Selegiline Levodopa

LEVODOPA, SELEGILINE, POSSIBLY RASAGILINE, ENTACAPONE, TOLCAPONE MAOIs Risk of adrenergic syndrome -hypertension, hyperthermia, arrhythmias - and dopaminergic effects with selegiline Levodopa and related drugs are precursors of dopamine. Levodopa is predominantly metabolized to dopamine, and a smaller proportion is converted to epinephrine and norepinephrine. Effects are due to inhibition of MAOI, which breaks down dopamine and sympathomimetics Avoid concurrent use. Onset may be 6-24 hours after ingestion. Carbidopa and benserazide, which inhibit dopa decarboxylase that converts L-dopa to dopamine, is considered to minimize this interaction. However, MAOIs should not be used in patients with Parkinson s disease on treatment with levodopa. Imipramine and amitriptyline are considered safer by some clinicians... 

The drug is contraindicated in patients with a history of psychosis The drug should not be administered to patients already taking levodopa Mental disturbances occur more commonly with levodopa than with bromocriptine A 72-year-old patient with parkinsonism presents with swollen feet. They are red, tender, and very painful. You could clear up these symptoms within a few days if you told the patient to stop taking (A) Amantadine Benztropine Bromocriptine Levodopa Selegiline... 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Monoamine oxidase exists in two forms, MAOa and MAOb. The former is more active against NA and 5-HT than it is against DA, which is a substrate for both, even though, like S-phenylethylamine, it is more affected by MAOb. H seems likely that MAOb is the dominant enzyme in human brain and inhibitors of it, such as selegiline, have some value in the treatment of Parkinson s disease by prolonging the action of the remaining endogenous DA as well as that formed from administered levodopa. 

MAOb inhibitors include selegiline and rasagaline. They may provide mild symptomatic benefit for those patients who choose to delay dopaminergic medications. Combining selegiline or rasagaline with levodopa in early treatment may delay motor complications. In patients with advanced disease, they decrease off time and improve wearing-off symptoms in patients with motor fluctuations. 

Inhibitors of monoamine oxi-dase-B (MAOb). This isoenzyme breaks down dopamine in the corpus striatum and can be selectively inhibited by selegiline. Inactivation of norepinephrine, epinephrine, and 5-HT via MAOa is unaffected. The antiparkinsonian effects of selegiUne may result from decreased dopamine inactivation (enhanced levodopa response) or from neuroprotective mechanisms (decreased oxyradical formation or blocked bioactivation of an unknown neurotoxin). 

In medical practice, four types of dopaminergic drags are used, and they can be characterized as dopamine precursors (levodopa), dopamine-releasing drugs (amantadine), dopamine receptor agonists (bromocriptine), and dopamine inactivation inhibitors (selegiline). 

This drug is a selective inhibitor of monoaminooxidase B, which suppresses dopamine-inactivation processes and facilitates an increase of its level in the brain. In treating Parkinsonism, selegiline is usually used in combination with levodopa. The most common synonyms of selegiline are deprenyl, eldepryl, eldopal, and others. 

After 2 to 3 days of treatment, attempt to reduce the dose of levodopa/carbidopa. A reduction of 10% to 30% appears typical. Further reductions of levodopa/carbidopa may be possible during continued selegiline therapy. 

Levodopa side effects Some patients given selegiline may experience an exacerbation of levodopa-associated side effects, presumably caused by the increased amounts of dopamine reacting with supersensitive postsynaptic receptors. 

Several placebo-controlled studies have demonstrated a significant delay in the need to initiate levodopa therapy in patients who receive selegiline in the early phase of the disease... 

Neither selegiline nor rasagiline should be taken by patients receiving meperidine. They should be used with care in patients receiving tricyclic antidepressants or serotonin reuptake inhibitors because of the theoretical risk of acute toxic interactions of the serotonin syndrome type (see Chapter 16), but this is rarely encountered in practice. The adverse effects of levodopa may be increased by these drugs. 

Selegiline Like rasagiline, adjunctive use with levodopa, parkinsonism may be less potent than rasagiline in MPTP-induced ... 

L-deprenyl (selegiline), a monoamine oxidase B inhibitor, clonidine and guanfacine, a2-adreno-receptor agonists, and levodopa (L-dopa) have been reported to improve cognitive function in some subjects. Zimeldine, citaloprani, and alaproclate — selective serotonin uptake blockers — have no beneficial effects. 

Myllyla W, Heinonen EH, Vuorinen JA, Kilkku OI, Sotaniemi KA. Early selegiline therapy reduces levodopa dose requirement in Parkinson s disease. Acta Neurol Scand 1995 91 177-182. 

Later, the disease does not respond to the drug and doses are required to be given in combination with carbidopa. Levodopa is effective in relieving bradykinesia and other disorderly voluntary movements. Parkinson s disease is not a hereditary disease. Drugs such as levodopa, carbidopa, benserazide, bromocriptine, pergolide, selegiline, and amantadine are used as therapeutic agents.61... 

Monoamine-oxidase B inhibitors, such as selegiline and rasagiline, have a use alone in the management of early disease. Early treatment with selegiline alone has been shown to delay the need for levodopa therapy for some months, but other more effective drugs are preferred. Both dmgs can be used in conjunction with levodopa preparations to reduce end-of-dose deterioration in advanced disease. 

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