I Switched Back to DynaCirc CR

I Gave Generic Isradipine a 3 Week Trial but...

About a month ago I switched from DynaCirc CR to the generic form of Isradipine, which is not CR. I switched because I could save $1800 a year with the generic form of the drug. My doctor said they would both work about the same and if I got side affects I would get over them in a few weeks time. He suggested I take the generic for a month and see what happened.

So what happened was my left arm tremor which was almost gone came back strongly. People who know me commented on it. It wasn't as bad as before I started DynaCirc CR but it seemed to be getting worse I also started having swallowing problems again along with speaking problems. Sometimes I couldn't think of the a word or follow through on a thought process. Also having occasional trouble thinking about what's coming next. My typing problems are nothing new but the very act of typing seemed to be more difficult; my typing was worse.

All of these worsening symptoms prompted me to email one of the Isradipine researchers to get his opinion of the two drugs. This was the reply: "The CR formulation maintains a more stable serum concentration of Isradipine than the non-CR pill. This should better protect the DA neurons. So if you can afford it, stay on the CR format. If it is a matter of going off the drug or using the non-CR format, obviously I would recommend the non-CR format."

So I switched back to DynaCirc CR(R) 10 mgs a few days ago and my symptoms are already improving although it will take time for that process to complete itself. Another positive side is I feel I have more energy and that I am less tired during the day. I'd already stopped taking naps but I would still tire by early evening. I would have been happy to have that money each month but I'm not going to be selling any of my dopamine neurons for $1800, I've lost enough as it is.

The point is that Isradipine was helpful, no question about it. If your only choice is generic I think the suggestion to try it at the 2.5mg dosage 4 times a day is a good one. Since I can get DynaCirc CR through my plan although not at any appreciable discount, I'm back on it because the steadier time-release is very important to maintain the levels of the medication in the bloodstream. If they ever come out with the generic as a controlled-release, I would certainly be willing to try it because there is no question that DynaCirc CR is very tough on the budget.

The Future of Isradipine and Parkinson's Disease

Can Isradipine reverse neuronal degeneration in Parkinson's?
Parkinson's is a common neurological disease, affecting over 1.5 million people in the USA alone. The risk of PD increases as we get older, especially after we pass sixty. PD progression is the result of the damage and on-going deterioration of the dopamine neurons.

Because dopamine is a chemical messenger for the brain, the death of its neurons causes an ever increasing slow loss of motor control as it causes the typical PD symptoms: tremor, balance, loss of sense of smell, stiffness, inability to dress one's self, swallowing and speaking problems, sleeping issues, sexual dysfunction, dystonia, depression, apathy and many others.

There is a great deal of research underway but there is no cure. The only drug that has some proven neuro-protection thus far is Azilect.

Researchers understand that the neurons die but not much about how or why. While there are signs of the disease process in many regions of the brain, the core symptoms of PD occur when the dopamine neurons in an area of the brain called the substantia nigra pars compacta are damaged. Although in their youthful stage they relied upon sodium channels, as these neurons age they rely on calcuim channels to maintain autonomous activity. This reliance puts the metabolic mitocondria under sustained stress causing cell aging and death.

The calcium channels underlying the autonomous activity of the dopamine neurons are similar to the L-type channels of the heart and smooth muscles. Systemic administration of Isradipine, an L-type blocker of C type channels (Ca2+) causes a reversion to a sodium mechanism to produce independent activity.

Reversion to the sodium and HCN channels found in the juvenile substantia nigra offers protection from toxins to lab rodents with experimental PD. In a few years this could result in a Parkinson's Disease neuroprotective usage for a drug class that has been safely used by cardiac patients for decades. There is the possibility that reversing the synaptic dysfunction, neuron degeneration and reduced plasticity can restore brain cellular and molecular homeostasis; a return to normalcy.

Now there is a fresh approach to combating this disease, a different viewpoint. Isradipine Phase II clinical trials for safety and efficacy begin May 2009.

This research also suggests that although genetic and environmental factors can hasten its onset, PD is programed into all humans, if we live long enough we may all get it.

Resources:

10/06/2007
Calcium, aging and neuronal vulnerabilty in Parkinson's Disease
PUB MED NIH
D. J. Surmeier

07/05/07
Parkinson's disease: return of an old prime suspect
PUB MED NIH
D Sulzer, Y Schmitz

06/06/07
Calcium and Neurodegeneration
PUB MED NIH
MP Mattson

06/28/07
"Rejuvenation" protects neurons in mouse models of Parkinson's disease
PUB MED NIH
CS Chan, JN Guzman, E Ilijic, JN Mercer, C Rick, R Tkatch, GE Meredith, DJ Surmeier

Isradipine Phase II Trials for Parkinson's Disease

Professor D. James Surmeier's exciting work investigating the relationship between calcium and sodium channel modulation and Parkinson's disease has been widely known in the Parkinson's community since his June 2007 article in Nature. The article described how isradipine restores older dopamine neurons to their youthful condition. In it Dr Surmeier describes how he feels that people may be able to take isradapine to protect brain cells from Parkinson's like they now take baby aspirin for their hearts. He also hopes that Isradipine can extend by two to three times the therapeutic window that patients have to continue taking L-DOPA before it loses its effectiveness or starts to have serious side effects.

A small clinical trial has been completed at Northwestern University proving the safely and tolerance of Isradipine in PD patients. The phase II trial, Safety and Tolerability of Isradipine (a potential neuroprotective agent) in Patients with Parkinson's Disease - Stage II is still in recruitment. (see: below)

With funding from the Michael J. Fox Foundation Dr Surmeier is now working with fellow Northwestern chemistry professor Dr Richard Silverman to develop a new drug (calcium channel blocker) that will just target one of the two calcium ion channels, Cav1.3 L-type calcium channel antagonist to slow or stop progression of the disease. Success could bring a patent and marketing by a major drug company.

Source: http://www.michaeljfox.org/research_MJFFfundingPortfolio_searchableAwardedGrants_3.cfm?ID=492

Full text of clinical trial: http://clinicaltrials.gov/ct2/show/NCT00753636

Isradipine or DynaCirc

Isradipine, the generic instead of DynaCirc CR (R)

I've been taking Isradipine for one and one-half years to control my high blood pressure and to see if it would be effective in controlling my Parkinson's disease symptoms while slowing or stopping the progression of the disease.

Keep in mind no two Parkinson's patients are the same, so what has helped me may not help you at all, or you may not even be able to tolerate it.

That said, when I started DynaCirc CR within the first two weeks I noticed that my swallowing problems had decreased greatly, co-workers asked me why my voice sounded so much better. I felt better like I had more energy and that helped me get rid of a lot of my depression. I had been taking Mirapex, I was able to stop taking it. Once the Mirapex was out of my system, I stopped having most of the hallucinations and complusiive behavior that had been plaguing me.

My PDRS has been at 14-18, pretty much straight-lined since I started Dynacirc CR and these are the medicinal and supplemental treatments I have been taking:
Azilect 1mg/day
CoQ10 1200mg/day
Sublingual L Glutathione 300 mg daily under tongue
Atenolol 50mg/day
Lovastatin 40mg/day.
I take the following herbs and supplements: Turmeric, Saw Palmetto, Milk Thistle, Nettle Root, Omega 3 fish oils, Slippery Elm, Fenugreek, Green Tea extract, Vitamin B complex and Zinc on a temporary basis to see if it will improve my senses of taste and smell.

The last few weeks I have been comparing Dynacirc CR which contains Isradipine, a calcium agonist that crosses the blood brain barrier, with generic Isradipine because the generic drug costs me $3.00 /month and Dynacirc CR cost $151.00 for the same 30 day supply. My doctor told me they should work the same, plus or minus side effects.

I've been using generic Isradipine for three weeks now. The only negative things are having to take two 5 mg capsules instead of one. I don't think I'm taking it at the same time each day and that's giving me a little more tremor than Dynacirc CR which stays at the same level in your blood all day. It has been suggested that I could take four 2.5mg capsules to come closer to the time release effect but that would just be two more pills which I could forget to take because I hate taking any pills.

Positive effects are that I have more energy than I had before. With Dynacirc CR I took naps several days a week. Now I take naps only infrequently.

Parkinson's Patient Changes Doctors

I have switched to a new health plan as of the first of the year and I'm in the process of getting new doctors. I'd been hoping that I could find doctors from University Hospital which my Kaiser plan didn't allow but the Aetna plan does.

Ten days ago I had my first appointment with a University Hospital internist. As a Parkinson's patient it can be difficult to change doctors. Is he/she going to be traditional (sinemet) or alternative (CoQ10). This is my life and I want my doctor to see me and not a disease. I need to be proactive the the medical decisions made about my life.

On the phone, I had let the receptionist know that we were looking for a doctor with an open mind to possibilities. She advised me that while the doctor was not a Parkinson's specialist, he sounded like the person I needed.

As she suggested, I requested my medical records immediately so that I could carry them with me to the appointment although I should probably have dropped them off a day early.

She also advised me that Kaiser could take a while getting the records ready. The form actually had spaces for "pickup" and my phone number except the RUSH, added by a kindly intake woman at Kaiser. Days went by and no one called as we were told, instead Kaiser sent a letter telling me what I owed for the records. I received that letter on the day we drove over to pay for and pickup the package.

When I went to the appointment I was hoping not to hear any of the wrong words but I was prepared to keep on shopping if I needed too. We had made a list.

He began the appointment by greeting me and saying, "I understand meeting a new doctor can be stressful". That put me at ease as he looked through my medical records and asked me questions about what he saw.

My biggest concern was that I would not be able to find a doctor who would okay my prescription for DyaCirc which I am taking off label for my Parkinson's. That turned out to be no problem as he understood it could be used for PD.

He gave me the name of a movement disorder specialist (MDS) at the medical school with whom to make additional appointments, since I had never seen one under my Kaiser health plan. While I had seen a neurologist, she was not a movement disorder specialist. He also sent me to a dermatologist for head lesions that I've had for several years and so far always biopsy as benign.

He also encouraged me to see if switching from DynaCirc to its generic, Isradipine, would work for me. If isradipine helps me and I can tolerate it, the savings will be close to $1,800 a year.

One other good sign: I had printed out the information I had about Dynacirc CR and when I presented it, he asked if he could keep those copies for review with his students.

My impression of him: warm and friendly, easy to talk to. And willing to learn new things. He's going to be my doctor!

NIFEDIAC vs DYNACIRC

I am still living with the hope that a generic version of Dynacirc will become available soon.

Dynacirc CR is the calcium channel blocker which I had been taking until its manufacture ceased and none was available. Calcium channel blockers prevent calcium from entering the dopamine neurons, thereby preventing their deterioration. In essence this CCB causes a revesal to the more youthful saline environment.

I have already written about Dynacirc and the change of my meds to Nifidiac CC. Below is my comparison table to answer questions about the differences which I observed between the two. Both do cross the blood-brain barrier which is why they can affect Parkinson's symptoms.

I still have some hope that we will see a generic Dynacirc in November or thereafter if all of the patents have expired and any legal issues are resolved.

SYMPTOM	NIFEDIAC CC NIFEDIPINE	DYNACIRC CR ISRADIPINE
Swallowing	Not as effective	Rarely choked
Mild dizziness-lightheadedness	not as effective	less often
Balance	Weakening sense of balance	Improved when taking
Stiffness - Rigidity - Gait	Returning in foot, hand, neck	Improved when taking
Tremor	Not as effective	Slight improvement
Erectile Dysfunction	Might have improved	Reviews say better
Energy and clarity	Not as effective	Improved when taking
Sense of smell and taste	No change	No change
Hearing and vision	No change	No change

Table explanation:

Difficulty swallowing is common PD symptom. It is a direct factor in the leading cause of death of Parkinson's Disease patients, aspiration pneumonia. Related to the inhale-exhale cycle, it has been learned that the normal adult pattern is to swallow during exhalation; PD patients often inhale during this process. If the result goes beyond choking, the lungs will inspire bits of foodstuff which can result in aspiration pneumonia. Dr. Roxann Gross, PhD at the University of Pittsburgh School of Medicine is currently working with PD patients to retrain and re-coordinate their patterns of breathing and swallowing.

Mild dizziness-Lightheadedness, a difficult symptom to describe is a side effect of any blood pressure medication. Because both Dynacirc and Nifediac are blood pressure medications, the side effect is not unexpected

Balance has more to do with the sense of balance. You feel that you are straight but in fact you are not. It is one of the reasons that I use a cane for protection against falling, the second leading cause of Parkinson's deaths.

Stiffness-rigidity often on one side of the body. Commonly seen in face, neck, arms, legs, hands and ankles and feet. I have stiffness in my left arm and hand and my left leg, ankle and foot.

Tremor is another typical PD symptom. It is the one symptom most commonly associated with Parkinson's. My tremor is just in my left arm. There was a time when it would manifest in my left leg when I was stressed but that did stop after I began to take Dynacirc.

Erectile Dysfunction is thought by some to be a causative factor and not simply a symptom of PD. I am being told that the ED was helped by the Dynacirc.

Gait is related to the stiffness and to balance. My gait is stiff and my steps shorter.

Senses of smell, taste, hearing and vision. I rarely can smell anything these days. Fortunately my wife doesn't make me clean the kitty litter boxes because of my balance issues. Although I have lost 95% of my sense of smell, I can still taste. I prefer hotter seasonings, however.
Energy and clarity were immediately increased to a level I had not felt in a few years when I began taking Dynacirc CR. I do not feel that same energy on Nifedipine-Nifidiac CC.

What I Did When DynaCirc Wasn't Available - so glad it's back for my PD

While I just take a few medications and supplements for Parkinson's disease: Azilect, CoQ10, Creatine and DynaCirc. Azlicet has been proven in a large trial approved by the FDA to slow the progression of PD. DynaCirc CR is in trials now. Preliminary testings shows it either slows or stops PD progression and possibly grows new neurons as well.

DynaCirc is a calcium channel blocker of the Dihydropyridine subclass used mainly for blood pressure control but it has an open label that allows it to be prescribed for other treatment like PD. I've been using it for more than a year.

When I first started taking it I immediately noticed certain improvements. My swallowing difficulties and voice pitch problems were eased. Friends asked what had I done to improve my voice so much. Although I stopped taking Mirapex and Selegiline, my tremor actually improved a little; I still had a tremor when I felt emotional. My left arm still didn't swing naturally when I walked. My fibular brevis muscle and the associated flexor tendons continued to pull my toes up in my left leg when I walked or lay in bed.

But I felt good. I didn't think I was getting worse and just maybe I might be getting a little bit better.

Because it had happened before, I wasn't surprised when I went to Walgreens to get my Dynacirc prescription refill at the beginning of July and the Tech told me they didn't have any Dynacirc but would get it from another Walgreens and have it for me the next day. What surprised me was the next month, August, when they told me that they had none and neither did any other Walgreens. They suggested I talk to my doctor about a replacement drug. I was told that their supplier was out and they didn't know when it would be back in stock.

When I talked to my MD he looked at the schedule D calcium chanel blockers which are the only options on the Kaiser list and chose Amlodipine from the three listed. I started taking that medication on August 28.

After a few days I began to feel less coordinated, less balanced; my voice was regressing as the muscles in my throat tightened, the trouble I had swallowing was back, my body felt very stiff. I thought these were just side effects from the new medicine; I thought I would get used to it.

After about a week I felt so stiff that I could barely get out of my wife's car. It seemed as if the PD was progressing at a rapid pace each day. After another week I started thinking about what was different: treatments? medication? Then I realized I wasn't taking Dynacirc any more; now I am taking Amlodipine and that was when the deterioration had begun.

I emailed my medical situation to a friend who works in a research lab at local university medical center. In less than an hour he emailed me back that " Amlodipine was an unfortunate choice" as it does not go through the brain blood barrier (BBB). That meant I hadn't received medicinal benefit from the Amlodipine which would affect my PD or did it mean that Amlodipine just didn't work as well for me. Subsequent to posting this article I learned that aplodipine does cross the blood brain barrier. So I guess it wasn't the medication for my Parkinson's symptoms.

We posted a chart of Calcium Channel Blockers which cross the Blood Brain Barrier on 4/4/2010.

I called my MD and had the names of the two calcium channel blockers that go through the BBB ready for him: Nifedipine and Felodipine. I'll start taking Nifedipine (Nifediac) tomorrow morning. It is a generic and considerably less expensive.

2/05/09 note: Dynacirc CR has been back on the market since November 2008
The lesson learned was that if a med you are taking is unavailable - an unusual situation - that you need to ask what about it worked for you and why. Then you won't waste time and possibly jeopardize your health taking a "substitute" which won't perform in the same way.

Additional note: When I switched health insurance we had to go with a generic unless a specific prescription was submitted by the prescribing physician.  I briefly tried Isradipine, the generic version of DynaCirc.  Among other issues with taking this generic was the fact that it was not a controlled release.  Even taking 5mgs 2X a day was not the same. I wrote about my isradipine experience on 2/08/09

Massage Therapy and PD

Keeping my Parkinson's disease progression as slow as possible


I've had Parkinson's disease for 5+ years now. I've been trying to avoid taking levodopa because of its possible side effects that often start after 5 years of increasing dosage. Medications I now take are azilect, COQ10, and isradipine for PD. They eliminate or reduce my symptoms of tremor, soft voice and foot drop, while leaving me with slowly progressing muscular rigidity, gait difficulty and slowness of movement.

Seven months ago I began massage therapy for arthritis in my knees because I had read about positive results in a Yale University study for the CDC. The study showed that Swedish massage therapy reduced pain while improving flexibility and range of motion in arthritis patients.

I've been getting a one hour massage every week and the pain in my knees is mostly gone, unless I lift heavy things or wear shoes that are not soft, flexible and low heeled. In recent months I've been wearing Dr Scholl's Lara medium or wide width with the gel insole. Yes, I am gellin' and it seems to help my comfort level.

Most large metro areas will have lots of Massage Therapists. Find one who is familiar with Arthritis and Parkinson's and is listed by the American Massage Therapy Association. Most will offer several different styles of massage. Each of us is different, but Swedish massage has tested as pain relieving for arthritis.

In a small study conducted by Touch Research Institute at the University of Miami 16 adults diagnosed with Parkinson's disease were randomly assigned to either progressive muscle relaxation exercise or massage for 30 minutes twice a week.

The results were that those in the massage group had improvements in daily functioning and urine tests showed a reduction in stress hormone norepinephrine and the massage group had fewer sleep disturbances.

I will discuss my own massage therapy in more detail in an upcoming Parkinson's Focus Today post.