Levodopa- Anti-parkinson drug

Levodopa

Pharmacodynamics

Levodopa (L-dopa) is used to replace dopamine lost in Parkinson's disease because dopamine itself cannot cross the blood-brain barrier where its precursor can. However, L-DOPA is converted to dopamine in the periphery as well as in the CNS, so it is administered with a peripheral DDC (dopamine decarboxylase) inhibitor such as carbidopa, without which 90% is metabolised in the gut wall, and with a COMT inhibitor if possible; this prevents about a 5% loss. The form given therapeutically is therefore a prodrug which avoids decarboxylation in the stomach and periphery, can cross the blood-brain barrier, and once in the brain is converted to the neurotransmitter dopamine by the enzyme aromatic-L-amino-acid decarboxylase.

Mechanism of action

Striatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine.

Absorption

Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.

Protein binding

High

Metabolism

95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromatic amino acid decarboxylase (AAAD) enzyme in the stomach, lumen of the intestine, kidney, and liver. Levodopa also may be methoxylated by the hepatic catechol-O-methyltransferase (COMT) enzyme system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.

Half life

50 to 90 minutes

Drug drug interaction

Acebutolol + Levodopa = Acebutolol may increase the orthostatic hypotensive activities of Levodopa.

Acetazolamide + Levodopa = Acetazolamide may increase the orthostatic hypotensive activities of Levodopa.

Aldesleukin + Levodopa = Aldesleukin may increase the orthostatic hypotensive activities of Levodopa.

Aliskiren + Levodopa = Aliskiren may increase the orthostatic hypotensive activities of Levodopa.

Amiloride + Levodopa = Amiloride may increase the orthostatic hypotensive activities of Levodopa.

Therapeutic Uses

Treating symptoms associated with Parkinson disease and parkinsonism-like symptoms

Toxicity

Agitation
Anxiety

Clenching or grinding of teeth

Clumsiness or unsteadiness

Confusion

Difficulty swallowing

Dizziness

Reference- Tripathi KD "Essential of medical pharmacology" 7th edition, page no- 425