Anti-

Parkinson’s
Drugs
C a n d i c e R a c h e l U. C a n l a s , L P T - M D

School of Nursing

Emilio Aguinaldo College - Cavite

 What is Dopamine?

✓ A catecholamine (increase hear t rate,

blood pressure, breathing rate, muscle
strength and mental aler tness)
✓ A neurotransmitter (inhibitor y to
acetylcholine, which is excitator y)
✓ Plays impor tant roles in brain functions
such as executive functions, motor
control, motivation, arousal,
reinforcement, and reward
✓ It is 80% of catecholamine content in
the brain
 WHAT IS PARKINSON’S DISEASE?

✓ A l s o c a l l e d “s h a k i ng p a l s y ”

✓ C h r o n i c , p r o g r e s si ve , n e u r o d e g e ne ra ti ve d i s o r de r
a f f e c t i n g t h e d o p a m i ne - pr o du ci ng n e u r o n s o f t h e b ra i n

✓ B e c o m e s a p p a r e nt b e t w e e n 4 5 t o 6 5 ye a r s o f a g e , w i t h
m e a n o n s e t o f 5 6 ye a r s o l d

✓ S o m e t i me s o c c u r s i n yo u n g e r p a t i e nts a f t e r a c u t e
e n c e p ha l i ti s o r c a r b o n m o n ox i de o r m e t a l l i c p o i s o n i n g

✓ Re s u l ts a s a n e u r o t ra ns mi tte r i m b a l a nc e o f d o p a m i ne
( i n h i bi to r y) a n d a c e t yl c ho l i ne ( e x c i ta to r y) f u n c t i o n s i n
t h e b ra i n

✓ I m b a l a nc e i s c a u s e d b y f a i l ur e o f t h e n e r ve t e r m i na l s
i n t h e s u b s t a nti a n i g ra t o p r o d u c e d o p a m i n e

✓ C l a s s i c s y m p to m s: b ra d y ki n e s i a , p o s t u ra l i n s t a bi l ity,
r i g i di ty, a n d t r e m o r s o r T R A P ( t r e m o r, r i g i d i t y,
a k i n e s i a [ mo r e o f b ra d y k i n es i a ] , p o s t u ra l
instability)

❖ B ra d yk i ne s i a – s l o w n e s s o f m ove me nt

❖ A k i n e si a – n o m ove m e nt
What decreases Dopamine?
✓ T h e s u b s t a nti a n i g ra i s p a r t o f t h e b a s a l g a n g l i a
o f t h e c e r e b ra l c o r t e x r e s p o n s i bl e f o r p r o d u c i n g
d o p a m i ne

✓ D o p a mi n e a c t s i n t h e b a s a l g a n g l ia t o c o n t r o l
m ove m e nt s

✓ D e s t r uc ti o n o f t h e s u b s t a nti a n i g ra b y
Pa r k i ns o n’s d i s e a s e l e a ds t o d o p a m i ne d e p l e ti o n
a n d r e s u l t s i n e x c e s si ve , u n o p p o s e d
a c e t yl c ho l i ne ( c h o l i ne r g i c ) a c t i vi ty

T h e o r i es o n w h a t c a u s e s d o p a m i n e d e p l e t i o n :

➢ Re s u l t o f a n e a r l i e r h e a d i n j u r y

➢ E x c e s s i r o n i n t h e s u b s t a nti a n i g ra w h i c h c a n
f o r m t ox i c f r e e ra d i c a l s

➢ P r e m a tu re a g i n g o f n i g r o s tri a t a l c e l l s o f t h e
s u b s t a nti a n i g ra r e s u l ti n g f r o m e nv i r o nme n ta l o r
i n t ri n si c b i o c h e mi ca l f a c t o r s o r b o t h
 Goals of Drug
Therapy

1. Increase dopamine production

2. Replace dopamine
exogenously
3. Decrease breakdown of
dopamine in the system
4. Decrease cholinergic activity
First-Line Drugs
1. Non-dopamine dopamine receptor agonists (NDDRAs) – ergot /non-
ergot drugs
2. Dopamine Replacement Drugs
3. Anticholinergics
Non-dopamine Dopamine Receptor Agonists
(NDRRAs)

Traditional Role: Adjunct s to levodopa for motor f luctuations; Now of ten used as 1 st line
therapy drugs

Uses: As initial monotherapy and as combinat ion therapy with low -dose levodopa (to either
delay levodopa therapy or reduce dosage of levodopa and its associated motor complications)

Mechanism of Action : Direct stimulat ion of presynaptic and /or postsynaptic dopamine
receptors in the brain

Indications : Treat various stages of Parkinson’s disease

Contrai ndi cati ons : Known allergy, not to be used with concurre ntly adrenerg ic drugs due to
cardiovas cular risk for excessive catecholamine activity

Drugs: Bromocrip ti ne and Pramipexol

 Bromocriptine

✓ Ergot alkaloid similar to ergotamine

✓ Works by activating presynaptic dopamine receptors (D2 subclass receptors) to

stimulate the production of more dopamine

✓ Inhibits the production of the hormone prolactin (used to treat galactorrhea) and
treatment for prolactin -secreting tumors

✓ Indicated for Parkinson’s disease as well as hyperprolactinemia

 Pramipexol

✓ Non-ergot NDDRA

✓ H a ve b e t t e r a d ve rs e e f f e c t s p r o f i l e ( c a u s e f e w e r d y s k i n e s i a s )

✓ H a s m o r e s p e c i f i c D 2 s u b f a mi l y o f d o p a mi n e r e c e p to r a c t i vi ty = m o r e s p e c i f i c a n t i pa rk i ns o n s e f f e c t s

✓ E f f e c t i ve i n b o t h e a r l y a n d l a t e s t a g e Pa r k i n so n’s d i s e a s e a n d a p p e a r t o d e l ay t h e n e e d f o r l e vo do p a
t h e ra py

✓ C o n t ra i n di ca te d w i t h p a t i e nt s w i t h k n o w n d r u g a l l e r g y

✓ A d ve r se e f fec t s : D i z z i ne s s , G I u p s e t , a n d s o m n o l e n c e

✓ D r u g I n t e ra c t i o n s : O c c u r w i t h a ny d r u g m e t a b o l ize d b y c y t o c h r o m e P - 4 5 0 e n zym e 1 A 2 ( i . e . Wa r f a ri n
a n d c i p r o f l oxa ci n)
Dopamine Replacement Drugs: Carbidopa-Levodopa
(Sinemet)

Levodopa

✓ Tr a d i t i o n a l c o r n e r s t o n e f o r t h e r a p y o f P a r k i n s o n ’s D i s e a s e

✓ Biologic precursor of dopamine required by the brain for dopamine synthesis; Can cross the blood -brain barrier

✓ High doses is needed because it is broken down by an enzyme dopa decarboxylase before it reaches the brain;
Large peripheral doses can result in side effects and adverse reactions

Carbidopa

✓ Levodopa enhancer and allows for much lower doses of levodopa to be used

✓ Also reduces the side effects associated with high -dose levodopa

✓ Peripheral decarboxylase inhibitor; inhibits breakdown of levodopa in the periphery; thus allowing small doses of
levodopa do be used

Combination of Carbidopa + Levodopa

✓ Provide exogenous sources of dopamine that directly replace dopamine in the substantia nigra

✓ D r u g o f c h o i c e f o r l a t e - s t a g e P a r k i n s o n ’s D i s e a s e
 Pharmacokinetics: Carbidopa + Levodopa
(Sinemet)

Me ch a n i s m o f Act i o n : Sti m u late p r e s y n a p tic d o p a m in e r e ce p to rs to i n cr e as e b ra i n l e ve ls o f

d o p a m in e

In d i ca t i o n s : Re s to r e d o p a m in er gic a cti v ity i n Pa r k in s on’s d i s e a s e

C o n t ra i n d i ca t i o n : A n g l e- clos u re g l a u co ma, u n d i a gn os e d s k i n co n d i tion s l i ke m e l a n oma s

Ad ve rse E f fe cts : C a rd iac d y s r hy th mias , hyp oten sio n , ch o r e a , m u s cl e cra m p s , a n d G I d i s tr e s s

In t e ract i o n s : P y r i d oxin e ( v i ta min B 6 ) r e d u ce s th e e f f e ctiven es s o f ca r b i d o pa -levod op a

 Anticholinergics: Benztropine mesylate

Mechanism of action : Block ef fects of the neurotransmitter acetylcholine at cholinergic receptors in the brain as well as in
the rest of the body

I n d i c a t i o n : U s e d a s a d j u n c t t h e r a p y i n P a r k i n s o n ’s d i s e a s e d u e t o a n t i - t r e m o r p r o p e r t i e s ; h e l p a l l e v i a t e c o g w h e e l r i g i d i t y,
muscle tremors due to overstimulation of the cholinergic excitatory pathways

❖ Acetylcholine – causes SLUDGE (increased salivation, lacrimation , urination, diarrhea , and GI motility and emesis)

Caution: Do not use in hot weather or during exercise because it may cause hyperthermia

Adverse effects: Disorientation, confusion, toxic psychosis constipation, nausea and vomiting, urinary retention, visual
blurring, tachycardia, and increased intraocular pressure

Interactions: Alcohol is best avoided

Adjunct Drugs

1. Indirect-Acting Dopaminergic Drugs: Monoamine Oxidase

Inhibitors (MAOIs)
2. Dopamine Modulators
3. Catechol Ortho-Methyltransferase Inhibitors (COMT Inhibitors)
 MAO (Monoamine Oxidase)

✓ Enzyme that causes breakdown of catecholamines (epinephrine,

norepinephrine, and dopamine) as well as serotonin in the body

✓ 2 Subclasses: MAO -A and MAO-B

✓ Widely distributed in the body with highest concentrations in the liver,

kidney, stomach, intestinal wall, and brain

✓ Drugs target this enzyme to increase dopamine in the brain

Indirect-Acting Dopaminergic Drugs:
Monoamine Oxidase Inhibitors (MAOIs)

✓ N o n s e le ctive M A O Is i n h i bit b o th M A O - A a n d M A O - B

✓ Im p r ove the ra p e utic e f f e ct o f l e vo d op a b y p r e ve nting its m e ta b olic b r e a k d ow n

✓ I N DIC ATION S : U s e d a s m o n o th erap y o r i n co n j u n ction w i th l e vo d op a th erapy ( a s

a d j u n ctive d r u g s )

✓ C O N T R AIN DICATION S : D ru g a l l er gy, co n cu r r e n t u s e w i th m e p e r id ine ( D e m e ro l)

✓ MA JO R A D V ERS E E F F E CT : C h e e se e f fe ct – i n te ract w ith t y ra m i n e -co n ta i n i n g

fo o d s ( ch e e s e , r e d w i n e , b e e r, a n d yo g u r t) , w h i ch ca n ca u s e hy p e r ten si o n

✓ I N T ERAC TION S : Me p e ri d i n e ( ca u s e s d e l i riu m, m u s cl e r i g idity, a n d hy p e r p yr exia) :

ty ra min e - co ntainin g f o o d s ( hy p e r te ns io n)
MAOIs: Rasaligine (Azilect) and Selegiline (Selegos)

✓ Indication: Selective MAO-B inhibitor indicated for Parkinson’s disease

✓ Adverse effects: Increased with higher than recommended doses as they lose
their selectivity for MAO-B
Dopamine Modulator: Amantadine

✓ 1 st recognized as an antiviral drug to treat influenza virus infections and

still used for this purpose
Pharmacokinetics: Amantadine

M E C H A N I S M O F A C T IO N :

✓ C a u s e t h e r e l e a s e o f d o p a mi n e a n d o t h e r c a t e c ho l a min e s f r o m t h e i r s t o ra g e s i t e s i n t h e
p r e s y na p ti c f i b e rs o f n e r ve c e l l s w i t hi n t h e b a s a l g a n g l i a t h a t h a ve n o t b e e n d e s t r oye d b y t h e
disease process

✓ B l o c k s t h e r e u p t a ke o f d o p a m i ne i n t o t h e n e r ve f i b e r s = r e s u l t s i n h i g he r l e ve l s o f d o p a m i n e i n
t h e s y n a p s e s b e t w e e n n e r ve s a n d i m p rove d n e u r o tra n s mis s i o n b e t w e e n n e u r o n s

I N DICAT IO N S : E a r l y s t a g e s o f Pa r k i ns o n’s d i s e a se ( e f f e c ti ve f o r o n l y 6 - 1 2 m o n t h s )

C O N T R A I N DICATIO N S : D r u g a l l e r g y

A D V E R S E E F F E C TS : M I L D a n d i n c l u de d i z z i ne s s , i n s o m ni a , a n d n a u s e a

D R U G I N T E R ACT IO N S : I n c r e a s e d a n t i c h o l in e rg i c a d ve r se e f f e c t s w h e n g i ve n w i t h a n t i c ho l i ne r g i c
drugs
Catechol Ortho-Methyltransferase Inhibitors
(COMT inhibitors)

Mechanism of Action: Work pre-synaptically and block COMT

❖ COMT – enzyme that breaks down the body ’s catecholamines

Drug Effects: Prolong the duration of action of levodopa

Contraindications: Drug allergy

Adverse Effects: GI upset and urine discoloration; can worsen any dyskinesia

Interactions : Not to be taken with nonselective MAOIs due to cardiovascular

risk; but can be taken with SELECTIVE MAOIs such as rasagiline and
selegiline
COMT Inhibitors: Entacapone and Tolcapone

Entacapone To l c a p o n e

✓ A c t s p e r i p he ra l l y; c a n n o t c r o s s
t h e b l o o d - b ra i n b a r r i e r
✓ Ta ke n w i t h l e vo d o p a
✓ E f f e c t i ve f r o m t h e 1 s t d o s e a n d
b e n e f i ts a r e s e e n i n a f e w d a y s
✓ A c t s b o t h p e r i phe ra l l y a n d c e n t ra l l y
✓ C o n t ra i nd i c a t ed i n c a s e s w i t h l i ve r f a i l u r e
✓ C o n s i de r e d o n l y i n p a t i e nts w h o d o n o t
r e s p o n d t o o t h e r Pa r k i ns o n’s d i s e a s e d r u g
t h e ra py

✓ H e l ps m i n i mize w e a r i ng -o f f e f f e c t

✓ C o n t ra i n di ca te d i n p a t i e n ts w i t h
k n o w n d r u g a l l e rg y a n d u s e d w i t h
c a u t i o n i n p a t i e nt s w i t h p r e -
e x i s ti ng l i ve r d i s e a s e
Adverse Effects
of Anti-
Parkinson’s
Drugs
Drug-to-Drug
Interactions