Antidiarrheals / Types / Opiates
Opiates
DIPHENOXYLATE, LOPERAMIDE
- failed antipsychotic drugs (GI effects with limited CNS effects - remember Dr. Lichtblau's opiate lecture from Neuro)
- DIPHENOXYLATE was derived from meperedine
- LOPERAMIDE from haloperidol
Mechanism of action
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increase phasic colonic segmenting activity by activating κ and μ receptors → inhibition of both cholinergic neurons that increase motility and VIP/NO neurons that cause relaxation → increased transit time due to decreases peristaltic reflex (indirectly causes increased water absorption)
- also promote constipation by direct inhibition of neurons in the submucosal plexus that promote water excretion
LOPERAMIDE does not cross the blood-brain barrier à no analgesic or addictive properties à available OTC
-
DIPHENOXYLATE has no analgesic properties at standard doses, but higher doses have CNS effects à available by prescription; commercial preparations contain ATROPINE to discourage overuse
Therapeutic uses
- most effective antidiarrheals
- useful for most forms of diarrhea
Side effects
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abdominal cramps
-
toxic megacolon if administered in patients with severe ulcerative colitis
- at high doses, DIPHENOXYLATE causes euphoria à morphine-like physical dependence can occur with chronic administration
- probability of dependence is decreased by adding ATROPINE to the formulation; ATROPINE will also decrease motility (antimuscarinic), and has unpleasant side effects