Loperamide
Loperamide
- A surprise entry in the opioid section, loperamide is a synthetic piperidine derivative much like fentanyl
- This gives it MOP receptor agonist properties
- It is used to treat diarrhoeal illness, including that associated with inflammatory bowel diseases, short bowel syndrome and chemotherapy-induced diarrhoea
- Usual dose 2-4mg, up to 16mg/day
- Loperamide is administered orally, and it exerts its MOP agonist effect in the GI tract
- Entry from the GI tract into the systemic circulation is limited by the action of P-glycoprotein, and systemic levels are further reduced by hepatic 1st pass metabolism
- What little systemic loperamide there is also fails to cross the BBB due to the action of P-glycoprotein
- This generally limits its effects to the peripheral nervous system
- These intrinsic mechanisms can be overcome by those seeking to use loperamide as a drug of abuse by two mechanisms:
- Extremely high doses of loperamide (>70mg), which saturate P-glycoprotein and can lead to CNS effects
- Use of P-glycoprotein inhibitors such as quinidine, ketoconazole, ritonavir
- It is metabolised to an MPTP-like compound which, unlike actual MPTP, is not neurotoxic