Too Much Levodopa...means too much Dopamine and bad side effects...Part 1

More than 35 years after its introduction, levodopa still remains the most effective treatment for Parkinson’s disease and is considered as the “gold standard” therapy. In fact, the diagnosis of Parkinson’s disease becomes questionable if a patient fails to respond to an adequate dose of levodopa. However, within a few years of introduction of levodopa, clinicians recognised several problems associated with its continued use.

In the early stages of the disease the response to levodopa is sustained, despite its relatively short half life (∼1.5 hours). This is presumably due to the preserved capacity of the presynaptic nerve terminals to store dopamine.Patients do not notice any deterioration in their symptoms of Parkinson’s disease even if they miss out a few doses.

As the disease progresses, with continued loss of substantia nigra, the beneficial effect of each dose of levodopa progressively gets shorter. Patients notice deterioration in their symptoms an hour or two before their next due dose, the so-called “end of dose deterioration” or “wearing off”. With further progression of the disease, more unpredictable complications, such as motor fluctuations, “on/off” phenomena, and dyskinesias appear.Motor complications associated with long term levodopa treatment in Parkinson’s disease are common and they can be more disabling than the disease itself.

Recently, there has been a great interest in the study of mechanisms underlying the emergence of motor complications associated with the chronic use of levodopa and possible therapeutic strategies to prevent or treat these complications

Dopamine agonists have a longer half life and are being increasingly used in the treatment of Parkinson’s disease, either as monotherapy or in conjunction with levodopa. Several studies have shown significantly fewer motor complications with dopamine agonists as an initial therapy of Parkinson’s disease compared with treatment with levodopa. However, dopamine agonists may not be well tolerated by frail elderly patients and those with cognitive impairment. They are also associated with excessive daytime sleepiness. With progression of Parkinson’s disease, there is often a need to add levodopa when dopamine agonists alone fails to improve symptoms.

Because people with Parkinson’s usually visit their doctor when they are ‘on’ (i.e. medication working), your doctor may not realise that your symptoms return between doses of medication. Don’t wait for your doctor to ask about wearing-off – tell them how long each dose of medication is working for and what happens when it wears off.

Leonard327 My breathing becomes laboured, hard to swallow, talk, eat,, difficulty walking, tremors increase and I become confused during my wear off periods

What happens when my brain's Dopamine is being eaten by the PD MONSTERS?

Dopamine's activity spans across a wide psychosomatic spectrum of manifestations. It is an integral part of the reward-motivation circuits and aversion-learning circuits. It also is involved in neuronal circuits for vomiting and lactation. So, predictably dopamine blockade will cause a myriad of effects.Due to its role in reward motivation, aversion-learning circuits and maintenance of mood, long term dopamine blockage may cause Depression

Dopamine is a major neurotransmitter in the nigro striatal pathway, an important component of the Basal Ganglia which is involved in motor modulation. Long term blockade may cause Parkinsonism, which is characterised by tremors, rigidity of muscles and generalised motor dysfunction (bradykinesia, characterised by reduced ability to achieve movement).Dopamine is also responsible for impetus to accomplish tasks. In Parkinsonism and prolonged dopamine blockade, the levels fall down significantly in the nucleus accumbens which results in reduced impetus, often exacerbating cognate motor dysfunctions.

Similarly, Dopamine is one of the inhibitory hormones elaborated by the hypothalamus to regulate prolactin secretion. Prolactin causes milk production and proliferation of glandular tissue of the breast. Normally constitutive inhibitory action of Dopamine keeps the prolactin levels ebbing below the bare minimum. Removal of the inhibition by using dopamine receptor antagonists causes hyperprolactinemia which if persists for quite a while may result in gynaecomastia in males and galactorrhea.Dopamine is one of the mediators involved in the pathways responsible for vomiting. The vomiting centre and the Chemoreceptor trigger zone (the higher centres of vomiting in the brainstem) have D2 receptors which upon stimulation bring about vomiting. view post remove from favorites

I recently started taking my carbadopa levadopa Instead of 3 to 4 times daily every 4 to 5 hours I have been splitting them in half An taken every three hours seems to be working better less off time

Off times” are more common as disease progresses

“Off times” become more common after people with PD have been taking medication for a longer time and as their disease progresses. While the presence of “off times” happens as a normal progression of PD, there are things that can help manage or reduce these episodes:Tell your doctor. Be sure to talk to your doctor about the “off time” episodes you’re experiencing.

Note if they occur at the same time (before your next dose of medication) or sporadically. It is recommended that people with PD go to a doctor who is a movement disorders specialist. This is a specially trained neurologist who is fully educated in conditions like PD and understands the interactions of drugs used to treat the symptoms, as well as how some medications may worsen symptoms of PD.

Your medication dosage or timing may be changed. Your doctor may change the amount of medication you’re taking or the timing of the dose. Adjustments to the dosage or timing may reduce “off times.”

The type of carbidopa/levodopa you’re taking may be changed. Your doctor may change the form of therapy you’re receiving. Some forms of carbidopa/levodopa are extended-release formulations that release the medication steadily for a longer period of time. There are also formulations that are available as a tablet that dissolves in your mouth or a suspension that is delivered directly into your small intestine via a tube.
Another medication may be added. Your doctor may add a different kind of medication to your current regimen.

Consider deep brain stimulation. Some people are good candidates for deep brain stimulation (DBS), a type of surgery in which a device is implanted in the brain to deliver electrical pulses and decrease the motor symptoms of PD. Ask your doctor if DBS is an option for you.
Your diet may need adjusting. What you’re eating and when, and how that coincides with your medication schedule, can impact the presence of “off times.” Talk to your doctor and a nutritionist to determine if changing your diet can help manage your “off time.”

Each individual responds differently to the various treatments available for PD, and there is no one solution that works for everyone. In addition, your needs change as the disease progresses. By working with your doctor and telling him or her about the symptoms you’re experiencing, including any “off time” you may be having, you can best manage your symptoms.