2. Constipation Pharmacotherapy
Rastegarpanah
Clinical pharmacy Department
Shariati GI Research Center
Tehran university of medical sciences

3. DEFINITION A Disturbance In Bowel Function.
Stools Too Hard Or Too Small, Defecation Too Difficult Or Infrequent.
“Normal” 3 Times / Day To 3 Times / Week
A Stool Frequency Of Less Than Three Per Week

4. EPIDEMIOLOGY Prevalence 12-19%
Prevalence Chronic Constipation Rises With Age, (65 Years Of Age Or Older).
In Old Age, 26% Of Men & 34% Of Women
Common In Pregnancy.

5. Digestion period
Stomach:
3hours
Small intestine:
4 – 6 hours
Large intestine:
12 – 72 hours

6. Small intestine
Duodenum
25-30cm
Jejunum
2 metres
Ileum
3 metres

7. Large intestine Ascending colon Transverse colon Descending colon
Sigmoid colon

8. Peristalsis

9. Excretion Muscles work together to propel waste matter (Peristalsis)
substances not absorbed by the body becomes faeces
Faeces arrives in rectum to be expelled

11. What affects the bowel? Poor diet Lack of fluid Low Mobility
Medications
Surgery

12. PATHOPHYSIOLOGY 
Constipation = disordered movement of stool through colon or rectum
Slowing of colonic transit idiopathic or:
Due to diseases
Side effect of drugs

13. Etiology: Disease-Induced: Irritable bowel syndrome
Metabolic disorders (diabetes),
Endocrine disorders (hypothyroidism),
Neurogenic disorders (Diabetes mellitus, Multiple sclerosis , Spinal cord injury).
Drug-Induced
Psychogenic causes
Life-style factors
Old age
Children

15. Drugs associated with constipation

16. Constipation in Elderly
Constipation Is Common:
Improper Diets (Low In Fiber And Liquids)
Diminished Abdominal Wall Muscular Strength
Possibly Diminished Physical Activity
Frequency Of Bowel Movements Is Not Decreased With Aging.
Diseases Such As Colon Cancer And Diverticulitis,
Drugs In Elderly:
Anticholinergics, Aspirin, Furosemide, Nitroglycerin, Amitriptyline

17. Signs and Symptoms : Decrease in frequency of fecal elimination
Difficult passage of dry hard stools
Straining to have stool

18. Diagnostic Criteria Diagnosis Based On Presence Of Following For
At Least Three Months (With Symptom Onset At Least Six Months Prior To Diagnosis).

19. Diagnostic Criteria Must Have Two Or More Of Following:
Hard Stools In 25% Of Defecations
Sensation Of Incomplete Evacuation For At Least 25% Of Defecations
Sensation Of Anorectal Obstruction / Blockage For At Least 25% Of Defecations
Fewer Than Three Defecations Per Week

20. Ten markers daily for six days
CONSTIPATION
Diagnostic Studies:
Colonic Transit Time (CTT): radio-opaque markers & day 4 X-ray.
Ten markers daily for six days
No laxative and drugs

23. CTT In Evaluating Patients With Chronic Idiopathic Constipation.
It Is Available And Has No Complication.
No Surgical Intervention Without Colonic Transit Study Is Recommended .

24. Patient Assessment
Obtain Lifestyle And Medical History Before Making Any Recommendations
Determine Reason For Use Of A Laxative
1. To Relieve Constipation
2. To Evacuate The Bowel Prior To An Upcoming Radiologic Or Endoscopic Examination
Inquire About The Patient’s Current And Past Use Of Laxative Products

25. Treatment
If Underlying Disease Is Recognized, Cause Should Be Correct It.
GI Cancer Removed Via Surgery.
Endocrine And Metabolic Dz Corrected.
If Hypo-thyroidism, Thyroid-replacement Therapy .

26. Refer to M.D. When…… Symptoms Have Persisted For More Than 2 Weeks
Recurred After Previous Dietary Or Lifestyle Changes Or Laxative Use
Patients With Blood In The Stool

27. Management Dietary Modification. Increase In Daily Fiber.
Exercise (Even By Walking After Dinner)
Bowel Habits, Regular & Adequate Time To Respond To Urge To Defecate.
Increase Fluid Intake.

28. Non-drug Treatment
High Fiber Food: Wheat Grains, Oats, Or Fruits & Vegetables
Adequate Fluid Intake
Exercise
Avoid Foods That Cause Constipation: (Cheeses & Sweets)

29. NON-PHARMACOLOGIC THERAPY
Fiber
Increases Stool Bulk,
Retention Stool Water & Increases Rate Transit
Increase Frequency Of Defecation
Fruits, vegetables, cereals have highest fiber
Bran, a by-product of milling of wheat,
Trial of dietary high-fiber should be for at least 1 month before effects on bowel function are determined

32. Non Prescription Medications Over The Counter (OTC)
Types of laxatives:
Bulk Forming
Emollient
Lubricant
Saline
Hyper-osmotic
Stimulant

33. DRUG CLASSES Most Induce Bowel Evacuation By:
Active Electrolyte Secretion
Decreased Water And Electrolyte Absorption
Increased Intraluminal Osmolarity
Increased Hydrostatic Pressure In The Gut

34. Semifluid Stool In 6 To 12 Hours (Bisacodyl);
Three Classifications:
Softening Of Feces In 1 To 3 Days (Bulk-forming Laxatives, And Lactulose)
Semifluid Stool In 6 To 12 Hours (Bisacodyl);
Evacuation In 1 To 6 Hours (Magnesium Hydroxide, Castor Oil, And Polyethylene Glycol-electrolyte Solution).

35. Dosage Recommendations for Laxatives and Cathartics

36. Bulk Forming Laxatives
Derived From Agar, Or Psyllium Seed
Synthetic, Methylcellulose & Carboxymethyl Cellulose Sodium
Dissolve In Intestinal Fluid, Thus Creating Emollient Gels That Increase Passage Of Intestinal Contents
Stimulate Peristalsis
No Systemic Absorption

37. Bulk Forming Laxatives
Onset of action is 12-24hrs
physiologic in promoting evacuation
FIRST choice for constipation
Examples are:
Citrucel powder, Metamucil, Mitrolan Chewable Tablets

38. Bulk Forming Laxatives
Caution In Younger Than 6 Yrs Of Age
Avoid In Intestinal Ulcerations, Stenosis
Interact With Anticoagulants, Digitalis Glycosides, And Salisylates
Not Used For A Fast Clearing Effect Before A Diagnostic Procedure
Used Daily And Continued In Most Patients, With Chronic Constipation.

39. Emollient Laxatives Anionic Surfactants, Softening Of Stool
Systemically Absorbed (Solid)
Onset Of Action (Oral) 24-72hrs
As A Stool Softener, & To Prevent Constipation And Maintain Regularity
Example : Docusate Sodium
Avoid In Pts Who Have Nausea, Vomiting, Or Undetermined Abdominal Pain

40. Saline Laxatives
Non-absorbable Cations & Anions - Draw Water Into Intestine - Increase In Intra-luminal Pressure, Stimulates Intestinal Motility
Onset Of Action (Oral) 30min-3 Hrs,
(Rectal) 2-5min
ONLY When Fast Clearance Of The Bowel Is Required
Ex: Fleet Phospho-soda
Avoid In Pts With CHF, Ileostomy, Renal Function Impairment, Or Younger Than 6 Yrs Old

41. SALINE CATHARTICS
Saline Cathartics Poorly Absorbed Ions Magnesium Sulfate Effects By Osmotic Action In Retaining Fluid In GI.
Magnesium Stimulates The Secretion Of Chole-cystokinin, A Hormone That Causes Stimulation Of Bowel Motility And Fluid Secretion.

42. M.O.M May Be Given Orally Or Rectally.
Bowel Movement Within A Few Hours After Oral Doses And In 1 Hour Or Less After Rectal
May Cause Fluid And Electrolyte Depletion.
Magnesium Or Sodium Accumulation In Patients With Renal Dysfunction

43. Hyper-Osmotic Laxatives
Combine An Osmotic & Local Effect Of Sodium Stearate, Draws Water Into Rectum  bowel Movement
Onset Of Action (Rectal) 30 Min
Suppository Form
Minimal Side Effects
Example: Glycerin Suppositories
Avoid In Pts With Rectal Irritation

44. GLYCERIN
Glycerin as a 1 & 3 g suppository and exerts its effect by osmotic action in the rectum.
onset of action is less than 30 minutes.
Glycerin is very safe infants, children.
Its use is acceptable on for
constipation, in children.

45. Lubricant Laxatives
Prevent colonic absorption of fecal water, thus soften the stool
minimally absorbed
Onset of action (oral)6-8 hrs, (rectal) 5-15 min
Avoid prolonged use
cause mal-absorption of fat-soluble vitamins
Example: Mineral oil

46. LUBRICANTS Mineral oil (Paraffin) only lubricant laxative Mechanism
from petroleum, coating stool and allowing for easier passage
inhibits colonic absorption of water, increasing stool weight and decreasing stool transit time

47. Dose and ADR Mineral Oil
Orally Or Rectally In A Dose Of 15 To 45 Ml
Effect On Bowel After 2 Or 3 Days Of Use.
In Debilitated Or Recumbent Patients, May Aspirated, Lipoid-pneumonia
ADR: Decrease Absorption Of Fat-soluble Vitamins (A, D, E, And K) With Chronic Use
Even Orally, May Leak From The Anal Sphincter, Causing Soiling Of Clothing.

48. LACTULOSE Lactulose - Disaccharide, used Orally Or Rectally
Metabolized By Colonic Bacteria To Low-molecular-weight Acids, Result In Osmotic Effect = Fluid Is Retained In The Colon.
The Fluid Retained In The Colon Lowers The Ph And Increases Colonic Peristalsis

49. LACTULOSE
Not First-line, Not More Effective Than Sorbitol Or Milk Of Magnesia
Alternative For Acute Constipation,
Useful In Elderly Patients
Lactulose May Result Flatulence, Cramps, Diarrhea, And Electrolyte Abnormality.

50. Lactulose Dose
Initial Dose 5 To 30 Ml Daily PO In A Single Dose Or In 2 Divided Doses; Doses Up To 45 Ml Daily
Dose Is Adjusted To Patient's Needs
Children
5 To 10 Years Initial Doses Of 10 Ml Twice Daily
1 To 5 Years, 5 Ml Twice Daily
Under 1 Year, 2.5 Ml Twice Daily.

51. Sorbitol A Monosaccharide, Osmotic Action,
Primary Agent In Functional Constipation
As Effective As Lactulose, Less Expensive.
Sorbitol By Mouth Or Rectally As An Osmotic Laxative; Doses Of 20 To 50 G.

52. Stimulant Laxatives 2 Classes: - Diphenylmethane (Bisacodyl)
- Anthraquinone (Senna)
Increases Propulsive Peristaltic Activity By Local Irritation Of Mucosa
Onset Of Action:
Senna (PO) 8-12 Hrs
Bisacodyl: Oral/Rectal 15-60min,
Systemically Absorbed
Major Use: For Evacuation Of Bowel Prior To GI Surgery Or Examination

53. Bisacodyl Stimulating Mucosal Nerve Plexus Of Colon
Significant Inter-patient Variability Exists With Dosing
A Dose That Causes No Effect In One Patient May Result In Excessive Cramping And Fluid Evacuation In Others.
Not Recommended For Regular Daily Use.

54. Bisacodyl
Acceptable Intermittently (Every Few Weeks) To Treat Constipation Or As A Bowel Preparation
Cause Abdominal Cramping
Significant Fluid And Electrolyte Imbalances With Chronic Use.
Should Not Use In Appendicitis Is A Possibility (Perforation Of The Appendix May Result) Or During Pregnancy Or Lactation

55. ANTHRAQUINONE Cascara, Sennosides, And Casanthrol.
Gut Bacteria Metabolizes These Agents To Their Active Compounds,
Exact Mechanisms Of Action Not Understood.
Effects Are Limited To The Colon,
Use Of These Agents Are Similar To Those For The Diphenylmethane Derivatives.
Intermittent Use Is Acceptable; Daily Use Discouraged

56. Stimulant Laxatives
Sennakot, Sennakot S (With Sodium Docusate), Exlax, Dulcolax, Fijan Syrup (5.85 Mg Sennoside/5 Ml)
Interact With H1 Blockers, Antacids If Administered Within 1 Hr
Avoid In Pregnancy
Breast Feeding: Senna Laxative Reported Brown Discoloration Of Breast Milk
Adverse Effects:
Severe Cramping, Electrolyte & Fluid Deficiencies, Metabolic Acidosis/Alkalosis

57. CASTOR OIL
Castor Oil Metabolized In GI To Active Compound, Ricinoleic Acid,
Stimulates Secretory Processes, Decreases Glucose Absorption, And Promotes Intestinal Motility, In Small Intestine.
Castor Oil Results In A Bowel Movement 1 To 3 Hours.
Because Strong Purgative Action, Should Not Used For Routine Treatment Of Constipation.

58. Polyethylene Glycol
PEG Become Popular For Colon Cleansing Before Diagnostic Procedures Or Colorectal Operations.
Four Liters Of This Solution Is Administered Over 3 Hours
Not Recommended For Routine Treatment Of Constipation And Should Be Avoided In Patients With Intestinal Obstruction.

59. Acute Constipation
infrequent use (less than every few weeks) of laxative is acceptable.
Relieved by use of a tap-water enema or a glycerin suppository;
if ineffective, use of oral sorbitol, low doses of diphenylmethane or anthraquinone laxatives, or saline laxative (e.g., milk of magnesia)
If laxative is required for longer than 1 week, consult a physician

60. Bedridden or Geriatric patients
For some bedridden or geriatric patients, or with chronic constipation, bulk-forming laxatives first line of treatment,
Use of laxatives may be required frequently.
Lowest effective dose and infrequently as possible to maintain regular bowel function (more than three stools per week).
Milk of magnesia, and sorbitol or lactulose.
Mineral oil should be avoided

61. Patient Counseling
Laxative use to treat constipation should be only on a temporary measure
If laxatives are not effective after 1 week, a physician should be consulted

62. Management
1-Management of chronic constipation due to slow transit including:
patient education
behavior modification
dietary changes
drug therapy

63. 2-Management of defecation involves:
biofeedback
sensory training
relaxation exercises
suppository programs

64. Patient education: reassurance explanation of normal bowel habits
reduce use of laxatives and cathartics
increase fluid and fiber intake
use normal postprandial increases in colonic motility by instructing patients to defecate after meals
important in the morning when colonic motor activity is highest

65. What Can You Do? Become more physically active
A 30 minute walk every day may help keep you more regular
As we said earlier, too much inactivity like sitting and watching TV, riding in a car, or on an airplane can contribute to constipation. Make an effort to walk 30 minutes every day. You can space it out into minutes sessions several times a day.
Other good activities include swimming or bicycling.
If you have difficulty walking or can’t swim, there are armchair videos available to help increase your physical activity while sitting in a chair.

66. What Can You Do? Eat more fiber
More beans, whole grains and bran cereals, fresh fruits, vegetables
Limit foods with no fiber (cheese, meat, sweets, processed foods)
There are several things you can do to prevent and treat constipation.
Eat more fiber (both soluble and insoluble). Americans eat too many refined and processed foods in which the natural fiber has been removed.
Choose breakfast cereals with more than 4 grams of dietary fiber per serving such as All-Bran, All-Bran with Extra Fiber, Bran Buds, Bran Flakes, and Raisin Bran.
If you add bran to your diet, be sure to do it slowly so your system gets used to it. This can help prevent a lot of gas and bloating.
Eat more fresh fruits and vegetables. Add fresh fruit to your cereal and as snacks and dessert. Dried fruit such as apricots, prunes, and figs are especially high in fiber. Eat more salads and cooked vegetables. A good goal is to eat at least 2 vegetables or fruits at each meal.

67. What Can You Do? Fiber supplements are best choice
Absorb water and make stool softer
Safe to use everyday
Be sure to drink at least 8 to 10 glasses of water everyday
Add to diet slowly to prevent
problems with gas
Brand names of fiber supplements include Metamucil, Citrucel, Fiberall, Konsyl.
Fiber supplements can interfere with absorption of some medicines, so be sure to check with your doctor about using these.

68. What Can You Do?
Drink more water and other liquids (8 eight-ounce glasses a day)
Liquid helps keep the stool soft
Avoid caffeine or alcohol which can dehydrate you
Make a special effort to drink more water, vegetable juices, clear broth, and fruit juices.
Use decaffeinated beverages instead of those that contain caffeine like coffee, tea, and colas. They, like, alcohol, can have the opposite effect - they can dehydrate you.

69. Treatment algorithm for normal transit constipation

70. Treatment algorithm for slow-transit constipation

71. Thank you for your attention

72. Constipation in Infants & children
Constipation common.
neurologic, metabolic, or anatomic abnormalities.
Management:
Dietary modification with high-fiber foods

73. Magnesium Hydroxide (Milk of magnesium MOM)240cc 8% Susp
Drugs for Constipation:
Fluid & High fibers
Laxatives -osmotic:
Polyethylene glycol (70 g powder)
  Lactulose (10g/15 ml syrup)
    Sorbitol (5g powder)
Glycerin
Laxatives - stimulant:
Bisacodyl (Dulcolax, Correctol) 5 mg tab;5,10 mg supp.  
Castor oil
Senna
Figan syrup (5.85 mg sennoside B/5 ml)
Magnesium Hydroxide (Milk of magnesium MOM)240cc 8% Susp

74. Thank you for your attention
Rastegarpanah