Laura’s Pharmacology Degree

I’ve been researching Parkinson’s drugs lately because soon I will have my regular 6-month check in with my neurologist.  My symptoms are still pretty mild, but have been increasing and I’m wondering whether I’m at the point where I need to switch to heavier pharmaceutical ammo.  I have decided I’m not going to switch yet, but we’ll see what the doctor says.  In the meantime, I have a whole new respect for pharmacists.

When I was first diagnosed with Parkinson’s, I thought: shortage of dopamine? Just take more dopamine, right? – kinda like insulin for diabetics?  But that won’t work because of something called the “Blood-Brain Barrier”.  This is a membrane around your brain that lets small stuff in but not blood or bacteria (sounds good) or large molecules like dopamine (dang).

However, there is a chemical precursor to dopamine, levodopa (sometimes called L-Dopa). Much as you might take apart the table to move it through the door, levodopa is small enough to pass through the barrier and voila, turns into dopamine.  (Simplistic – just go with the flow here – real pharmacists could explain this better.)

So, problem solved, right?  Nope.  Think about the journey the pill takes on its way to your brain.  You swallow the pill, it goes to your stomach, then intestine, then is transported by the bloodstream to that Blood-Brain Barrier, works its way through the membrane, does some chemical hocus-pocus and voila, there’s only 1-3% of the original levodopa left to turn into dopamine.  So you need to swallow LARGE quantities of levodopa to get something to your brain.

Well, not as large as the original formulation back in the 1960s.  The pharmacy wizards have added another component, carbidopa, which reduces by 75% the amount of levodopa digested by your gut.  The levodopa/carbidopa combo is typically referred to by its brand name, Sinemet.

Alas, speaking of digestion, you have to watch your timing on when you eat vs when you take your pills.  Why?  Since levodopa competes with certain amino acids for transport across the gut wall of your intestines on its way to the brain barrier, the absorption of levodopa may be impaired by a diet of steaks and pepperoni pizzas (or other high proteins).

But there can be much more serious side effects of Sinemet besides restricting your pizza input.  (Keep in mind drug actions and side effects vary dramatically from one Parky to another, and also over time.)  One is the roller coaster effect – you’re “on”, then you crash as the levodopa wears off.  The next step is usually working with your neurologist to finesse the therapy by adjusting dosage and timing.

The other side effect after long-time use of levodopa can be dyskinesia – uncontrollable movements, head bobbing, fidgeting, and the like.  If you’ve seen Michael J. Fox lately, he displays dyskinesia.

So that’s why I’m not eager to switch from my current drug, a dopamine agonist called Ropinirole.  It makes what dopamine you have left work better, but eventually loses efficacy.  And oh yes, it has its own potential side effects.  But so far, so good.