Carbidopa

Table 15 gives a sampling of other pharmaceuticals derived from hydraziae. Cefazolin, a thiadiazole tetrazole derivative, is one of the most widely used antibacterial dmgs in U.S. hospitals (see Antibiotics, P-LACTAMs). Procarbazine, an antineoplastic, is a monomethyUiydrazine derivative (220). Fluconazole has shown some promise in the treatment of AIDS-related fungal infections. Carbidopa is employed in the treatment of Parkinson s disease. FurazoHdone is a veterinarian antibacterial. 

Captopril 3, 128 Caramiphen 1, 90 Carbacephal othin 1, 420 Carbadox 390 Carbamazepine 403 Carbantel 57 Carbaprost 1 Carbazeran 195 Carbenicillin l, 414 2, 437 Carbetidine 1, 90 Carbidopa 2 119 Carbimazole 1, 240... 

The main clinical use of COMT inhibitors is as adjunct (or additional adjunct) in the therapy of Parkinson s disease. The standard therapy of Parkinson s disease is oral L-dopa (as a drug levodopa) given with a dopa decarboxylase (DDC) inhibitor (e.g. carbidopa and benserazide), which does not reach the brain. When the peripheral DDC is inhibited, the concentration of 3-O-methyldopa (3-OMD), a product of COMT, in plasma is many times that of L-dopa. Since the half-life of 3-OMD is about 15 h, compared to about 1 h for L-dopa, the concentration of 3-OMD remains particularly high during chronic therapy, especially if new slow release L-dopa preparations are used. A triple therapy (L-dopa plus DDC inhibitor plus COMT-inhibitor) will... 

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

Dopaminergic drug are drug that affect the dopamine content of the brain. These drag include levodopa (Larodopa), carbidopa(Ladosyn), amantadine (Symmetrel),... 

Levodopa is a chemical formulation found in plants and animals that is converted into dopamine by nerve cells in the brain. Levodopa does cross die blood-brain barrier, and a small amount is dien converted to dopamine. This allows the drug to have a pharmacologic effect in patients witii Parkinson s disease (Pig. 29-1). Combining levodopa witii another drug (carbidopa) causes more levodopa to reach die brain. When more levodopa is available, the dosage of levodopa may be reduced. Carbidopa has no effect when given alone. Sinemet is a combination of carbidopa and levodopa and is available in several combinations (eg, Sinemet 10/100 has 10 mg of carbidopa and 100 mg of levodopa Sinemet CR is a time-released version of die combined drugs). 

During early treatment witii levodopa and carbidopa, adverse reactions are usually not a problem. But as the disease progresses, die response to die drug may become less, and the period of time tiiat each dose is effective begins to decrease, leading to more frequent doses, and more adverse reactions. 

Chap. 31), and during lactation. Levodopa is used cautiously in patients with cardiovascular disease, bronchial asthma, emphysema, peptic ulcer disease, renal or hepatic disease and psychosis. Levodopa and combination antiparkinsonism drugs (eg, carbidopa/levodopa) are classified as Pregnancy Category C and are used with caution during pregnancy and lactation. 

Levodopa interacts with many different drugs. When levodopa is used with phenytoin, reserpine, and papaverine, there is a decrease in response to levodopa The risk of a hypertensive crisis increases when levodopa is used with the monoamine oxidase inhibitors (see Chap. 31). Foods high in pyridoxine (vitamin B6) or vitamin B6 preparations reverse the effect of levodopa However, when carbidopa is used with levodopa, pyridoxine has no effect on the action of levodopa hi fact, when levodopa and carbidopa are given together, pyridoxine may be prescribed to decrease the adverse effects associated with levodopa... 

The COMT inhibitors are used as adjuncts to levodopa7 carbidopa in Fhrkinson s disease Tolcapone is a potent COMT inhibitor that easily crosses the blood-brain barrier. However, the drug is associated with liver damage... 

Ms. Whitman is taking two drugs for Parkinson s disease levodopa and carbidopa. Ms. Whitman questions you as to why she received two drugs while her friend with Parkinson s disease is taking only one drug. Discuss how you would explain this to Ms. Whitman. 

Nacom (Du Pont Pharma)-comb. with carbidopa... 

Sinemet (Merck Sharp Dohme)-comb. with carbidopa Larodopa (Roche) Madopar (Roche)-comb. with benserazide Sinemet (Du Pont)-comb. with carbidopa Doparl (Kyowa)... 

Dopasol (Daiichi) Dopaston (Sankyo) Larodopa (Roche) Neodopaston (Sankyo)-comb. with carbidopa USA Larodopa (Roche)... 

Sinemet (Du Pont)-comb. with carbidopa generic... 

---