Levodopa side effects

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. 

Initial treatment and adjunct to levodopa ° Side effects dyskinesias and psychosis Dopamine-receptor agonists ... 

FTamipexole is an agonist at dopamine receptors and may have greater selectivity for D receptors in the striatum. It is not an ergot and appears to be less toxic than bromocriptine and pergolide. Pramipexole and ropinirole are often chosen for initial treatment of Parkinson s disease and sometimes have value in patients who have become refractory to levodopa. Side effects of these drugs include dyskinesias, postural hypotension, and somnolence. The answer is (E). 

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. 

ExCDDIs certainly improve the efficacy and duration of action of levodopa so that it can be given in a smaller dose (e.g. 25%) and generally in a 4 1 ratio, levodopa ExCDDI. As might be expected, some DA side-effects such as dyskinesia and psychoses are worse, but hypotension is less (no peripheral effects of DA) and vomiting is actually much reduced or abolished. This is because the chemoreceptor trigger zone of the vomiting centre while in the brain is on the blood side of the blood-brain barrier and will not be stimulated since no DA is formed peripherally (Fig. 15.5). That an... 

Carbidopa, a dopa-decarboxylase inhibitor, is added to the levodopa in order to decrease the peripheral conversion of levodopa to dopamine. It does not cross the blood-brain barrier and does not interfere with levodopa conversion in the brain. Concomitant administration of carbidopa and levodopa allows for lower levodopa doses and minimizes levodopa peripheral side effects such as nausea, vomiting, anorexia, and hypotension. For most patients, at least 75 to 100 mg daily of carbidopa is required to adequately block dopamine decarboxylase in the peripheral metabolism of levodopa in most patients. Taking extra carbidopa may reduce nausea related to initiating levodopa.8,16... 

Side effects include dyskinesias, orthostatic hypotension, dizziness, nausea, insomnia, sleep attacks, pathologic gambling, discoloration of urine/sweat, and psychiatric effects (confusion, hallucinations, nightmares, and altered behavior). Dyskinesias caused by adding other PD drugs to levodopa may be improved by decreasing the levodopa dose. Motor complications occur in about 40% of patients within 4 to 6 years of starting levodopa.1,8,24,25,37... 

These symptoms are alleviated by administering levodopa (L-dopa), a precursor for dopamine. L-dopa is taken up by the axon terminals of dopaminergic neurons and used to form dopamine. Interestingly, in some patients, a side effect of dopamine replacement therapy is the development of symptoms characteristic of schizophrenia. (Recall that this mental disorder is caused by overactive dopaminergic neurons.) On the other hand, drugs used to treat schizophrenia — dopamine receptor antagonists — may elicit symptoms of Parkinson s disease. 

Hallucinations Dopaminergic therapy in Parkinson s disease patients has been associated with hallucinations. In clinical trials, hallucinations developed in approximately 4% of patients treated with 200 mg entacapone or placebo. Dyskinesia Entacapone may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate pre-existing dyskinesia. 

Drugs that may increase the effects or side effects of bupropion include levodopa, MAOIs, ritonavir, antidepressants, antipsychotics, beta blockers, type 1C antiarrhythmics. 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

If levodopa is administered alone, it is extensively metabolized by L-aromatic amino acid decarboxylase in the liver, kidney, and gastrointestinal tract. To prevent this peripheral metabolism, levodopa is coadministered with carbidopa (Sinemet), a peripheral decarboxylase inhibitor. The combination of levodopa with carbidopa lowers the necessary dose of levodopa and reduces peripheral side effects associated with its administration. 

Since Parkinson s disease arises from a deficiency of DA in the brain, the logical treatment is to replace the DA. Unfortunately, dopamine replacement therapy cannot be done with DA because it does not cross the blood-brain barrier. However, high doses (3-8 g/day, orally) of L(-)-DOPA (levodopa), a prodrug of DA, have a remarkable effect on the akinesia and rigidity. The side effects of such enormous doses are numerous and unpleasant, consisting initially of nausea and vomiting and later of uncontrolled movements (limb dyskinesias). The simultaneous administration of carbidopa (4.75) or benserazide (4.76)—peripheral DOPA decarboxylase inhibitors—allows the administration of smaller doses, and also prevents the metabolic formation of peripheral DA, which can act as an emetic at the vomiting center in the brainstem where the blood-brain barrier is not very effective and can be penetrated by peripheral DA. 

When used along with levodopa, the plasma half life of levodopa is prolonged and dose may be markedly reduced. Also the most common side effect i.e. nausea and vomiting are not prominent and cardiac complications are minimized. It has no effect on involuntary movements, behavioral abnormalities and postural hypotension. 

The results of levodopa treatment are dramatic. However, many of the side effects can be as bad or worse than the condition itself especially later in the course of the disease when doses are... 

It is used in the early stages of PD and to extend Sinemet treatment. Its side effects are similar to that of levodopa. 

Amantidine is believed to enhance the release of DA from undestroyed neurons. Though not as effective as levodopa, it has fewer side effects. 

Drug Levodopa Mechanism of Action Resolves dopamine deficiency by being converted to dopamine after crossing blood-brain barrier. Special Comments Still the best drug for resolving parkinsonian symptoms long-term use limited by side effects and decreased efficacy. 

Dopamine agonists Bromocriptine Cabergoline Pergolide Pramipexole Ropinirole Directly stimulates dopamine receptors in basal ganglia. May produce fewer side effects (dyskinesias, fluctuations in response) than levodopa preliminary evidence suggests that early use may also delay the progression of Parkinson disease. 

Postural hypotension can also be an extremely troublesome problem in a patient taking levodopa. Again, this side effect is usually diminished when peripheral decarboxylation is inhibited and peripheral dopamine levels are not allowed to increase exces-... 

---