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Parkinsn Current Topics
Medications in PD
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.
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 AND OTHER AGENTS OCCASIONALLY USED TO TREAT ASSOCIATED PROBLEMS OF PARKINSON'S DISEASE
BETA BLOCKERS
INDERAL (PROPRANOLOL), TENORMIN (ATENOLOL) AND OTHERS
Beta blockers are of no direct value in the treatment of Parkinson's symptoms and may occasionally limit levodopa effectiveness. Some patients with Parkinson's, however, have an action or intention tremor brought on by elevation or movement of their arms and which is different from their usual rest tremor. This tremor can at times be reduced in severity by the use of beta blockers.
SIDE EFFECTS OF BETA BLOCKERS
+ Fatigue, nausea and vivid dreaming + Occasional reports of increased forgetfulness + Wheezing, difficulty breathing, fatigue
CONTRAINDICATIONS
Patients with a history of congestive heart failure, slow heart rate, asthma, bronchitis or emphysema; and people with diabetes who are taking insulin usually should not take beta blockers. Patients on this class of medication should know how to take their own pulse and should contact their physicians if their pulse rate falls below 50-60 beats per minute.
SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS (SSRI) ANTIDEPRESSANTS
PROZAC (FLUOXETINE), ZOLOFT (SERTRALINE), PAXIL (PAROXETINE) AND OTHERS
Depression is more common in Parkinson's disease than in other chronic illnesses of similar severity, probably due to an alteration of neurotransmitter levels in the brain, including the levels of serotonin and norepinephrine. Depression in the Parkinson's patient can worsen virtually all symptoms of the disorder, which in turn can deepen the patient's depression, causing a vicious circle of physical and mental impairment. Often, in order for a patient to get maximal benefit from anti-parkinsonian medications, the depression must be treated.
The selective serotonin re-uptake inhibitors (SSRI) antidepressants appear to work by raising serotonin levels in the brain. While they cause few of the side effects associated with the older generation antidepressants, they are much more expensive. Parkinsonian signs often improve following treatment with SSRI antidepressants as depression resolves. In selected patients, SSRI antidepressants may have a more direct effect in relieving certain symptoms of Parkinson's disease by potentiating the effects of dopamine.
SIDE EFFECTS OF SSRI ANTIDEPRESSANTS
+ Nausea, diarrhea, headache, sleepiness, loss of appetite, fatigue and problems having an ejaculation + Prozac and to a lesser degree Zoloft, can cause tremor, insomnia and anxiety. + If taken in the morning, Paxil and Zoloft can cause excessive sleepiness. + Note: On occasion these medications can actually worsen the symptoms of Parkinson's disease or cause a sense of physical restlessness.
CONTRAINDICATIONS
When combined with Eldepryl (selegiline), these medications 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 these
medications and Eldepryl should be discussed with your physician.
OTHER ANTIDEPRESSANT MEDICATIONS
TRICYCLIC ANTIDEPRESSANTS: E.G., ELAVIL (AMITRYPTYLINE), PAMELOR (NORTRIPTYLINE), NORPRAMIN (DESIPRAMINE), TOFRANIL (IMIPRAMINE)
OTHER TYPES OF ANTIDEPRESSANTS: E.G., WELLBUTRIN (BUPROPRION), DESYREL (TRAZADONE)
Most of these antidepressant medications have been available for many years and are as effective in the treatment of depression as the SSRI antidepressants They tend to be less expensive, but usually have more side effects.
SIDE EFFECTS OF ANTIDEPRESSANT MEDICATIONS
+ Dryness of the mouth, blurring of near vision, constipation, urinary hesitancy and retention (especially in men) + Abnormal heart rhythms, low blood pressure, upon standing causing symptoms of lightheadedness, excessive sedation or sleepiness and weight gain + Impaired memory function, especially in older patients or those who are already having problems with mental clarity + Confusion and sleepiness which can contribute to walking imbalance and, therefore, to falls
SIDE EFFECTS OF SPECIFIC ANTIDEPRESSANT MEDICATIONS
+ Wellbutrin (buproprion)-seizures + Desyrel (trazadone)--sleepiness, abnormally prolonged erections.
CONTRAINDICATIONS
Patients who have certain types of glaucoma, who have severe problems with
urination or urinary retention, or who have moderate problems of
forgetfulness or dizziness due to low blood pressure, should in most
instances not take tricyclic antidepressant medications. When combined with
Eldepryl (selegiline), these medications can rarely 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 these medications and Eldepryl should be
carefully discussed with your physician.
ANTI-ANXIETY AND SLEEPING MEDICATIONS
ANTI-ANXIETY: E.G., VALIUM (DIAZEPAM), ATIVAN (LORAZEPAM), KLONOPIN (CLONAZEPAM), BUSPAR (BUSPIRONE)
SLEEPING MEDICATIONS: E.G., HALCION (TRIAZOLAM), AMBIEN (ZOLPIDEM)
All of these medications are classified as sedative-hypnotic agents and can be beneficial in reducing anxiety and promoting sleep. Since some Parkinson's symptoms can be worsened by anxiety, these medications can help relieve symptoms such as tremor and dyskinesia. Klonopin appears to have some unique characteristics and has been used in the treatment of several abnormal movement types. Buspar has been used to treat dyskinesias with variable success.
SIDE EFFECTS OF ANTI-ANXIETY AND SLEEPING MEDICATIONS
+ Sedation (excessive sleepiness): This can interfere with one's ability to operate machinery, such as a motor vehicle and contribute to waling imbalance and falls. + Occasionally, patients can become psychologically, as well as physically, dependent upon these medications and experience withdrawal symptoms upon their discontinuation. + Patients who depend upon these medications to sleep can have aftereffects lasting into the next day, which can impair memory and other thinking functions. Under these conditions, patients may have greater problems with walking balance and be more susceptible to falls. + Buspar (buspirone) appears to have a lower risk of physical and psychological dependence, but some patients may experience a worsening of Parkinson's symptoms.
MEDICATIONS TO TREAT CONFUSION (MAJOR TRANQUILIZERS)
TYPICAL TRANQUILIZERS E.G., THORAZINE (CHLORPROMAZINE), HALDOL (HALOPERIDOL), MELLARIL (THIORIDAZINE), RISPERDAL (RISPERIDONE)
ANTI-NAUSEA, ANTI-EMETIC AGENTS: E.G., COMPOZINE (PROCHLORPERAZINE), TIGAN, PHENERGAN
These medications, which sometimes are referred to as "neuroleptics," are used to treat various psychiatric problems such as confusion, frightening hallucinations and delusions. They can also be useful in treating problems of nausea and vomiting. In general, they are contraindicated for the Parkinson's patient since they may severely worsen the symptoms of Parkinson's disease. Even in persons who do not have Parkinson's, the prolonged use of neuroleptics has been associated with "drug induced" or symptomatic Parkinson's.
ATYPICAL TRANQUILIZERS
CLOZARIL (CLOZAPINE)
Clozaril appears to be unique in that it can help relieve the symptoms of confusion and hallucinations without significantly worsening the symptoms of Parkinson's in most patients. It has also been used to treat a number of movement problems associated with Parkinson's such as severe dyskinesias.
SIDE EFFECTS OF CLOZARIL
+ Sedation (excessive sleepiness): a drop in blood pressure on standing, causing faintness; and hypersalivation with increased drooling + Seizures: generally at higher doses than those used in Parkinson's patients + Severe lowering of white blood cell count (agranulocytosis), which can compromise a person's ability to fight infection and has led to a number of deaths in patients treated with Clozaril. For this reason, weekly blood counts must be taken on all patients receiving Clozaril and no patient may receive more than a one week's supply of medication at a time.
SOME OTHER MEDICATIONS USED IN PARKINSON'S PATIENTS
LODOSYN (CARBIDOPA)
Upon first taking Sinemet (levodopa / carbidopa), some patients experience nausea and vomiting. For some, this problem can persist for months and prevent them from taking Sinemet as prescribed. By taking supplemental carbidopa pills, this problem can sometimes be effectively controlled.
MOTILIUM (DOMPERIDONE)
This medication has not been approved by the Food and Drug Administration and is not available by prescription within the United States. It is, however, available in many European countries, Mexico and Canada. Its primary value for the Parkinson's patient is in preventing levodopa-associated nausea and vomiting when extra carbidopa is ineffective. Preliminary studies would suggest that this is generally a safe medication and one that is well tolerated by patients.
ZOFRAN (ONDANSETRON)
This is a very expensive medication that is primarily used with cancer chemotherapy to prevent nausea. There are several brief reports of its value in relieving confusion, hallucinations and delusions in Parkinson's patients. In general, this medication is very well tolerated, with the major side effects being headaches, diarrhea and fatigue. The high cost of this medication, however, is frequently a prohibitive factor for treatment.
HYDERGINE (COMBINATION OF ERGOLOID MESYLATES)
This agent was introduced many years ago for the treatment of senile dementia. Despite years of study, there is still controversy whether Hydergine improves thinking abilities and /or behavior in those with dementia: Some of the agents contained in Hydergine have dopamine agonist properties and have been shown in both human and animal studies to have anti-parkinsonian effects. The doses used in these studies are, however, many times those customary for Hydergine use in medical treatment. Even at high doses, the ergoloid mesylates have not been directly compared to available dopamine agonists, such as pergolide, to see if they have any special advantages. Hydergine and its related compounds are. claimed to have anti-oxidant properties, but the clinical significance of these effects is unknown. Side effects of treatment include nausea, stomach upset, headache and low blood pressure. At high dose, these agents may also be associated with spasm of the blood vessels in the arms or legs.
BOTOX (BOTULINUM TOXIN A)
This is one of the most potent biological toxins known to man. When injected into a muscle, botulinum toxin poisons nerve endings, causing muscle weakening and wasting, which can persist for several months. Some patients with Parkinson-related dystonia can have the severity of their dystonia reduced by receiving injections into the dystonic muscles. Treatment with this agent, however, is very expensive.
FLORINEF (FLUDROCORTISONE ACETATE)
This is the most commonly used medication to treat symptoms of orthostatic hypotension, which is a severe drop in blood pressure caused by standing. Florinef causes the body to hold onto salt and water and can increase the volume of fluid within the circulatory system. Ankle swelling and weight gain are expected side effects of treatment. Persons receiving Florinef should cautiously increase their salt intake to enhance its actions. Potassium supplements are additionally indicated in many patients to prevent potassium levels from falling dangerously low. Patients taking Florinef should record their weights on a daily basis, particularly when this medication is first started, or when doses are raised.
Note: Florinef used with caution when there is a history of heart disease since it can cause congestive heart failure and high blood pressure when one is lying down.
DDAVP (DESMOPRESSIN)
Available in nose-spray and nose-drop preparations, this hormone analogue decreases the production of urine. It has been approved as a means of preventing bed wetting in children. When taken as a single dose at night, it may help Parkinson's patients who have severely reduced bed mobility, by decreasing their need to urinate at night. Due to water retention, Desmopressin may cause severe electrolyte disturbances and high blood pressure and its use must therefore be carefully monitored.
LIORESAL (BACLOFEN)
This medication is primarily used to reduce spasticity. It is also of benefit in patients with certain forms of dystonia. When taken at night it may help reduce painful ankle dystonia and muscle cramps which are experienced by some Parkinson's patients at night or upon awakening in the morning. Potential side effects include sleepiness, a sense of generalized weakness and fatigue and confusion.
STIMULANTS
CYLERT (PEMOLINE), RITALIN (METHYLPHENIDATE), DEXEDRINE (DEXTROAMPHETAMINE), CAFFEINE AND OTHERS
Stimulants are occasionally used to offset the sedative effects of levodopa and other Parkinson's medications and may additionally have mild anti-depressant and analgesic effects. Ritalin and Dexedrine are tightly controlled and require special prescriptions.
SIDE EFFECTS OF STIMULANTS
Weight loss, agitation, insomnia, palpitations, anxiety, physical and psychological dependence
CONTRAINDICATIONS
Patients with advanced heart disease, hyperthyroidism, or a history of drug dependency should not take stimulants.
PROPULSID (CISAPRIDE)
Propulsid increase the motility or contractions of the stomach, allowing food and medications to pass more quickly from the stomach into the small intestine. Some Parkinson's patients have difficulty with stomach emptying, which in turn can cause a delay in the absorption of levodopa. Propulsid may help make drug absorption quicker and more predictable in such patients. Reglan (metoclopramide) has similar actions, but may cause confusion and worsen Parkinson's symptoms. For these reasons, its use is contraindicated in Parkinson's disease. Propulsid has also been used in the treatment of constipation, with variable success. Some Parkinson's patients have recently been reported to have increased tremor while taking Propulsid.
ANTIOXIDANT VITAMINS
VITAMIN C-ASCORBIC ACID, VITAMIN E, BETA-CAROTENE
Knowledge is rapidly evolving on the importance of antioxidant agents in laboratory animal models of Parkinson's disease. It is hoped that the use of antioxidant agents can slow the progression of Parkinson's disease and, in some instances, improve related symptoms. To date, however, there is no large, well-controlled study indicating any benefit of antioxidant vitamins for Parkinson's patients. Generally, the vitamins listed above are safe, though high doses of Vitamin C have been associated with stomach upset and kidney stones.
LAXATIVES AND STOOL SOFTENERS
Chronic constipation can cause considerable discomfort for Parkinson's patients. In some patients, inadequately treated constipation can contribute to loss of appetite and weight loss, inactivity, fatigue, discouragement and even confusion. Others can experience problems associated with unpredictable medication absorption such as unpredictable dyskinesias and "off" periods. Various over-the-counter and prescription medications are available to treat this problem. Your doctor can help you develop a sensible and effective bowel regimen.
MELATONIN
Melatonin is a natural hormone produced by the pineal gland of the brain. It has been promoted as a sleep-inducing aid and has traditionally been available through various health food stores. There is still considerable question whether melatonin is safe and effective in the treatment of insomnia or for use as an antioxidant. Some scientists question the safety, purity and potency of unregulated off-the-shelf melatonin purchased through health food stores. There are concerns that unanticipated adverse effects or contaminants can cause serious toxicity. Comparisons have been made to tryptophan, an amino acid which until recently was also sold as a sleeping aid in health food stores. Tryptophan was taken off the market after nearly 40 people died and hundreds were disabled following its use.
DRUG INTERACTIONS
There are many real and potential drug interactions with new interactions recognized on an ongoing basis. The following list, while incomplete, highlights several drugs that could have potentially significant interactions. Also see Appendix B and C for a list of drugs that may be contraindicated in Parkinson's disease.
+ Prozac, Paxil, Zoloft and other Serotonin Enhancing Medications and Eldepryl (see "Serotonin Syndrome" in Eldepryl section). + Demerol and Eldepryl
APPENDIX A
CITY OF HOPE NATIONAL MEDICAL CENTER
CITY OF HOPE
City of Hope is comprised of City of Hope National Medical Center and Beckman Research Institute, both of which are located on a 100-acre campus in Duarte, California. Founded in 1913, City of Hope is a Clinical Cancer Research Center, a designation it received from the National Cancer Institute in 1981.
For the past 82 years, City of Hope has employed the expertise of health care professionals and scientists who are the finest in their fields and who are committed to working together to provide the latest advances in clinical care and to conduct innovative basic research into cancer as well as other major diseases such as diabetes. Through their collaboration, these professionals are committed to furthering City of Hope's dedication to providing compassionate, quality care.
CITY OF HOPE PARKINSON'S CLINIC
NEW PATIENT REFERRAL INFORMATION
Those wishing to make an appointment at the City of Hope Parkinson's Clinic may do so by contacting the City of Hope Patient Referral Department at (818) 359-8111, Ext. 3292. All patients are encouraged to bring copies of pertinent medical records including brain MRI or CT scans to their appointments. Health maintenance organization (HMO) patients who do not have prior authorization from their HMO can be seen on a second-opinion basis.
NATIONAL PARKINSON'S FOUNDATION (NPF)
Founded in 1957, NPF is headquartered at the University of Miami, where it supports a multidisciplinary Parkinson's treatment and research program. In addition, NPF funds 31 Research Centers of Excellence located in prestigious medical institutions around the world. During 1995, NPF has added several more Research Centers of Excellence and a number of newly designated Clinical Centers of Excellence, including one at City of Hope National Medical Center. Many of the Research Centers and all of the Clinical Centers provide diverse services for patients and their families, including diagnosis, treatment, educational services, information and referrals and the sponsorship of support groups in neighboring areas. In addition to its headquarters in Miami, NPF also has an office in Encino, California. Questions about NPF can be directed to Mary Willis, City of Hope, NPF Parkinson's Coordinator (818-301-8985) or to Kim Seidman, NPF West Coast Director (800-400-8448).
APPENDIX B
MEDICATIONS TO BE AVOIDED OR USED WITH CAUTION BY PARKINSON'S PATIENTS
LISTED BY MEDICATION TYPE
Medication Type Brand Name Generic Name Risk Factor Analgesic Demerol Meperidine High* Anti-Anxiety Buspar Buspirone Low Anti-Vomiting Compazine Prochlorperazine High Anti-Vomiting Reglan Metoclopramide High Anti-Vomiting Tigan Trimethobenzamide Moderate Anti-Vomiting Torecan Triethylperazine High Antidepressant Ascendin Amoxapine Moderate Antidepressant Nardil Phenelzine High Antidepressant Parnate Tranylcypromine High Antidepressant Paxil Paroxetine Low Antidepressant Prozac Fluoxetine Low Antidepressant TriaviI Perphenazine** High Antidepressant Zoloft Sertraline Low Antipsychotic Haldol Haloperidol High Antipsychotic Loxitane Loxapine High Antipsychotic Mellaril Thioridazine Moderate Antipsychotic Moban Molindone Moderate Antipsychotic Navane Thiothixene High Antipsychotic Orap Pimozide High Antipsychotic Permitil Fluphenazine High Antipsychotic Prolixin Fluphenazine High Antipsychotic Risperdol Risperidone Moderate Antipsychotic Stelazine Trifluoperazine High Antipsychotic Trilafon Perphenazine High Antipsyehotic Thorazine Chlorpromazine High Blood Pressure Aldomet Alpha-methyldopa Low Blood Pressure Cardizem Diltiazem Low Blood Pressure Catapres Clonidine Low Blood Pressure Demi-Regroton Reserpine High Blood Pressure Diupres Reserpine** High Blood Pressure Enduronyl Deserpidine** High Blood Pressure Harmonyl Deserpidine High Blood Pressure Hydropres Reserpine** High Blood Pressure Oreticyl Deserpidine High Blood Pressure Raudixin Rauwolfia S. High Blood Pressure Rauzide Rauwolfia S.** High Blood Pressure Regroton Reserpine High Blood Pressure Salutensin Reserpine High Blood Pressure Ser-Ap-Es Reserpine High Manic Depression Lithobid Lithium Low
* If taking Eldepryl ** Constituent product
APPENDIX C
MEDICATIONS TO BE AVOIDED OR USED WITH CAUTION BY PARKINSON'S PATIENTS
LISTED BY BRAND NAME OF MEDICATION
Brand Name Generic Name Medication Type Risk Factor Aldomet Alpha-methyldopa Blood Pressure Low Ascendin Amoxapine Antidepressant Moderate Buspar Buspirone Anti-Anxiety Low Cardizem Diltiazem Blood Pressure Low Catapres Clonidine Blood Pressure Low Compazine Prochlorperazine Anti-Vomiting High Demerol Meperidine Analgesic High* Demi-Regroton Reserpine Blood Pressure High Diupres Reserpine** Blood Pressure High Enduronyl Deserpidine** Blood Pressure High Haldol Haloperidol Antipsychotic High Harmonyl Deserpidine Blood Pressure High Hydropres Reserpine** Blood Pressure High Lithobid Lithium Manic Depression Low Loxitane Loxapine Antipsychotic High Mellaril Thioridazine Antipsychotic Moderate Moban Molindone Antipsychotic Moderate Nardil Phenelzine Antidepressant High Navane Thiothixene Antipsychotic High Orap Pimozide Antipsychotic High Oreticyl Deserpidine Blood Pressure High Parnate Tranylcypromine Antidepressant High Paxil Paroxetine Antidepressant Low Permitil Fluphenazine Antipsychotic High Prolixin Fluphenazine Antipsychotic High Prozac Fluoxetine Antidepressant Low Raudixin Rauwolfia S. Blood Pressure High Rauzide Rauwolfia S.** Blood Pressure High Reglan Metoclopramide Anti-Vomiting High Regroton Reserpine Blood Pressure High Risperdol Risperidone Antipsychotic Moderate Salutensin Reserpine Blood Pressure High Ser-Ap-Es Reserpine Blood Pressure High Stelazine Trifluoperazine Antipsychotic High Thorazine Chlorpromazine Antipsyehotic High Tigan Trimethobenzamide Anti-Vomiting Moderate Torecan Triethylperazine Anti-Vomiting High TriaviI Perphenazine** Antidepressant High Trilafon Perphenazine Antipsychotic High Zoloft Sertraline Antidepressant Low
* If taking Eldepryl ** Constituent Product
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