agents
- name?
- MOA/?
- mode of admin?

Back 52

= Octreotide = somatostatin analog, but has longer t1/2 and greater potency

MOA:
- hyperpolarizes gut neurons --> decrease ACh release --> slows peristalsis
- prevents release of secretion-inducing neurotransmitters like VIP and serotonin

- SUBCUTANEOUS INJECTION

Front 53

Octreotide
- indication?

Back 53

- severe refractory diarrhea (AIDS diarrhea)

- endocrine tumor-related diarrhea

Front 54

Octreotide
- contraindications?
- AE?
- interactions?

Back 54

Contra:
- hypersensitivity to it

AE
- gallbladder stasis
- pancreatic secretions

InterX
- may decrease levels of cyclosporin

Front 55

What is the main mechanism (in general) of all drugs used to treat diarrhea??
- EXCEPT which 2??

Back 55

- all have mechanical effects

EXC narcotics and octreotide - receptor-mediated

Front 56

What are the categories of GI mucosal protective agents?

Back 56

- topical
- systemic

Front 57

What is the main TOPICAL mucosal protective agent?
- common example?

Back 57

Sucralfate
= salt of sucrose complexed to sulfated Al(OH)3

- example: Pepto Bismol (bismuth subsalicylsate)

Front 58

Sucralfate
- indication?
- MOA?

Back 58

Indication: treat duodenal/gastric ulcers (usually complimentary) (NOT NSAID ulcers)

MOA
- forms a complex with proteinaceous exudeate at ulcer site and adheres to ulcer --> acts as barrier to further damage by acid, pepsin, bile salts
- may absorb bile salts
****REQUIRES AN ACIDIC PH TO FUNCTION

Front 59

Sucralfate
- contraindications?
- adverse effects?
- interX?

Back 59

Contra:
- Al may accumulate with decreased renal function

AE: few noted

InterX
- REQUIRES ACIDIC pH, so.....
- antacids
- H2 receptor antagonists
- proton pump inhibitors

- may bind to other meds and impair absorption - separate by 2 hours

Front 60

What is the main SYSTEMIC GI mucosal protective agent?

Back 60

= Misoprostol = synthetic PGE1 analog

Front 61

Misoprostol
- MOA?

Back 61

= PGE1 analog - PGEs and PGI2 are major PGs synthesized by gastric mucosa --> inhibit acid production by binding EP3 receptor on parietal cells --> inhibit adenylyl cyclase and decrease cAMP
- stimulate secretion of mucin and bicarbonate
- improve mucosal blood flow

**thus, misoprostol has anti-secretor effects and mucosal protective properties

Front 62

Misoprostol
- indications?

Back 62

- prevention of NSAID-induced gastric ulcers or mucosal injury

- induction of labor
- incomplete and therapeutic abortions

Front 63

Misoptorstol
- contraindications??
- adverse effects?
- drug interX?

Back 63

PREGNANCY CATEGORY X!!!!!!!!!!!!
- should not be used in woman of child-bearing age without effective contraception

- patients with PG allergy
- patients with IBD

AE: minor
InterX: reduced avail when taken with antacids

Front 64

Misoprostol
- pharmacokinetics?

Back 64

- rapidly absorbed
- rapid first-pass metabolism

Front 65

What drugs have largely replaced Antacids as therapy for peptic ulcer disease and GE reflux?

Back 65

H2 receptor blockers
Proton Pump Inhibitors

Front 66

What is the physiology behind antacids and their MOA?
- indications?

Back 66

Presence of food in stomach elevates gastric pH to 5 (for ~1 hour)....
After mean, gastric acid is produced 45 mEq/hour.....

**Antacids neutralize gastric contents
- Reach with HCl to form Cl, H2O, CO2

Indications: relief of GI sx - symptom management only!

Front 67

What is ANC??

Back 67

ANC = Acid-Neutralizing Capacity
- varies greatly among antacids

= 1 N HCl (mEq) that can be brought to pH 3.5 in 15 min

Front 68

How do antacids differ from each other?

Back 68

Antacids differ in their composition, formulation, ANC

Front 69

What are the main components of antacids?
- most common?

Back 69

- Al(OH)3 and Mg - most common components (try to balance each other out - Al causes constipation; Mg causes diarrhea)

Also...
- NaHCO3
- CaCO3
- Carbonates
- Silicates
- Phosphates
- Simethicone
- Alginic Acid

Front 70

Antacids
- contraindications?
- adverse effects?
- interactions?

Back 70

Contraindications:
- use cautiously in patients with decreased renal function - DON'T USE Mg or Al ones

AE: minimal

Drug InterX:
- A LOT!!!!!!!!! bc absorb things in stomach
- antibiotics
- tetracycline
- isoniazid
- ketoconazole
- iron
- theophylline
- fluoroquinolone