management of parkinson's disease management of parkinson's disease in the management of parkinson's disease, due to the chronic nature of parkinson's disease (pd), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. at present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms. management of parkinson's diseasespecialtyneurology while many medications treat parkinson's, none actually reverses the effects of the disease. furthermore, the gold-standard treatment varies with the disease state. people with parkinson's, therefore, often must take a variety of medications to manage the disease's symptoms. several medications currently in development seek to better address motor fluctuations and nonmotor symptoms of pd. however, none is yet on the market with specific approval to treat parkinson's. medication pharmacological treatment of parkinson's disease the main families of drugs useful for treating motor symptoms are levodopa, dopamine agonists, and mao-b inhibitors. the most commonly used treatment approach varies depending on the disease stage. two phases are usually distinguished: an initial phase in which the individual with pd has already developed some disability which requires pharmacological treatment, and a second stage in which the patient develops motor complications related to levodopa usage. treatment in the initial state aims to attain an optimal tradeoff between good management of symptoms and side effects resulting from enhancement of dopaminergic function. the start of l-dopa treatment may be delayed by using other medications such as mao-b inhibitors and dopamine agonists, in the hope of delaying the onset of dyskinesias. in the second stage, the aim is to reduce symptoms while controlling fluctuations of the response to medication. sudden withdrawals from medication, and overuse by some patients, also must be controlled. when medications are not enough to control symptoms, surgical techniques such as deep brain stimulation can relieve the associated movement disorders. levodopa stalevo, a commercial preparation combining entacapone, levodopa, and carbidopa for treatment of parkinson's disease circuits of the basal ganglia in treatment of parkinson's disease – model of the effect of medication on motor symptoms: levodopa, dopamine agonists and mao-b inhibitors stimulate excitatory signals from the thalamus to the cerebral cortex by effects on the striatum, compensating for decreased dopaminergic signals from substantia nigra (seen at bottom right). levodopa (or l-dopa) has been the most widely used treatment for over 30 years. l-dopa is transformed into dopamine in the dopaminergic neurons by dopa-decarboxylase. since motor symptoms are produced by a lack of dopamine in the substantia nigra, the administration of l-dopa temporarily diminishes the motor symptoms. only 5–10% of l-dopa crosses the blood–brain barrier. the remainder is often metabolised to dopamine elsewhere, causing a wide variety of side effects including nausea, dyskinesias, and stiffness. carbidopa and benserazide are peripheral dopa decarboxylase inhibitors. they inhibit the metabolism of l-dopa in the periphery, thereby increasing levodopa delivery to the central nervous system. they are generally given as combination preparations with levodopa. existing preparations are carbidopa/levodopa (co-careldopa, trade names sinemet, pharmacopa, atamet) and benserazide/levodopa (co-beneldopa, trade name madopar). levodopa has also been related to a dopamine dysregulation syndrome, which is a compulsive overuse of the medication, and punding. controlled, slow-release versions of sinemet and madopar spread out the effect of the levodopa. duodopa is a combination of levodopa and carbidopa. slow-release levodopa preparations have not shown an increased control of motor symptoms or motor complications when compared to immediate-release preparations. tolcapone inhibits the catechol-o-methyltransferase (comt) enzyme, which degrades dopamine and levadopa, thereby prolonging the therapeutic effects of levodopa. it, alongside inhibitors of peripheral dopa decarboxylase, have been used to complement levodopa. however, due to its possible side effects such as liver failure, it is limited in its availability. a similar drug, entacapone, has not been shown to cause significant alterations of liver function and maintains adequate inhibition of comt over time. entacapone is available for treatment alone (comtan) or combined with carbidopa and levodopa (stalevo). levodopa results in a reduction in the endogenous formation of l-dopa, and eventually becomes counterproductive. levodopa preparations lead in the long term to the development of motor complications characterized by involuntary movements called dyskinesias and fluctuations in the response to medication. when this occurs, pd patients change rapidly from stages with good response to medication and few symptoms ("on" state) to phases with no response to medication and important motor symptoms ("off" state). for this reason, levodopa doses are kept as low as possible while maintaining functionality. delaying the initiation of dopatherapy, using instead alternatives for some time, is also common practice. a former strategy to reduce motor complications was to withdraw patients from l-dopa for some time. it is discouraged now since it can bring dangerous side effects such as neuroleptic malignant syndrome. most people eventually need levodopa and later develop motor complications. the on-off phenomenon is an almost invariable consequence of sustained levodopa treatment in patients with parkinson's disease. phases of immobility and incapacity associated with depression alternate with jubilant thaws. both pharmacokinetic and pharmacodynamic factors are involved in its pathogenesis, but evidence is presented to indicate the importance of levodopa handling has been underestimated and progressive reduction in the storage capacity of surviving nigrostriatal dopamine terminals is not a critical factor. redistribution of levodopa dosage which may mean smaller, more frequent doses, or larger less frequent increments, may be helpful in controlling oscillations in some patients. dietary protein restriction and the use of selegiline and bromocriptine may also temporarily improve motor fluctuations. new approaches to management include the use of subcutaneous apomorphine, controlled-release preparations of levodopa with a peripheral dopa decarboxylase inhibitor and the continuous intraduodenal administration of levodopa. in animal models it was shown that the intake of adenosine receptor antagonists together with levodopa can amplify its therapeutic effects. dopamine agonists dopamine agonists in the brain have a similar effect to levodopa since they bind to dopaminergic postsynaptic receptors. dopamine agonists were initially used for patients experiencing on-off fluctuations and dyskinesias as a complementary therapy to levodopa, but they are now mainly used on their own as an initial therapy for motor symptoms with the aim of delaying motor complications. when used in late pd, they are useful at reducing the off periods. dopamine agonists include bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine, and lisuride. agonists produce significant, although mild, side effects including somnolence, hallucinations, insomnia, nausea, and constipation. sometimes, side effects appear even at the minimal clinically efficacious dose, leading the physician to search for a different agonist or kind of drug. when compared with levodopa, while they delay motor complications, they control worse symptoms. nevertheless, they are usually effective enough to manage symptoms in the initial years. they are also more expensive. dyskinesias with dopamine agonists are rare in younger patients, but along other side effects, more common in older patients. all this has led to agonists being the preferential initial treatment for the former as opposed to levodopa in the latter. agonists at higher doses have also been related to a wide variety of impulse-control disorders. apomorphine, which is a dopamine agonist not orally administered, may be used to reduce off periods and dyskinesia in late pd. since secondary effects such as confusion and hallucinations are not rare, patients under apomorphine treatment should be closely monitored. apomorphine can be administered by subcutaneous injection using a small pump which is carried by the patient. a low dose is automatically administered throughout the day, reducing the fluctuations of motor symptoms by providing a steady dose of dopaminergic stimulation. after an initial "apomorphine challenge" in hospital to test its effectiveness and brief patient and primary caregiver (often a spouse or partner), the latter of whom takes over maintenance of the pump. the injection site must be changed daily and rotated around the body to avoid the formation of nodules. apomorphine is also available in a more acute dose as an autoinjector pen for emergency doses such as after a fall or first thing in the morning. nausea and vomiting are common, and may require domperidone (an antiemetic). in a study evaluating the efficacy of dopamine agonists compared to levodopa, the results showed patients who took dopamine agonists were less likely to develop dyskinesia, dystonia, and motor fluctuations, although were more likely to discontinue therapy due to negative side effects such as nausea, edema, constipation, etc. mao-b inhibitors monoamine oxidase inhibitors (selegiline and rasagiline) increase the level of dopamine in the basal ganglia by blocking its metabolization. they inhibit monoamine oxidase-b (mao-b) which breaks down dopamine secreted by the dopaminergic neurons. therefore, reducing mao-b results in higher quantities of l-dopa in the striatum. similarly to dopamine agonists, mao-b inhibitors improve motor symptoms and delay the need of taking levodopa when used as monotherapy in the first stages of the disease, but produce more adverse effects and are less effective than levodopa. evidence on their efficacy in the advanced stage is reduced, although it points towards them being useful to reduce fluctuations between on and off periods. although an initial study indicated selegiline in combination with levodopa increased the risk of death, this has been later disproven. metabolites of selegiline include l-amphetamine and l-methamphetamine (not to be confused with the more potent dextrorotary isomers). this might result in side effects such as insomnia. another side effect of the combination can be stomatitis. unlike other nonselective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis. other drugs some evidence indicates other drugs such as amantadine and anticholinergics may be useful as treatment of motor symptoms in early and late pd, but since the quality of evidence on efficacy is reduced, they are not first-choice treatments. in addition to motor symptoms, pd is accompanied by a range of different symptoms. different compounds are used to improve some of these problems. examples are the use of clozapine for psychosis, cholinesterase inhibitors for dementia, modafinil for day somnolence, and atomoxetine for executive dysfunction. a preliminary study indicates taking donepezil (aricept) may help prevent falls in people with parkinson's. donepezil boosts the levels of the neurotransmitter acetylcholine, and is currently an approved therapy for the cognitive symptoms of alzheimer's disease. in the study, participants taking donepezil experienced falls half as often as those taking a placebo, and those who previously fell the most showed the most improvement. the introduction of clozapine (clozaril) represents a breakthrough in the treatment of psychotic symptoms of pd. prior to its introduction, treatment of psychotic symptoms relied on reduction of dopamine therapy or treatment with first generation antipsychotics, all of which worsened motor function. other atypical antipsychotics useful in treatment include quetiapine (seroquel), ziprasidone (geodon), aripiprazole (abilify), and paliperidone (invega). clozapine is believed to have the highest efficacy and lowest risk of extrapyramidal side effect. getting medication on time parkinson's patients who do not get the correct medicine at the right time when they are in hospital, (frequently they are in hospital due to unrelated illnesses) sometimes cannot talk or walk. the health of a majority deteriorated due to unsatisfactory medication management when they are in hospital. parkinson's uk believes the nhs could save up to £10m a year and improve the care of parkinson's patients if mandatory training is introduced for all hospital staff. parkinson uk found: "nearly two thirds of people who have parkinson's don't always get their medication on time in hospital." "more than three quarters of people with parkinson's that we asked reported that their health deteriorated as a result of poor medication management in hospital." "only 21% of respondents told us they got their medication on time without having to remind hospital staff." surgery illustration showing an electrode placed deep-seated in the brain treating pd with surgery was once a common practice, but after the discovery of levodopa, surgery was restricted to only a few cases. studies in the past few decades have led to great improvements in surgical techniques, and surgery is again being used in people with advanced pd for whom drug therapy is no longer sufficient. less than 10% of those with pd qualify as suitable candidates for a surgical response. the three different mechanisms of surgical response for pd are: ablative surgery, (the irreversible burning or freezing of brain tissue), stimulation surgery or deep brain stimulation (dbs), and transplantation or restorative surgery. target areas for dbs or lesions include the thalamus, the globus