NU R S 36 6

15
GI DRUGS
2 0
in g
Spr Alison J. Mo
ntpetit, RN,
PhD
I. Drugs for Peptic Ulcer Disease
A. Goals
1. Alleviate symptoms
2. Promote healing
3. Prevent complications
4. Prevent recurrence
B. Drug Therapy
1. 3 ways to promote ulcer healing:
1. eradicate H. pylori 2. reduce acid 3. increase mucosal defenses
a) Eradication of H. pylori – the only cure
(1) Antibiotics – use 2-3 to reduce resistance
(a) Clarithromycin
(b) Metronidazole (Flagyl)
(c) Tetracycline
(d) Amoxicillin
(e) Bismuth
(2) Recurrence rates 10% with therapy, 80% without
b) Reduce gastric acid
(1) Antisecretory agents (H2 receptor antagonist, proton
pump inhibitors)
(2) Antacids
(3) Misoprostol (suppresses gastric acid)
c) Enhance mucosal defenses
(1) Sucralfate
(2) Bismuth
(3) Misoprostol (stimulates secretion of mucus, bicarb)
2. Evaluation of effect
a) Pain does not always mimic healing; pain may be
gone before or after completely healed
b) Very high recurrence rate
(1) Most drugs only heal ulcer, not cure disease
(2) Antibiotics can cure due to eradication of H. pylori
c) Effect of drugs on pH and pepsin
(1) With small increase in stomach pH, pepsin
(proteolytic enzyme) activity increases which increases
gastric cell damage.
(2) With larger increase in pH (above 4-5), pepsin
becomes inactive
(3) pH goal = 5 to avoid pepsin activation
C. Drugs
1. Histamine2 receptor antagonist –
Cimetadine
a) Histamine receptor activation
(1) H1 = vasodilation, capillary permeability,
bronchoconstriction
(2) H2 = secretion of gastric acid, acts directly on
parietal cells to promote acid release
 IgE hypersensitity
• ReceptorsTARGET bronchoconstrictio
– H1 receptor
CELL n
• Proinflammatory edema
vasodilation
• Present in smooth muscle
cells of the bronchi
– H2 receptor
• Anti-inflammatory Gastrointestinal allergy
• Present on parietal cells of Vomiting, diarrhea,
abdominal pain
the stomach mucosa
– Induces the secretion of gastric
acid
b) Action
(1) Selective blockade of histamine2 receptor
(2) Decreases production of gastric acid (volume and H ion content)
(3) Can reduce basal, food-stimulated and nocturnal secretion of gastric acid by 90%
with single dose
(4) All agents are equally effective
(5) Some pts are refractory to (elderly, smokers)
c) Pharmacokinetics
(1) Effective with one bedtime dose
(2) Food decreases rate of absorption
(3) Primarily renal elimination
(check BUN - Cr)
(4) Short half life (2 hrs)
d) ADRs
(1) Binds to androgen receptors - gynecomastia,
reduced libido, impotence
(2) CNS effects (restlessness, confusion,
hallucinations), elderly with renal or hepatic disease

e) DI
(1) Inhibits hepatic drug metabolizing enzymes
(2) Increased levels of other drugs - coumadin,
phenytoin, theophylline,
(3) Antacids - give at least an hour apart
f) Drugs
(1) Cimetidine (Tagamet)
(2) Ranitidine (Zantac)
(a) more potent than cimetidine
(b) fewer side effects, DI
(c) weak inhibitor of hepatic enzymes
(d) antacids have little blocking effect
(3) Famotidine (Pepcid) and Nizatidine (Axid)
(a) No hepatic effect
(b) No antiandrogenic effect
2. Proton pump inhibitor (PPIs):
Omeprazole (Prilosec) – “prazoles”
a) Action
(1)Is a prodrug - activated inside parietal cell
(2)Inhibits H+,K+-ATPase - enzyme that generates gastric
acid and moves it out of the cell
(a) Has to make new enzyme to secrete again
(b) Reduces acid by 97%
(3) Reduces basal and stimulated acid secretion
(4) Most effective drugs for reducing gastric acid
secretion
(5) PPI are more effective than H2 blockers for treatment
and maintenance therapy for PUD and GER
(6) Fewer side effects
(7) PO admin – more expensive than others
b) Pharmacokinetics
(1) Affected by acid, so placed in capsule that is dissolved in stomach
(2) Drug granules dissolve in alkaline duodenum
(3) 50% reaches blood (hepatic metabolism), short half-life, 1 hr, but
irreversible effect, so long lasting
(4) Treatment limited to 4-8 weeks, but healing and relapse rate same as
H2RA
c) ADRs
(1) HA, diarrhea, vomiting
(2) Gastric Cancer with long term use
d) Other PPIs
(1) Esomeprazole (nexiuim) – “purple pill”
(a) metabolized more slowly, higher blood levels, effects last longer
(2) Lansoprazole (prevacid)
(3) Rebeprazole (aciphex)
(4) Pantoprazole (protonix – given IV)
3. Other Antiulcer Drugs
Sucralfate, Misoprostol and Antacids

a) Sucralfate (Carafate)
(1) Action
(a) creates protective barrier against acid and
pepsin
(b) in slightly acidic environment (pH < 4.0)
becomes viscous, sticky substance that adheres
to ulcer crater
(c) no neutralizing action
(d) does not decrease acid production
(e) attachment lasts up to 6 hrs
(2) Pharmacokinetics
(a) For acute and maintenance therapy
(b) 90% eliminated in stool
(c) As good as H2 blockers
(d )Taken 4 times a day; large pills; separate admin from meals
(3) ADRs
(a) few since it is not absorbed
(b) constipation
(4) DI
(a) antacids may raise pH > 4.0 and action decreased
(b) admin at least 30 minutes apart
(c) may decrease absorption of drugs
b) Misoprostol (cytotec)
(1) Action
(a) Synthetic PGE1 analog - similar to prostaglandin
(b) suppresses gastric acid, promotes bicarb and
mucus
(c) maintain blood flow
(d) Only approved for ulcer prophylaxis for long term
NSAID users
(2) ADRs
(a) Diarrhea
(b) Abdominal pain
(c) Dysmenorrhea, spotting - can stimulate uterine
contractions
c) Antacids
(1) Actions
(a) Neutralize stomach acid
(b) May stimulate prostaglandins
(c) Do not coat ulcer and protect it
(d) Potency is shown as acid neutralizing capacity (ANC)—mEq/5 ml
(e) Should not be primary therapy for PUD
(2) Admin
(a) should be taken on regular schedule not prn
7X/day; 1 and 3 hrs after meals bedtime
(b) dose based on ANC
(c) should raise gastric pH to > 5.0
(d) not well tolerated, pts not compliant
(e) tablets should be chewed thoroughly and followed with liquid
(3) ADRs
(a) constipation - aluminum hydroxide
(b) diarrhea - magnesium hydroxide
(c) combine these to even it out
(d) Sodium overload
(4) DIs
(a) affect absorption of many drugs
(b) admin 1 hr apart of H2 blockers and sucralfate
(5) Drug types
(a) Aluminum compounds (amphogel, alternaGEL)
(b) Magnesium compounds (MoM)
(c) Calcium compounds (Calcium carbonate)
(d) Sodium compounds (Sodium bicarbonate)
(e) Aluminum and Magnesium (Mylanta, Maalox)
d) Bismuth (Pepto-Bismol)
(1) Promotes ulcer healing
(2) Forms protective coating
(3) Promotes bicarb secretion and prostaglandin
(4) Suppresses growth of H. pylori - disrupts cell
wall
(5) Well tolerated
(6) Makes stool black
 II. Prokinetic agent
A. General
1. Increase tone and motility of GI tract
2. Increase gastric emptying
3. Used for GER, diabetic gastroparesis, chemotherapy
induced N&V, to move enteric tubes
B. Metoclopramide (Reglan)
1. Suppresses emesis by blocking dopamine and serotonin receptor in
the chemoreceptor trigger zone – vomiting center
2. Increases upper GI motility by enhancing actions of acetylcholine
– increases gastric emptying
3. ADRs – drowsiness, irritability
 III. Laxatives
A. General
1. Laxative effect – soft, formed stool over 1 or more days, mild
2. Catharsis (cathartic) – prompt, fluid evacuation of bowel
3. Normal bowel pattern ranges from several times a day to 2 times
per week
4. Constipation is defined based on stool consistency (hard stool), not
frequency (infrequent)
5. Laxative abuse
a) Misconception that normal is daily BM
b) Strong laxatives purge bowel, BMs delayed, causing more use
c) Chronic use decreases defactory reflexes
 Laxatives, cont.
6. Laxative use
a) Straining dangerous
b) Stool sample
c) Bowel evacuation for dx or
therapy
d) Parasite removal
7. Contraindications
a) abdominal pain, appendicitis
b) nausea, cramps, bowel obstruction
 Laxatives, cont.

B. Types of Agents
Bulk forming, Surfactants, Stimulants, Osmotics, other
1. Classified based on therapeutic response
a) Lehne Table 79-3
b) Speed of action: 2 hr to 3 days
c) Consistency of stool: watery to soft
 Laxatives, cont.
2. Bulk forming agents
a) Drugs: Methylcellose, Psyllium
b) Act similar to dietary fiber
c) Swell in water to increase fecal mass, stimulates
peristalsis
d) Preferred treatment for constipation
e) Few ADRs, not absorbed
(1) esophageal obstruction if swallowed without
water
(2) admin with full glass of water
 Laxatives, cont.
3. Surfactants
a) Drugs: Docusate, Colace
b) Lower surface tension of stool
c) Helps water move into feces to make it softer
d) Decreases water absorption from stool
e) Admin with full glass of water
 Laxatives, cont.
4. Stimulant (Contact) laxatives
a) Drugs: Bisacodyl (Dulcolax), Castor Oil, Exlax
b) Stimulate intestinal motility
c) Act on intestinal wall to increase fluid and elec. in
lumen
d) Decrease water and electrolyte absorption from stool
e) Produce semifluid stool in 6-12 hrs
f) Are widely abused
 Laxatives, cont.
5. Osmotic Laxatives
a) Drugs: MOM, Mg citrate
b) Poorly absorbed salts that create osmotic action
and draw fluid into intestine
c) Enlarged stool mass increases peristalsis
d) High doses used for bowel prep for x-rays,
surgery
6. Misc Laxative
a) Lactulose
(1) Poorly absorbed, not digested
(2) Metabolized into acids by colon bacteria,
causing osmotic action
(3) Acidity causes ammonia to be pulled from
plasma into GI tract, then eliminated – to reduce
ammonia levels in hepatic disease
 IV. Drugs for Inflammatory
Bowel Disease
A. Sulfasalazine
1.Similar to sulfonamide antibiotics, but don’t treat infection
2.Approved only for IBD
3.Metabolized by intestinal bacteria to active compound 5-
aminosalicylic acid (5-ASA)
4. 5-ASA is an anti-inflammatory
5.Best for mild-moderate IBD
B. Other similar drugs
1.Mesalamine
2.Olsalazine
 V. Antiemetics
A. Serotonin receptor antagonists
B. Dopamine antagonists
C. Cannabinoids
 VI. Antidiarrheal Agents
A. Opioids
Diphenoxylate (Lomotil)
Loperamide (Imodium)