Utcom Beavis Gi Drugs: Laxatives

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Mg2+ salts: MgSO4 - Epsom Salt; and Mg(OH)2 - Milk of Magnesia
SORBITOL

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OSMOTIC LAXATIVES
MECHANISM
They are non-absorbed molecules, which retain water in the GI tract by virtue
of the osmotic pressure they generate. If they are administered in hypertonic
solutions, they will draw water from the blood and increase the water content of the
GI tract. They act in both the small intestine and the colon. Note: Unlike urine in the
kidney tubules, the contents of the GI tract tend to remain isotonic with blood.
 Hypertonic solutions  dehydration
 Mg2+ toxicity if renal function impaired
 Cramps and flatulence with lactulose
 Na+ should be avoided in patients with congestive heart failure
IMPORTANT: Osmotic laxatives are used in conjunction with charcoal to minimize
absorption and accelerate elimination in cases of drug overdose. Important
properties are rapid action, act in both small intestine and colon and most
important they are not adsorbed by charcoal.

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Lactulose

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OSMOTIC LAXATIVE
Lactulose (Chronolac®, Cephulac®) - can lower blood NH3 in patients with
chronic liver disease

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PHENOLPHTHALEIN

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STIMULANT LAXATIVE
These drugs increase salt (and water) secretion and decrease the transit time.
The mechanism appears to involve generation of NO, PGE2 and activation of protein
kinase C.
Excessive use can lead to fluid and electrolyte deficits
PHENOLPHTHALEIN Withdrawn from market due to risk of cancer.

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Psyllium

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FIBER
Metamucil®) - from plantago seed
 Bind water and ions - increase mass of feces
 Through distention increases GI motility
 Binds bile acids
 Helps to relieve “irritable bowel syndrome”
 Helps prevent diarrhea by binding water

SE: Binds coumarin

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BISACODYL

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STIMULANT LAXATIVE
These drugs increase salt (and water) secretion and decrease the transit time.
The mechanism appears to involve generation of NO, PGE2 and activation of protein
kinase C.
Excessive use can lead to fluid and electrolyte deficits
bacteria remove the glucuronate groups and
release the active drug.
IMPORTANT: Bisacodyl tablets are enteric-coated to prevent action in the upper small
intestine and stomach, which can induce vomiting. Tablets should not be
chewed or crushed or administered with antacids or other drugs that raise
gastric pH as this can cause premature loss of the enteric coating.

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Senna

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STIMULANT LAXATIVE
ANTHRAQUINONE
These drugs increase salt (and water) secretion and decrease the transit time.
The mechanism appears to involve generation of NO, PGE2 and activation of protein
kinase C.
Excessive use can lead to fluid and electrolyte deficits
Glycosides of danthron and other related substances such as dianthrones (sugar
residues added to the -OH moieties) are found in senna, cascara sagrada,
rhubarb and aloe. These are acted upon in the colon by bacteria to release the
active drug. Danthron itself is not used due to reports of hepatic and intestinal
tumors in lab animals.

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A word on stimulant laxatives

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1) The actions of phenolphthalein and bisacodyl are prolonged by
enterohepatic cycling. Glucuronidation in the liver prevents effect being
produced until the drug reaches the colon where bacteria remove the
glucuronate.
2) These drugs are absorbed  saliva, milk, urine
3) Chronic use of these agents is NOT recommended
Note: In 1996, the FDA reclassified these laxatives as category III laxatives,
which means more data are needed to determine safety and efficacy. Data concerning
bisacodyl and senna was received the others were removed from market.

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CASTOR OIL

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Stimulant Laxative
Ricinoleic acid is released by pancreatic lipases in small intestine.
Ricinoleate acts on small intestine stimulating peristalsis and fluid secretion
producing complete emptying in 1-6 hr. NOT RECOMMENDED FOR
COMMON CONSTIPATION. Can induce uterine contraction in pregnant women.

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DOCUSATE

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STOOL SOFTENER
Mechanism of action
uncertain, but probably the same as stimulant laxatives.

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USES OF LAXATIVES

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Before Drugs are Used Try:
1) Fiber rich diet, bowel-training, increase fluid intake, exercise
2) Correct any underlying disease
3) If constipation is induced by another drug, adjust dose or change drug
Then: Bulk forming agents
Finally: stimulant laxatives at LOWEST effective dose, as INFREQUENTLY as
possible and DISCONTINUE promptly and COMPLETELY

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Abosorption of water in the colon

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Most of the absorption
of H2O by the colon accompanies the reabsorption of Na+, Cl-, and HCO3
-. This flux is
driven by the gradient generated by Na/K+-ATPase pumps that drive Na+ from the mucosal
cell to the blood. Cl-/HCO3
- exchange, Na+/H+ exchange, and NaCl cotransport and Na+
channels mediate influx from the lumen into mucosal cells. Cl- and K+ channels also exist
and permit these ions to pass from the mucosal cell into the lumen and be secreted.
The net flux is controlled by the enteric nervous system and a large number of
neurotransmitters, hormones and autacoids. As with gastric acid secretion, cAMP stimulates
salt/fluid secretion and inhibits absorption - choleratoxin is the most dramatic example of an
agent that induces diarrhea by elevating cAMP. Factors that lower cAMP or inhibit
acetylcholine release increase reabsorption - e.g., opioids.