GASTROINTESTINAL ` GASTROINTESTINAL—PHARMACOLOGY SEC TION III 407
Pancreatic Very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular
adenocarcinoma infiltration A ); often metastatic at presentation, with average survival ~ 1 year after diagnosis.
A
Tumors more common in pancreatic head B (lead to obstructive jaundice). Associated with CA
-
19-9 tumor marker (also CEA, less specific).
-
T
E
Risk factors:
wTobacco smoking (strongest risk factor)
3
1/2 mutation
+ BRCA genes
Chronic pancreatitis (especially > 20 years)
W that are
responsible for
W Diabetes DNA repair
w Age > 50 years + K-RAS
gene (Ch RD) mutated
in 90 .
%
Often presents with: + SMAD 4
gene (ch 189) inactivated 60 -
in %
B Abdominal pain radiating to back
W
W Weight loss (due to malabsorption and anorexia)
mMigratory thrombophlebitis—redness and tenderness on palpation of extremities (Trousseau
syndrome) A Thromosis/ inflammation of that Migrates
veins due to the
below the skin
hypercoagulable state
Obstructive jaundice with palpable, nontender gallbladder (Courvoisier sign)
~
` GASTROINTESTINAL—PHARMACOLOGY
Acid suppression therapy
GRP
Parasempathetic
Vagus nerve
-
G cells ECL cells
Ach Gastrin Histamine Somatostatin Prostaglandins
z
un n
H2 blockers
Atropine -
CCKB H2 receptor
M3 receptor receptor =
CI– Gq D
G s
Gi
=
HCO3– HCO3 – + H+ O
cAMP
”alkaline tide”— ↑ blood pH IP3 /Ca2+
E after gastric acid secretion
(eg, after meals, vomiting) 3 H2CO3
CI– Gastric
parietal
Carbonic anhydrase =
cell
CO2+ H2O
ATPase
Proton pump inhibitors Lumen
E
Misoprostol
Antacids H+ K+ Sucralfate,
-
I
bismuth
m
HC)
hydrochloric
Acid
408 SEC TION III GASTROINTESTINAL ` GASTROINTESTINAL—PHARMACOLOGY
H2-blockers Cimetidine, famotidine, nizatidine. Take H2 blockers before you dine. Think “table
for 2” to remember H2.
MECHANISM Reversible block of histamine H2-receptors H+ secretion by parietal cells.
CLINICAL USE Peptic ulcer, gastritis, mild esophageal reflux.
ADVERSE EFFECTS Cimetidine is a potent inhibitor of cytochrome P-450 (multiple drug interactions); it also has
antiandrogenic effects (prolactin release, gynecomastia, impotence, libido in males); can cross
blood-brain barrier (confusion, dizziness, headaches) and placenta. Cimetidine renal excretion
of creatinine. Other H2 blockers are relatively free of these effects.
Proton pump inhibitors Omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole.
MECHANISM Irreversibly inhibit H+/K+-ATPase in stomach parietal cells.
CLINICAL USE Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome, component of therapy for
H pylori, stress ulcer prophylaxis.
ADVERSE EFFECTS risk of C difficile infection, pneumonia, acute interstitial nephritis. Vitamin B12 malabsorption;
serum Mg2+/Ca2+ absorption (potentially leading to increased fracture risk in older adults).
Antacids Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and
urinary pH or by delaying gastric emptying. All can cause hypokalemia.
Aluminum hydroxide Constipation, Hypophosphatemia, Aluminimum amount of feces
Osteodystrophy, Proximal muscle weakness, CHOPS
Seizures
Calcium carbonate Hypercalcemia (milk-alkali syndrome), rebound Can chelate and effectiveness of other drugs
acid (eg, tetracycline)
Magnesium hydroxide Diarrhea, hyporeflexia, hypotension, cardiac Mg2+ = Must go 2 the bathroom
arrest
Bismuth, sucralfate
MECHANISM Bind to ulcer base, providing physical protection and allowing HCO3– secretion to reestablish pH
gradient in the mucous layer. Sucralfate requires acidic environment, not given with PPIs/H2
blockers.
CLINICAL USE ulcer healing, travelers’ diarrhea (bismuth). Bismuth also used in quadruple therapy for H pylori.
Misoprostol
MECHANISM PGE1 analog. production and secretion of gastric mucous barrier, acid production.
CLINICAL USE Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production). Also used off-label
for induction of labor (ripens cervix).
ADVERSE EFFECTS Diarrhea. Contraindicated in patients of childbearing potential (abortifacient).
GASTROINTESTINAL ` GASTROINTESTINAL—PHARMACOLOGY SEC TION III 409
Octreotide
OND
MECHANISM Long-acting somatostatin analog; inhibits secretion of various splanchnic vasodilatory hormones. *Phosphe
C
lipase
-
CLINICAL USE Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors. *
↑ cat
ADVERSE EFFECTS Nausea, cramps, steatorrhea. risk of cholelithiasis due to CCK inhibition. *
vasoconstriction
-
gall stones
AE
↑
E Sulfasalazine Olsalazine,
-
Balsalazide 3 Aminosalicylates" ①Prostagland
in 2 Leulstriesproduction
MECHANISM A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory).
-
-
Activated by colonic bacteria.
CLINICAL USE Ulcerative colitis, Crohn disease (colitis component). & IBD3
3
25 - - -1
Malaise, nausea, sulfonamide toxicity, reversible oligospermia.
-
ADVERSE EFFECTS u ·
GE upset , Medache
Hypersensivity Beamme on
u
Arutholagia , Myglias
m -
,
Severe
=
urticaria, angioedema, anaphylaxis, skin rashes, drug fever, polyarthritis, hemolytic e
& HAnalagi
=
anemia, and agranulocytosis.
Loperamide Diphenoxylate
catinfllux
Th
Refflux
*
2
at μ-opioid receptors; slows gut motility. Poor CNS penetration (low addictive potential).
*
MECHANISM -
Causing Hyperpolariza
Agonist
Diarrhea. is
idlige dis
CLINICAL USE is en
-
ADVERSE EFFECTS Constipation, nausea.
Contraindication Bloody Diarrhea :
,
Fever , Systemic toxicity 33 "'528 &
-
Antiemetics All act centrally in chemoreceptor trigger zone of area postrema.
DRUG MECHANISM CLINICAL USE ADVERSE EFFECTS
~ Serotonin
Ondansetron, 5-HT3-receptor antagonists
m
Nausea and vomiting after Headache,z constipation,
granisetron Also act peripherally ( vagal chemotherapy, radiotherapy, QT-
interval prolongation,
-m
Polasetron
Palonosetron
stimulation) or surgery Anesthesia
m
serotonin syndrome
-
-
-Located in the basal ganglia Anasthesia Parkinosim Like
Prochlorperazine, D2-receptor antagonists Nausea and vomiting During Extrapyramidal symptoms,3-Syndrome
↳
Post
Doest &
Chemo
ne
metoclopramide Metoclopramide also causes Metoclopramide is also used hyperprolactinemia, anxiety,
z
I
-
m
↳
BBB Domperidone gastric emptying and LES in gastroparesis (eg, diabetic),n
drowsiness, restlessness, Limbic systeathology
zu
Hallusinations
tone persistent
m
GERD Last choice depression, GI distress
Aprepitant, NK1 (neurokinin-1) receptor Chemotherapy-induced nausea Fatigue, GI distress· Dizziness
fosaprepitant antagonists and vomiting
⑦ CYP3A4
NK1 receptor = substance P
receptor
have manyeaction .
Orlistat
MECHANISM Inhibits gastric and pancreatic lipase breakdown and absorption of dietary fats. Taken with
fat-containing meals.
CLINICAL USE Weight loss.
ADVERSE EFFECTS Abdominal pain, flatulence, bowel urgency/frequent bowel movements, steatorrhea; absorption of
mis
fat-soluble vitamins. -
Ex
·
Night color blindness due to Vitamin A Loss
410 SEC TION III GASTROINTESTINAL ` GASTROINTESTINAL—PHARMACOLOGY
Anticonstipation drugs
DRUG MECHANISM ADVERSE EFFECTS
Bulk-forming laxatives Soluble fibers that draw water into gut lumen, forming Bloating
Methylcellulose, viscous liquid that promotes peristalsis
psyllium
Osmotic laxatives Provide osmotic load to draw water into GI lumen Diarrhea, dehydration; may be misused
Lactulose, magnesium Lactulose also treats hepatic encephalopathy: gut by patients with bulimia
citrate, magnesium microbiota degrades lactulose into metabolites (lactic
hydroxide, acid, acetic acid) that promote nitrogen excretion as
polyethylene glycol NH4+ by trapping it in colon
Stimulant laxatives Enteric nerve stimulation colonic contraction Diarrhea
Bisacodyl, senna
Emollient laxatives Surfactants that stool surface tension, promoting Diarrhea
Docusate water entry into stool
Lubiprostone Chloride channel activator intestinal fluid Diarrhea, nausea
secretion
