Parkinson's Disease

Question 1

Parkinson’s Disease

• _____ is the most apparent and well known symptom
• _______(slowness of movement)/hypokinesia
• _______: stiffness and resistance to limb movement
• postural instability, _____
• speech and swallowing disturbances
• mask like faces
• cognitive dysfunciton/psychosis/hypotension/GI dysmobility

Answer 1

tremor
bradykinesia
rigidity
falls

Question 2

Drugs for Parkinson’s Disease

• Neurodegenerative disease
• imbalance between ________ and _______
• genetically linked - juvenile parkinsonism
• ________ cause
• ______ stress theory
• -_______ generated from dopamine oxidation destroy dopamine neurons

Answer 2

dopaminergic, cholinergic
autoimmune
oxidative
free radicals

Question 3

Drugs for Parkinson’s Disease

• irreversible loss of neuronal function
• degeneration of _______ neurons in the ________ and projections into other structures in the _______
• loss of dopaminergic neurons in the substatia nigra
• -dopamine concentration ______ in parksinonism
• a ________ approach is to restore dopaminergic activity

Answer 3

dopaminergic
substantia nigra
reduced
therapeutic

Question 4

Biogenic Amines - Dopamine
Five receptor subtypes (D1-D5)
-Dopamine is metabolized to __________ by ____ and ____
-HVA is excreted in the ____
-high concentration in
-nigrostriatal pathways, __________
-effects: behavioral and drug reinforcement, emesis, hormone release (prolactin),, mood, motor coordination

Answer 4

homovanillic acid (HVA)
MAO, COMT
urine
chemoreceptor trigger zone

Question 5

Drugs for Parkinson Diseases
Drugs that increase dopamine levels
-______(L-DOPA), _______(Lodasyn); __________(Symmetrel); _________ (Eldepryl)(MAOI)

Dopamine receptor agonist

• ________ (Parlodel); _________(Premax);
• _________(Requip)
• ______

Anticholinergic (antimuscarinic) receptor
-________(Cogentin)

Answer 5

levadopa, carbidopa, amantadine, seligiline
bromocriptine, pergolide,
robinirole
benztropine

Question 6

Levadopa
Levadopa is the biosynthetic precursor of _________
-dopamine cannot cross the ____
-L-dopa can cross the BBB
-absorbed in the __________
–dietary _______ compete with L-dopa for transport
—high _____ diet decreases effectiveness of L-DOPA

Answer 6

dopamine
BBB
duodenum
aminoacids
protein

Question 7

Levadopa

• ______ first pass effect before L-dopa reaches target in CNS due to metabolism in peripheral tissues by ____ and ___
• L-aromatic amino acid decarboxylase (LAAD)
• catechol-O-methyltransferase
• large first pass effect (__)

Answer 7

large
LAAD, COMT
95%

Question 8

Levadopa
Levadopa is metabolized in _________
-drugs that inhibit peripheral ______ increase the amount of L-DOPA entry into the CNS
–______ inhibits LAAD
–_______ inhibits ______
-LAAd requires vitamin _______ (pyridoxine) as a cofactor
–vitamin B6 supplements should not be admistered with L-DOPA

Answer 8

peripheral tissues
metabolism
Cardidopa
Tolcarpone
B6

Question 9

Levadopa - Adverse Effects

• Peripheral dopamine effects
• -nausea and vomiting; ________ hypotension; cardiac arrythmias
• -these effects are significantly reduced when co-administered with ______
• Central (excessive) dopamine effects
• ______; psychotic effects
• -dyskinesis; psychotic effects
• sedative effects, agitation, delirium, vivid dreams or nightmares
• pleasant euphoria

Answer 9

cardidopa

central dopamine effcts

Question 10

Levadopa - Interactions
Anticholinergics
-increase drug absorption by delaying \_\_\_\_\_\_\_\_\_\_ time
-Antacids and Cisapride
--increase \_\_\_\_\_\_ of L-DOPA-
-MOAI (non selective): \_\_\_\_\_\_\_\_
--\_\_\_\_\_\_\_\_\_
-Antipsychotic agents
--reduce \_\_\_\_\_\_\_\_ of L-DOPA

Answer 10

gastric emptying
bioavailability
phenelzine
hypertensive crisis
effectiveness

Question 11

Levadopa - Carbidopa
Carbidopa
-_____ of L-dopa
-inhibits the conversion of L-dopa to dopamine by ____ in peripheral tissues
-is highly _________ at physiological pH and does not cross the _____
-combination therapies of L-dopa and carbidopa allow for a ______ in the. amount of L-dopa needed

Answer 11

analog
LAAD
ionized
BBB
reduction

Question 12

Tolcapone

• inhibits ______
• increases ___ bioavailability and half life of L-dopa
• _________ competes with L-dopa for transport across the BBB

Answer 12

COMT
oral
3-O–methyldopa

Question 13

Amantadine

• Antiviral drug
• Mechanism
• -increases the release of _____ from nigrostriatal neurons
• -inhibits _____ of dopamine
• better tolerated but much less effective than L-dopa

Answer 13

dopamine

reuptake

Question 14

Selegiline (MAO B Inhibitor)

• selective inhibitor of ______ which breaks down dopamine
• -increases dopamine levels in the _______
• suggested to delay the disease progression by inhibiting free radical formation or by inhibiting the formation of a toxic metabolite
• -controversial

Answer 14

MAO-B

basal ganglia

Question 15

Dopamine receptor agonist

• Activates __ receptors directly
• -do not require functional dopaminergic nerves
• helpful in advance cases
• _______, ______
• -are ergot alkaloids
• -_______ is a D2 agonist
• -_______ is a D1 and D2 agonist
• -side effects include ____ due to stimulation of dopamine receptors in the vomiting centre of the medulla
• -dose related effects in the CNS include confusion, dyskinesia, sedaiton, vivid dreams and hallucinations

Answer 15

D2
Bromocriptine, Peroglide
Bromocriptine
Pergolide
nausea

Question 16

Acetylcholine receptor antagonists
Anticholinergics (Antimuscarinics)
-\_\_\_\_\_\_ (Cogentin)
-less effective than \_\_\_\_\_\_ drugs
-more effective in reducing \_\_\_\_\_\_\_

Answer 16

Benztropine
dopaminergic
tremor