Parkinson’s Disease
History
1. How long has Parkinson’s been around?
Ans. Probably more than 182 years.
2. Who was the disease named after?
Ans. James Parkinson in 1817.
What Is It?
1. What is Parkinson’s disease?
Ans. Parkinson’s disease is a neurodegenerative disease. Parkinson’s
Disease is defined by its cardinal features.
2. What are the cardinal features of Parkinson’s disease?
Ans. They are:
i. Bardykinesia- which is slowness of movement, which includes
difficulty initiating movements, incompleteness of ongoing
movements, and arrest of on going movements.
ii. Muscle rigidity- which is an increased resistance to stretch at major
joints. It can be felt at one, several, or all major joints.
iii. Resting Tremor- occurs when muscles are relaxed
iv. Postural Instability- is the inability to respond to or compensate for
hidden changes such as an abrupt turn
3. Who does Parkinson’s diseases effect?
Ans. 1% of all adults over 65. There seems to be a correlation; the older
you are the more likely you are to get Parkinson’s disease.
4. At what level of dopamine depletion in Parkinson’s considered a clinical disease?
Ans. When 80% of dopamine neurons are lost and your body has been
depleted of dopamine to about 20%.
5. What is the cause of Parkinson’s disease?
Ans. The cause is unknown. There is no test that reveals a cause or
confirms the diagnosis of the disease.
6. Is there a cure for Parkinson’s disease?
Ans. NO
Biological Aspects
1. What occurs in the brain of someone who has Parkinson’s?
Ans. What happens is the part of the brain that produces dopamine, the
substantia nigra, begins to decrease in number, which causes decrease
amount of available dopamine. Your brain is also breaking down
dopamine in the synapse naturally by MAO-B. This leaves you with little
dopamine, and the loss of dopamine throws off the neural balance of
dopamine/ acetlycholine.
Carbidopa/Levodopa
TRADE NAME: Sinemet
USEFUL DAILY DOSE: 200-1200 mg
DRUG CLASS AND MECHANISM: Levodopa-carbidopa is a combination of two drugs,
levodopa and carbidopa. When levodopa is taken orally, it crosses through the "blood- brain
barrier." Once it crosses, it is converted to dopamine. The resulting increase in brain
dopamine concentrations is believed to improve nerve conduction and assist the movement
disorders in Parkinson disease. Carbidopa does not cross the blood-brain barrier.
Carbidopa is added to the levodopa to prevent the breakdown of levodopa before it crosses into
the
brain. The addition of carbidopa allows lower doses of levodopa to be used. This reduces
the risk of side effects from levodopa such as nausea and vomiting. This combination medicine
was approved by the FDA in 1988.
PHARMACOKINETICS: SinemetTM is administered orally. Following oral administration,
amino acid transport mechanisms carry levodopa across the membrane of the GI tract, with
approximately 30-50% of the drug entering the circulation. As a result, high
concentrations of amino acids in the GI tract (i.e., a high- protein diet) can interfere with
absorption of levodopa. Bioavailability of controlled-release preparations of levodopacarbidopa is approximately 71% compared with 99% for regular- release preparations.
Levodopa-carbidopa distributes throughout the body, but due to peripheral metabolism,
less than 1% of levodopa reaches the CNS; carbidopa does not penetrate the CNS.
Approximately 95% of a dose of levodopa is metabolized to dopamine by L-aromatic
amino acid decarboxylase in the stomach, intestines, and liver. Carbidopa is not appreciably
metabolized. The onset of action of levodopa-carbidopa can be observed 2-3 weeks after
therapy is initiated, but some patients require up to 6 months of therapy before beneficial effects
are seen. The plasma half-life of both levodopa and carbidopa is roughly 1-2 hours, and
the duration of action of a dose is 5 hours. Levodopa-carbidopa is eliminated renally as dopamine
metabolites and small amounts as unchanged drug.
DRUG INTERACTIONS: The use of amantadine (Symmetrel), benztropine (Cogentin),
procyclidine (Kemadrin), or trihexyphenidyl (Artane) with levodopa-carbidopa can enhance the
antiParkinson's effects of levodopa. Droperidol, haloperidol (Haldol), loxapine (Loxetine),
metoclopramide (Reglan), phenothiazines such as prochlorperazine (Thorazine); thioxanthenes
as
thiothixene (Navane) inhibit dopamine in the brain. These drugs, therefore, can worsen
Parkinson's disease and reverse the beneficial effects of levodopa. Methyldopa (Aldomet) and
reserpine also can interfere with the beneficial actions of levodopa- carbidopa and can
increase the risk of side effects.
Phenytoin (Dilantin) can increases the break-down of levodopa- carbidopa, reducing its
effectiveness.
Use of levodopa-carbidopa with monoamine oxidase inhibitors (MAOI's) antidepressants,
for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and
procarbazine (Matulane), can result in severe and dangerous elevations in blood
pressure. MAOI's should be stopped 2-4 weeks before starting levodopa-carbidopa therapy.
The side effects associated with levodopa, including dizziness upon rising, confusion,
movement disorders, nausea, and hallucinations, all can be increased by selegiline (Eldepryl).
PREGNANCY: Although there are no human studies that have examined the effects of
levodopa-carbidopa on the fetus, animal studies have shown adverse effects. Therefore, in
prescribing levodopa- carbidopa for a pregnant woman, the physician must weigh the
potential risks to the fetus against the potential benefits to the mother. Levodopa is also
distributed
into breast milk. It also may inhibit production of milk. It is generally
recommended that levodopa-carbidopa should not be given to women who are breast- feeding.
SIDE EFFECTS: Serious side effects with levodopa-carbidopa include difficulty passing
urine, dizziness, lightheadedness or fainting spells, fast or irregular heartbeat (palpitations),
mental depression, mood changes such as aggressive behavior or hallucinations,
stomach pain, uncontrolled movements of the mouth, head, hands, feet, shoulders, eyelids or
other unusual muscle movements, unusual bleeding or bruising, and unusual tiredness. Minor
side effects include memory loss, anxiety, mental depression or euphoria, confusion, or
nervousness, constipation, diarrhea, dry mouth, flushing of the skin, headache, loss of
appetite, muscle twitches, nausea/vomiting, nightmares, trouble sleeping, and unusual tiredness
or weakness. Infrequently, patients may develop a drop in white blood cell count during
levodopa-carbidopa therapy. This is a cause to temporarily, if not permanently, stop treatment.
Pergolide
TRADE NAME: Permax
USEFUL DAILY DOSE: 0.75-5.0 mg
DRUG CLASS AND MECHANISM: Pergolide (PermaxTM ) can help correct an
imbalance of chemicals in the brain thought to be responsible for Parkinson's disease. Pergolide
helps to improve muscle control and movement difficulties. Pergolide will not cure Parkinson's
disease, but will help to control the symptoms and slow down the progression of the disease.
Pergolide tablets are taken together with other tablets that control parkinsonian
symptoms. As a potent dopaminergic agonist, pergolide, taken orally, directly stimulates
postsynaptic
dopamine receptors in the nigrostriatal system. The dopamine-agonist
properties of pergolide are not associated with presynaptic dopamine synthesis or stores;
pergolide is an agonist at postsynaptic receptors. Pergolide is one of the most potent
dopaminergic agonists. Unlike bromocriptine, pergolide stimulates both DA and DA receptors.
Pergolide also causes less
nausea and orthostatic hypotension than does bromocriptine and
may be effective in patients who have become tolerant to bromocriptine. Pergolide is
administered orally and is well absorbed. It is approximately 90% bound to plasma proteins.
The drug undergoes metabolism to 10 metabolites, some of which are pharmacologically active.
Elimination of the drug is
primarily renal. The elimination half-life has been
reported as 27 hours.
DRUG INTERACTIONS: Pergolide is a potent dopamine-receptor agonist. Dopaminereceptor antagonists, including the neuroleptics (phenothiazines, haloperidol, and thiothixene), or
metoclopramide should not be administered concurrently because they can antagonize
the effects of pergolide. Other medicines that can interact with pergolide include medicines for
mental problems and psychotic disturbances.
Concomitant administration of amantadine, benztropine, procyclidine, or trihexyphenidyl
with levodopa-carbidopa can enhance the therapeutic effects of levodopa but should not be used
in patients with a history of psychosis.
Droperidol; haloperidol; loxapine; phenothiazines; thioxanthenes (thiothixene and
chlorprothixene); and possibly papaverine inhibit dopamine receptors in the brain, exacerbating
parkinsonism and antagonizing the therapeutic effects of levodopa. Molindone can block
dopamine receptors in the brain, interfering with the antiparkinsonian effects of levodopa and
levodopa can antagonize the antipsychotic effects of molindone.
Phenytoin can interfere with the effects of levodopa-carbidopa by enhancing the
metabolism of the drug.
The concomitant administration of bromocriptine with levodopa-carbidopa can result in
additive effects that can be used to therapeutic advantage and allow for reduced dosages of
levodopa-carbidopa.
High-protein diets can interfere with the absorption of levodopa from the GI tract, thereby
delaying its effects. Amino acids can compete with levodopa for transport into the brain,
producing an erratic response to the drug.
Concomitant use of monoamine oxidase inhibitors (MAOIs) with levodopa-carbidopa can
result in hypertensive crisis. Simultaneous use of these agents is contraindicated. MAOIs should
be discontinued 2-4 weeks before initiation of levodopa- carbidopa therapy.
PREGNANCY: Pergolide is classified as pregnancy category B. No adequate studies
have examined the effects of pergolide on the human fetus. Animal reproduction studies have
shown no adverse fetal effects.
SIDE EFFECTS: Serious side effects with pergolide include anxiety, restlessness,
confusion, double vision, or other vision problems, fainting spells, hallucinations, headache,
mental
changes, palpitations, and uncontrollable movements of the arms, face, hands,
head, mouth, shoulders, or upper body. Minor side effects with pergolide include constipation or
diarrhea, difficulty sleeping, dizziness or drowsiness, flu-like symptoms
(fever/chills/muscle aches), loss of appetite, lower back pain, chest or neck pain, nausea/vomiting,
runny or
stuffy nose, stomach pain, unusual weakness, and weight change.
Bromocriptine
TRADE NAME: Parlodel
USEFUL DAILY DOSE: 3.75-40 mg
DRUG CLASS AND MECHANISM: Bromocriptine (ParlodelTM ) comes from a group of
medicines known as ergot alkaloids. It blocks the release of a hormone, called prolactin, that
affects the menstrual cycle and breast milk production. Bromocriptine is useful in treating
menstrual and fertility problems, and abnormal milk production. Bromocriptine can be used to
treat Parkinson's disease. It is also helpful in treating acromegaly (excessive growth
hormone). Related agents include pergolide and lisuride, which have 10 to 1000 times the
potency
of bromocriptine on a milligram basis.
Bromocriptine stimulates dopamine type-2 receptors and antagonizes type-1 receptors in
the hypothalamus and the neostriatum of the CNS.
Pergolide, another ergot derivative,
stimulates both type-1 and type-2 receptors. Prolactin secretion from the anterior pituitary
gland is suppressed. Following bromocriptine-induced reductions in serum prolactin levels,
ovulation and ovarian function will resume in amenorrheic patients, and lactation will be
suppressed in women with normal ovarian activity. Bromocriptine also induces menses in
amenorrheic women with normal levels of serum prolactin (possibly via the release of
luteinizing hormone), and may have a direct stimulatory effect on ovarian dopaminergic
receptors.
Resumption of menses usually occurs within 6-8 weeks following administration
of the drug.
Patients with Parkinson's disease usually do not develop tolerance to the neurological
effects of bromocriptine as they do to levodopa therapy. Bromocriptine also slightly increases
sodium excretion and can reduce blood pressure. High doses of the drug can induce
vasoconstriction.
PHARMACOKINETICS: Although 28% of an orally administered dose of bromocriptine is
absorbed across the GI tract, only 6% reaches the circulation due to significant hepatic
metabolism. Oral administration of a single 1.25-5.0 mg dose results in serum prolactin
reductions within 2 hours. Bromocriptine therapy produces maximal reductions in the serum
prolactin levels of hyperprolactinemic patients within 4 weeks and significantly reduces
growth hormone levels in acromegaly patients within 1-2 hours. The drug binds extensively (9096%) to serum albumin and does not appear to distribute into erythrocytes. More than
90% of an absorbed dose undergoes first-pass metabolism, with the remainder of the dose
hydrolyzed in the liver to inactive metabolites. Bromocriptine has a half-life of 3 hours.
Metabolites are eliminated in the bile, with only a small amount excreted by the kidneys.
PREGNANCY: Bromocriptine is pregnancy risk category C. Although no adequate
human studies have been performed on the effects of this drug on the fetus, animal reproduction
studies have shown adverse fetal effects. Therefore, in making the decision to administer
this drug during pregnancy, the potential risks to the fetus must be weighed against the
potential benefits to the mother. Bromocriptine should not be given to patients planning
to breast-feed. Bromocriptine interferes with lactation and therefore should not be used during
breast-feeding. Bromocriptine can cause hypotension and should not be administered
during the postpartum period unless vital signs are normal and at least 4 hours have passed.
DRUG INTERACTIONS: Drugs that increase the concentration of prolactin, such as
butyrophenones including haloperidol; loxapine; molindone; monoamine oxidase inhibitors
(MAOIs);
imipramine; amitriptyline; methyldopa; phenothiazines; thioxanthines; and
reserpine, can antagonize the effects of bromocriptine. Estrogens or progestins can produce
amenorrhea or galactorrhea when administered, and use during bromocriptine administration is
not recommended.
High doses of bromocriptine can decrease the tolerance to ethanol, so patients should be
warned of this effect and advised to lessen ethanol consumption while receiving bromocriptine.
A disulfiram-like reaction can occur during concomitant use of bromocriptine and ethanol,
which is manifested as chest pain, tachycardia, throbbing headache, flushing of the face, severe
weakness, sweating, nausea, vomiting, and blurred vision.
Bromocriptine and levodopa are both dopamine agonists. Concomitant use of
these agents can cause additive neurologic effects. Although this drug combination may be
necessary in some patients, dosages of levodopa may require reduction if bromocriptine
is added.
Case reports have documented hypertension and seizures occurring as a result of
concomitant use of bromocriptine and phenylpropanolamine. Until more data are available, this
drug
combination should be avoided whenever possible.
SIDE EFFECTS: Large doses of bromocriptine can cause mental status changes
including confusion, so the drug should be used with extreme caution in parkinsonian patients
who
exhibit signs of dementia. Hallucinations can develop in patients receiving bromocriptine
alone or in combination with levodopa. Dosage reduction usually eliminates these
hallucinations, but discontinuation of the drug may be required. Prolonged therapy with
bromocriptine has resulted in the development of pulmonary infiltrates, thickening of the pleura,
and pleural effusion. Serious side effects with bromocriptine include blurred vision,
confusion or hallucinations, difficulty breathing, fainting spells, dizziness or lightheadedness,
irregular
heartbeat, chest pain or palpitations, persistent and watery nasal discharge,
seizures (convulsions), and weakness or tiredness. Minor side effects include diarrhea or
constipation, drowsiness, dry mouth, headache, loss of appetite, nausea, vomiting, runny nose,
or stuffy nose, and stomach pain.
Selegiline
TRADE NAME: 1-Deprenyl-Eldepryl
USEFUL DAILY DOSE: 2.5-10 mg
DRUG CLASS AND MECHANISM: Selegiline (EldeprylTM ), also commonly known as
deprenyl or deprenil, helps to increase or extend the effects of levodopa or carbidopa, and slow
the
progression of Parkinson's disease. Selegiline belongs to a class of drugs, called
monoamine oxidase inhibitors (MAOIs), that block certain enzymes in the brain and change the
balance of certain chemicals in the brain. Selegiline is an oral agent used in the treatment
of idiopathic Parkinson's disease, in combination with levodopa or levodopa and carbidopa.
Due to its selectivity for MAO type B, selegiline is purported to possess fewer drug
interactions and a lower risk of hypertension than phenelzine (Nardil TM ). In controlled clinical
trials,
selegiline caused slight improvement in motor performance at the start of therapy
and worsening at its discontinuance; it also delayed the development of disability that requires the
addition of levodopa.
Selegiline is a noncompetitive antagonist of monoamine oxidase type B (MAO-B), the
main form of this enzyme in the human brain. Monoamine oxidase type B is responsible for the
oxidative deamination of dopamine in the brain. Blockade of this enzyme reduces the
metabolism of dopamine, decreases free radical production, and potentiates the effects of
administered levodopa. It is unknown whether the benefits seen in Parkinson's disease
occur from increased dopaminergic transmission or from a decreased rate of neuronal death due
to free radicals. Selegiline doses of 10 mg/day block essentially all the MAO-B in the
adult brain. Selegiline's duration of action depends on the time required to regenerate MAO type
B
At higher selegiline doses (e.g., 20-40 mg/day), brain MAO is blocked nonselectively,
predisposing patients to the risks of traditional MAOIs that block MOA type A (e.g., hypertension).
Like phenelzine, the effects of selegiline are cumulative, with beneficial effects seen in a
few days to several months.
PHARMACOKINETICS: Selegiline is administered orally and is readily absorbed from
the GI tract and crosses the blood/brain barrier. Peak serum concentrations are found in 0.5-2
hours. The drug is rapidly and completely metabolized to three active derivatives with the
following half-lives: N-desmethyldeprenyl, 2 hours; 1-amphetamine, 17.7 hours; and 1methamphetamine, 20.5 hours. Selegiline is eliminated slowly by the kidneys; about 45%
of a single 10 mg dose is eliminated in the urine as the three active metabolites in 48 hours.
PREGNANCY: Selegiline should be used cautiously in pregnant women. The effects on
the fetus during pregnancy are not known.
DRUG INTERACTIONS: Selegiline is a monoamine oxidase inhibitor. In general, tricyclic
antidepressants should be used cautiously, if at all, in patients receiving drugs with
monoamine oxidase inhibitor (MAOI) activity. Although at low doses selegiline is selective
for MAO type B, in doses above 30-40 mg/day, this selectivity is lost. Selegiline, despite its
selectivity, can provoke serious CNS reactions in patients receiving either tricyclic
antidepressants (clomipramine, desipramine, etc.) or fluoxetine. Concomitant administration of
selegiline and fluoxetine can cause mania and the development of a serotonin syndrome
(characterized by hyperthermia, diaphoresis, shivering, tremor, myoclonus, seizures, ataxia,
delirium, restlessness). Concurrent use of selegiline with fluoxetine is not recommended
because of this rare, but serious reaction. At least 2 weeks should pass between the last dose
of a MAO inhibitor and the first dose of fluoxetine. However, at least a 5-week interval is
needed between the last dose of fluoxetine and initiation of MAO-inhibitor therapy because of the
prolonged elimination of fluoxetine. It is unclear if selegiline interacts similarly with other
member of the selective serotonin reuptake inhibitors (SSRIs).
Administration of levodopa to patients receiving drugs that inhibit monoamine oxidase
(MAO) can produce a hypertensive response. While traditional MAOIs such as phenelzine inhibit
MAO type A and selegiline is selective for MAO type B, at doses above 30-40 mg/day,
this selectivity is lost. Selegiline can increase levodopa-induced dyskinesias, nausea, orthostatic
hypotension, confusion, and hallucinations. Reductions in levodopa dosage may be
necessary within a few days after the start of selegiline treatment. Even though Parkinson's
disease
is an indication for both selegiline and levodopa, and these 2 drugs may be
administered together safely in some cases, patients should be monitored closely for
hypertensive
responses, especially if selegiline doses higher than 10 mg/day are used.
At doses of 20 mg/day, selegiline can interact with foods and beverages containing high
concentrations of pressor amines such as tyramine. Sudden and severe hypertensive reactions
are possible. This reaction is believed to be a result of selegiline's effects on MAO type A,
which occurs at higher doses. Dietary restrictions should be observed for at least 2 weeks
after the last dose of any MAO inhibitor. Other catecholamine-releasing or
sympathomimetic agents (e.g., ephedrine, phenylpropanolamine) may induce drug interactions
with selegiline at higher doses.
SIDE EFFECTS: Serious side effects with selegiline include black, tarry stools, changes
in behavior (mood swings, irritability, confusion, agitation), chest pain, difficulty breathing,
difficulty speaking, enlarged pupils, fever, clammy skin, increased sweating,
hallucinations, headaches, lightheadedness or fainting spells, loss of balance, muscle or neck
stiffness or
spasms, slow/fast or irregular heartbeat (palpitations), uncontrollable muscle
movements or spasms of the head, face, arms, or legs. Minor side effects include anxiety or
nervousness, blurred vision, increased sensitivity of the eyes to light, changes in taste,
constipation or diarrhea, difficulty sleeping, drowsiness or dizziness, dry mouth, loss of appetite,
weight loss,
muscle aches or pains, nausea/vomiting, ringing in the ears, stomach
discomfort or pain, and unusual tiredness or weakness. Do not treat yourself for coughs, colds, or
allergies
without asking your doctor or pharmacist for advice. Some ingredients may
increase possible side effects to selegiline. Selegiline may cause the feet and legs to swell
because of
peripheral edema.
Amantadine
TRADE NAME: SymmetrelTM\
USEFUL DAILY DOSE:
DRUG CLASS AND MECHANISM: AMANTADINE (SymmetrelTM ) is an antiviral agent.
Amantadine prevents or treats certain influenza (flu) infections. It is not an effective treatment for
colds or other viruses. Amantadine can improve muscle control and reduce muscle
stiffness in patients with Parkinson's disease (shaking palsy) or similar movement disorders. It
was
introduced as an agent for prophylaxis of influenza A and was later found to cause
symptomatic improvement in parkinsonism. Amantadine's mechanism of action is not fully
understood. Antiparkinsonian actions are unrelated to the antiviral effects. Amantadine
appears to potentiate CNS dopaminergic responses. It may release dopamine and
norepinephrine from storage sites and inhibit the reuptake of dopamine and norepinephrine.
Amantadine is clearly less effective than levodopa but can offer additional benefit in patients
experiencing
maximal or waning effects from levodopa. As an antiviral, amantadine can inhibit
viral replication within the viral cell. Amantadine appears to block the uncoating of the virus
particle and
subsequent release of viral nucleic acid into the host cell. It also may interfere
with penetration of the cell wall by adsorbed virus. To prevent a viral infection, the drug should be
present
before exposure to the virus, but, if given within 24-48 hours of onset of
symptoms, the influenza may be less severe.
PHARMACOKINETICS: Amantadine is administered orally. Absorption from the GI tract
appears to be rapid and complete. Bioavailability is 86% in the elderly and greater than 90% in
young adults.• Peak plasma concentrations are achieved in about 2-4 hours following
oral administration. Steady-state concentrations following daily dosage are obtained in 2-4 days.
Amantadine crosses the blood-brain barrier and the placenta; distributes into tears, saliva,
and nasal secretions; and is excreted into breast milk.
Ninety percent of amantadine is excreted in the urine via glomerular filtration and tubular
secretion. Renal impairment reduces protein binding. The elimination half-life in patients with
normal renal function is about 11-15 hours but can be as long as 7-10 days for those with
severe renal impairment. Half- life in elderly patients is 24-29 hours. Acidifying the urine
increases the rate of excretion. Only a small amount of amantadine is removed by
dialysis. Because amantadine is primarily excreted unchanged in the urine, patients with renal
impairment should receive lower doses.
PREGNANCY: Amantadine is classified as a pregnancy category C drug. No complete or
well-controlled studies have been done. Use during pregnancy should be avoided unless the
potential benefits outweigh the possible risks to the fetus.
DRUG INTERACTIONS: Ethanol should not be used with amantadine because of the
possible increase of CNS effects such as dizziness, confusion, lightheadedness, fainting, or
orthostatic hypotension.
Amantadine should be used with caution with anticholinergics, tricyclic antidepressants,
antihistamines, or phenothiazines because of the possible increase of anticholinergic effects,
especially hallucinations, nightmares, or confusion. Reductions in the dosage of both
drugs may be necessary before using them together.
Amantadine can increase the efficiency of levodopa by its action on central nerve
terminals. Patients who exhibit psychoses should avoid this combination because of the
possibility of
an increased psychotic effect.
Amantadine used concomitantly with CNS stimulants can result in increased stimulant
effects, such as nervousness, irritability, or insomnia, and can lead to seizures or cardiac
arrhythmias. Close monitoring of the patient is recommended.
SIDE EFFECTS: Serious side effects with amantadine include changes in vision,
depression or thoughts of suicide, difficulty passing urine, fainting spells or lightheadedness,
hallucinations, movement difficulties, purplish spots or network on the skin, seizures,
swelling of the feet or legs. Minor side effects with amantadine include anxiety, irritability,
nervousness, diarrhea or constipation, difficulty sleeping, or nightmares, drowsiness, dry
mouth, headache, loss of appetite, unusual tiredness. If you are taking amantadine for a
movement disorder, do not suddenly stop taking it. You may get muscle stiffness,
paralysis, confusion, or find it difficult to pass urine. If you are taking amantadine for Parkinson's
disease, be careful not to overdo physical activity as your condition improves. Gradually
increase activity so that your body has time to adjust. Abrupt withdrawal of amantadine should
be avoided in patients with Parkinson's disease since this may precipitate symptoms of
increased rigidity, confusion, urinary retention, or bulbar palsy.