Medicines Acting on Specific Body Systems

Drugs for Constipation (Laxatives)

Constipation is a reduced frequency of defecation characterized by hardening of the stool, straining on defecation, or a feeling of incomplete evacuation. 

It may be caused by any of the following:

• Lack of fluid or fiber intake
• Lack of exercise
• Pregnancy
• Drugs like aluminum-containing antacids, codeine, or iron
• Irritable bowel syndrome
• Anorectal conditions like hemorrhoids
• Psychiatric and neurological disorders

Laxatives are drugs that stimulate defecation by forming bulk, stimulating peristalsis, or providing lubrication. 

They increase the frequency of bowel evacuation or the passage of softer or bulkier stool. Laxatives are used in the treatment of constipation and for bowel evacuation before investigational procedures, such as endoscopy, radiological examination, or before surgery.

Classification of Laxatives

Laxatives are classified according to their mode of action as follows:

• Bulk-forming laxatives
• Saline laxatives
• Lubricant laxatives
• Stimulant laxatives
• Osmotic laxatives

Bulk-Forming Laxatives

Mode of Action: Bulk-forming laxatives relieve constipation by absorbing water, thereby increasing fecal bulk, which stimulates peristalsis. They are useful for mild constipation, small hard stools, patients with hemorrhoids, fissures, and irritable bowel disease, and as adjuncts in ulcerative colitis. Adequate fluid intake is important to lubricate the colon and minimize the risk of intestinal obstruction.

Examples:

• Methylcellulose
• Wheat bran
• Ispaghula husk

Ispaghula Husk

Available Preparations:

• Granules: 3.5 g sachet

Available Brands: Fybogel®

Indications:

• Constipation, especially in diverticular disease and irritable bowel syndrome
• Constipation following anorectal surgery, hemorrhoids, pregnancy
• Management of diarrhea
• Adjusting fecal consistency in patients with colostomies

Contraindications:

• Difficulty in swallowing
• Intestinal obstruction
• Colonic atony
• Fecal impaction
• Hypersensitivity to any of the ingredients

Dosage:

• Adult: 1 sachet or 2 level 5 ml spoonfuls in water given morning and evening after meals
• Children (6-12 years): 1/2 – 1 level 5 ml spoonful in water twice daily
• Children (below 6 years): Give on doctor’s advice only

Side Effects:

• Flatulence and abdominal distension during the first few days of treatment
• Gastrointestinal obstruction or impaction
• Hypersensitivity reaction

Osmotic Laxatives

Mode of Action: Osmotic laxatives are poorly absorbed; therefore, the unabsorbed solute in the intestine draws water from the body into the bowel by osmosis, causing bowel distention, which in turn increases peristalsis. These drugs are used for acute and rapid evacuation of the bowel, except for lactulose.

Examples:

• Lactulose
• Magnesium salts

Lactulose

Available Preparations: Syrup: 3.350 g/5 ml

Available Brands: Laxolac®, Duphalac®, Sedalac®

Indications:

• Constipation
• Hepatic encephalopathy

Contraindications:

• Intestinal obstruction
• Known hypersensitivity to lactulose
• Galactosemia

Dosage:

Constipation:

• Adults: 15 ml twice daily
• Children (6-12 years): 10 ml twice daily, adjusted according to response
• Children (1-5 years): 5 ml twice daily, adjusted according to response
• Children (less than 1 year): 2.5 ml twice daily, adjusted according to response

Hepatic Encephalopathy: 30-45 ml 3 times daily, adjust dose to produce 2-3 soft stools per day

Side Effects:

• Flatulence
• Cramps
• Diarrhea
• Nausea
• Abdominal discomfort
• Vomiting if excess doses are given

Key Issues to Note:

• Administer the drug with juice, milk, or water to increase palatability
• Do not take other laxatives while on lactulose therapy

Lubricants and Fecal Softeners

Mode of Action: They promote stool passage by coating the fecal surface with an oil layer that retains fecal fluid and prevents absorption of fecal water by the colon.

Examples:

• Glycerol
• Docusate sodium
• Liquid paraffin
• Mineral oil

Glycerol

Available Preparations:

• Suppositories: 4 g

Indications:

• Constipation

Contraindications:

• Patients with known hypersensitivity to glycerin
• Glycerin suppositories are contraindicated in patients who are recovering from rectal surgery

Dosage:

By rectum:

• Adults: 4 g suppository moistened with water before use, once daily when required
• Children (1-12 years): 2 g suppositories as required
• Children (1 month – 1 year): 1 g suppository once daily when required

Side Effects:

• Rectal discomfort
• Diarrhea
• Rectal mucosal erosion
• Dizziness
• Mild headache
• Nausea
• Mild hyperglycemia
• Vomiting

Drug Interactions:

• Concomitant use with diuretics may result in an additive effect

Key Issues to Note:

• Onset of action is 5-30 minutes
• Do not use longer than 1 week
• Prolonged or frequent use may result in dependency

Stimulant Laxatives

Mode of Action: Stimulant laxatives increase peristalsis by directly stimulating nerve endings in the colonic mucosa, thereby increasing intestinal motility. They are useful for more severe forms of constipation, but tolerance is common with regular use, and they can produce abdominal cramps.

Examples:

• Bisacodyl
• Senna
• Castor oil

Bisacodyl

Available Preparations:

• Tablets: 5 mg
• Suppository: 10 mg

Available Brands: Dulcolax®

Pharmacokinetics: Absorption of bisacodyl after oral administration is minimal; the absorbed drug is metabolized in the liver and excreted in urine, feces, and breast milk.

Indications:

• Constipation
• Bowel evacuation before investigational procedures or surgery

Contraindications:

• Intestinal obstruction
• Appendicitis
• Severe dehydration
• Acute inflammatory bowel disease
• Hypersensitivity to the drug

Dosage:

Constipation:

• Adults: 5-10 mg daily administered at night or 10 mg as a suppository or enema administered in the morning
• Children (10-18 years): 5-10 mg at night, increased if necessary to max. 20 mg
• Children (5-10 years): 5 mg at night
• Children (2-5 years): 5 mg in the morning (rectally)

Complete Bowel Evacuation:

• Adult: 10-20 mg followed by 10 mg as a suppository the next morning
• Children (4-10 years): 5 mg at bedtime for 2 days before the procedure, increased if necessary by suppository 10 mg 1 hour before the procedure

Side Effects:

• Nausea
• Vomiting
• Diarrhea
• Faintness
• Mild cramps
• Abdominal discomfort
• Suppositories may cause irritation and proctitis

Drug Interactions:

• Antacids, cimetidine, famotidine, ranitidine, milk, and other drugs that increase gastric pH level may cause premature dissolution of the enteric coating of bisacodyl, resulting in abdominal cramping

Key Issues to Note:

• Patients should swallow tablets whole with a glass of water
• Do not administer bisacodyl within 1 hour of ingesting antacids, milk, or dairy products
• Bisacodyl is habit-forming; therefore, long-term use may result in laxative dependency and loss of normal bowel function
• Onset of action is 6-12 hours for tablets, 15-60 minutes for suppository
• Warn the patient that prolonged use of bisacodyl suppositories may cause proctitis

Antidiarrheal Drugs

Diarrhea is the frequent passage of watery stools at least 3 times or more in a day. It affects all age groups and is more severe and life-threatening in children and immunocompromised patients. Diarrhea may be caused by any of the following:

• Infections
• Inflammation
• Drugs such as antacids
• Malabsorption

Drugs used in the treatment of diarrhea include:

• Adsorbents
• Antimotility drugs
• Antisecretory compounds
• Antimicrobials
• Intestinal microflora

Adsorbent Drugs

Examples:

• Kaolin
• Pectin
• Activated charcoal

Adsorbent drugs act by absorbing the toxins produced by pathogens, thereby reducing GIT motility. These drugs are used for symptomatic relief of diarrhea. They are not recommended for infectious acute diarrhea and when the patient is taking other drugs (prevent absorption of other drugs).

Antisecretory Drugs

Examples:

• Bismuth subsalicylate

Bismuth subsalicylate appears to produce its antidiarrheal effect by inhibiting intestinal secretions. It is recommended in the treatment of infectious diarrhea such as traveler’s diarrhea. It is available in the form of tablets and suspension.

Intestinal Microflora

Example: Lactobacillus

These drugs are intended to replace colonic microflora, which restores intestinal function and suppresses the growth of pathogenic microorganisms.

Antimotility Drugs

Examples:

• Loperamide
• Codeine
• Diphenoxylate

Antimotility drugs act by reducing GIT motility, thereby allowing enough time for fluid absorption from gut contents. They are recommended in the treatment of acute and chronic diarrhea in combination with fluid replacement. They are not recommended in children less than 2 years and infectious diarrhea.

Loperamide

Available Preparations:

• Capsules: 2 mg
• Tablets: 2 mg

Available Brands: Imodium®, Loperium®, Loperax®, Kamodium®, Gallop®

Pharmacokinetics: About 40% of loperamide is absorbed from the gastrointestinal tract, undergoes first-pass metabolism in the liver, and is excreted in the feces as unchanged drug and a small amount in urine.

Indications:

• Acute diarrhea
• Chronic diarrhea
• Traveler’s diarrhea

Contraindications:

• Known hypersensitivity to loperamide
• Infants below 2 years of age
• Abdominal distension
• Acute inflammatory bowel disease
• Antibiotic-associated colitis
• Patients who must avoid constipation

Dosage:

Acute Diarrhea:

• Adult: 4 mg start followed by 2 mg after each loose stool until diarrhea is relieved. Max dose 16 mg daily
• Children (9-12 years): 2 mg 4 times daily up to 5 days
• Children (4-8 years): 1 mg 3-4 times daily for up to 3 days only

Chronic Diarrhea:

• Adult: 4-8 mg daily in 2 divided doses

Side Effects:

• Flatulence
• Blurred vision
• Drowsiness
• Headache
• Fatigue
• Constipation
• Dry mouth
• Hypersensitivity reaction
• Abdominal cramps
• Dizziness
• Nausea and vomiting
• Abdominal bloating
• Urticaria
• Toxic megacolon
• Paralytic ileus

Drug Interactions:

• Concomitant use of loperamide with opioid analgesics may cause severe constipation

Key Issues to Note:

• Advise the patient to drink plenty of fluids to prevent dehydration
• Do not exceed the maximum daily dosage
• Loperamide may impair the ability to perform activities requiring mental alertness
• Advise the patient to avoid the use of alcohol during treatment
• Loperamide should not be used alone in patients with dysentery

Codeine

Available Preparations:

• Tablets: 30 mg

Pharmacokinetics: Codeine is absorbed from the gastrointestinal tract, metabolized in the liver to morphine and other metabolites, and excreted in urine.

Indications:

• Diarrhea
• Pain
• Cough suppression (lower dosage)

Contraindications:

• Hypersensitivity to codeine
• Premature infants
• Conditions where inhibition of peristalsis should be avoided such as abdominal distension, ulcerative colitis, acute respiratory depression

Dosage:

• Adults: 30-60 mg 3-4 times daily
• Children: Not recommended

Side Effects:

• Headache
• Constipation
• Anorexia
• Abdominal pain
• Dizziness
• Hypotension
• Sedation
• Dry mouth
• Nausea and vomiting
• Respiratory depression
• Somnolence
• Decreased urination

Drug Interactions:

• Alcohol, narcotic analgesics, hypnotics, and tricyclic antidepressants may increase CNS or respiratory depression

Key Issues to Note:

• Administer codeine with water or food to decrease nausea and GI upset
• Avoid long-term use because of addictive potential
• Codeine may cause drowsiness; therefore, do not drive or operate machinery

Prokinetic Drugs

Prokinetic drugs enhance the tone and motility of the gastrointestinal tract. Examples include metoclopramide, domperidone, and cisapride. These drugs are used to treat gastroesophageal reflux disease (GERD), chemotherapy-induced nausea and vomiting, and diabetic gastroparesis. Metoclopramide, specifically, is used to suppress nausea and vomiting caused by anticancer drugs (e.g., cisplatin, dacarbazine), postoperative vomiting, radiation therapy-induced emesis, toxins, and opioids. It also treats diabetic gastroparesis and GERD.

Drugs for Obesity

Obesity is linked to numerous health problems, including diabetes mellitus, hypertension, and hyperlipidemia. Increased abdominal fat and waist circumference further elevate health risks.

Orlistat

Available preparations: 120mg capsules (brand name: Xenical®)

Mode of action: Inhibits lipases in the stomach and small intestine, preventing dietary fat absorption.

Indications: Obesity in adults with a body mass index (BMI) > 30, or > 27 with additional risk factors like hypertension or diabetes.

Contraindications: Chronic malabsorption syndrome, breastfeeding, cholestasis.

Dosage: Adults and children over 12 years: 120mg three times daily with each meal.

Side effects: Flatulence, fecal incontinence, headache, anxiety.

Drug interactions: Orlistat may reduce the absorption of fat-soluble vitamins. Supplementation with fat-soluble vitamins (including vitamin D and beta-carotene) may be necessary.

Key note: If a meal is fat-free, the dose can be omitted.