Chapter 62: Drugs Used in

the Treatment of
Gastrointestinal Diseases
ACID-PEPTIC DISEASE
GERD GASTROESOPHAGEAL REFLUX DISEASE
PEPTIC ULCER
o Gastritis
o Duodenal
o Helicobacter Pylori
o NSAIDS
STRESS-RELATED MUCOSAL INJRUY
AGGRESSIVE FACTORS
ACID
PEPSIN
BILE
DEFENSIVE FACTORS
BICARBONATE SECRETION AND MUCOS
PROSTAGLANDINS
BLOOD FLOW
PROCESS OF RESTITUTION & REGENERATION

Receptors stimulated by parietal cell

- GASTRIN (CCK-B)
- ACETYLCHOLINE (Muscarinic ,M2)
- HISTAMIN (H2)

Stimulate:
Proton Pump
(H+/K+ - ATP)
ECL - ENTEROCHROMAFFIN LIKE CELLS
- ACETYLCHOLINE
- GASTRIN

Production
of ACID
(H+)

AGENTS THAT REDUCE

INTRAGASTRIC ACDITY
ANTACIDS

SODIUM BICARBONATE
o Not recommended for hypertensive
patients due to production of NaCl
CALCIUM BICARBONATE
MAGNESIUM HYDROXIDE
ALUMINUM HYDROXIDE
USED FOR:
ACID PEPTIC DISORDERS
DYSPEPSIA

H2 RECEPTOR ANATAGONIST
Before meals & before sleep
CIMETIDINE Inhibits binding of Dihyroestosterone
(AR: gynecomastia, galactorrhea)
RANITIDINE
FAMOTIDIN
o First pass hepatic metabolism resulting in
bioavailability of 50%
NIZATIDINE 4 hrs. duration
USED FOR:
GERD
PEPTIC UCLER DISEASE
NONULCER DYSPEPSIA
PREVENTION OF BLEEDING FROM STRESS RELATED
GASTRINS

PROTON PUMP INHIBITORS

PRAZOLE Pro-drugs, weak bases -> small intestine
Once a day, before meals, 24hr duration
OMEPRAZOLE
ESOMEPRAZOLE
LANSOPRAZOLE
DEXALANSOPRAZOLE
RABEPRAZOLE
PANTOPRAZOLE
USED FOR:
GERD
PEPTIC ULCER DISEASE
o H. PYLORI
o NSAID ASSOCIATED ULCER
o PREVENTION OF REBLEEDING FROM PEPTIC
ULCER
GASTRINOMA & OTHER HYPERSECRETORY
CONDITIONS
NONUCLER DYSPEPSIA
ADVERSE EFFECT
VITAMIN B12
RESPIRATORY & ENTERIC INFECTION

MUCOSAL PROTECTIVE AGENTS

SUCRALFATE SALT OF SUCROSE & ALUMINUM

PROSTAGLADIN ANALOGS E&F MISOPROSTOL
(CYTOTECH)
BISMUTH COMPOUNDS
o BISMUTH SUBSALICYLATE
o BISMUTH SUBCITRATE POTASSIUM

Drugs stimulating GIT motility

(Prokinetic agents)
SUBMUCOSAL
PLEXUS
(SUBMUCOSA)

SERATONIN &
DOPAMINE

5HT3
ANTAGONIST
5HT4 AGONIST

MYENTERIC
PLEXUS

(MUSCLE LAYERS)

AUTONOMIC NERVOUS SYSTEM

CHLOINOMIMETIC AGENTS

NEOSTIGMIN ACETYLCHOLINESTERASE INHIBITOR

BETHANECHOL

D2 RECEPTOR ANTAGONIST

METOCLOPRAMIDE PLASIL
DOMEPERIDONE
o BOTH CHOLINERGIC
USED FOR:
GERD
IMPAIRED GASTRIC EMPTYING
NON ULCER DISEASE (DYSPEPSIA)
PREVENTION OF VOMITING (ANTIENEMIC)
POSTPARTUM LACTATION STIMULATION
ADVERSE EFFECT
DYSTOMA
AKATHISIA
PARKINSONIAN FEATURE

MACROLIDES MOTILIN RECEPTORS

ERYTHROMCIN

LAXATIVES
Constipation
High fiber diet
Adequate fluid intake
Exercise
Heeding natures call

BULK-FORMING LAXATIVES

NATURAL: PSYLLIUM, METHYLCELLULOSE

SYNTHETIC: POLYCARBOPHIL

STOOL SURFACTANT AGENTS

DOCUSATE (ORAL/ENEMA)
GLYCERIN SUPPOSITORY
MINERAL OIL Vitamin A, D, E, K

OSMOTIC LAXATIVES

NON ABSORBABLE SUGARS SALTS

o MAGNESIUM HYDROXIDE (MILK OF
MAGNESIA) AE: HYPERMAGNESEMIA
o SORBITOL & LACTULOSE
PURGATIVES
o MAGNESIUM CITRATE
o SODIUM PHOSPHATE
BALANCE POLYETHYLENE GLYCOL
o POLYETHYLENE GLYCOL (PEG)

STIMULANT LAXATIVE AE: DRUG DEPENDENCE

ANTHRAQUINO DERIVATIVES
o ALOE
o SENNA
o CASCARA
DIPHENYLMETHANE DERIVATIVES
o BISACODYL
o PHENOLPTHALEIN
o CASTOR OIL

CHLORIDE CHANNEL ACTIVATORS

LUBIPROSTONE
USED FOR:
CHRONIC CONSTIPATION
IRRITABLE BOWEL SYNDROME (IBS)

OPIOID RECEPTOR ANTAGONIST

METHYLNATREXONE
ALVIMOPAN

SEROTIN 5HT4 RECEPTOR AGONIST

TEGASEROD

CISAPRIDE
PRUCALOPRIDE

GUANYLATE CYCLASE AGONIST

LINACLOTIDE

ANTIDIARRHEAL AGENTS
CHRONIC DIARRHEA
IBS IRRITABLE BOWEL SYNDROME
o Idiopathic
o Chronic
o Relapsing disorder
o Abdominal discomfort
IBD INFLAMATORY BOWEL DISEASE
TREATMENT: FLUID & ELECTROLUTE RETENTION

OPIOID AGONIST

Loperamide
Diphenoxylate

COLLOIDAL BISMUTH COMPOUNDS

BISMUTH SUBSALICYLATE
BISMUTH SUBCITRATE POTASSIUM

BILE SALT BINDING RESINS

Cholestyramine
Colestipol
Olesevelam

SOMASTOSTATIN ANALOGUES
OCTREOTIDE
USED FOR
Inhibition of Endocrine Tumor Effects
Other Causes of Diarrhea
Other Uses
o sometimes used in gastrointestinal bleeding

DRUGS USED IN THE

TREATMENT OF IRRITABLE
BOWEL SYNDROME

IBS IRRITABLE BOWEL SYNDROME

o Idiopathic
o Chronic
o Relapsing disorder
o Abdominal discomfort
TREATMENT: FLUID & ELECTROLUTE RETENTION

ANTICHOLINERGICS

ANTISPASMODICS
o DICYLOMINE
o HYOSCYAMINE

SEROTNIN 5HT3 RECEPTOR ANTAGONIST

ALOSETRON

SEROTONIN 5HT4 RECEPTOP AGONIST

IBS W/ CONSTIPATION
TEGASEROD
CISAPRIDE
PRUCALOPRIDE

CHLORIDE CHANNEL ACTIVATOR

LUBIPROSTONE

ANTIEMETIC AGENTS
The chemoreceptor trigger zone or area postrema
Chemoreceptors
D2 receptor
NK1 receptor?
(5-HT3 receptor)
The vestibular system is
H1 receptor
M1 receptor
Vagal and spinal afferent nerves from the
gastrointestinal tract & heart
Mechanoreceptors
Chemoreceptors
5-HT3 receptor
The central nervous system, Vomiting center
(nucleus of tractus solitarius)
H1 receptor
M1 receptor
NK1 receptor?
(5-HT3 receptor)

SEROTONIN 5-HT 3 ANTAGONISTS

ONDANSETRON
GRANISETRON
DOLASETRON
PALONOSETRON
USED FOR
Chemotherapy-Induced Nausea and Vomiting
Postoperative and Postradiation Nausea and
Vomiting

CORTICOSTEROIDS

DEXAMETHASONE
METHYLPREDNISOLONE

NEUROKININ RECEPTOR ANTAGONISTS

APREPITANT
FOSAPREPITANT

PHENOTHIAZINES

PROCHLORPERAZINE
PROMETHAZINE
THIETHYLPERAZINE

BUTYROPHENONES

DROPERIDOL

SUBSTITUTED BENZAMIDES

METOCLOPRAMIDE
TRIMETHOBENZAMIDE

H 1 ANTIHISTAMINES

DIPHENHYDRAMINE
o Salt form: DIMENHYDRINATE
MECLIZINE

ANTICHOLINERGIC DRUGS

HYOSCINE

BENZODIAZEPINES

LORAZEPAM
DIAZEPAM

CANNABINOIDS

DRONABINOL
NABILONE

ANTIEMETIC AGENTS
Inflammatory bowel disease (IBD) comprises two
distinct disorders:
ulcerative colitis
Crohns disease
The etiology and pathogenesis of these disorders
remain unknown. For this reason, pharmacologic
treatment of inflammatory bowel disorders often
involves drugs that belong to different therapeutic
classes and have different but nonspecific mechanisms
of anti-inflammatory action.

AMINOSALICYLATES
5-aminosalicylic acid (5-ASA) have been
used successfully for decades in the treatment of
inflammatory bowel diseases ( Figure 628 ). 5-ASA
differs from salicylic acid only by the addition of an
amino group at the 5 (meta) position.
Azo Compounds
o Sulfasalazine
o Olsalazine
o Balsalazide
Mesalamine Compounds
o Pentasa (time release microgranules)
o Asacol (Enteric coated)
o Apriso (Enteric coated)
o Lialda (Enteric coated)
o Rowasa (Enema)
o Canasa (Suppository)

GLUCOCORTICOIDS

BUDESONIDE (Entocort) - potent synthetic analog of

prednisolone

ANTIMETABOLITES

PURINE ANALOGS
o Azathioprine
o 6-mercaptopurine (6-MP)
METHOTREXATE
o Crohns disease
o rheumatoid arthritis

ANTI-TUMOR NECROSIS FACTOR THERAPY

(TNF)

INFLIXIMAB
o antibodies of the IgG 1 subclass
ADALIMUMAB
o antibodies of the IgG 1 subclass
CERTOLIZUMAB
o recombinant antibody that contains an Fab
fragment that is conjugated to polyethylene
glycol (PEG)

PANCREATIC ENZYME
SUPPLEMENTS
Exocrine pancreatic insufficiency is most commonly
caused by cystic fibrosis, chronic pancreatitis, or
pancreatic resection.
PANCREATIN
PANCRELIPASE

BILE ACID THERAPY FOR

GALLSTONES

Ursodiol (ursodeoxycholic acid)

naturally occurring bile acid

DRUGS USED TO TREAT

VARICEAL HEMORRHAGE

ANTIDIARRHEAL AGENTS
o SOMATOSTATIN
o OCTREOTIDE
ANTIDIURETIC HORMONE AGONISTS
o VASOPRESSIN
o TERLIPRESSIN
NON SELECTIVE BETA-RECEPTOR-BLOCKING DRUGS
o Propranolol
o Nadolol

CHAPTER 20 DRUGS USED

IN ASTHMA
Asthma
o recurrent bouts of shortness of breath
o chest tightness
o wheezing
o often associated with coughing
PHYSIOLOGICALLY by widespread, reversible narrowing
of the bronchial airways and a marked increase in
bronchial responsiveness to inhaled stimuli;
PATHOLOGICALLY by lymphocytic, eosinophilic
inflammation of the bronchial mucosa & by
remodeling of the bronchial mucosa, with thickening
of the lamina reticularis beneath the airway epithelium
and hyperplasia of the cells of all structural elements of
the airway wallvessels, smooth muscle, and secretory
glands and goblet cells.
MILD ASTHMA - symptoms occur only occasionally, as
on exposure to
allergens
certain pollutants
on exercise
after viral upper respiratory infection
SEVERE FORMS OF ASTHMA - associated with frequent
attacks of wheezing dyspnea, especially at night, or with
chronic airway narrowing, causing chronic respiratory
impairment.
RELIEF OF ACUTE BRONCHOCONSTRICTION
(short-term relievers)
Beta- adrenoreceptor stimulants
Antimuscarinic
methylxanthine

REDUCTION IN SYMPTOMS AND PREVENTION OF

ATTACKS
(long-term controllers)
Corticosteriods
Leukotriene pathway antagonist
Anti IgE antibodies
Stabilizers of mast and other cells
The causes of airway narrowing in acute asthmatic
attacks, orasthma exacerbations, include
contraction of airway smooth muscle
inspissation of viscid mucus plugs in the airway
lumen
Thickening of the bronchial mucosa from edema
cellular infiltration
hyperplasia of secretory, vascular, and smooth
muscle cells.
FEV1 Force expiratory volume in 1 second
COPD Chronic obstructive pulmonary antagonist

AGENTS USED IN THE

TREATMENT OF ASTHMA
SYMPATHOMIMETIC AGENTS

NON SELECTIVE
o EPINEPHRONE
o EPHEDRINE
o ISOPROTENOL
BETA 2 - SELECTIVE
o ALBUTEROL
o TERBUTALINE
o METAPROTERENOL
o PIRBUTEROL
o SALMETEROL (a partial agonist)
o FORMOTEROL (a full agonist)
o INDACATEROL
ultra-long acting agonist
used only for the treatment of
chronic obstructive pulmonary
disease

METHYLXANTHINES

THEOPHYLLINE (TEA)
o AMINOPHYLLINE - A THEOPHYLLINEETHYLENEDIAMINE COMPLEX.
THEOBROMINE (COCOA)
CAFFEINE (COFFEE)
ROFLUMILAST
XANTHINE DERIVATIVES
o ENPROFYLLINE

ANTIMUSCARINIC AGENTS

DATURA STRAMONIUM
o ATROPINE, A POTENT COMPETITIVE
INHIBITOR OF ACETYLCHOLINE AT
POSTGANGLIONIC MUSCARINIC RECEPTORS,
AS A BRONCHODILATOR.
IPRATROPIUM BROMIDE QUATERNARY
AMMONIUM DERIVATIVE OF ATROPINE
TIOTROPIUM

CORTICOSTEROIDS
INHALED
BECLOMETHASONE
FLUTICASONE
BUDESONIDE
CICLESONIDE
FLUNISOLIDE
MOMETASONE
TRIAMCINOLONE
CICLESONIDE
SYSTEMIC
PREDNISONE
METHYLPREDNISOLONE

STABILIZERS OF MAST AND OTHER CELLS

CROMOLYN SODIUM (DISODIUM CROMOGLYCATE)
NEDOCROMIL SODIUM
ALSO USED FOR: ALLERGIC RHINOCONJUNCTIVITIS

LEUKOTRIENE PATHWAY INHIBITORS

ZILEUTON, A 5-LIPOXYGENASE INHIBITOR

ZAFIRLUKAST AND MONTELUKAST, LTD 4
RECEPTOR ANTAGONIST

ANTI-IGE MONOCLONAL ANTIBODIES

OMALIZUMAB - INHIBITS THE BINDING OF IGE TO

MAST CELLS BUT DOES NOT ACTIVATE IGE ALREADY
BOUND TO THESE CELLS AND THUS DOES NOT
PROVOKE MAST CELL DEGRANULATION.

ANTI-TNF ANTAGONIST

ETANERCEPT
INFLIXUMAB

CHAPTER 34 - Drugs Used in

Disorders of Coagulation
HEMOSTASIS refers to the finely regulated dynamic
process of maintaining fluidity of the blood, repairing
vascular injury, and limiting blood loss while avoiding
vessel occlusion (thrombosis) and inadequateperfusion
of vital organs.
Extremeexcessive bleeding
Thrombosisrepresents a breakdown of the
hemostatic mechanism.
THROMBOXANE A 2 (TXA 2 ) is synthesized from
arachidonic acid within platelets and is a platelet
activator and potent vasoconstrictor.
Products secreted from platelet granules include:
ADENOSINE DIPHOSPHATE (ADP),
A powerful inducer of platelet aggregation,
SEROTONIN (5-HT), Which stimulates aggregation
and vasoconstriction.
Platelet-rich thrombi (WHITE THROMBI) form in the
high flow rate and high shear force environment of
arteries.
Venous clots tend to be more fibrinrich, contain large
numbers of trapped red blood cells, and are recognized
pathologically as (RED THROMBI)

AGENTS USED IN COAGULATION

FIBRINOLYTIC AGENTS

INDIRECT THROMBIN INHIBITORS

HEPARIN

Fibrinolytic drugs rapidly lyse thrombi by catalyzing the

formation of the serine protease plasmin from its
precursor zymogen, plasminogen.
STREPTOKINASE is a protein (but not an enzyme in
itself ) synthesized by streptococci that combines
with the proactivator plasminogen. This enzymatic
complex catalyzes the conversion of inactive
plasminogen to active plasmin.
UROKINASE is a human enzyme synthesized by the
kidney that directly converts plasminogen to active
plasmin.
ANISTREPLASE (anisoylated plasminogen
streptokinase activator complex; APSAC) consists of
a complex of purified human plasminogen and
bacterial streptokinase that has been acylated to
protect the enzymes active site.

Unfractionated heparin (UFH)

o D-glucosamine-L-iduronic acid
o D-glucosamine-D-glucuronic acid
Low molecular- weight heparin (LMWH)
o ENOXAPARIN
o DALTEPARIN
o TINZAPARIN
o DANAPAROID
FONDAPARINUX - the synthetic pentasaccharide

* Excessive anticoagulant action of heparin is treated by

discontinuance of the drug. If bleeding occurs,
administration of a specific antagonist such as
PROTAMINE SULFATE is indicated.

ORAL DIRECT FACTOR XA INHIBITORS

RIVAROXABAN
APIXABAN

DIRECT THROMBIN INHIBITORS

PARENTERAL DIRECT THROMBIN
INHIBITORS
HIRUDIN is a specific, irreversible thrombin
inhibitor from leech saliva that is now available in
recombinant form as LEPIRUDIN
BIVALIRUDIN
ARGATROBAN

ORAL DIRECT THROMBIN INHIBITORS

DABIGATRAN ETEXILATE MESYLATE

WARFARIN AND OTHER COUMARIN

ANTICOAGULANTS

WARFARIN
o S-warfarin
o R-warfarin
o ANTIDOTE: vitamin K 1 (phytonadione),
fresh-frozen plasma, prothrombin complex
concentrates such as Bebulin and Proplex T,
and recombinant factor VIIa (rFVIIa).

ANTIPLATELET AGENTS

ASPIRIN
TICLOPIDINE, CLOPIDOGREL, & PRASUGREL
o inhibiting the ADP pathway of platelets
BLOCKADE OF PLATELET GLYCOPROTEINIIB/IIIA
RECEPTORS
o Abciximab
o Eptifibatide
o Tirofiban
ADDITIONAL ANTIPLATELET-DIRECTED DRUGS
o Dipyridamole - vasodilator
o Cilostazol - phosphodiesterase
inhibitor

CLINICAL PHARMACOLOGY OF
DRUGS USED TO PREVENT
CLOTTING
VENOUS THROMBOSIS
RISK FACTORS
Inherited Disorders
Acquired Disease
ANTITHROMBOTIC MANAGEMENT
Prevention
Treatment of Established Disease

ARTERIAL THROMBOSIS

DRUGS USED IN BLEEDING

DISORDERS

VITAMIN K
PLASMA FRACTIONS
Factor VIII deficiency (classic
hemophilia, or hemophilia A )
factor IX deficiency (Christmas
disease, or hemophilia B )
o DESMOPRESSIN ACETATE increases the
factor VIII activity of patients with mild
hemophilia A or von Willebrand disease.
o Autoplex (with factor VIII correctional
activity) and FEIBA ( F - actor E - ight I nhibitor B - ypassing A - ctivity) - used in
treating patients with inhibitors or
antibodies to factor VIII or factor IX.
o Recombinant activated factor VII
( NovoSeven ) is being increasingly used to
treat coagulopathy associated with liver
disease and major blood loss in trauma and
surgery
o Cryoprecipitate is a plasma protein fraction
obtainable from whole blood.
RECOMBINANT FACTOR VIIA
FIBRINOLYTIC INHIBITORS
o AMINOCAPROIC ACID (EACA)
o TRANEXAMIC ACID
SERINE PROTEASE INHIBITORS
o APROTININ