Drugs used in GI System

1. Drugs Used in
Gastrointestinal System
DR. SAROJ K. SUWAL

2.  Drugs used in treatment of Peptic Ulcer
 Drugs used in Vomiting and constipations
 Antispasmodics
 Anti diarrheal and ORS
 Drugs used in treatment of intestinal Worm
infestation

3. Drugs
in
GI SYS.
Drugs in
Peptic
Ulcer
Antiemetics
and
constipations
Antidiarrheal &
ORS
Anti
Spasmodi
c
anti Helmentics

4. Gastrointestinal
System
 Gastric Acid secretions

5. Cells in Stomach
 ECL → Enterochromaffin like cell

6. thinking about food ??
Acetylcholine released
by vagus nerve endings
Hypersecretion of Gastric
Acid
pepsin production

7. secretion of gastric acid

8. Defensive Vs Protective Mechanism of Stomach
Aggressive factors
• acid
• pepsin
• H.pylori
Defensive factors
• Mucin
• Bicarbonate
• Prostaglandins

9. Cell destructive effects by bacteria
 H. pylori,
 Spiral shaped, flagellated, Gram negative
bacterium
 bacteria found in the gastric mucosa
of most clients with chronic gastritis
 75% with gastric ulcers
 90% with duodenal ulcers
 Spread by oral fecal route
 affect mucosal function

10. How to protect stomach?

11. Different conditions in stomach
 Hyperacidity
 Gastritis
 PUD
GU
DU
 GERD

12. Hyperacidity→ Treatment
 inscrease H+ in stomach
 pH of gastric acid is 1.5 to 3.5
 Strategy of hyperacidity treatment
 Neutralize the released acid
 Block the acid release
 Protect the mucosa

13. Antacids
These are the weak bases
1) prevent injury from H+
2) neutralize gastric acid → reduce gastric
acidity→ reduce peptic activity
3) protect face of ulcer
Examples:
Mg(OH)2 , Al(OH)3 , CaCO3 , NaHCO3
Magnesium hydroxide • Magnesium trisilicate •
Magnesium-aluminum mixtures • Calcium
carbonate • Sodium bicarbonate

14. H2 receptor blockers
 Reduce basal and food stimulated
acid secretion
 50-60% acid is blocked
 Eg. Cimetidine , Famotidine ,
Ranitidine

15. MOA
 Inhibit the action of histamine at the H2 receptors of
parietal cells

16. Proton Pump Inhibitors (PPI)
 95% acid is blocked
 Examples
 Omeprazole (20mg),
 pantoprazole (40mg),
 Esomeprazole (20mg)
 Rabeprazole

17. MOA of PPI
 Block the final step in gastric acid
secretion
 by blocking combining with
hydrogen, potassium pump by
inhibiting H+ /K+-ATPase

18. Prostaglandins
 inhibit acid secretion
 E.g. misoprostol.
 0.1mg or 0.2 mg reduces 80-
90% acid
 Prevention of NSAIDS gastric
ulcers
 Side Effects
 • Diarrhea
 • Abortion • Exacerbate IBD
and should not be given

19. Gastro Esophageal Reflux Disease (GERD)
 common problem as ‘heartburn’
 acid eructation
 sensation of stomach contents coming
back in food pipe, especially after a large
meal
 Repeated reflux
 causes esophagitis, erosions, ulcers, pain on
swallowing, dysphagia (difficulty to swallow)
, and increases the risk of esophageal
carcinoma

20. Drugs used for GERD
 Proton Pump Inhibitors→
 Omeprazole, pantaprazole
 H2 blocker→
 ranitidine, cemetidine
 Antacids→
 MgOH, Al(OH)3
 Prokinetics->
 Hastens the gastric emptying by cholinergic activation
of intestinal peristalsis. Eg. Metoclopramide
 Sodium Alginate→
 Forms the foamy layer above the surface of gastric
content in stomach and blocks acid from entering to
oesophagus

21. Peptic Ulcer(PUD)
 A benign lesion of gastric or duodenal mucosa
occurring at a site where the mucosal epithelium
is exposed to acid and pepsin..
 Mucosal erosion >=0.5cm
 results due to an imbalance b/w the aggressive
(acid, pepsin, bile & H. pylori) & the defensive
(gastric mucus & bicarbonate secretion, PG etc.)
 Gastritis is precursor to PUD
 Two types
 Gastric Ulcer
 Duodenal Ulcer
 Diagnosis is by endoscopy and testing for H.
pylori.

22. Drugs used in peptic ulcer
1. Drugs that inhibit gastric acid secretion
2. Drugs that neutralize gastric acid (Antacids)
3. Ulcer protectives for Mucus
4. Anti H. pylori drug

23. Drugs that inhibit gastric acid secretion
 H2 receptor blockers:
 Cimetidine, Ranitidine, Famotidine
 Proton pump inhibitors:
 Omeprazole, Pantoprazole, esomeprazole
 Anticholinergics :
 Pirenzepine, and Telenzepine
Reduce meal stimulated HCl secretion by reversible
blockade of muscarinic (M1) receptors
 Prostaglandin analogues:
 Misoprostol

24. Drugs that neutralize gastric acid
(Antacids)
Systemic:
Sodium bicarbonate, sodium
citrate
Non systemic:
• Magnesium hydroxide, Mag.
Trisilicate, Aluminium hydroxide
gel, Magaldrate

25. Ulcer protectives
form a viscous paste-like substance;
adheres strongly to gastric and duodenum
mucosa
EG
Sucralfate
basic aluminum salt of sucrose octasulfate;
 Bismuth Sulfate

26. Anti H. pylori drugs
 Used for eradicating H.pylori bacteria
 used in as Triple and quad Therapy
 Antibiotics used
 Amoxicillin,
 Clarithromycin,
 Metronidazole,
 Tinidazole,
 Tetracycline

27. Triple therapy
 Two antibiotics + one PPI for 7 to 14 days
 Amoxycillin 750 mg BD + Clarithromycin 500 mg BD + PPI BD
 Amoxycillin 750 mg BD + Metronidazole 400/Tinidazole 500 mg
BD + PPI BD
 Amoxycillin 1000 mg + Clarithromycin 500 mg + Lansoprazole
30 mg all BD ( Recommended by US FDA)

28. The quad therapy
7 to 10 days
PPI BD + Bismuth subsalicylate 120 mg
QID + metronidazole 400 mg
QID/Tinidazole 500 TDS + Amoxicillin
500/ tetracycline 500 TDS

29. Anti Diarrheal
Drugs and ORS

30. Diarrhea
 Abnormal passage of stools with increased frequency,
fluidity with increased stool water excretion
increase bowel
motility
increase
secretion
retention of
fluids in the
intestinal lumen
cause
inflammation or
irritation of the
GI tract.
Results
•Fast propelling of
bowel content
•absorption of fluids
and electrolytes is
limited

31. Diarrhea may be classified into:
- Acute ( sudden onset )
 Food induced ( traveler’s ),
 Infections,(virus, bacteria,
parasites)
 medicines
- Chronic ( 2 weeks or longer )
IBD, Stress
Common parasite cause :
Entamoeba histolytica •Giardia lamblia •Cryptosporidium •Isospora

33. Goals of treatment
Control the loss of fluids
Identify and treat cause
Provide symptomatic relief (
antidiarrheal drugs )

34. Anti diarrhea Drugs
Pharmacological
 Locally acting agents ( Absorbents ):
 Kaolin -Pectin suspension
 Bismuth sub-salicylate
 Probiotics :yeast or bacteria, Lacto-bacillus Acidophilus
 Centrally acting agents
 codeine phosphate
 Drugs inhibiting of the peristaltic reflex
 loperamide, diphenoxylate
 Drugs killing bacteria
 metronidazole, ornidazole
Non Pharmacological
 ORS and electrolytes

35. Antidiarrheal agents
Locally acting agents ( Adsorbents ):
 Kaolin -Pectin suspension
 Bismuth sub-salicylate

36. Kaolin -Pectin suspension
 Most widely used preparation
 available in powder dosage form
 Mechanism of action
 adsorbs bacterial toxins,
 binds water and
decreases mucus secretion
 Indications
 Acute diarrhea (given after each loose bowel movement)
 Adverse effects:
 Not absorbed and has no adverse effects.

37. Bismuth subsalicylate
Insoluble mixture of bismuth and
salicylate
Mechanism of action:
Bismuth: antimicrobial
Salicylate: antisecretory
 Adverse effects:
blackening of tongue and stools

38. Centrally acting agents
( MOA-Inhibit defecation reflex )
Codeine
Has limited use because it leads to
tolerance and addiction
Diphenoxylate
Opium-like drug with less addictive
properties
Widely used combined with Atropine
(an
Anticholinergic which decrease
secretion of fluids)

39. inhibition of the peristaltic reflex
Loperamide
 Produces rapid and sustained
inhibition of the peristaltic reflex
slowing the passage of stools
through the intestines which will
allow more time for water and salts
in the stools to be absorbed back
into the body

40. Anti Microbial
 Indications:
 1. Patients with +ve stool culture
 2. Patients presented with dysentery
 3. Patients with suspected exposure to bacterial
infection.

43. Oral rehydration therapy
 made from a special combination
of salts and sugar mixed with
clean, safe water.
 Designed to help the body
replace fluids lost during illness.
 Most commonly used for diarrhea,
especially with children.

44. Why ORT???
 Diarrhea →the second leading cause of child
deaths and kills 1.9 million young children
every year, mostly from dehydration.
 ORS use is the simplest, most effective and
cheapest way
 solution is absorbed in the small intestine,
thus replacing the water and electrolytes lost
ORT does not stop diarrhea, just prevents the body from drying up.

45. When ORT????
 If child has three or more loose stools in a day,
begin to give ORS.
 In addition, for 10–14 days, give children over 6
months of age 20 milligrams of zinc per day (tablet
or syrup);
 give children under 6 months of age 10 milligrams
per day (tablet or syrup).
 One of the ORS drinks should be given to the child
every time a watery stool is passed.

46. ORS
 The composition of
different salts intended to
replenish the electrolyte
and water loss due to
diarrhea or other any
reasons.

47. Zinc therapy in diarrhea
 If Zinc deficiency
• increased risk of gastrointestinal
infections,
• adverse effects on the structure and
function of the gastrointestinal tract,
• and impaired immune function

48. Role of Zinc
 Zinc has an additional modest benefit in diarrhea
 • Reduces stool volume.
 30% reduction in stool volume
 Reduces duration of diarrhea.
 Reduces duration of diarrhea episode by up to 25%
 Decrease by about 25% the proportion of episodes lasting more than seven days
 Improves immunity
 Reduces severity of illness and mortality

49. Dose of Zinc in children in diarrhea
 Elemental Zinc
 10 mg/day for 2-6 months for 10 days
 20 mg/day for 6 months to 5 years child for 10 days
 • Any of zinc salts e.g., sulphate, gluconate or acetate may
be used.

50. Anti Emetics
DRUGS USED IN VOMITING

51. Emesis or Vomiting
 Forceful propulsion of gastric
contents out of mouth
 Not due to stomach contraction
 Stomach, esophagus and sphincter
are relaxed

52. Nausea, Retching and Vomiting
 Nausea
 unpleasant sensation of wanting to
vomit
 Retching
 strong involuntary effort to vomit
 Vomiting or emesis
 the forceful expulsion of the contents of
the gastrointestinal system out through
the mouth

53. Physiology of vomiting
 Is coordinated by vomiting center (
Medulla oblongata of brain stem)
 vomiting centers (present in the lateral
reticular formation of the medulla) are
stimulated.
 The following area can stimulate the
vomiting centre:
 The Chemoreceptor Trigger Zone: This
area is located in the floor of the 4th
ventricle of the brain.

54. Triggers of CTZ
 Histamines
 Dopamine
 Acetylcholine
 Serotonin
These neurotransmitter are
released by virtue of various
stimuli like drugs, smell, taste,
motion etc.

55. Antiemetics
Drugs used in Vomiting are called antiemetics
Five categories of antiemetics
1. Anticholinergics
2. Antihistamines
3. Neuroleptic agents
4. Prokinetic agents
5. Serotonin blockers

56. Nervous System
CNS
Brain
Spinal
cord
PNS
ANS
Sympathetic Parasympathetic
Somatic NS

57. Sympathetic Vs
Parasympathetic
action

58.  Ach is neurotransmitter ( chemical substance
released by neuron or nerve cell )
 acts on PNS and CNS both
 In PNS→ NMJ
 In CNS→ brain
Acetylcholine – major neurotransmitter
of PNS
Epinephrine or adrenaline,
Norepinephrine or Nor adrenaline →
hormones by medulla of adrenal
gland
Acetylcholine → neurotransmitters in
PNS

59. Ach in NMJ and Brain
Cognitive functions are mental
processes that allow us to carry out
any task
In PNS acetylcholine transmits signals between motor
nerves and skeletal muscles.
It acts at neuromuscular junctions and allows motor
neurons to activate muscle action. ...

60. Cholinergic receptors

61.  Drugs that mimics the
action of ACH→
cholinergic Drugs
 Drugs that stops the action
of Ach→ Anticholinergic
drugs

62. Anticholinergics antiemetics
 agents that block muscarinic
receptors and inhibit cholinergic
transmission from the vestibular
nuclei to the vomiting center
 block acetylcholine receptors→
block conduction of nerve impulses
 Prevent nausea stimuli from being
transmitted
 Eg Scopolamine
Esp. in vomiting due to motion sickness,
vertigo, migraines

63. Antihistamines
 Block H1 receptors, blocks the action of
histamines.
 Used in motion sickness, post operative
nausea.
 Eg
 Promethazine
 Meclizine
 is used to treat or prevent nausea, vomiting, and
dizziness caused by motion sickness
 Initial Dose: 25 to 50 mg orally 1 hour before travel
-Maintenance Dose: Repeat dose every 24 hours if
needed

64. Neuroleptic agents(antipsychotics)
 MOA
 Bind to the dopamine receptors and block
action→ Limit dopamine activity
 Used in drug and disease induced
vomiting( in adults)
 Eg
 Chlorpromazine,
 Prochlorperazine
 to control severe nausea and vomiting.

65. Prokinetic agents
 drug which enhances gastrointestinal motility
used for
Food and drug induced vomiting, motion sickness,
post operative vomiting
Eg Metoclopramide, domperidone
increase release of
acetylcholine from
nerve endings in
the GI tract
increases GI motility
inscrease the rate
of gastric emptying

67. Serotonin receptor blockers.
 Block serotonin receptors in the gastrointestinal tract
 Block serotonin receptors in the central nervous system
(emetic center)
 Used often in surgical prophylaxis
 when antineoplastic agents are being given
 not effective in motion sickness
 Eg Ondansetron, granisetron

68. Constipation
 passing hard stools or straining, incomplete or
painful defecation.

69. Drugs for constipation:
 laxatives
 are those which softens stool
Increase bowel movements

70. Laxatives :Mechanism of Actions
 – Work in three ways:
 • Direct chemical stimulation of the GI tract
 • Production of bulk or increased fluid in the lumen
 • Lubrication of the intestinal bolus to promote
passage through the GI tract

71. Indications –
 Short-term relief of constipation
 – Prevent straining when it is clinically undesirable
 – Evacuate the bowel for diagnostic procedures
 – Removal of ingested poisons
 – Adjunct in antihelmintic therapy

72. Indications for laxative
 Pain associated with bowel movements
 To decrease amount of strain under certain
conditions
 Evacuate bowel prior to procedures or
examinations
 Remove poisons
 To relieve constipation caused by pregnancy or
drugs

73. Contraindications –
 Acute abdominal disorders
 BOWEL OBSTRUCTIONS
• Caution
 – Pregnancy or lactation

74. Adverse Effects
 GI effects
 Diarrhea, abdominal cramping, and nausea
 CNS effects
 Dizziness, headache, and weakness
 CV effects
Sweating, palpitations, flushing, and fainting

75. Classifications of Laxatives
Bulk laxatives
Irritant laxatives = purgatives
Lubricant laxatives

76. Classification
 Bulk laxatives
 Non-absorbable carbohydrates
 Osmotically active laxatives
 Irritant laxatives = purgatives
 Small bowel irritants
 Large bowel irritants
 Lubricant laxatives
 Paraffin
 Glycerol

77. Bulk Laxatives
Increase in
bowel content
volume
triggers stretch
receptors in the
intestinal wall
Two Type of bulk laxatives
• Carbohydrate-based laxatives
• Osmotically active laxatives

78. Carbohydrate-based laxatives
Insoluble,non-absorbable and Non
digestible
 Expand upon taking up water in the
bowel hence softens the stool
 Must be taken with lots of water
Eg. Vegetable Fibers

79. Osmotically active laxatives
Partially soluble, but not absorbable
 accumulates water in the intestine and
colon region from the GIT cells by
osmosis.
 Effect in 1-3 hrs => used to purge
intestine
Eg. MgSO4 ( Epsom salt)
 Lactulose
 Glycerine suppository

80. Irritant laxatives: or Purgatives
 Mechanism of Action
Cause irritation of the enteric mucosa
 more water is secreted than absorbed
softer bowel content and increased peristaltic due to
increase volume
Two types:
Small bowel and large bowel irritants

81. Irritant laxatives contd….
Small bowel irritants
 Ricinoleic acid (Castor oil)
 Active ingredient of Ricinus
communis
Ricin

82. Large bowel irritants
Anthraquinones
Active ingredient of Senna sp.
contain inactive glycosides => active anthraquinones
released in colon
Bisacodyl
Oral administration: effect in 6-8 hrs
Rectal administration: effect in 1 hr

83. Lubricant laxatives
MOA
Decrease the friction between stool
and intestine, form a slippery coat on
the colonic contents
Eg, sorbitol, glycerine.paraffin

84. The laxative abuse
 The repeated use of laxative for following reason
After use of laxative, It takes long time to get colon
filled, Longer interval needed to refill colon
misinterpreted as constipation
 loss of water and salts Causes hypokalemia (reduced
potassium ion), which in turn reduces peristalsis. This is
then often misinterpreted as constipation => repeated
use,

85. The misuse of laxative for following
reason
Psychological dependence in elderly patients
Weight loss(myth………..??)

86. Whom laxative should not be
given???
 Patients with
Appendicitis
Ulcerative colitis
Undiagnosed abdominal pain, colic or vomiting.
Stricture or obstruction in bowel,
hypothyroidism,
hypercalcaemia,
malignancies

87.  Thanks