The following is most of the newsletter "Moving Forward" from City of Hope Parkinson's Center in Duarte, CA. This newsletter is all about medications using in the treatment of PD. I will be breaking the file into at least two parts so as not to over do the system. I think it will give us all a point of reference for the various medications. I have formatted this file such that titles are in capitals and each paragraph has a blank line preceeding it. Lines starting with "+ " are bulleted lines. Note: If you are on AOL and are using MS WORD 6.0 on a PC type computer, I will send the formatted DOC file to those requesting it. This is the full newsletter in one file. The file is 14 pages in length. Start part I ==================================================== AN EXAMINATION OF MEDICATIONS BOTH COMMONLY AND OCCASIONALLY USED IN TREATING PARKINSON'S DISEASE Neal Slatkin, MD NOTE: This paper is a reprint of most of the City of Hope Parkinson's Center Newsletter, Moving Forward, Summer 1995. This reprint is with the authors approval. The author would like to acknowledge and thank those who reviewed the paper for content. The reviewers were John S. Kovach, MD; Matt Kurth, MD, PhD; Jeff Chapman, PharmD; and Beatrice Decone, PharmD; with editing by Stephanie Unger and production by Robin Moore. INTRODUCTION In this special issue of Moving Forward we are providing an extended examination of the various medications that have been used by persons with Parkinson's disease. The purpose is to provide patients and caregivers with information on these medications as a clarification of the many approved and non-approved medications which have entered the array of medical treatments for Parkinson's disease and associated symptoms. The information contained in this newsletter is not intended as either medical advice to patients on the use of their medications or as a replacement for information received from the patient's physician. Patients having questions about their medications should discuss them with their physicians. Like all medications, those used in Parkinson's treatment require the regular guidance and monitoring of the prescribing physician. Two categories of medications are included in this discussion, as follows: + Those drugs intended to treat the primary motor symptoms of Parkinson's disease, such as rigidity, rest tremor and bradykinesia and + Those that are used in treating symptoms frequently associated with Parkinson's, such as depression, problems with sleep, action tremor, light-headedness, etc. For each class of medication three basic pieces of information are provided: + A description of its established or possible value in Parkinson's treatment and its basic mechanisms of action (if known). + Some of the possible side effects which might occur when these medications are taken + A description of situations in which the medications should be used with caution or avoided altogether, situations that are called contraindications by physicians and pharmacists. Since this information is intended to serve as a quick-reference resource, rather than as a comprehensive guide to each medication, only the most common or serious side effects and contraindications of each medication are provided. Moreover, although each medication approved for treatment within the United States undergoes extensive evaluation, new side effects are often recognized only after a medication has been in use for many years. Any list of potential medication-associated problems can therefore become quickly dated as new side effects and warnings are reported. This review is intended only as a means of enhancing your basic understanding of medication effects and facilitating communication with your physician. GENERAL APPROACH TO MEDICATIONS AND PRECAUTIONS Before leaving your doctor's office be sure that you thoroughly understand the following: + why a medication has been prescribed + how and when to take it + its possible side effects and contraindications. Always bring a list of all of your current medications with you to your appointments. It is also wise to keep an updated list in your purse or wallet. Some patients use several different pharmacies in an attempt to minimize the cost of their medications. In general, it is best to avoid using more than two pharmacies, including mail-order pharmacies. Some pharmacists can be very helpful in advising you about your medications by providing information on medication side effects and potential drug interactions. However, a pharmacist can only give you good advice if he or she knows the names of all of the medications you are taking. APPROVED MEDICATIONS Before a medication can be sold or distributed within the United States, it must be approved by the Food and Drug Administration (FDA) as safe and effective. Not all substances, however, which are promoted or used for medical purposes are classified as medications, or are subject to FDA regulations. For example, most substances sold in health food stores have neither been proven safe nor effective for their various promoted uses. Further complicating matters, it is common practice in medicine for even approved medications to be utilized for "unapproved" purposes, that is in conditions for which they have not been specifically proven safe or effective. With the exception of Motilium (domperidone) all of the medications discussed in this newsletter are FDA approved. You should understand, however, that some of these medications have not been specifically approved for the exact purposes discussed. A number of other substances which are not medications are also discussed. You are again reminded that these have generally not been rigorously tested or shown as safe or effective in the treatment of any condition. PREGNANCY AND BREAST FEEDING Most medications are contraindicated when a woman is pregnant or breast feeding. Women who are actively pursuing conception, or who are pregnant or breast feeding must consult with their physician before taking any medication. PREVENTING DRUG INTERACTIONS Whenever you have a new medication prescribed, make sure your physician knows the names of all other medications you are taking (including eye drops, non-prescription medications, special "health" and nutritional preparations, birth control pills, hormones, etc.). Combinations of medications can cause problems different from or more severe than side effects of individual medications. Alcohol use is contraindicated with a number of medications. Before taking alcohol and any medication, check with your doctor or pharmacist. SLEEPINESS Many medications can cause sleepiness, especially for the first several doses. Don't plan to operate potentially dangerous machinery or do much driving within the first several days of taking a new medication. STOPPING MEDICATIONS It is usually unwise to suddenly discontinue a medication that you have been taking for more than a month or two. Suddenly stopping stimulant medications, anti-seizure drugs, certain pain relievers, antidepressants, tranquilizers and various heart medications can lead to potentially severe withdrawal symptoms. Consult with your physician whenever possible before you stop taking a medication. If a new medication causes severe side effects, it may be acceptable to delay the next scheduled dose until you have had an opportunity to speak with your doctor. Finally, remember that each person is unique and that your reaction to a medication may be quite different from that of a friend or relative. If you expect side effects to occur, you are bound to experience them. Even placebos--inactive sugar pills--can have a high incidence of side effects, when patients expect or are fearful of bad reactions. IMPORTANT INFORMATION AND DISCLAIMER The information in this newsletter is provided solely for the purpose of the general information of the reader. It is not in any respect intended as medical advice for patients, nor does it imply treatment recommendations of City of Hope National Medical Center or the National Parkinson's Foundation. Some of the medications listed are not approved by the United States Food and Drug Administration (FDA) for the treatment of Parkinson's disease; and/or may not be approved for the purposes discussed; and/or may not be approved for use within the United States. You are strongly encouraged to consult your doctor should you have questions regarding these or other medications. MEDICATIONS USED TO TREAT PRIMARY MOTOR SYMPTOMS DOPAMINE REPLACEMENT MEDICATIONS SINEMET (CARBIDOPA/LEVODOPA) USUAL TABLET SIZES: 10/100 (OFTEN BLUE), 25/100 (OFTEN YELLOW), 25/250 (OFTEN BLUE) This is the most commonly used medication in the treatment of Parkinson's disease and, generally, the most effective. Levodopa is the active medication and must be converted by the brain into dopamine in order to have a beneficial effect. Carbidopa has no direct anti-Parkinson's effect, but instead facilitates entry of levodopa into the brain by preventing its metabolism into dopamine outside of the brain. In doing so, carbidopa also helps prevent some levodopa-related side effects such as nausea, vomiting and palpitations. Sinemet is the brand name of the original carbidopa-levodopa combination tablet. Many generic carbidopa-levodopa combinations are now available. For some patients, generic medications work as well as brand name Sinemet; for other patients, particularly those with troublesome on-off fluctuations or dyskinesias, treatment with brand name Sinemet may be preferred. When taking Sinemet for the first time, take it along with food to decrease the chance of nausea and vomiting. After Sinemet has been used for more than four to six months, most patients can begin to take it 30 to 45 minutes before meals. Taking Sinemet before meals ensures better and more predictable drug absorption. SIDE EFFECTS OF SINEMET (LEVODOPA) + Nausea and vomiting, as well as vague symptoms of gastrointestinal discomfort, which usually subside after weeks or months of treatment + Constipation that can cause discomfort and may require a change in diet or a special bowel program + A drop in blood pressure, the primary symptoms being those of light-headedness, dizziness, neck pain and/or increased imbalance + Increased sleepiness, particularly following the morning and afternoon dose of medication + Increased nightmares, hallucinations and confusion during the later part of the day or at night POTENTIAL DELAYED SIDE EFFECTS OF SINEMET (LEVODOPA) After five years of levodopa treatment, approximately 50 percent of patients develop delayed side effects. These can vary greatly in severity from patient to patient and some patients fail to develop significant long-term effects even after 10 to 15 years of therapy. Potential delayed side effects include: + Abnormal and involuntary movements: Twisting and dancing movements of the arms, legs and trunk (dyskinesias) and unusual muscle contractures or cramps, especially in the foot (dystonia) + Wearing off: A tendency for the benefits of each individual dose of medication to wear off in a predictable manner before the next is scheduled to be taken + On-off episodes: Unpredictable fluctuations in motor function, not clearly associated with the taking of medications + The potential for long-term complications of carbidopa/levodopa has led to controversy about when in the course of Parkinson's to start levodopa treatment. It is appropriate to discuss concerns about such matters with your doctor. CONTRAINDICATIONS + Certain forms of glaucoma Patients should have eye pressures checked at the beginning of treatment and at frequent intervals after starting treatment. + Malignant melanoma Controversial, but if a patient has a history of melanoma, this should be brought to the attention of his or her physician. + Peptic ulcer disease Having this disease may also be a relative contraindication. + Stopping levodopa In general, levodopa should be slowly tapered off over the course of several days. Abruptly stopping Levodopa can lead to a severe syndrome of increased muscular rigidity, elevated body temperature and increased confusion (malignant hyperthermia). If these problems develop, they require immediate medical attention. SINEMET CR (CONTINUOUS RELEASE CARBIDOPA/LEVODOPA) 25/100 PINK TABLET, 50/200 TAN TABLET Sinemet CR is a long-acting carbidopa /levodopa preparation that releases levodopa more slowly into the intestines. This results in more sustained levodopa absorption, with a longer duration of action and, in general, lower peak-dose effects. Due to lower peak-dose levels, some patients may not "turn-on" with Sinemet CR and may need to take regular Sinemet with it, especially at the time of the first morning dose. Sinemet CR may be broken in half, in which case its effects are intermediate between regular Sinemet and unbroken Sinemet CR. Crushing this medication is not advised, as it eliminates its slow-release properties. The four situations in which Sinemet CR is generally used are as follows: + Early in the course of treatment, as the initial form of levodopa therapy + When "wearing off" problems begin to appear (Sinemet CR can help by prolonging the duration of levodopa action) + When there are predictable peak dose dyskinesias (Sinemet CR can help by decreasing peak levodopa levels) + When there are parkinsonian mobility problems at night. (Sinemet CR can help by producing a more sustained level of levodopa through the night and improve sleep. This may also help to decrease early morning dystonia.) SIDE EFFECTS OF SINEMET CR (CONTINUOUS RELEASE LEVODOPA) The side effects for Sinemet CR are the same as for regular release Sinemet discussed earlier. Some older patients may show increased confusion with Sinemet CR, whereas others will have fewer problems on this preparation. Those patients who do not "turn on" with Sinemet CR, may need to couple this medication with a small dose of regular Sinemet. Sinemet CR may precipitate the appearance of dyskinesias in some patients, or cause an aggravation of pre-existing dyskinesias. DOPAMINE AGONISTS PERMAX (PERGOLIDE), PARLODEL (BROMOCRIPTINE), APOMORPHINE INVESTIGATIONAL AGENTS: CABERGOLINE, ROPINEROLE, PRAMIPEXOLE Dopamine agonists are commonly used as adjuncts to Sinemet in treating the motor symptoms of Parkinson's disease. Drugs in this class stimulate the brain directly by mimicking dopamine and do not have to be converted into other compounds. Although generally not as effective as Sinemet in decreasing symptoms, these agents may offer the Parkinson's patient other treatment advantages including: (a) a longer duration of action, (b) absorption which is generally not limited by the presence of food or protein; and, (c) effectiveness even when levodopa ceases to be effective (controversial). SIDE EFFECTS OF DOPAMINE AGONISTS + Low blood pressure upon standing, causing symptoms of light-headedness, dizziness, neck pain and imbalance + Hallucinations, confusion, or bad dreams + Nausea, stomach upset, constipation and occasional vomiting + Ankle swelling, or edema + New or worse dyskinesias, though these generally subside with lowering of the levodopa dose + Note: A rare side effect of treatment with some of these drugs is increased shortness of breath, caused by scarring around the heart or within the lung. This complication requires that the patient be promptly tapered off this medication. APOMORPHINE This dopamine agonist medication is no longer being manufactured in the United States and has not been approved by the Food and Drug Administration (FDA) as an anti-parkinsonian medication. It is being utilized in many other countries throughout the world as a dopamine agonist (see description above). Unlike other dopamine agonists available in the United States (pergolide, bromocriptine), Apomorphine can be injected. When administered in this manner, it has a rapid onset of action. It can be very useful for reversing off periods and may also be useful for the treatment of various parkinsonian dystonias. The major side effects of treatment are severe problems with nausea and vomiting and a fall in blood pressure upon standing. To a great extent, these side effects can be prevented by taking domperidone. Skin nodules can form, at frequent injection sites if apomorphine is injected subcutaneously. SYMMETREL (AMANTADINE) 100 MG CAPSULES (RED, YELLOW), SUSPENSION (50 MG / 5 CC = TEASPOON) Symmetrel (amantadine) is most frequently used as an adjunctive agent in the treatment of motor symptoms. It was initially introduced to prevent infection with influenza A virus. After its introduction, however, it was serendipitously found to have anti-Parkinson's effects. The mechanism of anti-parkinsonian action of this medication is still unclear, though it may increase dopamine release or block certain excitatory brain receptors (the NMDA receptors) and thereby improve movement. SIDE EFFECTS OF SYMMETREL (AMANTADINE) + Nausea, light-headedness, difficulty with sleep, ankle swelling or edema, hallucinations + Anxiety, bad dreams, dry mouth, difficulty with urination and increased problems of constipation + Occasional mottling of the skin (livedo reticularis), which may require discontinuation of this medication + Symmetrel should be slowly discontinued or malignant hyperthermia could result. (See earlier discussion on stopping carbidopa/levodopa.) ELDEPRYL (SELEGILINE) 5 MG WHITE TABLETS, MAXIMUM DOSE _ 10 MG/DAY Eldepryl (selegiline) is a monoamine oxidase type B inhibitor (MAO-B Inhibitor). Monoamine oxidase is an enzyme used by the brain to metabolize, or break down, dopamine. Eldepryl often prolongs the effects of levodopa therapy by prolonging dopamine action in the brain. The metabolism of dopamine can also cause potentially harmful substances (called free radicals) to accumulate in the brain. By inhibiting dopamine metabolism, Eldepryl may inhibit the production of these substances and thereby have a protective action. Eldepryl has been reported to be of value in three situations, as follows: + In the early symptomatic treatment of Parkinson's before levodopa is begun + For "wearing off" problems, by prolonging levodopa action + As a "neuro-protective" agent or "free-radical scavenger" to slow Parkinson's disease progression (controversial) SIDE EFFECTS OF ELDEPRYL + Nausea, stomach upset, light-headedness + Insomnia, especially if taken after 1 or 2 pm + Confusion, hallucinations and nightmares (more commonly encountered in older patients, or those who have had Parkinson's for many years) + Occasionally Eldepryl may worsen dyskinesias or cause other side effects similar to those of levodopa excess CONTRAINDICATIONS When combined with anti-depressant medications, Eldepryl can uncommonly cause a severe syndrome characterized by increased rigidity, jerking movements of the arms and legs, agitation, confusion, restlessness, fever, shivering and sweating ("serotonin syndrome"). The simultaneous use of anti-depressant medications and Demerol-a pain reliever _ should be avoided in patients taking Eldepryl. Patients taking Eldepryl may be advised to wear a Medic-Alert -type bracelet to decrease the likelihood of receiving a medication that may interact with Eldepryl. ANTI-CHOLINERGIC MEDICATIONS ARTANE (TRIHEXYPHENIDYL), COGENTIN (BENZTROPINE MESYLATE) AND OTHERS Anti-cholinergic medications are historically the first type of medications to be successfully used in the treatment of Parkinson's disease and may still be of adjunctive value in reducing tremor and rigidity. Many medications with strong anti-histamine properties such as Benadryl (diphenhydramine) and Periactin (cyproheptadine) also have anti-cholinergic effects and may also be useful. SIDE EFFECTS OF ANTI-CHOLINERGIC MEDICATIONS + Dry mouth, blurring of near vision, constipation, urinary hesitancy and retention (especially in men) + Mental confusion, decreased memory and hallucinations (especially in older patients or those who are already having problems with mental clarity) + Patients with hiatal hernia and gastroesophageal reflux may experience increased symptoms of "heart burn" CONTRAINDICATIONS Patients who have certain types of glaucoma, who have severe problems with urination, or who have unusually severe problems with confusion or forgetfulness, should not take anti-cholinergic medications. ==================================================== End Part I Regards, Alan