anti diarrhea
TRANSCRIPT
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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
Non Specific Antidiarrheal Drugs
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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.
Non Specific Antidiarrheal Drugs
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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.
Non Specific Antidiarrheal Drugs
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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).
Non Specific Antidiarrheal Drugs
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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.
Non Specific Antidiarrheal 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.
Specific Antidiarrheal Drugs
...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.
Specific Antidiarrheal Drugs
...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.
Specific Antidiarrheal Drugs
...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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