LEVODOPA

Day 1: Still the mainstay of Parkinson's disease (PD) treatment, #levodopa was extracted from faba bean seedlings in the early 20C. It was deployed in the 1960s with dramatic ‘wakening’ effects on immobile people with PD. Side-effects were also dramatic! The era of catecholamine pathway discovery followed & it was realised that dopamine couldn't cross the BBB, but prodrug L-dopa could via decarboxylation to dopamine in the brain; also rapidly converted in the gut (side-effects)

Day 2: #levodopa is always combined with a dopa decarboxylase inhibitor such as #carbidopa to inhibit the peripheral metabolism of #levodopa; this allows a lower dose & fewer side-effects, while more drug reaches the brain. I.r or m.r tablets in various combination strengths. Duodopa is an intestinal gel (levo+carbidopa) for advanced disease/tx for ‘on/off’ issues. Continuous jejunal delivery via percutaneous tube. Bypasses stomach/stabilises concentration/improves motor symptoms. Daily cassette £77/day. USA have inhaled L-dopa;not available UK

Day 3: #levodopa undergoes rapid enzymatic breakdown in blood which means a short t½. Breakdown is prevented by drugs like carbidopa & entacapone. Metabolised in blood & peripheral tissues into metabolites including epinephrine with predominantly renal excretion. Combined t½ 1-2 hrs