Levodopa combined with

However, levodopa combined with carbidopa remains the most effective symptomatic treatment for Parkinson s disease. 

Lees AJ (1995) Comparison of therapeutic effects and mortality data of lev-odopa and levodopa combined with selegiline in patients with early, mild Parkinson s disease. Br Med J 311 1602-1607 Libet B (1973) Electrical stimulation of cortex in human subjects, and conscious memory aspects. In Iggo A (ed) Handbook of sensory physiology, vol 2. Springer-Verlag, Berlin, Heidelberg, New York, pp 743-790 Levene M, Roberts P (eds) (1999) Massacre in history. Berghahn Books, New York... 

Levodopa combined with a peripherai dopa-decarboxyiase inhibitor Co-beneldopa (levodopa + benserazide) Co-careldopa (levodopa 1 carbidopa)... 

Parkinson s Disease Research Group of the United Kingdom. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson s disease. BMJ(. 995) 311,1602-7. 

An 81-year-old man with probable Parkinson s disease was given increasing doses of levodopa combined with benserazide. When the dose reached a total of 500 mg/day of levodopa he developed hiccups, which lasted for 3 days. He took no further levodopa and the hiccups stopped. On restarting at a dose of 100 mg the hiccups returned, though only for 1 hour. However, this was enough for the patient to refuse all follow-up and treatment. 

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. 

Trihexyphenidyl, an antiparkinsonian drug, possesses central and peripheral anticholinergic actions, as well as a direct relaxant effect on smooth muscle. It reduces muscle rigidity and general stiffness, and has a relatively minor effect on tremors. It is used in Parkinsonism in the form of monotherapy as well as in combination with levodopa. The most common synonyms are parkopan, parkinsan, and cyclodol. 

The therapeutic value of these drags is relatively small, and they are nsed either in combination with levodopa, or in cases of minor Parkinsonism. Drags described in Chapter 10—trihexyphenidyl (10.2.2), procyclidine (10.2.3), biperiden (10.2.4), benztropine (10.2.6), ethopropazine (10.2.7), and others belong to this gronp of drugs. 

Always administer entacapone in combination with levodopa/carbidopa. Entacapone has no antiparkinsonian effect of its own. 

Entacapone can be combined with the immediate- and sustained-release formulations of levodopa/carbidopa. 

Maintenance treatment - Pramipexole is effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses 3 times/day with or without concomitant levodopa ( 800 mg/day). When pramipexole is used in combination with levodopa, consider a reduction of the levodopa dosage. 

The optimum daily dosage of carbidopa, levodopa, and entacapone combination must be determined by careful titration in each patient. Carbidopa, levodopa, and entacapone combination tablets are available in 3 strengths, each in a 1 4 ratio of carbidopa to levodopa and combined with 200 mg of entacapone in a standard... 

Combined with levodopa and a decarboxylase inhibitor more stable levodopa levels can be obtained. Tolcapon has been withdrawn in many countries because of serious liverfunction disturbances, rhab-domyolysis and neuroleptic malignant syndrome. 

Amantadine is an old drug with several pharmacological properties warranting its (empirical) use in Parkinson s disease facilitation of dopamine release, blockade of dopamine re-uptake, anticholinergic effect, blockade of NMDA receptors. Amantadine is usually employed early in the disease process (monotherapy, 100 mg b.i.d.) and most often in combination with levodopa in more advanced stage disease (anti-dyskinesia effect ). 

For all agonists, it is advisable to progressively increase the daily dose to reach optimal dose by plateaus. The optimal dose is titrated individually. In combination with levodopa, dopaminergic agonists lower the daily requirements for dopa and, after years of treatment, would prolong the duration of on phases and limit fluctuations in motricity and dyskinesia. Apomorphine is only indicated for patients with on-off swings, either via single-dose subcutaneous injections or a continuous infusion. 

The two COMT inhibitors in clinical use are tol-capone (Tasmar) and entacapone fComtan). They are used in combination with levodopa-carbidopa. In patients with motor fluctuations, they increase the on time. Adverse effects are similar to those observed with levodopa-carbidopa alone. Tolcapone therapy can cause fatal hepatotoxicity and so should be used only in patients who do not respond to other therapies. Patients taking tolcapone require close monitoring of liver enzymes for signs of hepatic changes. 

Geriatric Considerations - Summary Levodopa is a percursor to dopamine and is converted to dopamine in the CNS. Clinical effectiveness is increased by taking in combination with carbidopa, a dopa decarboxylase inhibitor. This combination is often the initial treatment for Parkinson s disease. 

Geriatric Considerations - Summary Ropinirole is a nonergot dopamine agonist which directly stimulates dopamine Dj receptors. It can be used in combination with levodopa or as monotherapy. If discontinued, ropinirole should be slowly tapered because abrupt discontinuation can cause confusion, hallucinations, and a condition similar to neuroleptic malignant syndrome. 

Figure 9.2 illustrates the various inputs and outputs of a model built to demonstrate the 5-year results of therapy with entacapone (Comtan1 ), which represents a novel pharmacological principle used in combination with levodopa therapy. The inputs list the data fed into the model. The clinical effects of the therapy are taken from the clinical trials. The costs by disease stage are defined as costs for >25% OFF time per day (severe stage) and costs for <25% OFF time per day (less severe) and are taken from literature sources. Patient preference data (used to calculate QALYs) for these two disease stages are taken from a separate study of patient preferences. The outputs of the model list some of the more common uses of the model ... 

Presented in Fig. 9.3 is an example of a model used to extrapolate the 6-month trial results of a COMT inhibitor (entacapone) used in combination with levodopa versus levodopa alone in the treatment of Parkinson s disease. This particular model is an example of a Markov model... 

Carbidopa and benserazide are peripheral decarboxylase inhibitors used in combination with levodopa. They do not penetrate blood-brain barrier and do not inhibit the conversion into dopamine from levodopa in brain. 

When levodopa is given in combination with carbidopa, adverse gastrointestinal effects are much less frequent and troublesome, occurring in less than 20% of cases, so that patients can tolerate proportionately higher doses. 

A variety of cardiac arrhythmias have been described in patients receiving levodopa, including tachycardia, ventricular extrasystoles and, rarely, atrial fibrillation. This effect has been attributed to increased catecholamine formation peripherally. The incidence of such arrhythmias is low, even in the presence of established cardiac disease, and may be reduced still further if the levodopa is taken in combination with a peripheral decarboxylase inhibitor. 

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