The document discusses advanced pharmacology related to anti-diarrheal drugs, drugs for constipation, and irritable bowel syndrome. It covers the classification, mechanisms, and management of both diarrhea and constipation, including various drug types such as antimotility agents, laxatives, and antidiarrheals. It emphasizes the importance of rehydration in treating diarrhea and explores the use of specific drugs in conditions like irritable bowel syndrome.

1. SUBJECT : ADVANCED PHARMACOLOGY-II
TOPIC : ANTI-DIARRHEALS DRUGS
DRUGS FOR CONSTIPATION
IRRITABLE BOWEL SYNDROME
SAMIR PANDA
(I I ND SEM, M.PHARM)
DEPARTMENT OF PHARMACOLOGY

2. ANTI-DIARRHEALS DRUGS
• Anti-diarrheal drugs are a type of medication that is utilized to treat or manage
diarrhea, a condition that is noted for frequent, loose, or watery bowel
movements. These drugs use different mechanisms to alleviate the symptoms
associated with diarrhea. To provide an overview of anti-diarrheal drug
pharmacology, here are some important details to consider.
• Diarrhea refers to the frequent and sudden passing of poorly formed stools.
According to the WHO,
It is characterized by three or more loose or watery bowel movements within 24
hours.
This condition is caused by excess water in the faces due to decreased absorption
of electrolytes and water, increased secretion by the intestinal mucosa, increased
luminal osmotic load, or inflammation of the mucosa resulting in exudation into
the lumen.
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3. RELEVANT PATHOPHYSIOLOGY
• Water and electrolytes are absorbed as well as secreted in the intestine. Jejunum
is freely permeable to salt and water which are passively absorbed secondary to
nutrient (glucose, amino acids, etc.) absorption.
• In the ileum and colon active Na+K+ATPase-mediated salt absorption occurs,
primarily in the mature cells lining the villous tips, water follows isosmotically.
• In addition, glucose facilitates d Na + absorption takes place in the ileum by Na+
-glucose cotransporter; one Na + ion is transported along with each molecule of
glucose absorbed. This mechanism remains intact even in severe diarrhoeas.
• Bicarbonate is absorbed also by the secretion of H + (similar to that in the
proximal tubule of kidney) and Na+ accompanies it.
• K+ is excreted in faecal water by exchange with Na+.
• When non-absorbable solutes are present and in disaccharidase deficiency (which
occurs during starvation), the stool water is increased.
• Inhibition of Na+K+ATPase and structural damage to mucosal cells (by Rota
virus) causes diarrhea by reducing absorption.
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4. CONT…
Stimuli enhancing cAMP or cGMP cause net loss of salt and water, both by
inhibiting NaCl absorption in villous cells and by promoting anion secretion
(Na+ accompanies)
Many bacterial toxins, e.g. cholera toxin, exotoxin elaborated by Entero
toxigenic E. co li (ETEC), Staph aureus, Salmonella, etc. activate adenylyl
cyclase which enhances secretion.
Prostaglandins (PGs) and intracellular Ca2+ also stimulate the secretory process.
All acute enteric.
Infections produce secretory diarrhoea. Clostridium difficile and E. histolytica
cause accumulation of cGMP which also stimulates anion secretion (less potent
than cAMP) and inhibits Na+ absorption. Diarrhoea associated with carcinoid
(secreting 5-HT) and medullary carcinoma of the thyroid (secreting calcitonin) is
mediated by cAMP.Excess of bile acids also causes diarrhoea by activating
adenylyl cyclase.
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5. CLASSIFICATION OF ANTIDIARRHOEALS
• Non antimicrobial anti diarrhoeal.
I. Antimotility agents: diphenoxylate, loperamide, codeine.
II.Anticholinergic agents: atropine, scopolamine
• Specific anti-infective agents
I. Antimicrobials:
co-trimaxozole, norfloxacin, doxycycline, erythromycin, metronidazole
II Antisecretary agents: sulfasalazine, mesalazine
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6. MANAGEMENT OF DIARRHOEA
1. Oral and parenteral rehydration
2. Antimotility agents: Opioids: codeine, loperamide, diphenoxylate.
3. Antisecretory agents: Racecadotril, octreotide.
4. Probiotics.
5. Antimicrobial agent.
Oral Rehydration Solution (ORS):
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In acute diarrhea, it is important to maintain water
and electrolyte balance with proper fluid
replacement (rehydration). Oral rehydration seems
to be the simplest, safest and least expensive method
of choice for acute diarrhea.ORS contains

7. COMMON PROPERTIES
Opioid in nature.
• Actions are mediated through μ and Delta opioid receptors present in
enteric neuronals and direct action on intestinal smooth muscle is seen.
• Pharmacological Properties
Mu receptors
• ↓ propulsive movements, ↑ absorption,
• Increase small bowel tone.
• Delta receptors
• promote absorption and inhibit secretion.
• Diminish intestinal secretions.
Overall they increase the luminal transit time
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8. CODEINE
• Opioid alkaloid, dose - 60mgTDS
• Peripheral action on intestine and colon → constipation
• No central action
• Less dependence liablity
• Side effects: nausea, vomiting, dizziness
• Caution in children
Loperamide
• opiate analogue.
• peripheral μ opioid with weak anticholinergic activity.
• It inhibits secretion by directly interacting with calmodulin.
• More potent than codeine in causing constipation.
• CNS effects are rare.
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9. • Very little absorbed from intestine
• No abuse liability
• Longer duration (12 hours) than codeine and diphenoxylate. Most effective
and best tolerated antimotility drug.
Adverse effects:
• Abdominal cramps, rashes, paralytic ileus, toxic megacolon, abdominal
distension.
• Contraindicated in children <4 yrs
Uses:
• Antimotility drugs are used in-Non infective diarrheoa, traveller's
diarrheoa, idiopathic diarrheoa in AIDS
• C/I :In infective diarrhea, ulcerative colitis, irritable bowel syndrome( as
they ↑ intraluminal pressure).
• Loperamide -4 mg start;2mg every 6hrly
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10. DRUGS FOR CONSTIPATION
 Definition:
"constipation is defined as decreased frequency and difficulty in initiation or
passage, passage of firm or small-volume feces, or a feeling of incomplete
evacuation".
Causes:
• Constipation has many reversible or secondary causes like,
• Lack of dietary fiber, drugs,
• Hormonal disturbances,
• Neurogenic disorders, and
• Systemic illnesses.
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11. LAXATIVES(APERIENTS,PURGATIVES,CATHARTICS)
 Definition:
"These are drugs that promote evacuation of bowels. According to the
intensity of action it is categorised as .
a) Laxative or aperients: milder action,elimination of soft but formed
stools simply; The evacuation of formed fecal material from the rectum.
b) Purgative or cathartic: stronger action resulting in more fluid
evacuation simply the evacuation of unformed, usually watery fecal
material from the entire colon.
• Many drugs in low doses act as laxative and in larger doses as
purgative.
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12. CLASSIFICATION
• 1) Bulk forming:Ex-Dietary fibre: Bran, Psyllium (Plantago) Ispaghula,
Methylcellulose
2) Stool softener:Ex-Docusates (DOSS), Liquid paraffin.
3) Stimulant purgatives:
Ex-a)Diphenylmethanes: Phenolphthalein, Bisacodyl, Sodium picosulfate.
b) Anthraquinones(Emodins): Senna, Cascara sagrada.
c) 5-HT4 agonist: Prucalopride
d) Fixed oil: Castor oilMagnesium salts: sulfate, hydroxide
b)Sodium salts: sulfate, phosphate, Sod.
4) Osmotic purgatives - Ex- a) pot. Tartrate, Lactulose
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13. COMMON ACTION
• Laxatives generally act in one of the following ways:
• By enhancing retention of intraluminal fluid by hydrophilic or osmotic
mechanisms;
• By decreasing net absorption of fluid by effects on small- and large-bowel fluid
and electrolyte transport; or
• By altering motility by either inhibiting segmenting (nonpropulsive)
contractions or stimulating propulsive contractions.
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14. MECHANISM OF ACTION
• All purgatives increase the water content of the faeces by:
• A hydrophilic or osmotic action, retaining water and electrolytes in the
intestinal lumen-increase volume of colonic content and making it
easily propelled.
• Acting on intestinal mucosa decreases the net absorption of water and
electrolytes; intestinal transit is enhanced indirectly by the fluid bulk.
• Increasing propulsive activity as primary action allowing less time for
absorption of salt and water as a secondary effect.
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15. • Laxatives modify the fluid dynamics of the mucosal cell and may cause fluid
accumulation in the gut lumen by one or more of the following mechanisms:
• Inhibiting Na+K+ATPase of villous cells-impairing electrolyte and water
absorption.
• Stimulating adenylyl cyclase in crypt cells- increasing water and electrolyte
secretion.
• Enhancing PG synthesis in mucosa which increases secretion.
• Increasing NO synthesis which enhances secretion and
• inhibits non-propulsive contractions in the colon. Structural injury to the
absorbing intestinal mucosal cells.
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16. • USES OF LAXATIVES WITH PREFERRED PREPARATIONS
1. Acute functional constipation (atonic or spastic) – bulk laxatives.
2. To prevent straining during defaecation in patients with cardiovascular disease,
eye surgery, hernia, etc.docusates or bulk laxatives.
3. In patients with hepatic coma to reduce the blood ammonia level – lactulose.
4. Preoperatively in bowel surgery, colonoscopy and abdominal X-ray – osmotic
laxatives or bisacodyl.
5. Following anthelmintics (e.g. for Taenia solium) – saline laxatives are used to
expel the worm segments.
6. In drug poisoning to wash out the poisonous material from the gut saline
laxatives.
7. To treat constipation in children and pregnant women – lactulose.
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17. MECHANISM OF ACTION
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Stool Softeners (Emollient laxatives)
Docusates. Common docusate salts are dioctyl
sodium sulphosuccinate (DOSS) and
dioctyl calcium sulphosuccinate. They are
anionic surfactants. They lower the surface
tension of stool, thereby cause accumulation
of fluid and fatty substance, thus softening
the stools. These agents act within 1–3 days.
They are administered orally or as a retention
enema. Docusates increase the absorption of
liquid paraffin, hence should not be
given together.

18. • Liquid Paraffin (Note the ‘Ls’). Liquid paraffin is a mineral oil and is
administered orally.
• It softens stools. It also has a Lubricant effect which helps in smooth
defecation.
• It is Useful in patients with cardiac disease because it prevents
straining during defecation.
Adverse Effects of Liquid Paraffin
• 1. Lipid pneumonia may occur due to the entry of drugs into lungs;
hence, liquid paraffin Should not be given at bedtime and in a lying
down position.
2. Long-term use may cause malabsorption of vitamins A, D, E and K
(fat-soluble vitamins).
3. Leakage of faecal matter through the anal sphincter may lead to
soiling of clothes.
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19. IRRITABLE BOWEL SYNDROME
• IRRITABLE BOWEL SYNDROME or IBS includes Crohn disease and
ulcerative colitis, which are characterized by diarrhoea, bleeding, abdominal
discomfort, anaemia and weight loss.
• COMMONLY USED DRUGS
1.Aminosalicylates: Sulphasalazine, mesalamine, olsalazine, balsalazide.
2.Glucocorticoids: Prednisolone, methylprednisolone, hydrocortisone,budesonide.
3.Immunomodulators: Azathioprine, 6-mercaptopurine (6-MP), methotrexate,
cyclosporine. 4. Biological response modifiers: Infliximab.
5. Antibiotics: Metronidazole, ciprofloxacin, clarithromycin.
6.Others: Probiotics.
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21. PATHOPHYSIOLOGY OF IBS
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22. • It is a prodrug and is composed of sulphapyridine and 5-aminosalicylic acid
(5-ASA). On oral administration, sulphasalazine reaches the colon, where it is
• broken down by colonic bacteria to 5-ASA and sulphapyridine. The released
5-ASA acts locally by inhibiting the production of inflammatory mediators.
Sulphapyridine gets absorbed and causes side effects like nausea, vomiting
and headache.
• Allergic side effects are skin rashes, fever, hepatitis, pancreatitis, pneumonitis,
etc. To avoid the side effects of sulphapyridine, several 5-ASA compounds
have been developed which can be directly targeted to the colon.
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AMINOSALICYLATES :SULPHASALAZINE,

23. GLUCOCORTICOIDS
• Glucocorticoids are used for the short-term treatment of moderate to severe
IBD.
• Various glucocorticoids used in IBD are prednisolone (oral),
methylprednisolone (oral, parenteral), hydrocortisone (enema, suppository) and
budesonide (oral).
• Prolonged use of glucocorticoids can lead to hypothalamic–pituitary–adrenal
axis suppression and
• other side effects like osteoporosis, peptic ulcer, infections and hyperglycaemia
Antibiotics Metronidazole, ciprofloxacin and clarithromycin are used as
adjuncts in patients with active Crohn disease.
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24. • Biological Response Modifiers
• Infliximab, adalimumab (TNF-% inhibitors) and certolizumab can be used in
severe
• cases of Crohn disease and refractory ulcerative colitis. The main
disadvantages of biologics are their cost and increased susceptibility to
infections.
• Probiotics
• Probiotics (e.g. Lactobacillus, Bacteroides, etc.) are used to restore the
intestinal flora;
• useful as adjunct therapy in patients with severe IBD.
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25. QUESTIONS
1. Classify drugs used in the treatment of constipation, write a note on
any one drug?
2. Write the mode of action of loperamide and kaolin?
3. Write the pharmacology of bulk laxatives?
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26. REFERENCE
1. Tripathi KD. Essentials of pharmacology for dentistry. 4th ed. New Delhi,
India: Jaypee Brothers Medical; 2020.
2. Irritable bowel syndrome [Internet]. Slideshare.net. [cited 2023 Sep 12].
Available from: https://www.slideshare.net/WisamAlsaedi/irritable-
bowel-syndrome-72314766.
3. Shanbhag TV, Shenoy S. Pharmacology for medical graduates - E-
book. 5th ed. New Delhi, India: Elsevier; 2022.
4. Knollmann B, Brunton L, Hilal-Dandan R. Goodman and gilman’s the
pharmacological basis of therapeutics. 13th ed. Columbus, OH: McGraw-
Hill Education; 2017.
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