Parkinson's disease (PD) affects 3% of the population older than 66 years of age; therefore, PD is encountered relatively commonly in clinical anesthesia practice. Symptoms include resting tremor, rigidity, akinesia, and postural instability. These symptoms are due to destruction of dopaminergic neurons in the substania nigra, a component of the basal ganglia. The basal ganglia relays motor signals from cortex to thalamus and brainstem nuclei. Loss of dopaminergic neurons increasingly activates basal ganglia inhibitory nuclei, thereby suppressing cortical motor signals and inhibiting brainstem locomotor areas. Such disturbances in signaling produce Parkinsonian symptoms. Pharmacologic agents treat PD symptoms, mostly through dopaminergic pathways.
L-DOPA AND DOPAMINE AGONISTS
The primary therapeutic goal is to replenish dopamine availability. L-dopa, a dopamine precursor, readily crosses the blood–brain barrier and converts to dopamine with DOPA decarboxylase. L-Dopa is administered with a peripheral DOPA decarboxylase inhibitor such as carbidopa. This prevents the peripheral side effects of dopamine such as nausea. As another side effect, L-dopa may potentiate hypotension by two means: central and peripheral. Central hypotension, similar to alpha-methyl dopa stimulation of presynaptic alpha-methyl dopaipherale, results in diminution of sympathetic response. Peripheral hypotension results from vasodilation. The 45–90 min L-dopa half-life necessitates that perioperative dosing regimens be strictly managed. L-Dopa may be administered intraoperatively via a nasogastric tube.
Dopamine agonists such as bromocriptine, pergolide, pramipexol, and ropinirole are utilized early in the disease process, delaying the need for L-dopa therapy. These agents may also be prescribed in conjunction with L-dopa. Using dopamine agonists before starting L-dopa therapy may delay tardive dyskinesia onset. Tardive dyskinesia occurs with phasic activation of dopamine receptors as a result of L-dopa's short half-life. Tonic activation is seen in non-Parkinson activation. Apomorphine is another dopamine agonist used to smooth movement or restore movement during reactivations. It may be administered subcutaneously intraoperatively if nasogastric administration of L-dopa is not possible.
MONOAMINE OXIDE INHIBITORS
Selegiline, a type B monoamine oxidase inhibitor (MAO-I), is also used to treat PD as it inhibits the degradation of dopamine by MAO-B. Selegiline has little therapeutic effect when administered alone, but rather acts to prolong the effect of L-dopa. At higher doses, selegiline inhibits the MAO-A enzyme responsible for norepinephrine (NE), epinephrine, and serotonin degradation. Accordingly, patients taking selegiline may demonstrate prolonged or increased response to vasopressors. Meperidine should be avoided in patients taking selegiline as it can precipitate serotonergic crisis. Consideration should be given to stopping MAO inhibitors 10–14 days prior to elective surgery because of these drug interactions. Some advocate continuing MAO-Idv and conducting an MAO-I safe anesthetic by avoidance of meperidine, epinephrine, ephedrine, cocaine, or other potentiating agents.
Catechol-O-Methyl Transferase (COMT) Inhibitors
COMT inhibitors such as entacopone and tolcapone act by inhibiting catechol-O-methyl transferase, an enzyme responsible for inactivating dopamine in the peripheral nervous system. This action leads to ...