anti diarrhea

7/28/2019 Anti Diarrhea

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Management & Pharmacotherapy

of Diarrhea

Nicolaski Lumbuun, dr., SpFK

Faculty of Medicine

UPH


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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


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Principle Management of Diarrhea

An appreciation and knowledge of the underlyingcausative processes facilitates effective treatment

Diarrhea can be caused by :

Increased osmotic load within the intestine

excessive secretion of electrolytes and water into theintestinal 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 byincreases in fractional water content.


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Primary Goal for the treatment of

acute diarrhea

Many patients with acute diarrhea have a benign, self-

limited 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 therapytherefore 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


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Antidiarrheal Agents

Principle of use :

1. May be used safely in patient w/ mild tomoderate acute diarrhea

2. Should not be used in bloody diarrhea,high fever, systemic toxicity

3. Should be discontinued when diarrhea isworsening despite therapy

4. Also used to control chronic diarrheacause by IBS (irritable bowel synd) orinflamatory bowel desease (IBD)


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Nonspecific antidiarrheal agents typically do not addressthe underlying pathophysiology responsible

The principal utility is to provide symptomatic reliefin mildcases of acute diarrhea

Many of these agents act by decreasing intestinal motilityand should be avoided as much as possible in acutediarrheal 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.

Antidiarrheal Agents


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Opioid Agonists

increased colonic transit time & fecal water absorption

decrease mass colonic movements and the gastrocolicreflex

Loperamide = opioid agonist, does not cross the blood-brain 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 instandard doses; however, higher doses have CNS effectsand prolonged use can lead to opioid dependence.Commercial preparations commonly contain small amountsof atropine.The anticholinergic properties of atropine may

contribute to the antidiarrheal action.

Non Specific Antidiarrheal Drugs


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Coloidal Bismuth Compound

Bismuth subsalicylate a crystal complex consisting oftrivalent bismuth and salicylate suspended in a mixture ofmagnesium aluminum silicate

Have antisecretory, antiinflammatory, and antimicrobialeffects

Also relieve nausea and abdominal cramps

Used extensively for prevent & treatment traveler's diarrhea

Also is effective in other forms of episodic diarrhea and inacute gastroenteritis

Currently, as a common antibacterial use for the treatmentofHelicobacter pylori



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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 andsalicylate (262 mg each). For control of indigestion, nausea,

or diarrhea, the dose is repeated every 30 to 60 minutes, asneeded, up to eight times a day.

Adverse event

Dark stools (sometimes mistaken for melena) and blackstaining of the tongue in association with bismuthcompounds are caused by bismuth sulfide formed in areaction between the drug and bacterial sulfides in thegastrointestinal tract.



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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.



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Kaolin & Pectin Kaolin is a naturally occurring hydrated magnesium

aluminum silicate (attapulgite)

Pectin is an indigestible carbohydrate derived fromapples

Both appear to act as absorbents of bacteria, toxins, andfluid, thereby decreasing stool liquidity and number

May be useful in acute diarrhea but are seldom used on achronic basis

A common commercial preparation is Kaopectate. Theusual dose is 1.21.5 g after each loose bowel movement(maximum: 9 g/d). Kaolin-pectin formulations are notabsorbed and have no significant adverse effects exceptconstipation. They should not be taken within 2 hours ofother medications (which they may bind).



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Bile SaltBinding Resins Conjugated bile salts normally absorbed in terminal ileum.

Disease of the terminal ileum (eg, Crohn's disease) orsurgical resection leads to malabsorption of bile salts may cause colonic secretory diarrhea

Cholestyramine orcolestipol may decrease diarrheacaused 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 offat malabsorption. These agents bind a number of drugs

and reduce their absorption

they should not be givenwithin 2 hours of other drugs.



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Somatostatin is a 14 amino acid peptide, released in the GItract 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 ituitar hormones.

Specific Antidiarrheal Drugs

...Octreotide..


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Octreotide is a synthetic octapeptide with actions similar tosomatostatin.

administered intravenously, T 1.5 hours.

Also may be administered by subcutaneous injection, resulting in a 6-to 12-hour duration of action. A longer-acting formulation is availablefor 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 flushingand wheezing. For patients with advanced symptomatic tumors thatcannot be completely removed by surgery, octreotide decreasessecretory diarrhea and systemic symptoms through inhibition ofhormonal secretion and may slow tumor progression.


...Octreotide..


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Other Causes of Diarrhea

Octreotide inhibits intestinal secretion and has dose-related affects on bowel motility. In low doses (50 mcg

subcutaneously) it stimulates motility, whereas at higherdoses (eg, 100250 mcg subcutaneously), it inhibitsmotility.

Octreotide is effective in higher doses for the treatmentof diarrhea due to vagotomy or dumping syndrome aswell 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 inpatients with small bowel bacterial overgrowth orintestinal pseudo-obstruction secondary to scleroderma.


...Octreotide..


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Adverse Effects

Steatorrhea can lead to fat-soluble vitamin deficiency.

Nausea, abdominal pain, flatulence, and diarrhea.

Due to inhibition of gallbladder contractility & alterationsin fat absorption, long-term use can cause formation ofsludge or gallstones in over half of patients rarelyresults 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 inhypothyroidism. Octreotide also can cause bradycardia.


...Octreotide..


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CCK =Cholecystokinina, peptide hormone of the GI syst responsible for stimulating

the digestion offat and protein. Causes the release of digestive enzymes and bilefrom the pancreas and gallbladder
http://en.wikipedia.org/wiki/Peptide_hormonehttp://en.wikipedia.org/wiki/Digestionhttp://en.wikipedia.org/wiki/Fathttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Bilehttp://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Gallbladderhttp://en.wikipedia.org/wiki/Gallbladderhttp://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Bilehttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Fathttp://en.wikipedia.org/wiki/Digestionhttp://en.wikipedia.org/wiki/Peptide_hormone


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