Page 592 - First Aid for the USMLE Step 1 2020, Thirtieth edition [MedicalBooksVN.com]_Neat
P. 592
548 SecTioN iii Neurology aNd Special SeNSeS ` neurology—PhArmACology Neurology aNd Special SeNSeS ` neurology—PhArmACology
Parkinson disease Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity.
therapy Bromocriptine, Amantadine, Levodopa (with carbidopa), Selegiline (and COMT inhibitors),
Antimuscarinics (BALSA).
strAtegy Agents
Dopamine agonists Ergot—Bromocriptine.
Non-ergot (preferred)—pramipexole, ropinirole; toxicity includes nausea, impulse control disorder
(eg, gambling), postural hypotension, hallucinations, confusion.
dopamine availability Amantadine ( dopamine release and dopamine reuptake); toxicity = peripheral edema, livedo
reticularis, ataxia.
l-DOPA availability Agents prevent peripheral (pre-BBB) l-DOPA degradation l-DOPA entering CNS central
l-DOPA available for conversion to dopamine.
Levodopa (l-DOPA)/carbidopa—carbidopa blocks peripheral conversion of l-DOPA to
dopamine by inhibiting DOPA decarboxylase. Also reduces side effects of peripheral l-DOPA
conversion into dopamine (eg, nausea, vomiting).
Entacapone and tolcapone prevent peripheral l-DOPA degradation to 3-O-methyldopa
(3-OMD) by inhibiting COMT. Used in conjunction with levodopa.
Prevent dopamine Agents act centrally (post-BBB) to inhibit breakdown of dopamine.
breakdown Selegiline, rasagiline—block conversion of dopamine into DOPAC by selectively inhibiting MAO-B.
Tolcapone—crosses BBB and blocks conversion of dopamine to 3-methoxytyramine (3-MT) in
the brain by inhibiting central COMT.
Curb excess Benztropine, trihexyphenidyl (Antimuscarinic; improves tremor and rigidity but has little effect on
cholinergic activity bradykinesia in Parkinson disease). Park your Mercedes-Benz.
DOPA
DECARBOXYLASE Dopamine CIRCULATION 3-OMD
INHIBITOR – L-DOPA
Carbidopa DDC COMT – COMT INHIBITORS
(peripheral)
BLOOD-
BRAIN Entacapone
BARRIER Tolcapone
L-DOPA
DDC COMT INHIBITOR
(central)
PRESYNAPTIC
TERMINAL FROM THE Dopamine – Tolcapone
SUBSTANTIA NIGRA COMT
COMT
3-MT
DOPAC
–
Autoregulatory MAO TYPE B
receptor INHIBITORS
Reuptake
Selegiline
Rasagiline
DOPAMINE +
AVAILABILITY
Amantadine
Dopamine receptors + DOPAMINE AGONISTS
POSTSYNAPTIC
TERMINAL IN
THE STRIATUM Bromocriptine (ergot)
Pramipexole (non-ergot)
Ropinirole (non-ergot)
FAS1_2019_12-Neurol.indd 548 11/8/19 7:40 AM
