Diarrhea Presentation

8/6/2019 Diarrhea Presentation

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Diarrhea

According to WHO, Diarrhoea is the passage of 3 or more loose or liquid stools per day, or more

frequently than is normal for the individual.

Classification of diarrhea:

Osmotic, secretory and exudative

y Osmotic: osmotically active particle (eating sorbitol, mannitol, MgSO4, Mg(OH)2, anymalabsorption, osmotic laxatives-)

y Secretory: excessive secretion of GIT glands (Bacterial toxins, broad range of Drugs, VIPoma,Carcinoid, heavy metals, stimulant laxatives {aloe, senna, cascara}, bile salt diarrhea)

y Exudative: pus/blood in faeces (IBD, dysentery)Classification of antidiarrheal:

1. Electrolyte solutionsORS, Normal saline, Ringer lactate

2. Opioid Agonists (antimotility)Loperamide, Diphenoxylate

3. Colloidal bismuth compound (antisecretory)Bismuth subsalicylate

4. Locally acting agents (Adsorbents/bulking agents)Kaolin combined with pectin (Kaopectate)

5. Bile Salt binding resinsCholestyramine, Colestipol, Colesalvam

6. Somatostatin analogueOcreotide

7. Antispasmodic (anticholinergic antisecretory, antimotility)Dicyclomine Hyocyamine

General Contraindications:

Bloody diarrhea, High fever, systemic toxicity

1. Opioid Agonists:Mechanism of action:

Agonist action on meu (decreased peristalsis) and delta receptors (decrease secretion) in meissners and

myenteric plexus of GIT, causes inhibition of presynaptic release of acetylcholine

Indications: Control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea

associated with inflammatory bowel disease or gastroenteritis

Drugs:

Loperamide > Diphenoxylate (safety profile)


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Loperamide Diphenoxylate

Not cross the blood-brain barrier Crosses blood brain barrier at higher doses

no analgesic properties No analgesic properties in standard doses

(possible at higher doses)

no potential for addiction Prolonged use can lead to opioid dependence.

Tolerance to long-term use has not been reported. Higher doses have central nervous system effects

so Commercial preparations commonly contain

atropine to discourage overdosage (2.5 mg

diphenoxylate with 0.025 mg atropine)

Not well absorbed orally (40%) Well absorbed orally

Loperamide inactivated by liver p450 enzymes

mainly cyp34a

Diphenoxylate (with atropine) is activated to

difenoxin, its active major metabolite

Both drugs are distributed in serum, metabolized in the liver, and excreted primarily in stool.

Adverse effects:

Typical opioid side effects:

Respiratory depression, Euphoria, Sedation, increase ICP, stimulate CTZ, constipation, biliary colic,

urinary retention, bradycardia, hypotension, pruritis, tolerance, dependance

2. Bismuth Subsalicylates:Mechanism ofAction:

Not exactly established,

In ulcers and erosions they make protective layer agains acid and pepsin

a. Removes the stimulus of irritation of infections like,b. Has direct antimicrobial effects (e.g. against H. pylori)c. Binds enterotoxins (useful in preventing or treating traveler's diarrhea)d. Coats the food to retard their motility in GIT, and decrease their expulsion

Indications:

Treatment of dyspepsia & acute diarrhea

Prevention of traveler's diarrhea

Pharmacokinetics:

Bismuth 99% excreted, less than 1 % absorbed (rarely bismuth toxicity)

Salicylates rapid absorption, renal excretion

Adverse effects:

Excellent safety profile, harmful blackening of stools and tongue

Very high doses lead to salicylate toxicity (Mild (nausea, vomiting, tinnitus),Moderate (hyperventilation

and confusion) ,Serious (hallucinations, seizures, coma, cerebral oedema or pulmonary oedema)

3. Kaolin & PectinKaolin: naturally occurring hydrated magnesium aluminum silicate

Pectin: is an indigestible carbohydrate derived from apples.

A common nonprescription preparation is Kaopectate. The usual dosage is 1.21.5 g after each loose

bowel movement (maximum: 9 g/d).


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Mechanism of action:

Both appear to act as absorbents of bacterial toxins and fluid, thereby decreasing stool liquidity and

number

Indication: Acute Diarrhea

Contraindication: Chronic diarrhea

Adverse effects:

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).

4. OctreotideIt is a somatostatin agonist, Somatostatin is a 14-amino-acid peptide that is released in the

gastrointestinal tract and pancreas from paracrine cells, D cells, and enteric nerves as well as from the

hypothalamus

Mechanism of action:

It inhibits the secretion of numerous hormones and transmitters, including gastrin, cholecystokinin,

glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, vasoactive intestinal peptide, and

5-HT.

It reduces intestinal fluid secretion and pancreatic secretion.It slows gastrointestinal motility and inhibits gallbladder contraction.

Indications:

50 mcg Low dose facilitates motility (scleroderma, intestinal bacterial overgrowth)

100 200 mcg High dose decreases motility VIPoma, Carcinoid, vagotomy (dumping syndrome), short

gut syndrome

Other indications: pancreatic/pituitary tumour

Pharmacokinetics:

Orally ineffective, Intravenously, it has a serum half-life of 1.5 hours, subcutaneous and IM also available

Adverse Effects

Impaired pancreatic secretion may cause steatorrhea, which can lead to fat-soluble vitamin deficiency.

Alterations in gastrointestinal motility cause nausea, abdominal pain, flatulence, and diarrhea. Becauseof inhibition of gallbladder contractility and alterations in fat absorption, long-term use of octreotide can

cause formation of sludge or gallstones in over 50% of patients, which rarely results in the development

of acute cholecystitis. Because octreotide alters the balance among 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.

5. Bile acids sequestrant:Mechanism of action:

Colesevalem, Colistapol, Cholestyramine, anion exchange resins, bind to bile salts, facilitating their

removal, decreasing their interaction with colonic mucosa which stimulates water and electrolyte

secretion, leading to diarrhea

Indications:

Hyperlipidemia, Pruritis by obstructive jaundice, bile salt diarrhea

These products come in a variety of powder and pill formulations that may be taken one to three times

daily before meals.

Pharmacokinetics:

Oral, neither absorbed nor metabolized, totally excreted in faeces

Adverse effects:


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Bloating, flatulence, constipation, and fecal impaction. High doses, decreased fat soluble vitamin

deficiency,

Contraindication: In patients with diminished circulating bile acid pools, Cholestyramine and colestipol

bind a number of drugs further removal of bile acids may lead to an exacerbation of fat malabsorption

they should not be given within 2 hours of other drugs. Colesevelam does not appear to have significant

effects on absorption of other drugs.

6. Anticholinergics: (antisecretory, antimotility)Mechanism ofAction:

M3 blockers, reduces smooth muscle and secretory activity of gut

Indications

IBD, Minor Diarrhea

Pharmacokinetics:

Oral and parenteral, Short t1/2 Dicyclomine, Long t1/2 Hyoscyamine, positive interaction with other

anticholinergics

Adverse effects:

Tachycardia, Confusion, Urinary retension, increased IOP, constipation

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Diarrhea Presentation