Antidiarrheal Drugs. Causes of Diarrhea. Antidiarrheal Drugs
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1 Antidiarrheal Diarrhea Diarrhea is not a disease, but a symptom of some other problem characterized by either more frequent bowel movement and/or the consistency of the stool is softer and sometimes watery Infections o Bacterial o Viral o Protozoal Drug induced Nutritional Acute Diarrhea Causes of Diarrhea Chronic Diarreha Tumors Diabetes Addison s Disease Hyperthyroidism Irritable Bowel Syndrome Fluid Replacement Therapy Antidiarrheal Antimicrobial Therapy Administration of either o Oral Rehydration Salt o Cereal Rehydration Slat Is given depending on the severity of dehydration, usually 4 hours of admin This treatment is not curing the underlying causes of the diarrhea but rather prevent any worsening condition secondary to excessive loss of fluid and electrolytes Administration of Antidiarrheal drugs for o Mild to moderate diarrhea This is also does not cure any of the underlying causes of diarrhea, instead providing symptomatic relief to the patients Administration of either Antimicrobial agents if o The Diarrhea is of severe presentation with known causative agents of Microbial o Diarrhea persists for more than 3 days This will provide definitive treatment to the diarrhea
2 Antidiarrheal Antimotility and Antisecretory Absorbent Agents Alpha 2 Agonist Ocreotide adn Kaolin and Pectin Bile Acid Sequestrant Bismuth Subsalicylate Loperamide Clonidine Cholestyramine Cholestipol
3 Loperamide Antimotility and Antisecretory Agents Agonists Pharmacokinetics Mechanism of Action Clinical Uses Adverse Effects receptor agonist Travellers diarrhea Abdominal pain Poorly absorbed o Bind to µ receptor on the Chronic diarrhea Bloating Nausea orally Myenteric Plexus of GIT Vomiting Constipation Does not cross the BBB unless in a very Drug drug Reaction high dose, therefore doesn t lead to Contraindication o Quinidine o Omeprazole Children less in 2 o Ritonavir dependency years of age o Risk of fatal 97% bound to plasma protein Hepatic metabolism Urine Bile Good upon oral admin Active metabolite Difenoxin may pass the BBB Hepatic Urine Bile Stimulation of this receptor will lead to o Decrease the tone of longitudinal smooth muscle cells Increase transit time o Increase the tone of circular smooth muscle cells Increase the time for and capacity of intestine to absorb water o Inhibition of Gastrocolic reflex All and all, it reduces GIT motility and increase transit time Paralytic Ileus Diarrhea associated with organism that may penetrate the gut wall o E. coli o Salmonella Symptomatic Pseudomembranous Colitis o Risk of toxin retention o Precipitate Toxic Megacolon Hepatic failure o Precipitate Hepatic Encephalopathy If admin together with These are all CYP450 inhibitors which may elevate the plasma level of Loperamide to as high as 3 folds These drugs enable Loperamide to pass the BBB and lead to sedative effects of agonists Inclusion of Atropine Atropine is an Anticholinergic agent It synergizes the activity of in reducing GIT motility and increasing transit time Since Difenoxin is 3 to 4 times more potent than, it increases the potency of getting Dependency Atropine will reduce the dose required for
4 Alpha 2 Agonists Clonidine Antimotility and Antisecretory Agents Pharmacokinetics Mechanism of Action Clinical Uses Adverse Effects Binds to presynaptic Alpha 2 Diarrhea in Diabetic Rebound Good upon oral Adrenergic receptor patient hypertension admin It leads to reduction in the release Diarrhea due to Depression of Neurotransmitters by inhibition of withdrawal of Plasma protein Adenylate Cyclase bound Exerts its antidiarrheal effects through Hepatic o Reducing GIT motility by Increasing transit time Urine Increase GIT capacity Octreotide and Octreotide is a synthetic analogue for Octerotide has more potency compared to Complete absorption after S/C admin Distributed across body compartment Unknown Urine o of electrolytes and fluid o Reducing secretion of fluid Resembles the activity of o Inhibits the release of various hormones GIT hormones Gastrin CCK-PZ Secretin Pancreatic Polypeptide Vasoactive Intestinal Peptide Other Hormones Insulin Glucagon TSH Growth Hormone o Reduces fluid and electrolyte secretion from the Intestine o Reduces GIT motility o Vasoconstriction in the blood vessels Secretory diarrhea due to o Hormone secreting tumor of Pancreas or Intestine Chemotherapy HIV Diabetes Mellitus Hypothyroidism Hypo/ hyperglycaemia Reduce Insulin release QT prolongation Gallstones formation Bradycardia
5 Absorbent Agents Mechanism of Action Clinical Uses Adverse Effects Bulk-Forming and Hydroscopic Agents May work as gels to modify stool texture and viscosity Symptomatic relieve of Interfere with many oral drugs absorption in the GIT Kaolin Produce a perception of o Acute diarrhea o Naturally occurring hydrated decreased stool fluidity o Chronic diarrhea Magnesium Aluminum Silicate May bind bacterial toxins Pectin especially Enterotoxin o Indigestible carbohydrate May bind to bile salts derived from apples. Bile Acids Sequestrants Bile salt binding in the intestine Bile salt-induced Hypertriglyceridaemia Cholestyramine Leading to increase in bulk of diarrhea Constipation Cholestipol the stool o In patients with Bloating Make the stools less watery resection of the Flatulence distal ileum Heartburn Diarrhea Steatorrhea Malabsorption of Vitamin K o Hypoprothrombinaemia Gallstones formation Retarding the expulsion of fluids into Prophylaxis for Dark stools (sometimes the digestive system by irritated Traveller s diarrhea mistaken for melena) tissues, by "coating" them. Treatment of H. Black staining of the tongue Stimulation of absorption of fluids pylori infection and electrolytes by the intestinal wall (antisecretory action) Reducing inflammation/irritation of Bismuth Subsalicylate stomach and intestinal lining through inhibition of prostaglandin G/H Synthase 1/2 Reduction in hypermotility of the stomach Binding of toxins produced by E. coli Bactericidal action
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