This document summarizes various drugs acting on the gastrointestinal tract. It discusses emetics and their mechanisms of action including apomorphine and cephaeline. It also discusses various classes of antiemetics like anticholinergics, H1 antihistamines, neuroleptics, prokinetic drugs, and 5HT3 antagonists. Specific antiemetics discussed include hyoscine, promethazine, ondansetron, and granisetron. It also summarizes causes and treatment of diarrhea, including specific antimicrobial drugs and nonspecific antidiarrheal drugs like adsorbents, anti-secretory drugs, and antimotility drugs.
6. * EMETICS
Emetics drugs used to evoke vomiting.
Vomiting undesirable substances are ingested.
At emergency powdered mustard suspension or strong salt
solution may be used.
CLASSIFICATION.
Act on Chemoreceptor Trigger Zone(CTZ).
eg: Apomorphine.
Act reflexly and on CTZ.
eg: Cephaeline.
8. * APOMORPHINE.
Mechanism of action(MOA)
Acts centrally by stimulating the
medullary CTZ connected with
vomiting centre
Uses
As emetic.
HO OH
N
H
H3C
9. * CEPHAELINE
MOA.
Locally by irritating the gastric mucosa & centrally by
stimulating the medullary CTZ to induce
vomiting.
Uses – as emetic.
H3C
O
Chemically it is an alkaloid found in ipecac.
CH3
H
H
H3C
O
N
HN
O CH3
OH
10. * ANTIEMETICS
Anti emetics drugs used to prevent or suppress
vomiting.
CLASSIFICATION OF ANTI EMETICS
Anticholinergics
eg: Hyoscine,Dicyclomine.
H1 antihistamines.
eg: Promethazine, Diphenhydramine, Dimenhydrinate,
Doxylamine, Cyclizine, Meclizine, Cinnarizine.
12. *ANTICHOLINERGICS
HYOSCINE
MOA
Blocks conduction of
nerve impulses across a
cholinergic link in the pathway
leading from the vestibular
apparatus to the vomiting centre.
Uses
For motion sickness.
CH3
O
O
O
N OH
9-methyl-3-oxa-9-azatri
cyclo[3.3.1.02,4]non-7-yl
(2S)-3-hydroxy-2-phenyl
propanoate
13. * DICYCLOMINE
MOA
Same as that of hyoscine.
2-(diethyl amino)ethyl(bicyclohexane)-
1- carboxylate.
Uses
As antiemetic, spasmolytic, in motion sickness, morning
sickness.
O
O N
CH3
CH3
14. *H1 ANTIHISTAMINES.
MOA OF ANTIHISTAMINES
Act by both relaxing the smooth muscles and also act
centrally to depress vomiting centres.
They diminish vestibular stimulation & depress labyrinthine
function.
H1 antagonism.
15. * PROMETHAZINE
Uses
Antihistaminic
Antiemetic
sedative
S
N
H3C
10-(2-(dimethylamino)propyl)
phenothiazine.
CH3
N
CH3
16. S
N
H
PHENOTHAIZINE
S
N
NaNH2
ClCH2CHN(CH3)2
S
N
CH3
N
H3C
H3C
+
17. * DIPHENHYDRAMINE
Uses
Antihistaminic
Antiemetic
Antitussive
2-(diphenylmethoxy)
Sedative N,N-dimethylethanamine.
CH3
O
N
CH3
18. * MECLIZINE
Uses
Antihistaminic
Antiemetic
1-(p-chlorophenylbenzyl)-4-
(m-methylbenzyl)piperazine.
Cl
N N
CH3
19. * CYCLIZINE
H
N N CH3
1-(diphenylmethyl)-4-methyl piperazine.
Uses
In postoperative and drug induced vomiting.
In motion sickness.
C
C6H5
20. *
HN NH + CH3COCl N NH
H3C
O
CH3I
-HI
N N CH3
H3C
O
HCl
HN N CH3 +
Cl
N N CH3
-HCl
21. *NEUROLEPTICS
MOA – They block D2 receptors in the CTZ.
CHLORPROMAZINE.
Uses
Antipsychotic
Antiemetic
Antitussive
H3C
N CH3
N
2-chloro-10-(3-(dimethylamino)
propyl)phenothiazine.
S
Cl
22. * HALOPERIDOL
O
F N
4-(4-(p-chlorophenyl)-4-hydroxy
piperidone)-4-N-fluorobutyrophenone
Uses
Antipsychotic
antiemetic
CCH 2CH2CH2
Cl
OH
24. + H3C N N Cl
*
S
N
H
Cl
2 CHLORO PHENOTHAIZINE
-HCl
NaNH2/TOLUENE
H3C N N
S
N Cl
25. *PROKINETIC DRUGS
METOCLOPRAMIDE
MOA
D2 antagonism,
5HT3 antagonism,
5HT4 agonism in CTZ
or NTS.
Uses
Cl
Antiemetic 4-amino-5-chloro-N-(2-(diethyl-aminoethyl)-
2-methoxy benzamide
H2N
O
NH
N
CH3
CH3
O
CH3
26. * DOMPERIDONE
H
5-chloro-1-(1-(3-(2-oxo2,3-dihydro-1H-benzo
imidazol-1-yl)propyl)piperidin-4-yl)-1H-benzo
imidazol-2(3H)-one.
MOA – D2 antagonism in CTZ.
Uses
Antiemetic
O
N
N
O
N
N
H
N
Cl
27. *5HT3 ANTAGONISTS
ONDANSETRON
Act via CTZ or NTS
Uses
In chemotherapy induced vomiting.
In post operative vomiting.
CH O 3
N
N N
H3C
9-methyl-3-[(2-methyl-1H-imidazol-1-yl)
methyl]-1,2,3,9-tetrahydro-4H-carbazol-
4-one
28. * GRANISETRON
Has long half life compared to
ondansetron.
Uses
In chemotherapy induced vomiting
In post operative vomiting
H3C
O
N
H3C
NH
N
N
1-methyl-N-(9-methyl-9-azabicyclo
[3.3.1]non-3-yl)-1H-indazole-3-carb
oxamide
29. DIARRHOEA
Loose bowel movements resulting into the frequent
passage of watery,uniformed stools with or without
mucous and blood.
Classification
Osmotic diarrhoea
Something in the bowel draws water from the body into the
bowel.
Eg;Sorbitol is not absorbed by the body but draws water from
the body into the bowel, resulting in diarrhoea.
30. Secretory diarrhoea
Occurs when the body is releasing water into the bowel,
many infections, drugs causes secretory diarrhoea.
Exudative diarrhoea
Diarrhoea with the presence of blood and pus in the stool.
This occurs with inflammatory bowels disease (IBD), such as
Crohn’s disease or ulcerative colitis etc.
31. Acute diarrhoea
Sudden onset in a previously healthy person
Lasts from 3 days to 2 weeks
Self-limiting
Resolves without sequels
Chronic diarrhoea
Lasts for more than 3 weeks.
Associated with recurring passage of diarrhoeal stools, fever,
loss of appetite, nausea, vomiting, weight loss, and chronic
weakness
32. CAUSES OF DIARRHOEA
Acute Diarrhoea
Microbes
Drug induced
Nutritional
Chronic Diarrhoea
Tumours
Diabetes
Addison’s disease
Hyperthyroidism
Irritable bowel syndrome
E. Coli bacteria Rotavirus
33. DRUG THERAPY
i. Specific antimicrobial drugs
ii. Non specific antidiarrhoeal drugs
ORAL REHYDRATION
THERAPY
34. Specific anti microbial drugs
A. Antimicrobials are of no value
Due to non infective causes such as
Irritable bowel syndrome
Colic disease
Pancreatic enzyme deficiency etc
Rota virus causes acute diarrhoea, specially in children
35. B. Antimicrobials are regularly useful
cholera
Tetracyclines,
chloramphenicol
etc
Clostridium
difficile
Vancomycin,
metronidazole etc
amoebiasis
Metronidazole,
dioxonid
furoate
36. NON SPECIFIC ANTIDIARROEALS
1.Adsorbents
Eg; kaolin, pectin, calcium carbonate. Etc
2. Anti secretory drugs
Eg; sulphasalazine, bismuth sub salicylate,
atropine etc.
3.Antimotility drugs
Eg: codeine, loperamide, diphenoxylate etc
37. Functions of Antidiarrhoeal Drugs
Decrease irritation to the intestinal wall
Block GI muscle activity to decrease movement
Affect CNS activity that cause GI spasm and stop
movement
Relief of symptoms and compensation of fluid &
electrolyte loss
38. Non Specific Antidiarrhoeal Drugs
Adsorbents
Coat the walls of the GI tract
Bind to the causative bacteria or toxin, which is then
eliminated through the stool
Examples: bismuth subsalicylate, kaolin-pectin, activated
charcoal.
39. Side Effects
Increased bleeding time
Constipation, dark stools
Confusion
Hearing loss, metallic taste, blue gums
40. Anti secretory drugs
Agents which reduce the secretion
Decrease intestinal muscle tone and peristalsis of GI tract
Result: slowing the movement of faecal matter through the
GI tract
Examples: belladonna alkaloids, atropine, sulphasalazine,
hyoscyamine
42. Antimotility drugs
Decrease bowel motility and relieve rectal spasms
Decrease transit time through the bowel, allowing more
time for water and electrolytes to be absorbed
Examples: codeine, loperamide, diphenoxylate
44. O
N
N
CH2
C
C CH2
C
O
CH2
H3C
Diphenoxylate HCl
45. SYNTHESIS OF DIPHENOXYLATE HCL
CH3
H2C
NH
O
O
H2C
H2C
+ O
CH3
H2C
N
O
O
CH2
CH2
OH
ethyl 4-phenylpiperidine-4-carboxylate ethyl 1-(2-hydroxyethyl)-4-phenylpiperidine-4-carboxylate
CH3
H2C
N
O
O
CH2
CH2
Cl
H3C C
H +
N
CH2 N
O
C CH2
O
CH2
H3C
C
ethylene oxide
48. Synthesis of Sulphasalazine
O
OH
OH
H2N
Cl
N O
OH
OH
N
+
H
S
O
N N
O
H2N
H
N
N
O
S
N
N
HO
O
HO
O
5-amino-2-hydroxybenzoic acid
NaNO2/HCl
5-[(Z)-chlorodiazenyl]-2-hydroxybenzoic acid
4-amino-N-(pyridin-2-yl)benzenesulfonamide
2-hydroxy-5-{(E)-[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl}benzoic acid
49. Metabolism of Sulphasalazine
Sulphasalazine
[H]
Gut
H2N
O
OH
OH
5- Amino salicylic acid
+
H
O
S
N
O N
N-(pyridin-2-yl)benzenesulfonamide
Prodrug, having low solubility and poorly absorbed from
ileum.
The azo bond split by colon bacteria into Sulfapyridine and
5-amino salicylic acid.
Blocks cyclooxgenase and lipooxygenase pathway and
reduce mucosal secretion.
51. CONSTIPATION
Constipation is the infrequent and/or unsatisfactory
defecation fewer than 3 times per week.
Abnormally infrequent and difficult passage of faeces through
the lower GI tract
Symptom, not a disease
Disorder of movement through the colon and/or rectum
52. CAUSES OF CONSTIPATION
Diet
Lack of exercise
Irregular bowel habits
Drug induced
Disease States/Conditions
Spasm of colon
Dysfunction of myenteric plexus
53. SYMPTOMS OF CONSTIPATION
Infrequent defecation
Nausea
Vomiting
Anorexia
Feeling full quickly
Stools that are small, hard, and/or difficult
to evacuate
Rectal bleeding
Weight loss (in chronic constipation)
54. • Mild action,
elimination of soft
stools but formed
stools.
Laxative or
aperients
• Stronger action
resulting in more
fluid evacuation.
Purgative or
cathartic
LAXATIVES
Drugs that promote evacuation of bowels.
Based on intensity of action
57. 4. Osmotic purgative
Magnesium salts, lactulose
etc
Bulk Forming Laxatives
Improve stool consistency and frequency with regular use
Ensure good fluid intake to prevent faecal impaction
Onset of action 2-3 days
Side Effects may include bloating, flatulence, distension
58. Stool Softeners
May be useful with anal fissures of haemorrhoids
Liquid paraffin is not recommended for treatment of
constipation
- risk of aspiration and lipoid pneumonia
- long term use may result in depletion of Vitamins
A, D, E and K
59. Stimulant Laxatives
Increase intestinal motility by stimulating colonic nerves
Useful with opioids
Onset of action 8-12 hours
May develop tolerance
2nd line therapy in elderly due to risk of electrolyte
disturbances
Cramping, diarrhoea, dehydration
60. Osmotic Laxatives
Increase fecal water content
Result: bowel distention, increased peristalsis, and
evacuation
Improving stool frequency
Onset of action – up to 48 hours
Metabolized by bacteria flatulence
61. O
O
N
H O 3 C O
CH3
Bisacodyl
Synthesis of Bisacodyl
N O
CH + 2C6H5OH
H2SO4
(CH3CO)2O
N
O
O
O
C
CH3
CH3
C
O
pyridine-2-carbaldehyde
(pyridin-2-ylmethanediyl)dibenzene-3,1-diyl diacetate
62. O
O
OH
OH
Phenolphthalein
O
O
O
+
OH
OH
H2SO4
O
O
OH
OH
phathalic anhydride
phenol
3,3-bis(4-hydroxyphenyl)-2-benzofuran-1(3H)-one
phenolphthalein
Synthesis of phenolphthalein
63. N
-
-
Na S S
Na
O O
O
O
O
O O
O
sodium picosulphate
-{(pyridin-2-ylmethanediyl)dibenzene-4,1-diyl bis[hydrogenato(2-)-O sulfate]}disodate(2-)
64. OH
NH
N NH
NH
Tegaserod CH3
3-[(E)-{2-[(pentylamino)methyl]hydrazinylidene}methyl]-1H-indol-5-ol
It is 5HT4 agonist used for the management of
irritable bowel syndrome and constipation
65. *Contract stomach muscles and stimulate hunger
N
N
3-phenyl-3,4-dihydroquinazoline( Orexin)
Bitters – secretion of gastric juice
Eg: Quassins
66. *
*Disturbance of appestat – weight regulating
mechanism in hypothalamus
Eg: Dextro amphetamine
NH2
CH3
NH2
CH3
H3C
Aptrol
67. *
*HCl
*Pepsin
O
O
CH3
CH3
O
O
OH
CH3
Florantyrone
Si O
CH3
O
CH3
CH3
Si CH3
CH3
CH3
Si
CH3
H3C
n
Simethicone
68. *
*Protect sensitive surface from irritation
*Lozenges or gargles
*Cohesive substances like colloids, dextrins, sugar,
starches
*Eg: Acacia
Tragacanth
Liquorice
76. REFERENCE
1.Text Book of Medicinal Chemistry by V. Alagarsamy,
1st edition volume-II, page no:1137
2.Bently and Driver’s Text book of Pharmaceutical Chemistry
8th edition, page No. 724, 625.
3.Essentials of Medicinal Pharmacology by K D TRIPATHI,
6th edition page No. 651
4.Clinical Pharmacy and Therapeutics, by Roger Walker,
Cate Whitelsia, 4th edition, Page No: 824- 832
5. Foye’s principles of Medicinal Chemistry, 5th edition,
page No: 474-475