Levodopa Antimuscarinics

Antimuscarinic drugs such as atropine have been used to modest effect in the treatment of PD for more than a century attenuating tremor and rigidity but with little effect on akinesia. Currently benzhexol and benztropine are sometimes added to levodopa therapy but peripheral effects such as dry mouth, blurred vision and constipation are unpleasant. They are also often used to counteract neuroleptic-induced extrapyramidal effects. 

Bromocriptine is a dopamine agonist acting by direct stimulation of the dopamine receptors. In Parkinson s disease, it is reserved for use in patients who are intolerant to levodopa or in whom levodopa alone is not sufficient. Orphenadrine is an antimuscarinic indicated in Parkinson s disease. Antimuscarinics tend to be more effective than levodopa in targeting tremor rather than rigidity and bradykinesia. Moclobemide is an antidepressant referred to as a reversible monoamine oxidase inhibitor (RIAAA) type A. 

Co-careldopa is a combination of levodopa and the peripheral dopadecar-boxylase inhibitor. Co-careldopa is indicated in Parkinson s disease to improve bradykinesia and rigidity rather than tremor. Orphenadrine is an antimuscarinic agent indicated in patients with Parkinson s disease where tremor predominates. Trifluoperazine is a piperazine antipsychotic that should be used with caution in patients with Parkinson s disease as its use may exacerbate the condition. 

The treatment of Parkinson s disease is often an exercise in polypharmacy, since no single agent is fully effective over the course of the disease. Most antimuscarinic drugs promoted for this application (see Table 28-1) were developed before levodopa became available. Their use is accompanied by all of the adverse effects described below, but the drugs remain useful as adjunctive therapy in some patients. 

The pharmacologic basis of these disorders is unknown, and there is no satisfactory medical treatment for them. A subset of patients respond well to levodopa medication (dopa-responsive dystonia), which is therefore worthy of trial. Occasional patients with dystonia may respond to diazepam, amantadine, antimuscarinic drugs (in high dosage), carbamazepine, baclofen, haloperidol, or phenothiazines. A trial of these pharmacologic approaches is worthwhile, though often not successful. Patients with focal dystonias such as blepharospasm or torticollis often benefit from injection of botulinum toxin into the overactive muscles. The role of deep brain stimulation for the treatment of these conditions is being explored. 

The antimuscarinic agents are much less efficacious than levodopa and play only an adjuvant role in antiparkinsonism therapy. The... 

E. Antimuscarinic agents are generally less efficacious then levodopa in the treatment of Parkinson s disease. 

CNS Scopolamine is standard therapy for motion sickness this drug is one of the most effective agents available for this condition. A transdermal patch formulation is available. Benztropine, biperiden. and trihexyphenidyl are representative of several antimuscarinic agents used in parkinsonism. Although not as effective as levodopa (see Chapter 28), these agents may be useful as adjuncts or when patients become unresponsive to levodopa. Benztropine is sometimes used parenterally to treat acute dystonias caused by antipsychotic medications. 

A) Levodopa causes mydriasis and can precipitate an attack of acute glaucoma Useful therapeutic effects of amantadine continue for several years The primary therapeutic benefit of antimuscarinic drugs in parkinsonism is their abUily to relieve bradykinesia... 

The use of dopaminergic agents in combination with antimuscarinic drugs is common in the treatment of parkinsonism. Bromocriptine does not complicate treatment with antimuscarinic drugs or amantadine. If combined with levodopa, bromocriptine should be used in reduced doses to avoid intolerable adverse effects. Confusion, delusions, and hallucinations occur more frequently with bromocriptine than with levodopa. Bromocriptine does not require bioactivation for its antiparkinson effects. The answer is (C). 

Furthermore, both methyldopa and reserpine, that essentially interfere with the catecholamine synthesis as well as its storage, exacerbate the Parkinson syndrome and, therefore, antagonize the activity of levodopa. The pharmacological profile of levodopa actually synergized by antimuscarinics. 

Additive effect. Delayed gastric emptying may cause more levodopa to be metabolized within the wall of the gastrointestinal tract. Antimuscarinic effects i saliva production, which i dissolution of the tablet... 

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