Pharmacology for Dentistry

Drugs used in Parkinsonism 125

reached at 30 minutes to 2 hrs and
plasma half life is 1 to 3 hours. More
than 95 percent of oral dose is rapidly
decarboxylated peripherally mainly in
GIT, liver and other tissues to dopam-
ine and very little (less than 5%) is left
to enter the central nervous system.
Hence, levodopa is given along with
peripheral dopa decarboxylase inhibi-
tors (i.e. carbidopa, benserazide) so that
more and more levodopa enters into
CNS and is converted into dopamine in
CNS.

Levodopa is excreted in the urine as
conjugated metabolites and its main
metabolite is homovanillic acid (HVA).

Adverse Effects

Nausea and vomiting because of CTZ
stimulation, which can be minimized by start-
ing with a lower dose. It also causes confu-
sion, hallucinations, delusions and other
behavioural effects. Certain cardiovascular
effects such as palpitation, postural hypoten-
sion, sinus tachycardia and ventricular
arrhythmias have also been reported.

On prolonged administration, grimac-
ing facial tics and choreoathetoid move-
ments of limbs have been reported.

Drug Interaction with Levodopa

• Levodopa with MAO inhibitors may
  precipitate severe rise in blood pressure
  (MAO inhibitors should be stopped at
  least two weeks before levodopa
  therapy).


• Methyldopa intensifies the adverse
  effects of levodopa.


• Pressor agents (catecholamines such as

adrenaline and isoprenaline) should be

avoided in patients on levodopa

therapy.

• Pyridoxine accelerates the peripheral
  dopadecarboxylation of levodopa.

PERIPHERAL DECARBOXYLASE INHIBITORS

CARBIDOPA AND BENSERAZIDE

Carbidopa and benserazide are peripheral

decarboxylase inhibitors used in combination

with levodopa. They do not penetrate blood-

brain barrier and do not inhibit the conversion

into dopamine from levodopa in brain.

They make more of levodopa available

to cross blood-brain barrier where levodopa

is converted into dopamine and reach at the

site of action.

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.

DOPAMINERGIC AGONISTS AND

OTHER DRUGS

BROMOCRIPTINE (Bromoergocriptine)

It is an ergot preparation which has a

specific dopamine receptor agonist action

(acts mainly on D 1 receptors) and capable

of crossing the blood brain barrier. It is less

active than levodopa and used only in late

cases as a supplement to levodopa. Adverse

effects are vomiting hallucinations,

hypotension, nasal stuffiness.