Diphenoxylate and Atropine
**Diphenoxylate** is a synthetic phenylpiperidine-derivative opiate agonist, structurally related to meperidine. It is primarily used in veterinary medicine as an **antidiarrheal** and **antitussive** (cough suppressant) agent, most commonly in dogs. Key pharmacological features include: * **Motility Modification**: It slows gastrointestinal transit time, allowing for greater fluid absorption and reducing diarrhea. * **Abuse Deterrent**: Commercial formulations include a sub-therapeutic dose of **atropine sulfate**. At normal doses, the atropine has no clinical effect, but if taken in excessive amounts, it produces unpleasant anticholinergic side effects (e.g., dry mouth, tachycardia), discouraging abuse. * **Controlled Substance**: Due to its opiate nature, it is classified as a **Class-V controlled substance**. > **Clinical Pearl**: Use in cats is highly controversial due to the risk of paradoxical excitatory behavior. In dogs weighing less than 10 kg, liquid formulations are strongly preferred to allow for accurate dose titration and avoid accidental overdose from potent tablet forms.
Mechanism: Diphenoxylate exerts its effects primarily through interaction with opioid receptors in the gastrointestinal tract and central nervous system: * **GI Motility**: Binds to **μ-opioid receptors** in the enteric nervous system (myenteric plexus) → decreases the release of acetylcholine and prostaglandins → inhibits excessive GI propulsion and increases segmental (non-propulsive) contractions → **prolongs intestinal transit time**. * **Secretion Reduction**: Decreases intestinal secretion induced by cholera toxin, prostaglandin E2, and non-cAMP/cGMP mediated diarrheas. Enhances mucosal fluid and electrolyte absorption. * **Antitussive Effect**: Acts directly on the **medullary cough center** in the brain → depresses the cough reflex. * **Atropine Component**: Acts as a competitive antagonist at **muscarinic acetylcholine receptors**, though its dose in this combination is too low to exert significant systemic anticholinergic effects unless overdosed.
Dosing by species
- As an antidiarrheal · 0.08-0.1 mg/kg PO q12h · PO · q12h · Use in cats is controversial.
- As an antidiarrheal · 0.1-0.2 mg/kg PO q12h · PO · q12h
- As an antidiarrheal · 0.05 mg/kg PO three times a day · PO · TID · Maximum 5 days · Probably should not be given longer than 5 days and are potentially contraindicated when diarrhea is suspected to be caused by enteric infections
- As an antidiarrheal · 0.05-0.2 mg/kg PO q8-12h · PO · q8-12h
- As an antidiarrheal · 0.05-0.1 mg/kg PO three to four times a day. · PO · TID to QID
- As an antitussive · Approximately 0.25 mg/kg PO q8-12h · PO · q8-12h
- As an antitussive · 0.2-0.5 mg/kg PO q12h · PO · q12h · Until clinical signs subside · May be used for extended periods. Constipation is an occasional problem, but stool softeners can alleviate.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Known hypersensitivity to narcotic analgesics
- Patients receiving monoamine oxidase inhibitors (MAOIs)
- Diarrhea caused by toxic ingestion (until the toxin is eliminated from the GI tract)
- Intestinal obstruction
- Bacterial-induced acute diarrhea (may enhance bacterial proliferation)
Adverse effects
- Constipation
- Bloat
- Sedation
- Paralytic ileus (potential)
- Toxic megacolon (potential)
- Pancreatitis (potential)
- CNS depression or excitation
- Excitatory behavior (especially in cats)
Drug interactions
- CNS Depressant Drugs (anesthetics, antihistamines, phenothiazines, barbiturates, tranquilizers, alcohol) · May cause increased CNS or respiratory depression when used concurrently.
- Monoamine Oxidase Inhibitors (MAOIs) (e.g., amitraz, selegiline) · Contraindicated. Do not use opiate antidiarrheals for at least 14 days after receiving MAOIs due to risk of severe adverse reactions.
Monitoring
- Clinical efficacy (resolution of diarrhea or cough)
- Fluid and electrolyte status (especially in severe diarrhea)
- CNS effects (sedation or excitation), particularly if using high dosages
- Bowel movements (monitor for constipation)
- Plasma amylase and lipase (may be artificially increased for up to 24 hours post-administration)
Overdose
Acute overdosage can result in severe **CNS, cardiovascular, gastrointestinal, or respiratory toxicity**. * **Delayed Absorption**: Because opiates significantly reduce GI motility, absorption of the drug from the GI tract may be delayed and prolonged, meaning toxicity can worsen over time. * **Opiate Toxicity**: Signs include profound sedation, respiratory depression, and pinpoint pupils. **Naloxone** may be necessary to reverse the opiate effects. * **Atropine Toxicity**: Massive overdoses may induce atropine toxicity (dry mouth, tachycardia, hyperthermia, dilated pupils, agitation).
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.