1. www.pharmacology4students.com A ppt on DRUGS FOR CONSTIPATION
AND DIARRHOEA by
Dr DEEPIKIA SONI ,Dr. PRASHANT,MD.
Dr Swati Prashant,MD.

2. DRUGS FOR CONSTIPATION
LAXATIVE :- milder in action ,elimination of soft but formed stools.
PURGATIVE :- stronger in action, more fluid evacuation.

3. CLASSIFICATION BULK FORMING:- Dietary fiber :
Bran ,psyllium ,ispaghula ,methylcellulose
STOOL SOFTENER:-
Docusates(DOSS), Liquid paraffin
STIMULANT PURGATIVES:-
Diphenylmethane
Phenolphthalein,Bisacodyl,sodium picosulfate

4. 1 Diphenylmethane- Phenolphthalein,Bisacodyl,sodium picosulfate
STIMULANT PURGATIVES:-
1 Diphenylmethane- Phenolphthalein,Bisacodyl,sodium picosulfate
2 Anthraquinones(emodins)- senna ,cascara sagrada
3 Fixed oil-castor oil

5. OSMOTIC PURGATIVES Magnesium salts: suflate,hydroxide sodium salts: sulfate ,phosphate sod.pot.tartrate lactulose C/I Renal insuff TEGASEROD-5-HT-4 AGONIST-releases ACH,Calcitonin,CGRP,-IBS

6. BULK PURGATIVE:- DIETARY FIBRE:- BRAN
Consist of unabsorbable – cellulose ,pectins,glycoprotiens & other polysacchrides.

7. MECHANISM OF ACTION:-
Absorbs water in the intestines,swells,increases water content of faeces-softens it and facilitates colonic transit
binds bile acid & promote their excretion in faeces –degradation of cholestrol in liver is enhanced –plasma LDL-cholestrol is lowered

8. USES:- Reduces Recto sigmoid intraluminal pressure
Relieves symptoms of irritable bowel syndrome (IBS) including pain ,constipation as well as diarrhoea ,and colonic diverticulosis.

9. DRAWBACKS Unpalatable
does not soften faeces already present in colon or rectum
It should not be used in patients with gut ulcerations, adhesions stenosis & when feacal impaction possibility

10. PSYIIIUM & ISPAGHULA They contain natural colloidal mucilage
MECHANISM OF ACTION:
Forms a gelatinous mass by absorbing by water
USES:
Useful in both constipation & diarrhoea
DRAWBACKS:
If taken dry ,can cause esophageal impaction
DOSE:
3-12 gm refined husk freshly mixed with water or milk and taken daily –acts in 1-3 days.

11. STOOL SOFTNER MECHANISM OF ACTION : USES
DOCUSATES(DIOCETYL SODIUM SULFOSUCCINATE:DOSS
MECHANISM OF ACTION :
By a detergent action, it emulsifies the colonic content
USES
Indicated the when straining at stools must be avoided

12. DRAWBACK:
can disrupt the mucosal barrier and enhance absorption of many non-absorbable drugs, eg liquid- paraffin –should not be combined with it
Cramps and abdominal pain can occur.
It is bitter; liquid preparation may cause nausea.
Hepatotoxicity is feared on prolonged use.

13. LIQUID PARAFFIN DRAWBACK USES DOSE
It is a viscous liquid ;a mixture of petroleum hydrocarbon
DRAWBACK
-Unpleasant to swallow
-Carries away fat soluble vitamins with it into the stools; deficiency may occur on chronic use
USES
-Soften stools and is said to lubricate hard scybali by coating them
DOSE
15-30ml/day-oil as such or in emulsified form

14. STIMULANT PURGATIVES DOSE: DIPHENYLMETHANES Phenolphthalein Bisacodyl:
Activated in intestine by deactylation
Both this ,in colon: irritate the mucosa,& semiformed motions occur after 6-8 hours
DOSE:
-Phenolphthalein mg (not to be chewed)
-Bisacodyl: 5-15 mg: DULCOLAX 5 mg tab

15. DRAWBACK Mucosa becomes more leaky Allergic reaction-
skin rashes, fixed drug eruption
Stevens-Johnson syndrome have been reported

16. MACHANISUM OF ACTION:-
Sodium Picosulfate
MACHANISUM OF ACTION:-
It is hydrolyzed by colonic bacteria to the active form ,which then acts locally to irritate the mucosa and activate myenteric neurons
USES
Used to evacuate the colon for colonoscopy or surgery.
DOSE
5-10 mg at bed time

17. ANTHRAQUINONES
Senna is obtained from leaves and pod of certain Cassia sp., while Cascara sagrada is the powdered bark of the buck-thorn tree.
These contain anthraquinone-glycosides ,also called Emodins.

18. MACHANISM OF ACTION:-
In the colon bacteria liberate the active anthrol form, which either acts locally or is absorbed into circulation- excreted in bile to act on small intestine
The active principle acts on the myenteric plexus to increase peristalsis and decrease segmentation
DOSE PURSENNID 18 mg

19. DRAWBACK SKIN RASHES,FIXED DRUG ERUPTION ARE SEEN OCCASIONALY
REGULAR USE FOR 4-12 MONTHS CAUSES COLONIC ATONY AND MUMUSOSAL PIGMENTATION (MELONOSIS)

20. CASTOR OIL MECHANISM OF ACTION
Castor oil is a bland vegetable oil obtained from the seeds of ricinus communis
MECHANISM OF ACTION
It mainly contain triglyceride of ricinoleic acid which is a polar long chain fatty acid
Decreased intestinal absorption of water and electrolytes

21. DRAWBACKS Due to its unpalatably,
Frequent cramping, rather violent action, possibility of dehydration and after constipation (due to complete evacuation of colon ),it is no longer a favored purgative

22. OSMOTIC PERGATIVE DOSE
Solute that are not absorbed in the intestine retain water osmotic ally and distend the bowel –increasing peristalsis indirectly
DOSE
Mag.hydroxide (as 8% w/w suspension-milk of magnesia)30ml;bland in taste also used an antacid.
Mag.sulfate(epsom salt):5;15g;bitter in taste
Sod.sulfate (glauber’s salts): 10-15g ; bad in taste

23. Sod. phosphate:6-12,taste not unpleasant Sod. pot
Sod.phosphate:6-12,taste not unpleasant Sod.pot.tartrate (Rochelle salt ): 8-15 mg,relatively pleasant tasting
LACTULOSE
It is a semi synthetic disaccharide of fructose and lactose which is neither digested nor absorbed in the small intestine-retains water.

24. DIARRHOEA C) Drug therapy.
For the treatment of diarrhoea therapeutic measures may be grouped into:
A) Treatment of fluid depletion, shock and acidosis.
B) Maintenance of nutrition.
C) Drug therapy.

25. Treatment of fluid depletion, shock & acidosis.
REHYDRATION
INTRAVENOUS ORAL

26. NEW FORMULA WHO-ORS CONTENT CONCENTRATION NaCl :2.6g KCl :1.5g
Trisod.citrate :2.9g
Glucose :13.5g
Water :1 L
CONCENTRATION
Na (ion) : 75ml
K (ion) : 20ml
Cl (ion) : 65ml
Citrate : 10ml
Glucose : 75ml

27. MAINTENANCE OF NUTRITION
Boiled potato, buffalo milk ,rice ,chicken soup, banana, sago etc
DRUG THERAPY
Specific antimicrobial drugs
Nonspecific antidiarrhoel drugs

28. A . Antimicrobials are of no value :In diarrhoea due to noninfective causes, such as
Irritable bowel syndrome (IBS)
Coelic disease
Pancreatic enzyme deficiency
Tropical sprue (except when there is secondary infection)
thyrotoxicosis

29. B. ANTIMICROBIAL ARE USEFUL ONLY IN SEVERE DISEASE
Travelers diarrhoea :mostly due to ETEC , campylobacter or virus: cotrimoxazole, norfloxacin , doxycycline and erythomycin reduces the duration and total fluid needed only in severe cases.
EPEC:is less common ,but causes shigella like invasive illness. Cotrimoxazole,colistin,nalidixic acid or norfloxacin may be used in acute cases and in infants

30. Shigella enteritis:only when associated with blood and mucus in stools may be treated with ciprofloxacin ,norfloxin or nalidixic acid ; cotrimoxazole and ampicillin are alternatives
Salmonella typhimurium enteritis is often invasive ; severe cases may be treated with a fluroquinolone , cotrimoxazole or ampicillin
Yersinia enterocolitica :common in colder places , not in tropics. cotrimoxazole is the most suitable drug in severe cases ; ciprofloxacin is an alternative

31. ANTIMICROBIALS ARE REGULARLY USEFUL in:
Cholera :though not life saving ,tetracyclines reduce stool volume to nearly Cotrimoxazole is an alternative ,especially in children . Lately,multidrug resistant cholera strains have arisen:can be treated with norfloxacin/ciprofloxin ampicillin and erythromycin are also effective

32. CAMPYLOBACTER JEJUNI:NORFLOXIN AND OTHER FLUOROQUINOLONES ERADICATE THE ORGSNISM FROM THE STOOLS AND CONTROL DIARRHOEA.ERYTHOMYCIN IS FAIRLY EFFECTIVE IN CHIDREN.
CLOSTRIDIUM DIFFICILE :PRODUCE ANTIBIOTIC ASSOCIATED PSEUDOMEMBRANOUS ENTEROCOLITIS .THE DRUG OF CHOICE FOR IT METRONIDAZOLE ,WHILE VANCOMYCIN GIVEN ORALLY IS AN ALTERNATIVE .OFFENDING ANTIBIOTIC MUST BE STOPPED .

33. Diarrhoea associated with bacterial growth in blind loops/diverticulitis may be treated with tetracycline or metronidazole
Amoebiasis metronidazole , diloxanide furoate
Giardiasis are effective drugs

34. NONSPECIFIC ANTIDIARRHOEAL AGENTS AND THEIR INDICATION
ABSORBANTS
ISPAGHULA
PSYLLIUM
METHYLCELLULOSE
(IBS) ILEOSTOMY/COLOSTOMY DIARRHOEA
ANTISECERTORY
SULFASALAZINE
MESALALAZINE
RECECADOTRIL
ULCERATIVE COLITIS, (IBD) TRAVELLERS DIARRHOEA ,CARCINOID,
ANTIMOTILITY
CODEINE
DIPHENOXYLATE-ATROPINE
LOPERAMIDE
NONINFECTIVE OR MILD TRAVELLERS DIARRHOEA ,IDIOPATHIC DIARRHOEA IN AIDS

35. ABSORBANTS
These are colloidal bulk forming substance which absorb water & swell. ispaghula and other bulk forming colloids are useful in both constipation and diarrhoea

36. ANTISECRETORY DRUGS
SULFASALAZINE (SALICYLAZOSULFAPYRIDINE) : it is a compound of 5- amino salicylic acid (5-ASA) with sulfa pyridine linked through an azo bond that has a specific therapeutic effect in inflammatory bowel diseases like ulcerative colitis and crohn’s disease

37. MECHANISM OF ACTION
The azo bond is split by colonic bacteria to release 5-ASAsulfapyridine
It inhibits both COX&LOX ,decrease PG and LT production.
Inhibition of cytokine ,PAF,TNF ALPHA NUCLEAR TRANSCRIPTION FACTOR GENERATION
THUS MIGRATION OF inflammatory cells into bowel wall is interfered and mucosal secretion is reduced

38. DOSE A dose of 3- 4 gm /day induces remission over a few weeks
Maintenance therapy with gm/day has been found to postpone relapse as long as taken

39. DRAWBACKS Rashes ,fever joint pain , haemolysis and blood dyscrasias
Nausea ,vomiting , headache, malaise and anaemia are other frequent side effect
Oligozoospermia and male infertility is reported.
sulfasalazine interferes with folate absorption

40. MESALAZINE
These are 5-ASA is the active moiety in ulcerative colitis, formulated as delayed release preparation by coating with acrylic polymer .
MECHANISM OF ACTION:-
(same as sulfasalazine)
Less than half of the 5-ASA released from these preparation is absorbed , acetylated in the liver and excreted in urine

41. DRAWBACK
Nausea ,diarrhoea, abdominal pain and headache but are mild and less frequent.
Rashes and hypersensitivity reaction are rare
Has nephrotoxic potential
Contraindicated in renal and hepatic impairment.
DOSE
A DAILY DOSE OF 2.4 g

42. RACECADOTRIL
This is a prodrug is rapidly converted to thiorphane ,an enkephalinase inhibitor
MACHANISM OF ACTION
Decreases intestinal hypersecrition ,without affecting motility by lowering mucosal Camp due to enhanced ENK action.

43. 100mg (children 1.5 mg/kg) TDS for not more than 7 days
DRAWBACK
Nausea, vomiting, drowsiness flatulence
DOSE
100mg (children 1.5 mg/kg) TDS for not more than 7 days

44. ANTIMOTILITY DRUG
These are OPIODS drugs which increase small bowel tone and segmenting activity, reduce propulsive movement and diminish intestinal secretion while enhancing absorption

45. CODIENE
This opium alkaloid has prominent constipating action at a dose of 60 mg TDS.
SIDE EFFECTS ARE Nausea, vomiting and dizziness.

46. DIPHENOXYCOLATE
Synthetic opioids, chemically related to pethidine; used exclusively as constipating agent ; action is similar to codeine

47. LOPRAMIDE
It is an opiate analogue with major peripheral opioids and additional weak anticholinergic property
DOSE
4mg followed by 2mg after each motion (max in a day);2mg BD for chronic diarrhoea

48. BIBLIOGRAPHY
K.D TRIPATHY

49. THANKYOU