Antiparkinson

Question 1

What part of the brain is initially effected by parkinsons/huntingtons and alzheimers disease?

Answer 1

Parkinsons/huntington: basal ganglia–>altered voluntary movement

AD: hippocampal & cortical neurons–> impaired memory formation and cognitive deficit

Question 2

What is the pathophysiology of Parkinsons? what are the misfolded proteins?

Answer 2

accumulations of alpha-synucelin proteins (misfolded proteins)–>form lewy bodies–>increased production of free radicals–>interfere with neuronal function lead to atrophy/death

Degeneration of D2 neurons in substantia nigra of basal ganglia:–>increased activity of ACh in basal ganglia

• increased inhibition of VA/VL thalamus
• reduced excitatory input to cortex
• diminished execution of motor movement
• overtime will spread to other parts of brain

Question 3

What are the signs and symptoms of Parkinsons

Answer 3

Bradykinesia
Muscular rigidity
Resting tumor (goes away with voluntary movement)
Postural instability

Question 4

which drug cause dopamine replacement?

Answer 4

Levodopa

Question 5

what drug improves bradykinesia and rigidity

Answer 5

Levodopa

Question 6

adverse effects of taking LDOPA?

Answer 6

LDOPA thoses its therapeutic effect over time (3-4 yrs of therapy) and patient will be less responsive to LDOPA

• dyskinesia
• response fluctuation (randomly loss of effect, or rapid return of muscle rigidity before end of dosing interval

-GI: nausea/vomiting
postural hypotension

Question 7

how should response fluctuation problem be addressed

Answer 7

“drug holiday” by stop taking drug in order for body to improve response to fluctuation prob

Question 8

Carbidopa and its effects with LDOPA

Answer 8

it is an inhibitor of DOPA decarboxylase in PERIPHERY
inhibit premature breakdown of LDOPA in periphery–does not cross BBB
Helps increase amt of LDOPA delivered to brain( 10% vs 2%-LDOPA alone)!

Question 9

WHat are the dopamine receptor agonists agent?

Answer 9

Pramipexole, ropinirole,Apomorphine(less used)

Question 10

which agent is used for temporary relief as the “rescue treatment” in LDOPA induced dyskinesia

Answer 10

Apomorphine

Question 11

which agents are used as 1st line or initial therapy for PD

Answer 11

Dopamine receptor agonists: pramipexole, ropinirole, Apomorphine

Question 12

what are the MAO-B inhibitors? and what do they do

Answer 12

Selegiline, rasagiline; decrease dopamine metabolization

Question 13

What can cause serotonin syndrome?

Answer 13

MAO-B inhibitors + SSRI/TCA

Question 14

Entacapone

Answer 14

PERIPHERAL COMT inhibitor

Question 15

Tolcapone

Answer 15

CENTRAL and PERIPHERAL COMT inhibitor

Question 16

Which COMT inhibitor is preferred? why?

Answer 16

Entacapone, Tolcapone has risk for acute hepatic toxicity

Question 17

what is the benefit of COMT inhibitors as adjuncts with LDOPA

Answer 17

helps prolong action of LDOPA diminishing peripheral metabolism

Question 18

what drug increases dopamine release into CNS?

Answer 18

Amantadine

Question 19

Amantadine characteristic and side effects

Answer 19

Antiviral agent w/ antiparkinoism properties. Short duration/short lived–short therapeutic effectiveness

SE: livedo reticularis

Question 20

What are the anticholinergic agents for Parkinsons? what are their benfits?

Answer 20

Benztropine, trihexyphenidyl.

Reduce tremor and rigidity; little effect on bradykinesia

Question 21

what agents will lower incidence of response fluctuation and dyskinesis that are associated with long term Levodopa use?

Answer 21

Pramipexole, Ropinirole, Apomorphine

D2 receptor agonists

Question 22

what would you avoid Selegiline with?

Answer 22

SSRI; TCAs to avoid serotonin syndrome

and LDOPA @ high concentration=hypertensive crisis

Question 23

what improves bradykinesia and rigidity?

Answer 23

LDOPA

Question 24

what happens with drug interaction with pyridoxine (Vitamin B)

Answer 24

it enhances peripheral conversion of LDOPA–>DOPAMINE in periphery!