1. Lecture 14 Gastrointestinal Disorders Constipation and Diarrhoea
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY II
PHCY 410
Lecture 14 Gastrointestinal Disorders Constipation and Diarrhoea
Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcomes
Upon completion of this lecture the students will be able to
Describe etiology, clinical manifestations and diagnosis of constipation and diarrhea.
Develop skills for monitoring drug therapy and patient education in patients with constipation and diarrhea.
Explain drug related problems and develop pharmaceutical care plan in patients with constipation and diarrhea.

3. Constipation
It is defined as, fewer than three stools per week for women and five for men despite a high-residue diet.
PATHOPHYSIOLOGY
Constipation is not a disease but a symptom of an underlying disease or problem.
Disorders of the gastrointestinal (GI) tract (e.g., irritable bowel syndrome), metabolic disorders (e.g., diabetes), or endocrine disorders (e.g., hypothyroidism) may cause constipation.
Other causes include pregnancy, psychiatric disorders
Constipation commonly results from a diet low in fiber or from use of constipating drugs such as opiates.
Constipation may sometimes be psychogenic in origin.

4. Drugs Causing Constipation
Analgesics
Inhibitors of prostaglandin synthesis
Opiates
Anticholinergic
Antihistamines
Antiparkinsonian agents (e.g., benztropine or trihexyphenidyl)
Phenothiazines
Tricyclic antidepressants
Antacids containing calcium carbonate or aluminum hydroxide
Barium sulfate
Calcium channel blockers
Clonidine
Diuretics (non potassium-sparing)
Ganglionic blockers
Iron preparations
Nonsteroidal antiinflammatory agents

5. CLINICAL PRESENTATION
Signs and symptoms
Infrequent bowel movements, stools of insufficient size, a feeling of fullness, or difficulty and pain on passing stool.
Signs and symptoms include hard, small or dry stools, bloated stomach, cramping abdominal pain and discomfort, straining or grunting, sensation of blockade, fatigue, headache, and nausea and vomiting.
Laboratory tests
A series of examinations, including proctoscopy, sigmoidoscopy, colonoscopy, or barium enema, may be necessary to determine the presence of colorectal pathology.
Thyroid function studies may be performed to determine the presence of metabolic or endocrine disorders

6. TREATMENT DIETARY MODIFICATION AND BULK-FORMING AGENTS
The dietary modification to increase the amount of fiber consumed.
Patients should be advised to include at least 10 g of crude fiber in their daily diets.
Fruits, vegetables, and cereals have the highest fiber content.
A trial of dietary modification with high-fiber content should be continued for at least 1 month before effects on bowel function are determined.
The patient should be cautioned that abdominal distention and flatus the first few weeks, particularly with high
bran consumption.

7. PHARMACOLOGIC THERAPY
The various types of laxatives are divided into three general classifications:
(1) those causing softening of feces in 1 to 3 days (bulk-forming laxatives, docusates, and lactulose);
(2) those that result in soft or semifluid stool in 6 to 12 hours (diphenylmethane derivatives and anthraquinone derivatives);
(3) those causing water evacuation in 1 to 6 hours (saline cathartics, castor oil, and polyethylene glycol-electrolyte lavage solution).
For bedridden or geriatric patients, or with chronic constipation, bulk-forming laxatives remain the first line of treatment.
Agents include diphenylmethane and anthraquinone derivatives, milk of magnesia, and lactulose.

8. In hospitalized patient without GI disease, constipation may be related to the use of general anesthesia and/or opiate substances and most orally or rectally administered laxatives may be used.
For prompt initiation of a bowel movement, a tap-water enema or glycerin suppository is recommended, or milk of magnesia.
The treatment of constipation in infants and children should consider neurologic, metabolic, or anatomic abnormalities when constipation is a persistent problem.
When not related to an underlying disease, the approach to constipation is similar to that in an adult.

9. For acute constipation and particularly useful in elderly patients.
Emollient Laxatives (Docusates)
These products result in a softening of stools within 1 to 3 days.
They may be helpful in situations where straining at stool should be avoided, such as after recovery from myocardial infarction, with acute perianal disease, or after rectal surgery.
Lubricants(Mineral oil)
Helpful in situations similar to those suggested for docusates.
For acute constipation and particularly useful in elderly patients.
Lactulose and Sorbitol
Lactulose is a disaccharide that causes an osmotic effect and Sorbitol, a monosaccharide.

10. Saline Cathartics
Composed of relatively poorly absorbed ions such as magnesium, sulfate, phosphate, and citrate, effects by osmotic action to retain fluid in GI tract.
Used primarily for acute evacuation of the bowel, which may be necessary before diagnostic examinations, after poisonings, and in conjunction with some anthelmintics to eliminate parasites.
milk of magnesia (an 8% suspension of magnesium hydroxide) may be used occasionally (every few weeks).
Castor Oil
metabolized in GI tract to active compound, ricinoleic acid, that stimulates secretory processes, decreases glucose absorption, and promotes intestinal motility, primarily in the small intestine (within 1 to 3 hours).
Glycerin
Used on an intermittent basis for constipation in children.

11. Diarrhea
Diarrhea is an increased frequency and decreased consistency of fecal discharge as compared with an individual's normal bowel pattern.
Frequency and consistency are variable within and between individuals.
For example, some individuals defecate as many as 3 times a day, while others defecate only 2 or 3 times per week.
Most cases of acute diarrhea are caused by infections with viruses, bacteria, or protozoa and are generally self-limited.

12. PATHOPHYSIOLOGY
Diarrhea is an imbalance in absorption and secretion of water and electrolytes.
Four broad clinical diarrheal groups: secretory, osmotic, exudative, and altered intestinal transit.
Secretory diarrhea occurs when a stimulating substance (e.g., vasoactive intestinal peptide [VIP], laxatives, or bacterial toxin) increases secretion or decreases absorption of large amounts of water and electrolytes.
Poorly absorbed substances retain intestinal fluids, resulting in osmotic diarrhea.
Inflammatory diseases of the GI tract can cause exudative diarrhea by discharge of mucus, proteins, or blood into the gut.
Intestinal motility can be altered by reduced contact time in the small intestine, premature emptying of the colon, and by bacterial overgrowth.

13. Drugs Causing Diarrhea
Laxatives
Antacids containing magnesium
Antineoplastics
Auranofin (gold salt)
Antibiotics
Clindamycin
Tetracyclines
Sulfonamides
Any broad-spectrum antibiotic
Antihypertensives
Cardiac agents: Quinidine, Digoxin
NSAIDs
Proton pump inhibitors
H2-receptor blockers

14. Clinical Presentation
Many agents, including antibiotics and other drugs, cause diarrhea.
Laxative abuse for weight loss may also result in diarrhea.
Abrupt onset of nausea, vomiting, abdominal pain, headache, fever, chills, and malaise.
Bowel movements are frequent and never bloody, and diarrhea lasts 12 to 60 h.
When pain is present in large intestinal diarrhea, it is a gripping, aching sensation with tenesmus (straining, ineffective and painful stooling).
In chronic diarrhea, a history of previous attacks, weight loss, anorexia, and chronic weakness are important findings.

15. Rehydration and maintenance of water and electrolytes are the primary treatment measures until the diarrheal episode ends.
If vomiting and dehydration are not severe, enteral feeding is the less costly and preferred method.
Pharmacologic Therapy
These drugs are grouped into several categories: antimotility, adsorbents, antisecretory compounds, antibiotics, enzymes, and intestinal microflora.
Usually, these drugs are not curative but palliative.
Loperamide is often recommended for managing acute and chronic diarrhea.
Diarrhea lasting 48 hours beyond initiating loperamide warrants medical attention.
Adsorbents (such as kaolin-pectin) are used for symptomatic relief.

16. Adsorbents are nonspecific in their action; they adsorb nutrients, toxins, drugs, and digestive juices.
Bismuth subsalicylate is often used for treatment or prevention of diarrhea (traveler's diarrhea) and has antisecretory, anti-inflammatory, and antibacterial effects.
Lactobacillus preparation is intended to replace colonic microflora.
This restores intestinal functions and suppresses the growth of pathogenic microorganisms.
A dairy product diet containing 200 to 400 g of lactose or dextrin is equally effective in recolonization.

17. Anticholinergic drugs, such as atropine, block vagal tone and prolong gut transit time but use is limited by side effects.
Octreotide, a synthetic octapeptide analog of endogenous somatostatin, is prescribed for the symptomatic treatment of carcinoid tumors and VIP-secreting tumors (VIPomas).
Octreotide blocks the release of serotonin and other active peptides and is effective in controlling diarrhea and flushing.