Antidiarrheal Drugs

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

Causes of Diarrhea
Acute Diarrhea Chronic Diarreha
 Infections  Tumors
o Bacterial  Diabetes
o Viral  Addison’s Disease
o Protozoal  Hyperthyroidism
 Drug induced  Irritable Bowel Syndrome
 Nutritional

Fluid Replacement Antidiarrheal Antimicrobial

Therapy Drugs Therapy

 Administration of either  Administration of Antidiarrheal drugs for  Administration of either Antimicrobial

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
o Mild to moderate diarrhea agents if
 This is also does not cure any of the o The Diarrhea is of severe
underlying causes of diarrhea, instead presentation with known
providing symptomatic relief to the causative agents of Microbial
patients o Diarrhea persists for more than 3
days
 This will provide definitive treatment to
the diarrhea
 Antidiarrheal Drugs

Antimotility and
Absorbent Agents
Antisecretory

Drugs Drugs

Ocreotide adn Bile Acid Bismuth

Opioid Alpha 2 Agonist Kaolin and Pectin
Somatostatin Sequestrant Subsalicylate

Loperamide Diphenoxylate Clonidine Cholestyramine Cholestipol

 Antimotility and Antisecretory Agents
Opioid Agonists
Drugs Pharmacokinetics Mechanism of Action Clinical Uses Adverse Effects
Absorption  Opioid 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
Distribution  Stimulation of this receptor will  Constipation
 Does not cross the lead to
BBB unless in a very o Decrease the tone of Drug drug Reaction
high dose, therefore longitudinal smooth muscle  If admin together with
doesn’t lead to cells Contraindication o Quinidine
 Children less in 2 o Omeprazole
Loperamide Opioid  Increase transit time o Ritonavir
dependency o Increase the tone of circular years of age  These are all CYP450
 97% bound to smooth muscle cells o Risk of fatal inhibitors which may
plasma protein  Increase the time for and Paralytic Ileus elevate the plasma level
 Diarrhea associated of Loperamide to as high
Metabolism capacity of intestine to
with organism that as 3 folds
 Hepatic metabolism absorb water  These drugs enable
Excretion o Inhibition of Gastrocolic may penetrate the Loperamide to pass the
 Urine reflex gut wall BBB and lead to sedative
 Bile  All and all, it reduces GIT o E. coli effects of Opioid agonists
Absorption motility and increase transit o Salmonella Inclusion of Atropine
 Good upon oral time  Symptomatic  Atropine is an
admin Pseudomembranous Anticholinergic agent
Colitis  It synergizes the activity of
Distribution Diphenoxylate in reducing
 Active metabolite o Risk of toxin GIT motility and increasing
Difenoxin may pass retention transit time
Diphenoxylate
the BBB o Precipitate Toxic  Since Difenoxin is 3 to 4
Metabolism Megacolon times more potent than
 Hepatic failure Diphenoxylate, it increases
 Hepatic the potency of getting
Excretion o Precipitate Dependency
 Urine Hepatic  Atropine will reduce the
 Bile Encephalopathy dose required for
Diphenoxylate
 Antimotility and Antisecretory Agents
Drugs Pharmacokinetics Mechanism of Action Clinical Uses Adverse Effects
Alpha 2 Agonists Absorption  Binds to presynaptic Alpha 2  Diarrhea in Diabetic  Rebound
 Clonidine  Good upon oral Adrenergic receptor patient hypertension
admin  It leads to reduction in the release  Diarrhea due to  Depression
Distribution of Neurotransmitters by inhibition of withdrawal of
 Plasma protein Adenylate Cyclase Opioid
bound  Exerts its antidiarrheal effects
Metabolism through
 Hepatic o Reducing GIT motility by
Excretion  Increasing transit time
 Urine  Increase GIT capacity
o Absorption of electrolytes and
fluid
o Reducing secretion of fluid
Octreotide and Absorption  Resembles the activity of Somatostatin  Secretory diarrhea  Hypothyroidism
Somatostatin  Complete o Inhibits the release of various due to  Hypo/
absorption after hormones o Hormone hyperglycaemia
 Octreotide is S/C admin  GIT hormones secreting tumor of  Reduce Insulin
 Gastrin
a synthetic Distribution Pancreas or release
 CCK-PZ
analogue for  Distributed Intestine  QT prolongation
 Secretin
Somatostatin across body  Pancreatic Polypeptide  Chemotherapy  Gallstones formation
 Octerotide compartment  Vasoactive Intestinal  HIV  Bradycardia
has 400-500 Metabolism Peptide  Diabetes Mellitus
more  Unknown  Other Hormones
potency Excretion  Insulin
compared to  Urine  Glucagon
Somatostatin  TSH
 Growth Hormone
o Reduces fluid and electrolyte
secretion from the Intestine
o Reduces GIT motility
o Vasoconstriction in the blood vessels

Drugs
Bulk-Forming and Hydroscopic
Agents
 Kaolin
o Naturally occurring hydrated
Magnesium Aluminum Silicate
 Pectin
o Indigestible carbohydrate
derived from apples.
Bile Acids Sequestrants
 Cholestyramine
 Cholestipol
Bismuth Subsalicylate
Absorbent Agents
Mechanism of Action Clinical Uses Adverse Effects
 May work as gels to modify stool  Symptomatic  Interfere with many oral
texture and viscosity relieve of drugs absorption in the GIT
 Produce a perception of o Acute diarrhea
decreased stool fluidity o Chronic diarrhea
 May bind bacterial toxins
especially Enterotoxin
 May bind to bile salts
 Bile salt binding in the intestine  Bile salt-induced  Hypertriglyceridaemia
 Leading to increase in bulk of diarrhea  Constipation
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
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