GASTROINTESTINIAL

DRUGS
By: Aleeza Ahmed
Abasyn University
Gastrointestinal Tract
• The gastrointestinal tract consist of the long tube through which food
travels through, which runs from mouth to the anus.
 MEDICAL CONDITIONS INVOLVING
THE GIT
1. Peptic ulcers and gastroesophageal reflux disease (GERD)
2. Chemotherapy-Induced emesis
3. Diarrhea
4. Constipation
5. Irritable bowel syndrome (IBS)
6. Inflammatory bowel disease (IBD).
GIT OVERVIEW
PEPTIC ULCER DISEASE
 OVERVIEW
Peptic ulcer is the
lesion/open sores in
the lining of the
digestive tract,
Increase
typically in stomach hydrochloric acid
or duodenum (HCl) secretion

Caused by Inadequate
infection of gram mucosal defense
negative against gastric
acid
Helicobacter
Pylori & the use
of Non-steroidal
anti-
inflammatory
drugs (NSAID’S)
CLASSIFICATION OF ANTIULCER AGENTS
 1. ANTIMICROBIAL AGENTS
• Quadruple therapy (First-line option)
1. Bismuth subsalicylate
2. Metronidazole
3. Tetracycline
4. PPI
• Triple therapy
1. PPI
2. Amoxicillin (metronidazole may
be used in penicillin-allergic patients)
3. Clarithromycin
2. H2 RECEPTOR ANTAGONISTS
• Cimetidine
• Famotidine
• Nizatidine
• Ranitidine
• MOA: Blocks H2 receptors in the Parietal cells
(Acid producing cells) of the
Stomach decreasing gastric acid secretion.
H2 RECEPTOR ANTAGONISTS
Pharmacokinetics:
• After oral administration, the H2 receptor antagonists distribute widely
throughout the body (including into breast milk and across the placenta)
• Excreted mainly in the urine.
• Half-life of these agents may be increased in patients with renal dysfunction, and
dosage adjustments are needed.
Adverse effects:
• Cimetidine can have endocrine effects, such as gynecomastia and galactorrhea
(continuous release/discharge of milk), because it acts as a nonsteroidal
antiandrogen.
• Famotidine: Seizures, QT prolongation, Steve-Johnson syndrome
• Prolonged use: Vit B12 Deficiency
H2 RECEPTOR ANTAGONISTS MOA
Drug Interaction:
• H2 receptor antagonists may reduce the efficacy of drugs that require
an acidic environment for absorption, such as ketoconazole.
• Cimetidine inhibits several
cytochrome P450 isoenzymes
and can interfere with the metabolism
of many drugs, such as
warfarin, phenytoin, and clopidogrel
3. Proton Pump Inhibitors (PPI)
• Dexlansoprazole
• Esomeprazole
• Lansoprazole
• Omeprazole
• Pantoprazole
• MOA:
The PPIs inhibit the H+ /K+ -ATPase enzyme on parietal cells in the
stomach
Suppress the secretion of hydrogen ions into the gastric lumen.
PPI
Pharmacokinetics:
• These agents are effective orally.
• For maximum effect, PPIs should be taken 30 to 60 minutes before
breakfast or the largest meal of the day.
• Long duration of action due to covalent bonding with the H+ /K+ -
ATPase enzyme.
• Metabolites of these agents are excreted in urine and feces.
PPI ADVERSE EFFECTS
PPI DRUG INTERACTIONS
• Omeprazole and esomeprazole may decrease the effectiveness of
clopidogrel because they inhibit CYP2C19 and prevent the conversion
of clopidogrel to its active metabolite. Concomitant use of these PPIs
with clopidogrel is not recommended due to increased risk of
myocardial infraction or death.
• PPIs may increase the risk of fractures, particularly if the duration of
use is 1 year or greater
• Prolonged acid suppression with PPIs (and H2 receptor antagonists)
may result in low vitamin B12 because acid is required for its
absorption in a complex with intrinsic factor.
4. PROSTAGLANDINS
• Prostaglandin E, produced by the gastric mucosa, inhibits secretion of
acid and stimulates secretion of mucus and bicarbonate
(cytoprotective effect).
• Misoprostol

• MOA:
PROSTAGLANDINS
• Side effects:
PROSTAGLANDINS
• Contraindications :
Misoprostol is contraindicated in pregnancy, since it can stimulate
uterine contractions and cause miscarriage.
5. ANTACIDS

• Aluminum hydroxide
• Magnesium hydroxide [Mg(OH)2
• MOA:
Antacids are weak bases that react with gastric acid to form
water and a salt to diminish gastric acidity.
ANTACIDS
• Adverse Effects:
6. MUCOSAL PROTECTIVE AGENTS /
CYTOPROTECTIVE COMPOUND
• Sucralfate
• Misoprostol (Prostaglandin analogue)
• Bismuth subsalicylate
• MOA:

Antimicrobial

Anti-inflammatory
MUCOSAL PROTECTIVE AGENTS

Sucralfate Side Effects Sucralfate Contraindication

• Renal disease patients: Al may
build up & cause toxicity
• Uncontrolled Diabetes mellitus
• Impaired swallowing or Gag
reflex
MUCOSAL PROTECTIVE AGENTS
• Bismuth Compounds Side effect:

 Can cause tongue & stool to turn black temporarily

Contains salicylate that is associated with ototoxicity (Hearing loss &
Tinnitus)
LIFESTYLE MODIFICATIONS TO REDUCE
GI IRRITATION
 Drugs Used to Control
Chemotherapy-Induced
Nausea and Vomiting
ANTI-EMETICS
OVERVIEW
• An antiemetic is a drug that is effective against vomiting and nausea.
• Antiemetics are typically used to treat motion sickness and the
side effects of opioid analgesics, general anesthetics, and
chemotherapy directed against cancer.
NAUSEA:
• A feeling of sickness or discomfort in the stomach that
may come with an urge to vomit.
• unpleasant sensation that precedes vomiting.

VOMITING OR EMESIS clinically defined as

the involuntary, forceful expulsion of
gastrointestinal contents, due to contractions of
the gut through the mouth & sometimes nose.
MECHANISM THAT TRIGGER VOMITING
• Two brainstem sites have key roles in the vomiting reflex pathway.
1. The chemoreceptor trigger zone (CTZ):
It is outside the blood– brain barrier. Thus, it can respond directly to
chemical stimuli in the blood or cerebrospinal fluid.
2. The vomiting center:
Coordinates the motor mechanisms of vomiting. The vomiting center
also responds to afferent input from the vestibular system, the
vestibular system functions mainly in motion sickness.
EMETIC ACTIONS OF
CHEMOTHERAPEUTIC AGENTS
• Chemotherapeutic agents can directly activate the medullary CTZ or
vomiting center.
• Several neuroreceptors, including dopamine receptor and serotonin type 3
(5-HT3 ), play critical roles.
• Often, the color or smell of chemotherapeutic drugs (and even stimuli
associated with chemotherapy) can activate higher brain centers and
trigger emesis.
• Chemotherapeutic drugs can also act peripherally by causing cell damage in
the GI tract and by releasing serotonin from the enterochromaffin cells of
the small intestine. Serotonin activates 5-HT3 receptors on vagal, which
then carry sensory signals to the medulla, leading to the emetic response.
ANTIEMETIC DRUGS CLASSIFICATION
1. DOPAMINE RECEPTOR ANTAGONISTS
CTZ stimulate by toxins &
circulating medications
(Chemotherapeutic drugs ) which
directly or indirectly stimulate D2
receptors

Dopamine receptor
antagonist directly block
the dopamine receptors
as a result level of
dopamine decrease

Preventing nausea & vomiting

after surgical anesthesia,
chemotherapy
2. 5HT3 RECEPTOR ANTAGONISTS
• MOA: Selective serotonin receptor (5-HT3) antagonists block serotonin both peripherally, on
gastrointestinal (GI) vagal nerve terminals, and centrally in the chemoreceptor trigger zone. This
blockade results in powerful antiemetic effects.
• Serotonin antagonists
• Ondansetron
• Used to control nausea and vomiting after surgical anesthesia, chemotherapy &
radiotherapy.
 3. SUBSTANCE –P/ NEUROKININ 1
RECEPTOR ANATGONIST
• Aprepitant
• MOA: These agents act centrally at NK-1 receptors in vomiting centers
within the central nervous system to block their activation by
substance P released as an unwanted consequence of chemotherapy.
4. ANTIHISTAMINE & ANTI-MUSCURANIC
• Vestibular nuclei (VN) plays an essential role in maintaining
equilibrium, posture, head position, and clear vision with movement.
• VN receives signals from inner ear that is sensitive to changes in
balance & motion
• Stimulating VN to release histamine and Acetylcholine
• In turn sends signals to vomiting center causing motion sickness
• This mechanism can be prevented by anticholinergic drugs i.e.
Scopolamine blocking muscarinic receptor & Antihistamines i.e.
Diphenhydramine , Promethazine, Meclizine
• Treat nausea and vomiting associated with motion sickness.
SUMMARY ANTI-EMETICS
ANTIEMETIC SIDE EFFECTS
• CNS toxicity: Headache, sedation , Dizziness
• GIT Disturbances: Constipation
• Arrythmias: QT prolongation
• Serotonin syndrome : Life- threatening , over stimulation of nervous
system

More chances of occurrence in patient those are taking

combination of ondansetron and antidepressant's
• Anticholinergic side effects
Antidiarrheals
OVERVIEW
• Antidiarrheals are group of medication that are used to treat diarrhea
• Diarrhea: Stool that contains fluid over 200g of fluid per day.
• Watery stool
• Only used to treat mild to moderate diarrhea. • Increase
• Causes of Diarrhea: frequency of
bowel movement
CLASSIFICATION OF ANTIDIARRHEALS
1. ANTIMOTILITY AGENTS / OPOIDS
• Diphenoxylate
• Loperamide
• MOA:

Increase segmentation
Mediated by binding Increase intestinal
and decrease
to opioid receptors transit time
propulsive movement

Increase absorption of
Feces become solid
water & electrolyte
2. ADSORBENTS
• Bismuth compounds
• Kaolin
• Pectin
• MOA:
Antimicrobial action: Kill causative bacteria
Antisecretory action: Increasing stool bulk & viscosity by decreasing
the fluid secreted into bowel movement
Protective action: Coat the walls of intestine.
SIDE EFFECTS
• Constipation
• CNS & Respiratory depression (If opioids combine with other CNS
depressants' like Benzodiazepines, Barbiturates & Alcohol).
• Loperamide: Torsades de pointes & sudden death with high dose.
• Bismuth subsalicylate temporarily turns the stool black.
LAXATIVES
OVERVIEW
• Relieve constipation
• Accelerate the motility of the bowel
• Soften the stool
• Increase the frequency of bowel movements.
• Route of administration: Orally, Rectally (in the form of enemas or
suppositories to cleanse the bowel before the procedure)
CLASSIFICATION OF LAXATIVES

OSMOTIC STIMULANT BULK FORMING EMOLLIENTS OR

LAXATIVE LAXATIVES AGENTS STOOL SOFTNERS
• Magnesium • Bisacodyl • Methylcellulose • Docusate
citrate • Senna • Psyllium
• Magnesium • Castor Oil
hydroxide
• PEG
• Lactulose
1. OSMOTIC LAXATIVES
• Magnesium citrate
• Magnesium hydroxide
• Polyethylene glycol (PEG) are used as colonic lavage solutions to
prepare the gut for radiologic or endoscopic procedures.
• Lactulose is a semisynthetic disaccharide sugar that acts as an
osmotic laxative. Lactulose is also used for the treatment of hepatic
encephalopathy, due to its ability to reduce ammonia levels.
• Lactulose CONTRAINDICATED in Diabetes Millietus
OSMOTIC LAXATIVES
• MOA:
In the intestine, osmotic agents pull water from the surrounding
tissues using a process known as osmosis.
Excess moisture in the intestine results in softer stools that are easier to
pass.
OSMOTIC LAXATIVES
• Side Effects:
 2. STIMULANT LAXATIVES /
IRRITANT LAXATIVES
• Bisacodyl
• Senna
• Castor Oil
• MOA:
 Work by irritating the nerve endings in the large intestinal walls
Stimulating smooth muscle contraction
Increasing Intestinal Peristalsis.
STIMULANT LAXATIVES
• Side Effects:
3. BULK FORMING AGENTS
• Methylcellulose
• Psyllium

• MOA:
 They form gels in the large intestine
Causing water retention
Increasing peristaltic activity.

Psyllium can reduce the absorption of other oral drugs, and administration of
other agents should be separated from psyllium by at least two hours.
BULK FORMING AGENTS
• Side Effects:
EMOILLENT/ STOOL SOFTNERS
• Docusate
• More effective in preventing rather than treating constipation.
• MOA:
Reducing the surface tension of the stools between water and oil
Allowing water and oil to enter the stool mass
Causing it to soften, which is then easier to pass.
• Side Effects:
 Diarrhea
 Abdominal cramping
Vomiting
LAXATIVES
• Contraindications:
 Not recommended for routine use
 Avoid if Intestinal Obstruction observed
• Nursing Considerations:
 Review medications supplements associated with constipation like :
Iron, Calcium, Antacids, Antihypertensives, Antidepressants
 Increase daily fluid intake
 Increase intake of fiber food
Regular physical activity
Irritable bowel
syndrome (IBS)
OVERVIEW
• Characterized by:
Chronic abdominal pain and altered bowel habits in the absence of
an organic cause.
IBS may be classified as constipation predominant (IBS-C), diarrhea
predominant (IBS-D), or a combination of both (IBS-M).
 Mechanism of cause not well understood.
IBS TREATMENT
Inflammatory Bowel
Disease (IBD)
OVERVIEW
• Inflammation in large & small intestine.
• Autoimmune condition
• IBD includes Crohn's disease and ulcerative colitis.
ULCERATIVE COLITIS
• Colon & rectum(Only large intestine part) become inflamed & ulcers
formed.
CROHN’S DISEASE
• Inflammation anywhere along the GIT (from mouth to anus)
CAUSES
Auto-immune disease
 Genetical factor
Contraceptives
 NSAIDS
Environmental factors
Spicy food
 Western style diet : High in sugar/ fat content
TREATMENT

ANTI-INFLAMMATORY IMMUNOSUPPRESENTS BIOLOGICS IMMUNODULATORS COLECTOMY

• Aminosalicylates • Tacrolimus • Tnf-α Inhibitors • Azathioprine • Removal of colon
• Corticosteroids • Azathioprine • α4- Integrin Inhibitors • 6-Mercaptopurine
• IL-12/23 inhibitors • Methotrexate
1. ANTI-INFLAMMATORY
• Sulfasalazine
• Mesalamine
• Olsalazine
• Hydrocortisone
• Prednisolone
• MOA: Inhibition of prostaglandins & leukotrienes
• Inhibition of cytokine synthesis
• Scavenging of free radicals
• Inhibition of t-cell proliferation, activation, and differentiation.
AMINOSALICYLATES
• Side Effects:
Headache, nausea, and fatigue are most common and are dose
related.
Serious reactions include hemolytic anemia, myelosuppression,
hepatitis, pneumonitis, nephrotoxicity, fever, rash, and Stevens-
Johnson syndrome.
Sulfasalazine also inhibits intestinal folate absorption, and folate
supplementation is recommended with chronic use.
BIOLOGIC AGENTS
• TNF-α inhibitors
• α-4 integrin inhibitors
• IL-12/23 inhibitor
• Use of these agents is associated with an increased risk for infection.
• Second line agents
Immunomodulators
• Methotrexate
• Thiopurines azathioprine
• 6- mercaptopurine (6-MP)
• Decrease the body's inflammatory response
• Methotrexate (MTX) also has therapeutic applications in cancer,
rheumatoid arthritis, and psoriasis
• Azathioprine is sometimes used in kidney transplant.
THANKS