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Sign and symptoms:

Watery bowel movements, the stool may also contain mucus, pus, blood or excessive amounts of fat.
Diarrhoea can be accompanied by:

• painful abdominal cramps;
• nausea;
• fever;
• bloating; and
• generalised weakness.

Diarrhoea can cause dehydration especially in young children and older people. Symptoms of dehydration in adults can include:

• thirst;
• lack of energy;
• passing less urine than normal;
• dizziness or light-headedness; and
• the skin on the back of your hand being slow to return to position after being pinched upwards.

Causes: 

Diarrhoea may have many different causes including the following.

• Infection (with a virus, bacteria or parasite). Infectious diarrhoea is most commonly caused by viruses passed from person to person, or by eating or drinking food or water contaminated with viruses, bacteria – such as salmonella, or a parasite – such as cryptospordium.
• Surgery
• A change in diet
• Malabsorption (e.g. due to problems with the pancreas).

Classification of diarrhoeal drugs: 

A. Antimicrobial drugs:

1. Norfloxacin
2. Ciprofloxacin
3. Ofloxacin
4. Rifaximin
5. Cotrimoxazole
6. Tetracycline
7. Erythromycin
8. Metronidazole

Norfloxacin, ciprofloxacin, cotrimoxazole reduce the duration of diarrhoea, mostly in case of travellers diarrhoea. Rifaximin is minimally absorbed orally. This drug is used for hepatic encephalopathy recurrance by suppressing NH3 forming gut bacteria. Some cases with blood in stool , fever, cramps caused by shigella, salmonella typhi treated by norfloxacin, ofloxacin, ciprofloxacin for symptomatic relief. Norfloxacin and other fluoroquinolones eradicate the organism from stools and control diarrhoea. Clostridium produces antibiotic associated pseudomembranous enterocolitis. The drug of choice for this superinfection is metronidazole, while vancomycin given orally is an alternative. Diarrhoea associated with bacterial growth treated with tetracycline or metronidazole.

Side effects: Side effects of Rifaximin are flatulence, defecation urgency, abdominal pain and headache.

B. Probiotics:

1. Lactobacillus sp
2. Bifidobacterium bifidum
3. Strep. faecalis
4. Enterocroccus sp.
5. Bacillus clausii
6. Saccharomyces baulardii

Probiotics are cell preparations either live cultures or lyophillised powders, that are used to restore and maintain gut flora or have other health benefits. Probiotics significantly reduce antibiotic associated diarrhoea, particularly c. difficile diarrhoea, acute infective diarrhoea and risk of traveller’s diarrhoea. Some probiotics are used in ulcerative colitis and also provide relief in flatulence and bloating. Probiotics are safe with rare side effects.

C. Drugs for inflammatory bowel disease:

IBD is chronic inflammatory disease of ileum, colon. The two major types of IBD are Ulcerative colitis and crohn’s disease. Drugs used in IBD are:

1. 5-ASA compounds:

a. Sulfasalzine

b.  Mesalazine

c. Balsalazine

d. Olsalazine

2. Glucocorticoids:

a. Prednisolone

b. Hydrocrtisone (enema)

3. Immunosuppressants:

a. Azathioprine

b. Methotrexate

c. Cyclosporine

d. TNF inhibitor- Infliximab

A. sulfasalazine: It is a compound of 5-Aminosalicylic acid with sulfapyridine linked through azo bond. This drug is poorly absorbed from ileum. The azo bond is split in to 5-ASA sulfapyridine  by colonic bacteria. 5-ASA inhibit COX and LOX and decreased PG & LT production. Inhibition of other inflammatory mediators ( cytokines, PAF, TNF alpha and nuclear transcription factor ) plays important role. Migration of inflammatory cells into bowel wall is interfered and it reduced mucosal secretions, provided symptomatic relief in UC. Sulfasalazine and other 5-ASA compounds have been used in colon- restricted CrD.

B. Mesalazine: Mesalamine may work by blocking the activity of cyclooxygenase and lipoxygenase, thereby, reducing the production of prostaglandins. Reduced production of prostaglandins decreases inflammation in the colon and the symptoms associated with ulcerative colitis.

Side effects: Abdominal pain, nausea, headache, fever, itching and leukopenia.

Drug interactions: Mesalazine enhance the gastric toxicity of glucocorticoids and hypoglycaemic action of sulfonylureas.

C. 5-ASA enema: 4gm enema  once or twice daily is given in distal ulcerative colitis.

D. Olsalazine: It is consist of two molecules of 5-ASA coupled together by azo bond. It is poorly ansorbed in the ileum. The azo bond split into 5-ASA locally in colon.

E. Balsalazine: This  is 5-ASA linked to 4-aminobenzoyl-Beta-alanine as the carrier which unlike sulfapyridine is inert. The 5-ASA is released in colon and poorly absorbed. It can be used as safer alternative to sulfasalazine.

F. Predisolone: Prednisolone is highly effective in controlling symptoms as well as in inducing remission in both UC and CrD.

G. Hydrocortisone: Hydrocortisone enema can be used topical treatment of proctitis and distal ulcerative colitis.

H. Azathioprine: The purine antimetabolites used in IBD. 6-mercaptopurine (azathioprine converted into 6-mercaptopurine in the body) can be used in its place. Azathioprine or 6-mercaptopurine are indicated in steroid-resistant , steroid dependent and relatively severe cases of IBD.

I. Methotrexate: This dihydrofolate reductase inhibitor with anti-inflammatory property and immunosuppressant property is a2nd line drug in IBD. And also used in CrD. It acts faster than azathioprine. It is very effectiva at higher doses in IBD and suppress TNF alpha expression in macrophages and monocytes. It is poorly absorbed orally. With higher toxicity. It is used in severe CrD and in patients not responsive to azatioprine.

J. Infiximab: It is chimeric anti TNF alpha antibody is used in severe active CrD  and severe UC which has not improved with i.v Corticosteroids and immunosuppressants. This drug is used in severe and refractory IBD also.

 D. Non-Specific antidiarroheal drugs:

1. Absorbants: Absorbants are colloidal bulk forming agents like ispaghula, methyl cellulose which absorb water and get swell. They modify the consistency and frequency of of stools but donot reduce water and electrolyte loss. Both of them are useful in constipation and in diarrohea.
2. Antisecretory drugs: 

a. Racecadotril: It reduces hypersecretion of water and electrolytes into the intestinal lumen by preventing the degradation of endogenous opioids (enkephalins). This antisecretory mechanism of action differs from that of loperamide which reduces intestinal lumen motility.  It decreases intestinal hypersecretions without affecting motility by lowering mucosal cAMP due to enhanced ENK action. It is not contraindicated in children.

Uses: It is used in acute secretory diarrhoeas.

b. Bismuth subsalicylate: It inhibits PG synthesis in the intestinal mucosa, thereby reducing cl secretions.

3. Antimotility drugs: Its mechanism of action mediated through u opioid receptors located on enteric neuronal network, but direct action on intestinal smooth muscles and secretory absorptive epithelium has also been demonstrated. The delta receptors are believed to promote absorption and inhibit secretion.

a. Diphenoxylate: It is synthetic opioid, used exclusively as constipating agent. The antidiarrhoeal action is most prominent but because it is absorbed systemically  and cross blood brain barrier- CNS effects do occur.

b. Loperamide:  Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency.

MCQS:

1. When your bowel movements become loose or watery. 

a. Constipation

b. Diarrhoea

c. Vomiting

d. None

 2. What are sign and symptoms of dairrhoea?

a. Painful abdominal cramps

b.  Nausea

c. Fever

d. All of above

    3. What are the causes of diarrhoea?

a. Surgery

b. A change in diet

c. Malabsorption

d. All of above

4. Which antimicrobial drug is used in diarrhoea?

a. Codiene

b. Norfloxacin

c. Loperamide

d. None of these

 5. Select probiotics.

a. Lactobacillus sp

b. Bifidobacterium bifidum

c. a$b

d. None

      6. Which 5-ASA compound is used in IBD?

a. Racecadotril

b. Loperamide

c. Sulfasalazine

d. Diphenoxylate

7. Leukopenia is a side effect of which drug?

a. Loperamide

b. Mesalazine

c. Ispaghula

d. Methylcellulose

     8. Which corticosteroids used in diarrhoea?

a. Prednisolone

b. Hydrocortisone

c. a$b

d. None

9. Which is antisecretory drug?

a. Bismuth subsalicylate

b. Racecadotril

c. a$b

d. None

10. Example of opioid agonist

a. Antimotility drugs

b. Antisecretory drugs

c. Absorbants

d. Antimicrobial drugs

11. Which is TNF alpha inhibitor?

a. Bismuth subsalicylate

b. Infiximab

c. Azathioprine

d. Olsalazine

12. Which drug is used as enema for treatment of diarrhoea?

a. Prednisolone

b. Hydrocortisone

c. a$b

d. None

13. Which is dihydrofolate reductase inhibitor?

a. Prednisolone

b. Hydrocortisone

c. Methotrexate

d. None

14. Which drug is used as both constipating and antidiarrhoeal agent?

a. Olsalazine

b. Hydrocortisone

c. Methotrexate

d. Diphenoxylate

15. What are two major types of IBD?

a. Ulcerative colitis

b. Crohn’s disease

c. a$b

d. None

Answers:

1. b

2. d

3. d

4. b

5. c

6. c

7. b

8. c

9. c

10. a

11. b

12. b

13. c

14. d

15. c

References:

1. “K.D.Tripathi”, Drugs for diarrhoea, page no: 730-737, 8th edition, june 2018.
2. “Chetan Rastogi”, Health medicine healthcare, 29th june 2014.
3.  “Health and medicine”, 22Aug 2018.

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