ANTIDIARRHEAL AGENTS

Diarrhea

Abnormal frequent passage of loose stool

or

Abnormal passage of stools with increased frequency, fluidity, and weight, or with increased stool water excretion.

Diarrhea is the condition of having three or more loose or liquid bowel movements per day. 

For adults on a typical Western diet, stool weight >200 g/d can generally be considered diarrheal.

Acute diarrhea Sudden onset in a previously healthy person

Lasts from 3 days to 2 weeks

Self-limiting

Resolves without sequelae

Chronic diarrhea

Lasts for more than 3 weeks

Associated with recurring passage of diarrheal stools, fever, loss of appetite, nausea, vomiting, weight loss, and chronic weakness

Diarrhea can be caused by

An increased osmotic load within the intestine (resulting in retention of water within the lumen)

Excessive secretion of electrolytes and water into the intestinal lumen.

Exudation of protein and fluid from the mucosa.

Altered intestinal motility resulting in rapid transit (and decreased fluid absorption).

Pharmacotherapy of diarrhea should be reserved for patients with significant or persistent symptoms.

Nonspecific antidiarrheal agents typically do not address the underlying pathophysiology responsible for the diarrhea; their principal utility is to provide symptomatic relief in mild cases of acute diarrhea.

ORS

Composition of ORS :

HOME WORK

Mechanism of Action

Adsorbents

Coat the walls of the GI tract

Bind to the causative bacteria or toxin, which is then eliminated through the stool.

Examples: bismuth subsalicylate (Pepto-Bismol), kaolin-pectin, attapulgite.

Clays such as kaolin (a hydrated aluminum silicate) and ot

her silicates such as attapulgite (magnesium aluminum disilicate) bind water avidly and also may bind enterotoxins.

However, this effect is not selective and may involve other drugs and nutrients; hence, these agents are best avoided within 2–3 hours of taking other medications.

A mixture of kaolin and pectin (a plant polysaccharide) is a popular over-the-counter remedy (kaolin-pectin) and may provide useful symptomatic relief of mild diarrhea.

Side Effects

Adsorbents

Constipation, dark stools

Confusion, twitching

Hearing loss, tinnitus, metallic taste, blue gums

Mechanism of Action

Anticholinergics

Decrease intestinal muscle tone and peristalsis of GI tract

Result: slowing the movement of fecal matter through the GI tract

Examples: Atropine

Side Effects

Anticholinergics

Urinary retention, hesitancy, impotence

Headache, dizziness, confusion, anxiety, drowsiness

Dry skin, rash, flushing

Blurred vision, photophobia, increased intraocular pressure

Antimotility and Antisecretory Agents

OPIOIDS

Opioids continue to be widely used in the treatment of diarrhea. 

They act principally through either µ- or δ- opioid receptors on enteric nerves, epithelial cells, and muscle.

These mechanisms include effects on intestinal motility (µ receptors), intestinal secretion (δ receptors), or absorption (µ and d receptors).

Commonly used antidiarrheals such as Diphenoxylate, and Loperamide act principally via peripheral µ-opioid receptors and are preferred over opioids that penetrate the CNS.

Loperamide

Loperamide a Piperidine butyramide derivative with µ-receptor activity, is an orally active antidiarrheal agent.

The drug is 40–50 times more potent than morphine as an antidiarrheal agent and penetrates the CNS poorly.

It increases small intestinal and mouth-to-cecum transit times.

Loperamide also increases anal sphincter tone, an effect that may be of therapeutic value in some patients who suffer from anal incontinence.

In addition, loperamide has antisecretory activity against cholera toxin and some forms of Escherichia coli toxin

Diphenoxylate and Difenoxin

Diphenoxylate and its active metabolite Difenoxin (diphenoxylic acid) are related structurally to meperidine.

As antidiarrheal agents, diphenoxylate and difenoxin are somewhat more potent than morphine.

Both compounds are extensively absorbed after oral administration, with peak levels achieved within 1–2 hours.

Both drugs can produce CNS effects when used in higher doses (40–60 mg/day) and thus have potential for abuse and/or addiction.

A/E

They are available in preparations containing small doses of atropine (considered subtherapeutic) to discourage abuse and deliberate overdosage.

With excessive use or overdose, constipation and (in inflammatory conditions of the colon) toxic megacolon may develop.

In high doses, these drugs cause CNS effects as well as anticholinergic effects from the atropine (e.g., dry mouth, blurred vision)

BULK-FORMING AGENTS

Hydrophilic and poorly fermentable colloids or polymers such as Carboxymethyl cellulose and Calcium Polycarbophil absorb water and increase stool bulk.

They usually are used for constipation but are sometimes useful in mild chronic diarrhea in patients suffering with Irritable Bowel Syndrome (IBS-A).

Antidiarrheal Agents: Interactions

Adsorbents decrease the absorption of many agents, including digoxin, clindamycin, quinidine, and hypoglycemic agents.

Nursing Implications

Obtain thorough history of bowel patterns, general state of health, and recent history of illness or dietary changes, and assess for allergies

DO NOT give bismuth subsalicylate to children younger than age 16 or teenagers with chickenpox because of the risk of Reye’s syndrome.

Anticholinergics should not be administered to patients with a history of glaucoma, urinary retention, cardiac problems, myasthenia gravis.

Constipation

Constipation

Difficult, incomplete sensation, or infrequent evacuation of dry hardened feces from the bowels

It is symptom, not a disease

Disorder of movement through the colon and/or rectum

Can be caused by a variety of diseases or drugs

Constipation can be corrected by adherence to a fiber-rich (20–30 g daily) diet, adequate fluid intake, appropriate bowel habits and training, and avoidance of constipating drugs.

Constipation related to medications can be corrected by use of alternative drugs where possible, or adjustment of dosage.

If nonpharmacological measures alone are inadequate, they may be supplemented with bulk-forming agents or osmotic laxatives.

When stimulant laxatives are used, they should be administered at the lowest effective dosage and for the shortest period of time to avoid abuse.

Habitual use of laxatives may lead to excessive loss of water and electrolytes; secondary aldosteronism may occur if volume depletion is prominent.

The terms laxatives, cathartics, purgatives, and evacuants often are used inter changeably.

There is a distinction, however, between laxation (the evacuation of formed fecal material from the rectum) and catharsis (the evacuation of unformed, usually watery fecal material from the entire colon).

Laxatives are employed before surgical, radiological, and endoscopic procedures where an empty colon is desirable.

Laxatives

1)Bulk laxatives: by increasing the volume of non-absorbable solid residues

Eg: Hydrophilic Colloids, Bran, Methylcellulose, Psyllium, Ispaghula

2)Osmotic laxative: by increasing the water content

Eg: Saline purgatives:MgSo4 (Epsom salts), Mg(OH)2 (MOM), Lactulose

3)Fecal Softners: by altering the consistency of feces Eg: DOSS (dioctyl sodium sulfosuccinate), Mineral oils,

Glycerin suppositories

4)Stimulant/Irritant Purgative/laxative: by increasing the motility and secretion Eg: Senna, Cascara, Castor oil, Bisacodyl. Phenolphthale

in

Bulk laxatives

Include hydrophilic colloids(prepared from indigestible parts of fruits, vegetables and seeds)

Forms gel in large intestinecause water retention and intestinal distension increase peristaltic activity

Are first line approach for most pts of simple constipation

Uses:

Habitual constipation in elderly pts hemorrhoids pts

Osmotic laxatives

Saline purgatives: Laxatives containing magnesium cations or phosphate anions commonly are called saline laxatives: magnesium sulfate, magnesium hydroxide, magnesium citrate,sodium phosphate

Solutes that are not absorbed in intestineretain more water osmoticallydistend the bowelincrease peristalsisleads purgation about an hour later

Abd. cramps can occur

Quick onset of action

Advised to take plenty of water administration of hypertonic sol may cause dehydration

Uses:

For preparation of bowel before surgery and colonoscopy

In food/drug poisoning

Lactulose

Semisynthetic disaccharide of fructose and galactosenot digested or absorbed in small intestineretains water

In colonbacteria convert it into two component sugarfermentationlactic acid and acetic acidfunction as osmotic laxative

After lactulose administration, gut contents have low pH than normaldecrease activity of ammonia producing organismhence used in treatment of hepatic encephalopathy

Fecal softeners

Promote more water and fat in the stools

Lubricate the fecal material and intestinal walls Emulsifying effect on fecesmake them retain more water

softer stooleasier to pass out

Abd cramps can occur

Uses: condition where straining at stool has to be avoided like hernia, piles, fissures, anal surgery

Stimulant laxative

They increase the peristalsis by stimulation of gut mucosa

Causes abd cramps, prolonged use cause atonic colon(sluggish bowel)

Used mainly for preparation of bowel for surgery, colonoscopy and abd X-rays

Bisacodyl: given orally and also as suppositorydefecation in 15-30min

Phenolphthalein: given orally

A/E:allergic rashes in skin

Laxatives: Side Effects

Bulk forming Impaction Fluid overload

Emollient (stool softener) Skin rashes Decreased absorption of vitamins

Hyperosmotic Abdominal bloating Rectal irritation

Saline

Magnesium toxicity (with renal insufficiency) Cramping Diarrhea Increased thirst

Stimulant

Nutrient malabsorption Skin rashes Gastric irritation Rectal irritation

All laxatives causes electrolyte imbalance

Laxatives: Nursing Implications

Assess fluid and electrolytes before initiating therapy

Patients should not take a laxative if they are experiencing nausea, vomiting.

A healthy, high-fiber diet and increased fluid intake should be encouraged as an alternative to laxative use

Long-term use of laxatives often results in decreased bowel tone and may lead to dependency

Abuse and danger of laxative

Repeated administration may produce:

GI disturbaces like spastic colitis, dyspepsia, anorexia and nausea

Nutritional deficiencies of calories, vitamins, minerals

Loss of fluids and electrolytes

Complete dependency on drugs

The End…..