OVERVIEW OF PARKINSONISM, HUNTINGTON’S
DISEASE, WILSON DISEASE, TOURETTE
SYNDROME AND ALZHEIMERS DISEASE
PARKINSONISM
Meet Mr. Parkinson’s Problem
Mr. Parkinson is an old guy with some serious movement troubles. He’s got:
Shaky hands (tremors)
Stiff muscles (rigidity)
Sluggish movements (bradykinesia)
Terrible balance (postural instability)
Why is Mr. Parkinson struggling?
His brain is running low on dopamine, the chemical that helps control movement.
Normally, the substantia nigra (a part of the brain) makes dopamine and sends it to
the corpus striatum, which controls movement. But in Parkinson’s disease, the
dopamine-producing cells are dying, and the brain is out of balance!
Imagine a seesaw: dopamine (smooth moves) vs. acetylcholine (excitable moves).
Less dopamine means acetylcholine goes wild, making movement jerky and
uncoordinated.
How Do We Help Mr. Parkinson?
Boost Dopamine!
i. Levodopa (L-Dopa): The star of the show! It turns into dopamine in
the brain.
ii. Carbidopa: Blocks L-Dopa from converting too early, so more
dopamine reaches the brain.
iii. Dopamine Agonists (Bromocriptine, Pramipexole, Ropinirole): Fake
dopamine that tricks the brain into working better.
Stop Dopamine from Being Destroyed!
i. MAO-B Inhibitors (Selegiline, Rasagiline, Safinamide): Prevents
dopamine breakdown. MAO-B Inhibitors: Monoamine oxidase-B
(MAO-B) is an enzyme in the brain that breaks down dopamine. In
Parkinson’s disease, where dopamine levels are already low, MAO-B
makes the problem worse by destroying the little dopamine that’s
left. MAO-B Inhibitors block the MAO-B enzyme, preventing
dopamine breakdown. Thus increasing the dopamine levels in the
brain and improving movement. They also extend the effect of L-
, Dopa, reducing "wearing off" periods. The side effects include
Insomnia (Selegiline) – Take in the morning! Nausea, dizziness,
headache. It can cause high blood pressure if taken with tyramine-
rich foods (cheese, wine, aged meats) – but this risk is lower than
with MAO-A inhibitors.
ii. COMT Inhibitors (Entacapone, Tolcapone): Helps L-Dopa last longer.
Catechol-o-methyltransferase (COMT) is an enzyme that breaks
down L-Dopa before it reaches the brain, reducing its effectiveness.
COMT Inhibitors block the COMT enzyme, preventing the breakdown
of L-Dopa Thus Extend the duration of L-Dopa’s effect, reducing
"wearing off" periods. Do NOT increase dopamine directly—they just
help L-Dopa last longer. Entacapone (most commonly used) Acts only
in the periphery (outside the brain). Tolcapone works both in the
brain and periphery (more potent) and has a rare risk of liver toxicity,
so it’s used less often. Opicapone (newer, long-acting) Once-daily
dosing, fewer side effects. COMT Side Effects include Dyskinesias (too
much dopamine action) – You may need to reduce the L-Dopa dose.
Nausea, diarrhoea, dizziness. Tolcapone → Rare liver toxicity (needs
liver function monitoring). Urine may turn orange-brown (harmless
but can surprise patients!).
Calm Down the Overactive Acetylcholine!
i. Anticholinergics (Benztropine, Trihexyphenidyl): Helps reduce
tremors.
Surprise Bonus Drug!
i. Amantadine: Originally a flu drug, it helps release dopamine and
ease symptoms.
Fun Facts About These Drugs!
L-Dopa is powerful but can wear off over time, leading to the "on-off
phenomenon" (one moment, you're fine; next, you're frozen stiff).
The "On-Off" Phenomenon of L-Dopa: Why Parkinson’s Patients Suddenly Freeze or
Move Uncontrollably
When taking L-Dopa, Parkinson’s patients sometimes feel great ("ON" state) and
suddenly become stiff or frozen ("OFF" state), even when they’re still on medication.
What Happens in the "ON" State? 🏃♂️
L-Dopa is absorbed well and converted into dopamine, and symptoms improve (less
tremor, stiffness, and slowness).
DISEASE, WILSON DISEASE, TOURETTE
SYNDROME AND ALZHEIMERS DISEASE
PARKINSONISM
Meet Mr. Parkinson’s Problem
Mr. Parkinson is an old guy with some serious movement troubles. He’s got:
Shaky hands (tremors)
Stiff muscles (rigidity)
Sluggish movements (bradykinesia)
Terrible balance (postural instability)
Why is Mr. Parkinson struggling?
His brain is running low on dopamine, the chemical that helps control movement.
Normally, the substantia nigra (a part of the brain) makes dopamine and sends it to
the corpus striatum, which controls movement. But in Parkinson’s disease, the
dopamine-producing cells are dying, and the brain is out of balance!
Imagine a seesaw: dopamine (smooth moves) vs. acetylcholine (excitable moves).
Less dopamine means acetylcholine goes wild, making movement jerky and
uncoordinated.
How Do We Help Mr. Parkinson?
Boost Dopamine!
i. Levodopa (L-Dopa): The star of the show! It turns into dopamine in
the brain.
ii. Carbidopa: Blocks L-Dopa from converting too early, so more
dopamine reaches the brain.
iii. Dopamine Agonists (Bromocriptine, Pramipexole, Ropinirole): Fake
dopamine that tricks the brain into working better.
Stop Dopamine from Being Destroyed!
i. MAO-B Inhibitors (Selegiline, Rasagiline, Safinamide): Prevents
dopamine breakdown. MAO-B Inhibitors: Monoamine oxidase-B
(MAO-B) is an enzyme in the brain that breaks down dopamine. In
Parkinson’s disease, where dopamine levels are already low, MAO-B
makes the problem worse by destroying the little dopamine that’s
left. MAO-B Inhibitors block the MAO-B enzyme, preventing
dopamine breakdown. Thus increasing the dopamine levels in the
brain and improving movement. They also extend the effect of L-
, Dopa, reducing "wearing off" periods. The side effects include
Insomnia (Selegiline) – Take in the morning! Nausea, dizziness,
headache. It can cause high blood pressure if taken with tyramine-
rich foods (cheese, wine, aged meats) – but this risk is lower than
with MAO-A inhibitors.
ii. COMT Inhibitors (Entacapone, Tolcapone): Helps L-Dopa last longer.
Catechol-o-methyltransferase (COMT) is an enzyme that breaks
down L-Dopa before it reaches the brain, reducing its effectiveness.
COMT Inhibitors block the COMT enzyme, preventing the breakdown
of L-Dopa Thus Extend the duration of L-Dopa’s effect, reducing
"wearing off" periods. Do NOT increase dopamine directly—they just
help L-Dopa last longer. Entacapone (most commonly used) Acts only
in the periphery (outside the brain). Tolcapone works both in the
brain and periphery (more potent) and has a rare risk of liver toxicity,
so it’s used less often. Opicapone (newer, long-acting) Once-daily
dosing, fewer side effects. COMT Side Effects include Dyskinesias (too
much dopamine action) – You may need to reduce the L-Dopa dose.
Nausea, diarrhoea, dizziness. Tolcapone → Rare liver toxicity (needs
liver function monitoring). Urine may turn orange-brown (harmless
but can surprise patients!).
Calm Down the Overactive Acetylcholine!
i. Anticholinergics (Benztropine, Trihexyphenidyl): Helps reduce
tremors.
Surprise Bonus Drug!
i. Amantadine: Originally a flu drug, it helps release dopamine and
ease symptoms.
Fun Facts About These Drugs!
L-Dopa is powerful but can wear off over time, leading to the "on-off
phenomenon" (one moment, you're fine; next, you're frozen stiff).
The "On-Off" Phenomenon of L-Dopa: Why Parkinson’s Patients Suddenly Freeze or
Move Uncontrollably
When taking L-Dopa, Parkinson’s patients sometimes feel great ("ON" state) and
suddenly become stiff or frozen ("OFF" state), even when they’re still on medication.
What Happens in the "ON" State? 🏃♂️
L-Dopa is absorbed well and converted into dopamine, and symptoms improve (less
tremor, stiffness, and slowness).
