1. Pharmacology of the GITPharmacology of the GIT
systemsystem

2. LECTURE OutlineLECTURE Outline
• REVIEW the Anatomy of the GIT
• REVIEW the physiology of the GIT
• Review common GI drugs in the following
categories:
– 1. Drugs affecting GI secretions
– 2. Laxatives
– 3. Anti-diarrheals
– 4. Emetics and anti-emetics

3. Drugs affecting GI secretionsDrugs affecting GI secretions
There are five types of drugs that affect gastric
acid secretions and are useful for the
treatment of peptic ulcer.
1. Histamine (H2) receptor antagonist/blockers
2. Antacids
3. Proton pump inhibitors
4. Mucosal protectants
5. Prostaglandin analogs

4. Drugs affecting GI secretionsDrugs affecting GI secretions
Histamine (H2) receptor blockers
• These drugs BLOCK the release of
hydrochloric acid in the stomach in
response to gastrin
• Preventing histamine fromPreventing histamine from
binding to its receptor inbinding to its receptor in
parietal cells.parietal cells.

5. Drugs affecting GI secretionsDrugs affecting GI secretions
Antacids
• These drugs interact with the
gastric acids at the chemical
level to neutralize them

6. Drugs affecting GI secretionsDrugs affecting GI secretions
Proton pump inhibitors
• These drugs suppress the
secretion of hydrochloric acid
into the lumen of the stomach
• Stimulation of proteinStimulation of protein
kinases that phosphorylatekinases that phosphorylate
H*/K* ATPase.H*/K* ATPase.

7. Drugs affecting GI secretionsDrugs affecting GI secretions
Mucosal protectants
• These are agents that coat any
injured area in the stomach to
prevent further injury from acid

8. Drugs affecting GI secretionsDrugs affecting GI secretions
Prostaglandin analogs
• These are agents that inhibit the
secretion of gastrin and increase
the secretion of mucus lining of
the stomach, providing a buffer.
• Activate inhibitory proteinsActivate inhibitory proteins
that block histaminethat block histamine
activation of adenylateactivation of adenylate
cyclasecyclase

9. The H2 Blockers- “tidines”The H2 Blockers- “tidines”
Prototype: Cimetidine
• 1. Ranitidine
• 2. Famotidine
• 3. Nizatidine

10. The H2 Blockers- “tidines”The H2 Blockers- “tidines”
Pharmacodynamics: Drug Action
• The H2 blockers are antagonists at the
receptors in the parietal cells of the stomach.
• The blockage results to inhibition of the
hormone gastrin.
• There will be decreased production of gastric
acid from the parietal cells.
• Also, the chief cells will secrete less
pepsinogen.

11. The H2 Blockers- “tidines”The H2 Blockers- “tidines”
Therapeutic use of the H2 blockers
• Short-term treatment of active duodenal ulcer or
benign gastric ulcer
• Treatment of hypersecretory conditions like the
Zollinger-Ellison syndrome
• Prevention of stress-induced ulcers and acute GI
bleeding
• Treatment of erosive GERD (reflux disease)
• Relief of Symptoms of heart burn and acid
indigestion

12. The H2 Blockers- “tidines”The H2 Blockers- “tidines”
Precautions and Contraindications
• Any known allergy is a clear
contraindication to the use of the agents.
Conditions such as pregnancy, lactation,
renal dysfunction and hepatic dysfunction
should warrant cautious use.
• Nizatidine can be used in hepatic
dysfunction.

13. The H2 Blockers- “tidines”The H2 Blockers- “tidines”
Pharmocodynamics- Side effects and adverse
effects
• GIT= diarrhea or constipation
• CNS= Dizziness, headache, drowsiness,
confusion and hallucinations
• Cardio= arrhythmias, HYPOTENSION (related to
H2 receptor blockage in the heart)
• Cimetidine= Gynecomastia and impotence in
males

14. The H2 Blockers- “tidines”The H2 Blockers- “tidines”
Drug-drug Interactions
• Cimetidine, Famotidine, Ranitidine are
metabolized in the liver- they can cause
slowing of excretion of other drugs
leading to their increased
concentration. These drugs can be
anticoagulants, phenytoin, alcohol,
antidepressants.

15. The AntacidsThe Antacids
• These are drugs or inorganic chemicals that
have been used for years to neutralize acid in
the stomach. The following are the common
antacids that can be bought OTC:
• Aluminum salts (hydroxide)
• Calcium salts (carbonate)
• Magnesium salts (milk of magnesia)
• Sodium bicarbonate
• Magaldrate (aluminum and magnesium
combination)

16. 2 types2 types
•Systemic
• NaHCO3, Na citrate
• alkalosis

17. • Non – systemic
• ALOH3 – adsorbs pepsin and
removes it from solution at Ph > 3
• Relaxes stomach,delays GET
• Stimulates secretion of mucus
enhancing mucosal barrier to acid

18. • MgOH - diarrhea
• CaCO3 – rebound acidosis

19. The AntacidsThe Antacids
Pharmacodynamics: drug action
• These agents act to neutralize the acidic
pH in the stomach.
• They do not affect the rate of gastric acid
secretion.

20. The AntacidsThe Antacids
Pharmacodynamics: drug action
• The administration of antacid may cause
an acid rebound.
• Neutralizing the stomach content to an
alkaline level stimulates gastrin production
to cause an increase in acid production
and return the stomach to its normal acidic
state.

21. The AntacidsThe Antacids
Therapeutic Indications
• Symptomatic relief of upset stomach
associated with hyperacidity
• Hyperacidic conditions like peptic ulcer,
gastritis, esophagitis and hiatal hernia

22. The AntacidsThe Antacids
Precautions of Antacid Use
• Known allergy is a clear contraindication.
Caution should be instituted if used in
electrolyte imbalances, GI obstruction and
renal dysfunction.

23. Antacids are combined toAntacids are combined to
• I.I. Antagonize the side effect ofAntagonize the side effect of
the other componentthe other component
II.II. Obtain a product with aObtain a product with a
rapid onset and sustained actionrapid onset and sustained action
III.III. Lower the dose of eachLower the dose of each
componentcomponent

24. • Slow onset,long duration – ALOH
• Fast onset,short duration – MgOH,Na
bicarb
• Fast onset, LONG duration – CaCO3

25. The AntacidsThe Antacids
Pharmacokinetics
• These agents are taken orally and act
locally in the stomach

26. The AntacidsThe Antacids
Pharmacodynamics: Effects of drugs
1. GIT= rebound acidity; alkalosis may occur.
• Calcium salts may lead to hypercalcemia
and milk-alkali syndrome.
• Magnesium salts can cause DIARRHEA
• Aluminum salts may cause CONSTIPATION
and hypophosphatemia by binding with
phosphates in the GIT.
2. Fluid retention due to the high sodium
content of the antacids.

27. The PPIThe PPI
These are the newer agents for ulcer
treatment
• The “prazoles”
Prototype: Omeprazole
• Lanisoprazole
• Esomeprazole
• Pantoprazole

28. The PPIThe PPI
Pharmacodynamics: drug action
• They act at specific secretory surface
receptors to prevent the final step of acid
production and thus decrease the level of
acid in the stomach.
• The “pump” in the parietal cell is the H-K
ATPase enzyme system on the secretory
surface of the gastric parietal cells

29. 3 therapy3 therapy
• Omeprazole
+chlarithromycin+amoxicillin
/metronidazole

30. The PPIThe PPI
Clinical use of the PPIs
• Short-term treatment of active duodenal
ulcers, GERD, erosive esophagitis and
benign gastric ulcer.
• Long-term- maintenance therapy for
healing of erosive disorders.
Precautions with the use of the PPIs
• Known allergy is a clear contraindication.
Caution if patient is pregnant

31. The PPIThe PPI
Pharmacodynamics: Adverse effects
• CNS- dizziness, headache, asthenia (loss
of strength), vertigo, insomnia, apathy
• GIT- diarrhea, abdominal pain, nausea,
vomiting, dry mouth and tongue atrophy
• Respi- cough, stuffy nose, hoarseness
and epistaxis.

32. The Mucosal ProtectantThe Mucosal Protectant
Sucralfate
• This is given to protect the eroded ulcer
sites in the GIT from further damage by
acid and digestive enzymes

33. SucralfateSucralfate
Pharmacodynamics: Action of drug
• It forms an ulcer-adherent complex at
duodenal ulcer sites, protecting the sites
against acid, pepsin and bile.
• This action prevents further breakdown of
proteins in the area and promotes healing.

34. SucralfateSucralfate
Clinical use of sucralfate
• Short and long term management of
duodenal ulcer.
• NSAIDs induced gastritis
• Prevention of stress ulcer
• Treatment of oral and esophageal ulcers
due to radiation, chemotherapy or
sclerotherapy.

35. SucralfateSucralfate
Precautions on the use of Sucralfate
• This agent should NOT be given to any
person with known allergy to the drug, and
to those patients with renal failure/dialysis
because of build-up of aluminum may
occur if used with aluminum containing
products.

36. The Mucosal ProtectantThe Mucosal Protectant
Pharmacodynamics: Side-effects & adverse
reactions
• Primarily GIT= CONSTIPATION,
occasionally diarrhea, nausea,
indigestion, gastric discomfort, and dry
mouth may also occur
• CNS= dizziness, drowsiness, vertigo
• Others= rash and back pain

37. The Mucosal ProtectantThe Mucosal Protectant
Drug-drug interactions
• If used with aluminum salts= high risk of
accumulation of aluminum and toxicity.
• If used with phenytoin, fluoroquinolones
and penicillamines- decreased levels of
these drugs when taken with sucralfate

38. Prostaglandin analogueProstaglandin analogue
Misoprostol
• This agent is a synthetic prostaglandin E1
analog that is employed to protect the
lining of the mucosa of the stomach

39. Prostaglandin analogueProstaglandin analogue
Misoprostol: Pharmacodynamics
• Being a prostaglandin analog, it inhibits
gastric acid secretion to some degree
• It INCREASES mucus production in the
stomach lining.

40. Prostaglandin analogueProstaglandin analogue
Misoprostol: Clinical use
• NSAIDs-induced gastric ulcers
• Duodenal ulcers unresponsive to H2
antagonists.

41. Prostaglandin analogueProstaglandin analogue
Precautions of Misoprostol Use
• This drug is CONTRAINDICATED during
pregnancy because it is an abortifacient.
• Women should be advised to have a negative
pregnancy test within 2 weeks of beginning
therapy and should begin the drug on the
second or third day of the next menstrual
cycle.
• They should be instructed in the use of
contraceptives during therapy.

42. Therapeutic Indications of theTherapeutic Indications of the
LaxativesLaxatives
• SHORT term relief of Constipation
• Prevention of straining in conditions like
CHF, post-MI, post partum, post-op
• Preparation for diagnostic examination
• Removal of poison or toxins
• Adjunct in anti-helminthic therapy

43. Contraindications in Laxative useContraindications in Laxative use
• ACUTE abdominal disorders
– Appendicitis
– Diverticulitis
– Ulcerative colitis

44. Pharmacokinetics:Pharmacokinetics:
Common Side-effects of the LaxativesCommon Side-effects of the Laxatives
• Diarrhea
• Abdominal cramping
• Nausea
• Fluid and electrolyte imbalance
• Sympathetic reactions- sweating,
palpitations, flushing and fainting
• CATHARTIC dependence

45. LaxativesLaxatives
• Generally used to INCREASE the
passage of the colonic contents
• The general classifications is as follows:
1. dietary fibers/Bulk formers
2. Mechanical /stimulant
3. Lubricants/emolient
4. Osmotic and saline laxatives

46. Bulk-forming LaxativesBulk-forming Laxatives
• - fiber (fruits, vegetables, cereals), bran,
methyl cellulose, psyllium
• - increases stool bulk causing peristalsis
• Increase bacteria

47. Osmotic LaxativesOsmotic Laxatives
• saccharides: lactulose, sorbitol

48. Stool Softeners/EmollientStool Softeners/Emollient
LaxativesLaxatives
• - docusate
• - surfactant which facilitates mixing of
water and oily materials
• - used to prevent constipation
• (post-MI, rectal surgery etc)

49. Stimulant LaxativesStimulant Laxatives
• - stimulates mucosal nerves in the colon
• diphenylmethane derivatives:bisacodyl,
phenolphthalein
• anthraquinone derivatives: cascara
sagrada, sennosides, casanthrol
• castor oil- active: ricinoleic acid
• S/E: dependence on laxatives; daily use is
discouraged

50. Lubricant laxativesLubricant laxatives
• Ex. Mineral oil
• Interferes with H2O and fat absorption

51. The Anti-diarrhealsThe Anti-diarrheals
• These are agents used to calm the irritation of
the GIT for the symptomatic relief of diarrhea
• General Classifications

52. Clinical Indications of drug useClinical Indications of drug use
• Relief of symptoms of acute and chronic
diarrhea
• Reduction of fecal volume discharges
from ileostomies
• Prevention and treatment of traveler's
diarrhea

53. Contraindications of anti-diarrhealContraindications of anti-diarrheal
UseUse
• Poisoning
• Drug allergy
• GI obstruction
• Acute abdominal conditions

54. Pharmacokinetics: Side effectsPharmacokinetics: Side effects
• Constipation
• Nausea, vomiting
• Abdominal distention and discomfort
• TOXIC MEGACOLON

55. Oral Rehydration Salts/ Oral Glucose-Oral Rehydration Salts/ Oral Glucose-
Electrolyte Solution (Oresol)Electrolyte Solution (Oresol)
• prevents dehydration
• - contains sodium, chloride, potassium,
glucose and citrate (245 mOsm/L)

56. AdsorbentsAdsorbents
• kaolin-pectin mixture, polycarbophil,
attapulgite
• Traditional remedies

57. Antimotility agents/Opiods
• - opiods: diphenoxylate (+ atropine),
loperamide, paregoric, opium tincture,
difenoxin (metabolite of diphenoxylate)
• Inc GIT contraction but non propulsive and
they close the sphincter

58. Antisecretory/ Astringents
• a. bismuth subsalicylate- treatment and
prevention of traveler’s diarrhea
• Local anti- inflammatory effect of salicylate
• Antibacterial effect of bismuth

59. The Anti-diarrhealsThe Anti-diarrheals
Type Prototype Action
Local reflex
inhibitor
Bismuth
subsalicylate
Locally coats the
lining of the GIT to
soothe irritation that
may stimulate the
reflex
Local anti-
motility
Loperamide Directly inhibits the
intestinal muscle
activity to SLOW
peristalsis
Central acting
agent
Opium
derivatives
(paregoric)
Stops GIT spasm by
CNS action

60. Emetics and Anti-emeticsEmetics and Anti-emetics
Emetic Agent
• Ipecac
Anti-emetics
• 1. Phenothiazines
• 2. Non-phenothiazines
• 3. Anticholinergics/Antihistamines
• 4. Serotonin receptor Blockers
• 5. Miscellaneous

61. EMETICEMETIC
• Prototype: Ipecac Syrup

62. EMETICEMETIC
Pharmacodynamics
• Ipecac syrup irritates the GI mucosa
locally, resulting to stimulation of the
vomiting center
• It acts within 20 minutes

63. EMETICEMETIC
Clinical Use of ipecac
• To induce vomiting as a treatment for drug
overdose and certain poisonings

64. EMETICEMETIC
Contraindications of Ipecac use
• Ingestion of CORROSIVE chemicals
• Ingestion of petroleum products
• Unconscious and convulsing patient

65. EMETICEMETIC
Pharmacokinetics: side effects of Ipecac
• Nausea
• Diarrhea
• GI upset
• Mild CNS depression
• CARDIOTOXICITY if large amounts are
absorbed in the body

66. ANTI-EMETICSANTI-EMETICS
• These are agents used to manage nausea
and vomiting
• They act either locally or centrally

67. ANTIEMETICSANTIEMETICS
Anti-emetic types Common examples
Phenothiazines Prochlorperazine,
promethazine
Non-phenothiazines Metoclopramide
Anticholinergics and
Antihistaminics
Meclizine, buclizine
Serotonin Receptor
blockers
“setron”- dolasetron
Miscellaneous Dronabinol, hydroxyzine

68. ANTIEMETICSANTIEMETICS
Types Pharmacodynamics
Phenothiazines Centrally block the vomiting
center in the medulla
Non-phenothiazine Reduces the responsiveness
of the nerve cell in the
medulla
Anticholinergics Block the transmission of the
impulses to the medulla
Serotonin receptor
blockers
Centrally and locally inhibits
the serotonin receptors
Miscellaneous Act in the CNS , either in the
medulla or in the cortex

69. ANTIEMETICSANTIEMETICS
Types Clinical Use
Phenothiazines N/V associated with
anesthesia, intractable
hiccups
Non-phenothiazine N/V associated with
chemical stimulation
Anticholinergics N/V associated with motion
sickness
Serotonin-receptor
Blockers
N/V associated with
chemotherapy
Miscellaneous N/V associated with
chemotherapy

70. ANTIEMETICSANTIEMETICS
Contraindications
• 1. Severe CNS depression
• 2. Severe liver dysfunction

71. ANTIEMETICSANTIEMETICS
Pharmacokinetics: Side-effects
1. PHOTHOSENSITIVITY
2. Drowsiness, dizziness, weakness and
tremors and DEHYDRATON
3. Phenothiazines= autonomic effects like
dry mouth, nasal congestion and urinary
retention

72. An example of a weakly basic prodrug thatAn example of a weakly basic prodrug that
when protonated,form covalent disulfidewhen protonated,form covalent disulfide
linkages with H+/K+ ATPase and inactivateslinkages with H+/K+ ATPase and inactivates
• A. maalox
• B. nexium
• C. tagamet
• D. buscopan

73. Anti – ulcerant drugs exert their effortAnti – ulcerant drugs exert their effort
through which of the ff mechanismsthrough which of the ff mechanisms
• I. stimulation of protein kinases that
phosphorylates H/K ATPase
• II. Prevent the histamine from binding to
its receptor in parietal cells
• III. Activate inhibitory proteins that block
histamine activation of adenylate cyclase
• A. I only C. I and II
• B. II only D. II and III only
• E. I , II, III

74. Which of the H2 receptor blocker has almostWhich of the H2 receptor blocker has almost
complete oral bioavailabiltycomplete oral bioavailabilty
• A. nizatidine
• B. famotidine
• C. ranitidine
• D. cimetidine

75. Evaluate the ff regarding emeticsEvaluate the ff regarding emetics
• I. they induce vomiting
• II. They cause vomiting reflex by irritating
the upper GI tract
• A. I only
• B. II only
• C. both
• D. none

76. Evaluate the ff statements regardingEvaluate the ff statements regarding
laxativeslaxatives
• I. they accelerate fecal passage in the
colon
• II. They increase fecal consistency
• A. I only
• B. II only
• C. both
• D. none

77. Different antacids are combined in oneDifferent antacids are combined in one
preparation topreparation to
• I. antagonize the side effect of one
component
• II. Obtain a product with rapid onset and
sustained action
• III. Lower the dose of each component
A. I only C. I and II
• B. II only D. II and III only
• E. I , II, III

78. Antacids prevent the formation of thisAntacids prevent the formation of this
proteolytic enzyme that is thought toproteolytic enzyme that is thought to
mediate tissue injury in gastric ulcerationmediate tissue injury in gastric ulceration
• A. pepsin
• B. pepsinogen
• C. chymotrypsin
• D. chymotrypsinogen

79. Gastric acid by parietal cells is/are regulatedGastric acid by parietal cells is/are regulated
byby
• I. neurocrine cells
• II. Paracrine cells
III. Endocrine cells
A. I only C. I and II
• B. II only D. II and III only
• E. I , II, III

80. This acts as the most common mediator andThis acts as the most common mediator and
the most potent stimulus of gastric acidthe most potent stimulus of gastric acid
secretionsecretion
• A. acetylcholine
• B. Histamine
• C. gastrin
• D. none

81. Prostaglandin analogs increases gastricProstaglandin analogs increases gastric
mucosal resistance to injury bymucosal resistance to injury by
• I. increasing mucus secretion
• II. Increasing bicarbonate secretion
• III. Increasing gastric emptying time
A. I only C. I and II
• B. II only D. II and III only
• E. I , II, III