Management & Pharmacotherapy of Diarrhea

Nicolaski Lumbuun, dr., SpFK Faculty of Medicine UPH

Learning Objectives
Define and indentify the common causes of acute/chronic diarrhea Establish primary goals for the treatment of acute diarrhea Recommended appropriate nondrug therapy for patients experiencing acute diarrhea Explain the place of drug therapy in the treatment of acute/chronic diarrhea

Principle Management of Diarrhea

An appreciation and knowledge of the underlying causative processes facilitates effective treatment Diarrhea can be caused by : Increased osmotic load within the intestine 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
In most instances, multiple processes are affected simultaneously, leading to a net increase in stool volume and weight accompanied by increases in fractional water content.

Primary Goal for the treatment of acute diarrhea

Many patients with acute diarrhea have a benign, selflimited illness requiring no treatment or evaluation In severe cases, dehydration and electrolyte imbalances are the principal risk, particularly in infants, children, and frail elderly patients. Oral rehydration therapy therefore is a cornerstone A balanced mixture of glucose and electrolytes in volumes matched to losses, can prevent dehydration Pharmacotherapy should be reserved for patients with significant or persistent symptoms

Antidiarrheal Agents
Principle of use : 1. May be used safely in patient w/ mild to moderate acute diarrhea 2. Should not be used in bloody diarrhea, high fever, systemic toxicity 3. Should be discontinued when diarrhea is worsening despite therapy 4. Also used to control chronic diarrhea cause by IBS (irritable bowel synd) or inflamatory bowel desease (IBD)

Antidiarrheal Agents
Nonspecific antidiarrheal agents typically do not address the underlying pathophysiology responsible The principal utility is to provide symptomatic relief in mild cases of acute diarrhea Many of these agents act by decreasing intestinal motility and should be avoided as much as possible in acute diarrheal illnesses caused by invasive organisms These agents may :
mask the clinical picture delay clearance of organisms increase the risk of systemic invasion by the infectious organisms also may induce local complications such as toxic megacolon.

Non Specific Antidiarrheal Drugs

Opioid Agonists increased colonic transit time & fecal water absorption decrease mass colonic movements and the gastrocolic reflex Loperamide = opioid agonist, does not cross the bloodbrain barrier, no analgesic properties or potential addiction. Tolerance to long-term use has not been reported. Administered in doses of 2 mg taken one to four times daily Diphenoxylate = opioid agonist, no analgesic properties in standard doses; however, higher doses have CNS effects and prolonged use can lead to opioid dependence. Commercial preparations commonly contain small amounts of atropine.The anticholinergic properties of atropine may contribute to the antidiarrheal action.

Non Specific Antidiarrheal Drugs

Coloidal Bismuth Compound Bismuth subsalicylate a crystal complex consisting of trivalent bismuth and salicylate suspended in a mixture of magnesium aluminum silicate Have antisecretory, antiinflammatory, and antimicrobial effects Also relieve nausea and abdominal cramps Used extensively for prevent & treatment traveler's diarrhea Also is effective in other forms of episodic diarrhea and in acute gastroenteritis Currently, as a common antibacterial use for the treatment of Helicobacter pylori

Non Specific Antidiarrheal Drugs

Coloidal Bismuth Compound A recommended dose of the bismuth subsalicylate (30 ml of regular strength PEPTO-BISMOL liquid or 2 tablets) contains approximately equal amounts of bismuth and salicylate (262 mg each). For control of indigestion, nausea, or diarrhea, the dose is repeated every 30 to 60 minutes, as needed, up to eight times a day. Adverse event Dark stools (sometimes mistaken for melena) and black staining of the tongue in association with bismuth compounds are caused by bismuth sulfide formed in a reaction between the drug and bacterial sulfides in the gastrointestinal tract.

Non Specific Antidiarrheal Drugs

2 Adrenergic Receptor Agonists Clonidine interact w/ specific receptors on enteric neurons & enterocytes stimulating absorption and inhibiting secretion of fluid and electrolytes and increasing intestinal transit time Have a special role in diabetics with chronic diarrhea, in whom autonomic neuropathy can lead to loss of noradrenergic innervation Oral clonidine (beginning at 0.1 mg twice a day) Clonidine also may be useful in patients with diarrhea caused by opiate withdrawal Side effects : hypotension, depression, and perceived fatigue may be dose limiting in susceptible patients.

Non Specific Antidiarrheal Drugs

Kaolin & Pectin Kaolin is a naturally occurring hydrated magnesium aluminum silicate (attapulgite) Pectin is an indigestible carbohydrate derived from apples Both appear to act as absorbents of bacteria, toxins, and fluid, thereby decreasing stool liquidity and number May be useful in acute diarrhea but are seldom used on a chronic basis A common commercial preparation is Kaopectate. The usual dose is 1.21.5 g after each loose bowel movement (maximum: 9 g/d). Kaolin-pectin formulations are not absorbed and have no significant adverse effects except constipation. They should not be taken within 2 hours of other medications (which they may bind).

Non Specific Antidiarrheal Drugs

Bile SaltBinding Resins Conjugated bile salts normally absorbed in terminal ileum. Disease of the terminal ileum (eg, Crohn's disease) or surgical resection leads to malabsorption of bile salts may cause colonic secretory diarrhea Cholestyramine or colestipol may decrease diarrhea caused by excess fecal bile acids The usual dose is 45 g (1-3X daily) before meals Adverse effects include bloating, flatulence, constipation, and fecal impaction In patients with diminished circulating bile acid pools, further removal of bile acids may lead to an exacerbation of fat malabsorption. These agents bind a number of drugs and reduce their absorption they should not be given within 2 hours of other drugs.

Specific Antidiarrheal Drugs

...Octreotide..

Somatostatin is a 14 amino acid peptide, released in the GI tract and pancreas from paracrine cells, D-cells, and enteric nerves as well as from the hypothalamus. It is a key regulatory peptide that has many physiologic effects: 1. It inhibits the secretion of numerous hormones and transmitters,
including gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, vasoactive intestinal peptide & 5-HT. 2. It reduces intestinal fluid secretion and pancreatic secretion.

3. It slows gastrointestinal motility and inhibits gallbladder contraction.

4. It induces direct contraction of vascular smooth muscle, leading to a reduction of portal and splanchnic blood flow. 5. It inhibits secretion of some anterior pituitary hormones.

Specific Antidiarrheal Drugs

...Octreotide..

Octreotide is a synthetic octapeptide with actions similar to somatostatin. administered intravenously, T 1.5 hours. Also may be administered by subcutaneous injection, resulting in a 6to 12-hour duration of action. A longer-acting formulation is available for once-monthly depot intramuscular injection Clinical Uses Inhibition of Endocrine Tumor Effects Two gastrointestinal neuroendocrine tumors (carcinoid, VIPoma) cause secretory diarrhea and systemic symptoms such as flushing and wheezing. For patients with advanced symptomatic tumors that cannot be completely removed by surgery, octreotide decreases secretory diarrhea and systemic symptoms through inhibition of hormonal secretion and may slow tumor progression.

Specific Antidiarrheal Drugs

...Octreotide..

Other Causes of Diarrhea Octreotide inhibits intestinal secretion and has doserelated affects on bowel motility. In low doses (50 mcg subcutaneously) it stimulates motility, whereas at higher doses (eg, 100250 mcg subcutaneously), it inhibits motility. Octreotide is effective in higher doses for the treatment of diarrhea due to vagotomy or dumping syndrome as well as for diarrhea caused by short bowel syndrome or AIDS. Octreotide has been used in low doses (50 mcg subcutaneously) to stimulate small bowel motility in patients with small bowel bacterial overgrowth or intestinal pseudo-obstruction secondary to scleroderma.

Specific Antidiarrheal Drugs

...Octreotide..

Adverse Effects Steatorrhea can lead to fat-soluble vitamin deficiency. Nausea, abdominal pain, flatulence, and diarrhea. Due to inhibition of gallbladder contractility & alterations in fat absorption, long-term use can cause formation of sludge or gallstones in over half of patients rarely results in the development of acute cholecystitis. Alters the balance between insulin, glucagon, and growth hormone, hyperglycemia or, less frequently, hypoglycemia (usually mild) can occur. Prolonged treatment with octreotide may result in hypothyroidism. Octreotide also can cause bradycardia.

CCK =Cholecystokinina, peptide hormone of the GI syst responsible for stimulating the digestion of fat and protein. Causes the release of digestive enzymes and bile from the pancreas and gallbladder