Trihexyphenidyl Levodopa

Concomitant use with levodopa Trihexyphenidyl 3 to 6 mg/day in divided doses is usually adequate. 

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. 

A 75-year-old man with a 10-year history of parkinsonism developed fever and acute delirium after taking levodopa plus trihexyphenidyl (658). He had visual hallucinations, was disoriented in time and place, and could respond only to simple questions. He was unable to stand or walk and had paratonic rigidity in all limbs and marked bradykinesia. There were occasional myoclonic jerks in the arms and legs. Deep reflexes were reduced bilaterally, and the plantar reflexes were absent. 

Orofacial dyskinesia, though familiar with dopaminergic drugs, can apparently also occur with some anticholinergic drugs for example, it has been described with trihexyphenidyl in a patient who did not have this reaction with levodopa (SEDA-18, 160). 

A 28-year-old man received interferon alfa (5 MU/day for 28 days) for chronic hepatitis B. At the end of treatment he developed a slight parkinsonian gait, and 8 days later had a fever with vomiting, insomnia, restlessness, and raised serum creatine kinase activity (4946 IU/1). He had severe akathisia with psychomotor excitement and parkinsonism. Despite treatment with clonazepam, thioridazine, propranolol, trihexyphenidyl, and bromocriptine, his condition progressively worsened. He was finally given intravenous levodopa for 8 days and recovered dramatically within the next few days. 

Parkinson s disease is caused by the oxidative stress-induced loss of dopaminergic neurons and can be effectively treated with levo-dopa in combination with dopa decarboxylase inhibitors such as carbidopa or catechoi-0-methyltransferase inhibitors such as tolca-pone. Levodopa is well known to increase the life spans of patients with Parkinson s disease. It may do this by enhancing brain dopamine levels and inhibiting tyrosine hydroxylase, which produces oxygen radicals. Several dopamine receptor agonists are available for use in Parkinson s disease and are extensively used in patients suffering from the adverse effects of levodopa. Anticholinergics such as trihexyphenidyl are also used in Parkinson s disease. 

The antiparkinsonian agents (except trihexyphenidyl) inhibited both Ap and aS oligomer formations, with dopamine, levodopa, prami-pexole, and entacapone displaying the strongest in vitro activity. 

Drugs used to increase DA fundion are levodopa, tolcapone, entacapone, bromocriptine, pramipexole, ropinirole, and selegiline. Drugs that decrease ACh fundion are benztropine, trihexyphenidyl, and amantadine. The properties of each are described. 

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 study in 6 healthy subjects and 6 patients with Parkinson s disease found that trihexyphenidyl 2 mg twice daily for 3 days lowered the peak plasma levels of a 500-mg dose of levodopa by 42% in the healthy subjects and 17% in the patients, although the interaction was present in only about half of the subjects. The AUC was reduced in both groups by less than 20%. ... 

A double-blind crossover trial in 9 patients with parkinsonism taking levodopa (range 100 to 750 mg daily) plus a dopa-decarboxylase inhibitor did not find any changes in disease control when they also took papaverine hydrochloride 150 mg daily for 3 weeks. Two patients were also taking bromocriptine 40 mg daily and two trihexyphenidyl 15 mg daily. ... 

The morphanthridine elantrine (XIII, Ex 10-029) has been tested in man and its pharmacological action appears to be mainly, but not exclusively, related to its anticholinergic action . Two clinical trials (25 and 13 patients) report efficacy alone at doses of 30-60 mg/day and with levodopa . Side effects were predominately of the anticholinergic type. A recent substantial multiclinic controlled study in 89 patients found that elantrine, UO mg daily, effectively reduced tremor and possibly rigidity more than the same dosage of trihexyphenidyl. Elantrine caused more dry mouth. Thus elantrine was effective but not clearly more selective. 

---