PHRM 211 Lecture Notes - Lecture 24: Comt Inhibitor, Entacapone, Nmda Receptor Antagonist
24. Therapeutics of Parkinson’s Disease (Part 4)
Other Drugs
- COMT Inhibitors (Entacapone)
- NMDA Antagonist (Amantadine)
- Anticholinergics
COMT Inhibitors
- Entacapone, Tolcapone
- Peripheral or central catechol-O-methyl transferase (COMT) inhibitors
- Tolcapone was first COMT inhibitor approved in Canada
– Discontinued due to hepatotoxicity
– Only available through HC’s Special Access Programme for exceptional cases
Entacapone Inh Key Notes
Evidence
STRIDE-PD trial
Benefits
Efficacy on early motor symptoms: NOT recommended
- Not effective as monotherapy
- Not used for early/initial disease (STRIDE-PD trial) showed increase in
dyskinesias in early PD
Dosing
Strategy
- 200 mg PO with each dose of L-Dopa (max 8 times/day)
- Short half-life (2 hrs) – must be taken at same time as each L-Dopa dose
- Available as a L-Dopa/carbidopa/entacapone combination product
- Consider reducing dose of L-Dopa by 25% when starting entacapone
Risks/
Monitoring
Associated motor complications (dyskinesias): Used as adjunct for
patients with wearing off
- Can increase adverse effects of L-Dopa
- Diarrhea
-Brown/orange urine discolouration
Amantadine
- Unknown MOA – NMDA antagonist, increases dopamine
- Not a first line drug
- Used in early PD patients and improve L-Dopa induced dyskinesias in later stages
Amantadine Inh Key Notes
Benefits
Efficacy on early motor symptoms: NOT recommended
-Early, mild disease: option for short-term monotherapy, but not first line
given ADR and limited, transient benefit
-Advanced disease: used if dyskinesia is not controlled by modifying
existing therapy
Dosing
- 100 mg PO BID
Document Summary
Tolcapone was first comt inhibitor approved in canada. Only available through hc"s special access programme for exceptional cases. Not used for early/initial disease (stride-pd trial) showed increase in dyskinesias in early pd. 200 mg po with each dose of l-dopa (max 8 times/day) Short half-life (2 hrs) must be taken at same time as each l-dopa dose. Consider reducing dose of l-dopa by 25% when starting entacapone. Associated motor complications (dyskinesias): used as adjunct for patients with wearing off. Unknown moa nmda antagonist, increases dopamine. Used in early pd patients and improve l-dopa induced dyskinesias in later stages. Early, mild disease : option for short-term monotherapy, but not first line given adr and limited, transient benefit. Advanced disease : used if dyskinesia is not controlled by modifying existing therapy. Leg edema, erythema, livedo reticularis (reversible bluish, mottled appearance of lower extremities) Can increase confusion for patients with cognitive impairment. Have been available for decades, before l-dopa.
