DRUGS USED IN THE TREATMENT OF GASTROINTESTINAL DISEASES

Drugs Pharmacodynamics/Pharmacokinetics Clinical Use Adverse Effects Drug Interactions

Agents that reduce intragastric acidity
1. Antacids Sodium Weak bases that react with gastric HCl to Dyspepsia Distention and belching All antacids may affect
bicarbonate form salt and water Intermittent heartburn (CO2) absorption of other drugs
(baking soda, Neutralization depends Acid-peptic disorders by:
Alka Seltzer) - Rate of dissolution Metabolic alkalosis at high 1. Binding to the
- Water solubility doses (milk alkali syndrome) drug
Calcium - Rate of reaction with acid 2. Increasing
Carbonate - Rate of gastric emptying Hypercalcemia intragastric pH
(tums, Os-Cal) Given 1-2 hr after meal Renal insufficiency Should not be given
within 2 hours of
Not recommended for treatment of active tetracycline,
Magnesium Osmotic diarrhea
peptic ulcer flouroquinolones,
hydroxide
itraconazole, and iron
Aluminum OH Constipatipaion

2. H2 receptor antagonist Competitive inhibition at the parietal cell H2 GERD Extremely safe drugs Cimetidine interfere
 Cimetidine receptor and suppress basal and meal PUD CYP450 – half-lives may
 Ranitidine stimulated acid secretion Non ulcer dyspepsia If IV – nosocomial be prolonged
 Famotidine Prevention of stress related pneumonia, mental status
 Nizatidine – little 1st Highly selective; no effect on H1 and H3 gastritis changes (elder, renal, Compete with creatinine
pass metab hepatic dysfunction) and procainamide for
Histamine released from ECL by gastrin or renal tubular secretion
vagal stimulation is blocked from binding to Gynecomastia (cimetidine)
parietal cell H2 receptor All except famotidine
Cross placenta, secreted in inhibit gastric 1st pass
Diminished direct stimulation of parietal cell milk metab of ethanol
by gastrin and Ach (women)
Rapid IV – bradycardia,
Effective inhibiting nocturnal acid secretion, hypotension
modest impact on meal stimulated acid
secretion
3. Proton Pump Inhibitor  Administered as prodrug 1. Most effective General – acute interstitial Alter absorption of
 Omeprazole and  Acid resistant enteric coated capsules treatment of GERD nephritis ketoconazole,
Lansoprazole  Should be administered on empty 2. PUD – more rapid itraconazole, digoxin,
(racemic) stomach – 1hr before meal symptom relief and Nutrition – subnormal vit atazanavir.
(bioavailability decreased by food) faster ulcer healing B12 levels with prolonged

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  Esomeprazole (S  Short half-life, concentrated and  H pylori assoc. therapy; hypomagnesemia Omeprazole inhibit metab
isomer or omep) and activated near site of action, long ulcers (heal and sec to hypocalcemia of warfarin, diazepam,
Pantoprazole – oral duration of action eradicate phenytoin
and IV  Inhibit both fasting and meal stimulated organism) Respiratory and enteric
 Dexlansoprazole (R secretion - Given as 14 days infections Lansoprazole enhance
isomer of lanso) “triple therapy”: PPI clearance of theophylline
 Rabeprazole – BID + clarithro + Rebound acid
sprinkled on food  Acid inhibition: 24 hrs. amox/metro hypersecretionwith Rabe and panto – no
 Serum t ½ : 1.5 hrs.  NSAID-assoc. increased dyspepsia and significant D/I
 Full acid inhibiting potential: 3-4 ulcers heartburn after d/c; gastric
days of daily medication  Prevent carcinoid tumor Could reduce clopidogrel
 18 hrs. – required for synthesis of rebleeding of activation (increase
new proton pump molecules ulcer Atrophic gastritis serious CV effects) – if
3. Non ulcer dyspepsia – must be given, panto and
modest efficacy rabe are preferred.
4. Prevent stress related
mucosal bleeding (oral
FDA approved –
omeprazole; suspension
– esomeprazole, omep,
panto)
5. Gastrinoma and other
hypersecretory
conditions
Mucosal Protective Agents
Sucralfate Salt of sucrose complexed to sulfated Given on an empty stomach Constipation Binds to other meds,
aluminum hydroxide (1hr before meal) impairing their absorption
Tenacious paste that bind selectively to Reduces incidence of Upper
ulcers for 6hrs GI bleed
Forms a physical barrier that restricts further Less effective than IV H2
caustic damage and stimulates mucosal antagonist
prostaglandin and HCO3 secretion
Prostaglandin Analogs Acid inhibitory and mucosal protective Reduce NSAID induced
1. Misoprostol – methyl properties ulcers
analog of PGE1 Stimulated mucus and HCO3 secretion and
enhance mucosal bld flow
Bismuth Compounds Coats ulcers and erosions, protective layer Prevention of traveler’s Harmless blackening of
1. Bismuth subsalicylate – against acid and pepsin diarrhea stools, tongue
nonprescription Against H. pylori (2nd line Taken only for short periods
formulation (Pepto- Direct antimicrobial effects and binds to therapy to triple therapy) and avoided in renal
Bismol, Kaopectate) enterotoxin Dyspepsia insufficiency
2. Bismuth subcitrate
potassium – rapid

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 dissociation within
stomach
Drugs stimulating GI motility
Cholinomimetic Agents
1. Bethanechol
2. Neostigmine – enhance
gastric, small intestine,
and colonic emptying
Dopamine D2 receptor
antagonist
1. Metoclopramide
2. Domperidone
Macrolide
1. Erythromycin
Toxicity: encephalopathy
(ataxia, headache, confusion,
seizure)
Bismuth subsalicylate – at
high doses : salicylate
toxicity
1. Increase lower esophageal sphincter pressure – GERD
2. Drugs that improve gastric emptying – gastroparesis, postsurgical gastric
emptying delay
3. Agents that stimulate small intestine – postoperative ileus, chronic intestinal
pseudo-obstruction
4. Agents that enhance colonic transit – treat constipation
Stimulate muscarinic M3 receptor on muscle GERD Excessive salivation
cells and myenteric plexus Gastroparesis Nausea
Vomiting
Neostigmine (IV) treatment Diarrhea
of acute large bowel Bradycardia
distention (colonic pseudo-
obstruction/ Ogilvie’s
syndrome)
Inhibit cholinergic smooth muscle Antinausea and vomiting Restlessnes, drowsiness,
stimulation (blockage of chemoreceptor insomnia, anxiety, agitation
trigger zone in medulla)
Increase esophageal peristaltic amplitude, Extrapyrimidal effects
inc LES pressure, enhance gastric emptying GERD; not in erosive
No effect in small intestine and colonic esophagitis Tardive dyskinesia
motility Tx of delayed gastric (metoclopramide)
emptying d/t postsurgical
disorders and diabetic Galactorrhea, gynecomastia,
gastroparesis impotence, menstrual d/o
Advancement of nasoenteric Domperidone does not cross
feeding from stomach to BBB
duodenum
(metoclopramide)
Chronic non ulcer dyspepsia
Promote postpartum
lactation (Domperidone)
Directly stimulate motilin receptors and Acute UGI Bleeding
promote onset of migrating motor complex
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Bulk Forming
1. Natural plant products
- Psyllium
- Methylcellulose
Promote gastric emptying of
blood before endoscopy
Laxatives
Indigestible, hydrophilic colloids that absorb Promote peristalsis Bloating and flatus
water

2. Synthetic
- Polycarbophil
Stool Surfactant Agents Prevent and treat fecal Aspiration>> lipid
(softeners) impaction in young children pneumonitis
1. Docusate (oral/enema) and debilitated adults
– common prescribed to Impair absorption of fat
prevent constipation soluble vitamins (ADEK)
and minimize straining
2. Glycerin suppository
3. Mineral Oil – lubricates
fecal material
Osmotic Laxatives Soluble but nonabsorbable compounds that
result in increased stool liquidity due to an
obligate increase in fecal liquid
Nonabsorbable Sugars and salts Treat acute constipation Severe flatus and cramps Sodium Phosphate not in
1. Magnesium hydroxide (milk of magnesia) –no in prolonged periods Prevent chronic constipation High volume of liquid stools frail and elderly
2. Sorbitol Prompt bowel evacuation Electrolyte abnormalities
3. Lactulose (purgation) within 1-3hrs Cardiac arrhythmia
4. Magnesium citrate Nehrocalcinosis
5. Sulfate solution
6. Combination of Mg, Na, citrate (Prepopik)
7. Sodium Phosphate – risk of hypherphosphatemia, hypocalcemia,
hypernatremia, hypokalemia

Balanced Polyethylene Glycol (PEG) (in lavage) Complete colonic cleansing No cramps, flatus, fluid shifts
- Balanced isotonic, osmotically active sugar with sodium sulfate, sodium before endoscopy
chloride, sodium bicarb, KCl.
Ingested on evening before
procedure

Stimulant Laxatives (cathartics) Direct stimulation of enteric nervous system Required in long term basis Dependence and destruction
1. Antraquinone and colonic electrolyte and fluid secretion (patients neurologically of myenteric plexus (colonic
Derivatives impaired and bed bound atony and dilation)
(Aloe, senna, cascara) patients

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 2. Diphenylmethane
Derivative:
Bisocodyl – tablet and
suppository ( used in
conjuction with PEG)
Chloride Channel Activators
1. Lubiprostone –
prostanoic acid
derivative
2. Linaclotide
Opioid Receptor Antagonists
1. Methylnaltrexone
bromide
2. Alvimopan
Serotonin 5-HT4 Receptor
Antagonist
1. Tegaserod (withdrawn)
2. Prucalopride
Antidiarrheal Agents
Opioid Agonist
1. Loperamide –
nonprescription, does
not cross BBB, no
analgesic, no addiction
2. Diphenoxylate
Colloidal Bismusth Compounds
Bile Salt-Binding Resins
1. Cholestyramine
2. Colestipol
3. Colesevelam
Octreotide
– synthetic octapeptide similar
to somatostatin; given
parenterally
Melanosis Coli (brown
pigmentation of colon) –
antraquinones
Stimulate type 2 chloride channels (CIC-2) Nausea Contraindicated in
Diarrhea pediatrics
Binds to and activates guanylyl cyclase-C,
increasing Cgmp activating CFTR (opposite
effect with Crofelemer- for HIV-induce
diarrhea)
Inhibit peripheral mu receptor without Alvimopan – short term use Possible CV toxicity
impacting analgesic effects for postoperative ileus;
given 5hrs preop
Metylnaltrexone (SubQ) –
opioid induced constipation
Stimulates second order enteric neurons to Chronic constipation in
promote the peristaltic reflex women (prucalopride)
Stimulate proximal bowel contraction (Ach
and subs P); distal bowel relaxation ( NO and
VIP)
Not in bloody diarrhea, high fever, systemic toxicity
Increase in colonic phasic segmenting activity Diphenoxylate (at high
Increase colonic transit time and fecal water doses) – dependence.;
absorption commercial prep commonly
Decrease mass colonic movements and have atropine to discourage
gastrocolic reflex overdosage
Decrease diarrhea caused by excess fecal Colonic secretory diarrhea Bloating Should not be given
acids Taken daily before meals Flatulence within 2hrs of other drugs
Constipation
fecal impaction Colesevelam – no effects
on absorption of other
drugs
Inhibits secretion of gastrin, CCK, glucagon, Inhibition of endocrine Steatorrhea leading to vit
GF, insulin, secretin, pancreatic polypeptide, tumor effects (carcinoid, ADEK deficiency
VIP, 5-HT VIPoma) Formation of sludge or
Reduces intestinal fluid and pancreatic gallstones
secretion At low dose: stimulate Hypothyroidism
Slows GI motility, inhibits GB contraction motility Bradycardia
Reduce portal and splanchnic bld flow At high dose: inhibit motility
Inhibit secretion of some ant. Pit hormones
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Antispasmodic (Anticholinergics)
1. Dicyclomine
2. Hyoscyamine
Serotonin 5-HT3 receptor
Antagonist
1. Alosetron
Chloride Channels Activators
1. Lubiprostone
2. Linaclotide –guanylyl
cyclase C agonist leads
to activation of CFTR
Antiemetic Agents
Serotonin 5-HT antagonist
1. Ondansetron
2. Granisetron
3. Dolasetron
4. Palonosetron – greater
affinity, long serum half-
life (40hrs)
5. Tropisetron
Corticosteroids
1. Dexamethasone
2. Methylprenisolone
Neurokinin Receptor Antagonist
1. Aprepitant (oral) –
highly selective; cross
BBB
2. Fosaprepitant – IV
Phenothiazines
1. Prochlorperazine
2. Promethazine
For diarrhea d/t vagotomy,
dumping syndrome, short
bowel syndrome, AIDS
Scleroderma
Drugs used in Irritable Bowel syndrome
Inhibit muscarinic cholinergic receptors in Dry mouth
enteric plexus and smooth muscle Visual disturbances
Urinary retention
Constipation
Inhibit colonic motility, esp in left colon: Women with severe IBS with Constipation
increase total colonic transit time diarrhea Episodes of ischemic colitis
Women with IBS with Avoided in women of
constipation child-bearing age
Important sources of afferent input to vomiting center (brainstem):
1. Chemoreceptor trigger zome – rich in dopamine D2 receptors and opioid
receptors, serotonin 5-HT receptors, and NK1 receptos
2. Vestibular system – rich in muscarin M1 and histamine H1 receptors
3. Vagal and spinal afferent nerve from GIT – 5-HT receptors
4. CNS
Chemotherapy induced N/V Headache Efficacy enhance by
Postoperative and Dizziness corticosteroid
postradiation N/V Constipation (dexamethasone) and NK1
Prolonged QT interval (more receptor antagonis
pronounced in dolasetron)
Acute and delayed N/V
Central blockage in the are postrema Fatigue, Dizziness, diarrhea Inc INR in pt taking
Inhibits metab ofCYP3A4 warfarin
(docetacel, paclitaxel,
etoposide, irinotecan,
imatinib, vinblastine,
vincristine)
Antiemetic prop mediated by dopamine, and Postoperative n/v Prolong QT interval, Vtach,
muscarine receptors Sedation for surgical and torsades de pointes
endoscopic procedure (droperidol)
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 3. Thithylperazine
Butyrophenones
1. Droperidol – IM or IV;
extremely sedating
Substituted Benzamines
1. Metoclopramide
2. Trimethbenzamide
H1 Antihistamines
1. Diphenhydramine
2. Dimenhydrinate
3. Meclizine – minimal
anticholinergic effect,
less sedation
Anticholinergic
1. Hyoscine (scopolamine)
– better tolerated as
transdermal patch
Benzodiazepine
1. Lorazepam
2. Diazepam
Cannabinoids
1. Donabinol
2. Nabilone
Aminosalicylates
1. Sulfasalazine
2. Olsalazine
3. Balsalazide
4. Mesalamine
 Pentasa
 Asacol and Apriso
 Lialda – multimatrix
core
 Rowasa – enema
 Canasa – suppository
Glucocorticoids
1. Prednisone
2. Prednisolone
3. Budesonide – synthetic
prednisolone
 Entocort – distal
ileum, colon
Neuroleptanalgesia
Induction and maintenance
of gen anesthesia
Dopamine receptor blockade Extrapyramidal: restlessness,
Weak antihistaminic activity dystonia, parkinsonian
symptoms
Prevent motion sickness and
tx of vertigo
Reduce anticipatory
vomiting before
chemotherapy
vomiting caused by anxiety
Appetite stimulant Euphoria, dysphoria,
Antiemetic sedation, hallucination, dry
Chemo-induce n/v mouth
Drugs used to treat Inflammatory Bowel Disease
Induce and maintain Oligospermia
remission in ulcerative colitis Impair folate absorption ond
1. 1st line tx for mild to mod processing
UC but unproven for Crohn’s
disease (colon or distal Olsalazine – may cause
ileum) secretory diarrhea
2. supp./enema – UC and
Crohn’s dis. in rectum
(proctitis) and distal colon
(proctosigmoiditis)
Mod-severe active IBD
Not useful in maintaining
disease remission
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  Uceris - colon
Purine Analogs Allopurinol markedly
1. Azathioprine reduce Xanthin oxide
2. 6-Mercaptopurine catabolism of purine
analogs
Methotrexate Inhibit dihydrofolate reductase Chrons disease Bone marrow depression
Interfere with IL1 Rheumatoid arthritis Megaloblastic anemia
Alopecia; Mucositis
Anti TNF Prevent cytokine from binding to its acute and chronic treatment
1. Infliximab receptors of mod to severe Crohn’s
2. Adalimumab Fc portion promotes Ab-mediated apoptosis, disease (Infliximab,
3. Golimumab complement activation and cellular Adalimumab, Certolimumab)
4. Certolizumab – cytotoxicity of activated T lymphocytes and – 30%
humanized; lacks Fc macrophages mod to severe UC
portion (Infliximab, Adalimumab,
Golimumab) – 60%
Anti-Integrin Crohn’s disease that have Risk: multifocal
1. Natalizumab – failed other therapies leukoencephalopathy (JC
humanized IgG4 virus- human polymavirus);
monoclonal Ab acute infusion reactions and
opportunistic infections
(small risk)
Pancreatic enzyme Supplements with meals and snack; swallowed, not steatorrhea, azotorrhea,
1. Pancreatin chewed vitamin malabsorptin and
2. Pancrealipase weight loss caused by cystic
fibrosis, chronic pancreatitis
or pancreatic resection
Glucagon like peptide 2 Analog Short bowel syndrome
1. Teduglutide
Bile acid Therapy Gallstone
1. Ursodiol
2. Methyl tert-butyl ether
– infusion to bile duct
3. Monoctanoin – infusion
to bile duct
Drugs Used to treat Variceal Hemorrhage
Somatostatin and Octreotide reduce portal blood flow and variceal
pressures
Vasopressin cause splanchnic arterial vasoconstriction
Terlipressin – vasopressin analog; that leads to reduced splanchnic perfusion
less adverse effect and lowered portal venous pressure for
acute GIT bleeding
Beta Bloackers

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