Post on 12-Nov-2014
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ANTIDIARRHOEAL DRUGS
Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.
1
Diarrhea: Too rapid evacuation of too fluid stools
Most patients with sudden onset of diarrhea have a benign self-limited illness requiring no treatment or evaluation.
Oral rehydration solution is the cornerstone for patients with acute illnesses resulting in significant diarrhea
Acute diarrheaRehydration. WHO ORS:
1.Sodium chloride: 3.5g
2.Sodium bicarbonate: 2.5g
Or
Trisodium citrate: 2.9g
3.Potassium chloride 1.5g
4.Glucose: 20g
5.Potable water: 1 liter
Rice based physiological solutions.
Rationale of ORS
Home solution:
½ tsp salt (3.5g)
1 tsp baking soda (2.5g NaHCO3)
8 tsp sugar (40g)
8 oz orange juice (1.5g KCl)
1 L water
Antidiarrheal drugs: treat only symptoms!
– Diarrhea is usually caused by infection (Salmonella, shigella, campylobacter,clostridium, E. coli), toxins, anxiety, drugs…
– In healthy adults mostly discomfort and inconvenience
– In children (particularly mal-nourished) a principal cause of death is due to excessive loss of water and minerals.
Antimotility agents:
– Muscarinic receptor antagonists (not useful due to side effects) and opiates:• Diphenoxylate •Difenoxin•Loperamide
– All have CNS effects – to be use carefully in treatment of diarrhea!
Antimotility agents & anti-secretory agents:
Opiods continue to be used widely
Mechanism of action: 1. Intestinal motility-- receptors2. Intestinal secretion-- receptors3. Intestinal absorption--- & receptors
All the commonly used opioids act principally via peripheral receptors and are preferred over opioids that penetrate central nervous system
Loperamide:
•40-50 times more potent than morphine as an anti- diarrheal agent
•Increases small intestinal and mouth to cecum transit time.
•Increases anal sphincter tone
•Anti-secretory activity against cholera toxin and some forms of E.coli toxin
Loperamide:
Half- life 11 hours
Dose: 4mg initially followed by 2mg after each subsequent stool, up to 16mg/day.
If clinical improvement does does not occur in acute diarrhea within 48 hours, DISCONTINUE loperamide
Not recommended in children <2 years.
Loperamide:
•Effective in travellers diarrhea
•Used alone or in combination with antimicrobial agents (trimethorim with or without sulfamethoxazole)
•Adjunctive treatment in almost all forms of chronic diarrheal diseases.
•Lacks significant abuse potential
•Overdose: CNS depression, paralytic ileus, toxic megacolon.
Difenoxin-
Active metabolite of diphenoxylateBoth combined with 25 mcg of atropine to prevent abuse.Excess dose: CNS effects, anticholinergic effects,
constipation, toxic megacolon
Other opioids:
1. Paregoric: 2mg morphine/5mL.2. Deodorized tincture of opium.
DO not use loperamide in:
1. Patients with bloody diarrhea
2. High fever
3. Systemic toxicity
4. Worsening diarrhea despite treatment
Racecadotril:
•A dipeptide•Reinforces effects of endogenous enkephalins on the opioid receptor•Leads to anti-diarrheal effect
Bismuth subsalicylate:
Trivalent bismuth suspended in a mixture of magnesium aluminium silicate clay.
In stomach: Combines with HCl Bismuth oxychloride + Salicylic acid
Bismuth subsalicylate
2 tab or 30mL up to 8 times daily
•Anti-inflammatory
•Anti-bacterial
•Anti- secretoty
•Also decreases vomiting
Diphenoxylate and atropine contraindicated in acute diarrhea because of rare precipitation of toxic megacolon.
GIVE APPROPRIATE ANTIBIOTICS, IF CAUSATIVE ORGANISM IS KNOWN
Rifaximin: Non absorbed oral antibiotic . 200mgtid x 3
days
Ciprofloxacin 500mg
Ofloxacin 400mg X 5 to 7 days
Norfloxacin 400mg bd
Levofloxacin 500mg od
Cortrimoxazole DS bd
Doxycycline 100mg bd
Liquid paraffin - No longer recommended - more ADR
Malabsorption of fat soluble vitamins
It foreign body reactions in small bowel (paraffinoma
fecal leak at anal canal & pruritus ani
Treatment of Chronic diarrhea
A number of antidiarrheal agents may be used in certain patients with chronic diarrheal conditions.
Opioids are safe in most patients with chronic, stable symptoms.
Loperamide: 4mg initially ,then 2 mg after each loose stool ( maximum: 16 mg/d).
Diphenoxylate with atropine: One tablet three or four times daily as needed.
Treatment of Chronic diarrhea
Codeine and tincture of opium: Chronic, intractable diarrhea. Codeine 15-60 mg every 4 hours
Tincture of opium: 10-25 drops every 6 hours
Clonidine:Inhibits intestinal electrolyte secretion
Used in:•Secretory diarrhea•Diabetic diarrhea•Cryptosporiodiosis
Dose: 0.1-0.6mg twice daily oral
Patch: 0.1-0.2mg/day
Octreotide: Somatostatin analog
•Stimulates intestinal fluid and electrolyte absorption•Inhibits intestinal fluid secretion•Inhibits release of gastrointestinal peptides.
Given for: secretory diarrheas due to tumors--- VIPomas, Carcinoid, AIDS related diarrhea
Dose: 50-250mcg subcutaneously three times daily.
Octreotide analogs
Lanreotide
Vapreotide.
Octreotide very useful for treating bleeding esophageal
varices.
Cholestyramine:
Bile salt binding resin
Used in: •Bile salt induced diarrhea•Intestinal resection•Ileal disease
Dose: 4g once to three times daily
Bulk forming and hydroscopic agents:
Carboxymethylcellulose & Calcium polycarbophil– absorb
water and stool bulk.
Useful in mild chronic diarrhea in patients with irritable
bowel syndrome
Mechanism of action: Works as a gel to modify stool
texture & viscosity to produce perception of decreased
stool fluidity.
Others:
Clays such as kaolin and other silicates like attapulgite
( magnesium aluminium disilicate) bind water avidly.
Kaolin and pectin: useful in mild diarrhea.
Calcium channel blockers like verapamil and nifedipine:
decrease gut motility, promote intestinal water absorption.