PHA 4140 - Diarrhea and Constipation

Instructor: Mark Laus, Pharm.D.

I. Introduction

a. Incidence of diarrhea in U.S. not usually tracked unless associated with infectious organism

b. Constipation in U.S.: there are > 125 laxative products available - a near billion-dollar-a-year business.

II. Physiology

A. Fluid movement

1. ~9 liters of hyperosmolar chyme is presented to the proximal intestine on a daily basis
2. Final water content of stool is ~100ml
3. Water is passively absorbed

B. Solute movement

1. Relies on both active and passive transport
2. As chyme moves through the intestine, it goes from hypertonic to isotonic

C. Normal bowel function depends upon:

1. The balance between absorption and secretion
2. Diet
3. Intact structure and function of the bowel
4. Problem: define a "normal" bowel movement

Both diarrhea and constipation may be viewed in terms of an abnomal balance between absorption, secretion and/or intestinal function (motility, or transit time)

III. Diarrhea

A. Etiology

1. Secretory results in large volume of stool, caused by decreased absorption or/and increased secretion
-Na>70 mmol/L, osmolar gap <50 mOsm, volume >20ml/kg-day whether fasting or not; pH >6; no fat/blood/pus or reducing substance
-laxatives; various hormones and hormone- secreting tumors; certain forms of cancer; colitis; excessive bile salts; Zollinger-Ellison Syndrome; bacterial toxins
2. Osmotic results form poorly-absorbed substances causing increased osmolarity
-Na<70mmol/L, osmolar gap >100 mOsm, volume <20ml/kg-day (<10ml/kg-day if fasting), pH<5, (+) for reducing substance, +/-blood/pus/fat
-lactose intolerance, certain antacids, poorly-soluble carbohydrates, celiac sprue, pancreatic insufficiency
-osmotic diarrhea stops/reduces when patient fasts
3. Exudative results from discharge of mucous, blood, and serum proteins into the gut lumen in the setting of inflammation
-graft versus host disease; radiation colitis; IBD; colonic neoplasm; infectious (invasive) agents
4. Altered intestinal motility/transit time
-prokinetic agents; surgery; irritable bowel syndrome; collagen vascular disease; "diabetic diarrhea"

B. Clinical presentation

1. Acute: abrupt onset of frequent, watery, loose stools and malaise, +/- abdominal pain

-increased frequency does not indicate diarrhea per se (the key is volume/mass i.e. typically >200gm/day)
-of less than 2 weeks in duration
-typically resolves in 72 hours, with or without treatment

2. Patient information

Dietary history
Medication history
Medical history
Travel history/Age

3. Medications causing diarrhea

-laxatives
-artificial sweeteners (mannitol, sorbitol, fructose)
-antiarrhythmics (quinidine, digoxin)
-antihypertensives (propranolol, guanethidine, methyldopa)
-CNS-active drugs (levodopa)
-diuretics (furosemide, ethacrynic acid)
-anti-arthritics (colchicine)
-hypolipidemics (gemfibrozil, lovastatin)
-antibronchospastics (theophylline)
-cholinergics (metoclopramide, bethanechol)
-antibiotics (alter intestinal flora)
-hormones (misoprostol, carboprost tromethamine)
-antineoplastics/radiation

C. Treatment of acute diarrhea (<72 hours in duration)

1. Self-treatment generally appropriate if no constitutional symptoms (fever, etc.) are present

-adjust diet (fluids and electrolytes)

a. Avoid solid foods for ~24 hours

-rice/starch: increase glucose content while minimizing osmolarity

b. Oral Rehydration Solutions

-medications

a. Antimotility

-diphenoxylate
-loperamide
-paregoric
-tincture of opium
-atropine
-Donnatol¨ (hyoscamine, atropine, scopolamine, & phenobarbital)

b. Adsorbants
-kaolin-pectin
-polycarbophil

c. Antisecretory

-bismuth subsalicylate
-psyllium

d. Supplementary enzymes/hormones/etc.

-lactase
-lactobacillus/acidophillus
-octreotide
-calcium

IV. Constipation

A. Definition

-variable
-2 or more of the following criteria exist when not taking laxatives:

>straining at least 25% of the time
>lumpy/hard stools at least 25% of the time
>feeling of incomplete evacuation at least 25% of the time
>2 or less bowel movements in a week

B. Etiology

1. Diet

-low-residue diet

2. Gastrointestinal disorders

-irritable bowel syndrome
-diverticulitis
-ulcerative proctitis or hemorrhoids
-bowel obstruction/infarction; fecal impaction

3. Endocrine disorders

-hypopituitarism
-hypothyroidism

4. Pregnancy

5. Neurogenic/psychogenic

-brain/spinal cord trauma (including stroke)
-Parkinson's disease

6. Drug-induced

a. Analgesics

-inhibitors of prostaglandin synthesis
-opiates

b.Anticholinergics

-antihistamines
-phenothiazines
-tricyclic antidepressants

c. Calcium- or aluminum-based antacids

d. Clonidine

e. Diuretics (non-potassium sparing)

f. Anesthetics

g. Iron preparations (oral)

h. Others (verapamil, barium-based contrast media, polystyrene sulfonate, ganglionic blockers)

C. Clinical Presentation

1. Symptoms

-abdominal distention/discomfort
-pain/bleeding

2. Treatment

a. Dietary

-increase dietary fiber intake
-fluids
-excercise

b. Bulk-forming agents (work in 1-3 days)

-psyllium/polycarbophil

c. Stool softeners (work in 1-3 days)

-docusate

>emollient: acts as surfactant, mixing liquid & fatty materials; may increase water & electrolyte secretion
>generally more effective for prevention than treatment
>safe

-mineral oil

>lubricant:makes stool easier to pass; decreases water absorption, thus increasing mass/weight of stool
>concerns:lipoid pneumonia, decreased vitamin absorption, "leaking"

-lactulose

>osmotic effect:non-absorbable disaccharide fluid is retained in colon
>concerns:cost-prohibitive, can cause flatulence and diarrhea

-sorbitol
>osmotic effect:non-absorbable monosaccharide
>less expensive than lactulose

d. Stimulants (work in 6-12 hours)

>promote intestinal motility/peristalsis
>not for routine use in normal circumstances
>avoid in pregnancy or breastfeeding

-bisacodyl

>effective dose varies

-phenophthalein

>undergoes enterohepatic recirculation
>turns urine pink

-cascara/senna/casanthranol

>may cause melanosis coli

e. Cathartics (work in 1-6 hours)

>increases motility

-magnesium citrate/hydroxide/citrate

>may be too effective...
>cautious use in renal dysfunction

-castor oil

>strong purgative; discourage routine use

-glycerin suppository

>acceptable for intermittent use

-sodium phosphates (Fleets¨ oral Phospho¨-Soda)

>relatively high sodium content

-PEG

>polyethylene glycol lavage solution

f. Others

-erythromycin
-prokinetic agents
-enemas
-buckthorn
-glycerol

Case: Constipation/Diarrhea

PM is 72 year-old male who is to undergo diagnostic procedures to rule out cancer of the GI tract. His wife comes to your pharmacy for the ‘bowel preparation’ medication that the MD has ordered, in this case 4 liters of PEG lavage solution (GoLytely¨). The physician's instructions are as follows:

Sig: Take in a clear liquid dinner the night before the test, and begin fasting after midnight. Beginning at 6 A.M the morning of the test, begin drinking the GoLytely¨ solution: Rapidly drink 8 oz. of the solution every 10 minutes until gone. Appear for office appointment at 12 noon.

The patient's wife asks for your advice in regards to administering her husband's evening and morning medications, whether her husband could still drink of water after midnight, etc. She also asks what results they should expect (the MD was a little vague), and what would happen if her husband didn't finish the entire 4 liters. You also learn that the couple live over an hour away from the physician's office. What do you suggest?

TT is a 32 year old male who presents to your pharmacy requesting assistance in choosing an appropriate medication to stop his diarrhea (day #8). He physically appears rather thin, and TT admits he "probably" has lost weight, but isn’t sure (he hasn't weighed himself in a while). TT does admit to feeling weak, and is unsure whether he has been running a fever. What are your medication recommendations? Any other recommendations?

Two days later, TT returns to your pharmacy with a prescription for Lomotil¨ (prn with each loose B.M., max. of 8 tabs per day). He admits that he is using loperamide currently with some relief. His doctor, he tells you, is "running some tests", the results of which he should hear in a day or two. Your questions/recommendations?

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