Anti-Parkinson

Question 1

concept: Why does increasing DOPA make sense

Answer 1

@ normal physiological context DOPA levels are negligilbe. since rate limiting step is tyrosine OHase above DOPA production, if you load up on substrate you can increased DA = good to go for parkinson hurrah.

Question 2

Goal of therapy for Parkinson

Answer 2

want to decrease GABA – normally DA stimulates GABA neurons and Ach decreased GABA – so goal is to get more DA and less Ach so that GABA activity is increased

Question 3

What happens when levidopa is decarboxylated in the periphery ie symptoms

Answer 3

nausea
vomiting
cardiac arrhtymias
hypotension

Question 4

Why does food slow the appearance of levidopa in the plasma?

Answer 4

amino acids compete with absorption from gut and transport from blood to brain

Question 5

Wearing Off Phenomenon VRS On-Off Phenomenon

Answer 5

wearing off - fluctuations due to timing of levodopa administration
On-off phenomenon - fluctautions not due to timing of levodopa administration

Question 6

How to treat the Offs of the ON Off phenomenon

Answer 6

give apomorphine

Question 7

What vitamin is contraindicated with levodopa and why

Answer 7

vitamin B6 because is a cofactor for DOPA decarboxylase and increases peripheral metabolism of levodopa

Question 8

Why cant you use levodopa with a nonspecific MAO inhibitor

Answer 8

hypertensive crisis

Question 9

What type of meds and patients shouldnt be given levodopa

Answer 9

healthy people and ppl on antipsychotics or with mental disturbances

Question 10

What eye probelms contraindicated levodopa

Answer 10

angle closure glaucoma

Question 11

What heart problems are significinat?

Answer 11

can cause arrhtymias in cardiac patients

Question 12

Name the ergot D2 agonist

Answer 12

Bromocriptine

Question 13

Name the nonergot D2 agonists

Answer 13

Pramipexole
Ropinirole (pin role = parkinson side effect ;))
Rotigotine

Question 14

Which nonergo D2 agonist is available only transdermal

Answer 14

Rotigotine`

Question 15

Ergot side effects please :) only the bolded ones

Answer 15

Bromocriptine: pulmonary infiltrates
plueral and retroperitoneal fibrosis
erythromelalgia (bouts of pain cuased by temperature, turns red, usually hands and feet)

Question 16

Nonergot side effects bolded please

Answer 16

Pramipexole
Ropinirole (Ro-pin roll)
Rotigotine

SOMNOLENCE

Question 17

~*~Contraindications and be careful pateints for DA agonists

Answer 17

psychotic illness
recent mi (causes arrhythmias)
periperal vascular disease (erytrmelalgia and vasospasm @ periphery)
puptic ulceration (makes em bleed)

Question 18

Who cares about Apomorphine and why

Answer 18

rescue for OFF episodes of akinesia

emetogenic so give an antiemtic first

other effects i dont have time for- not bolded

Question 19

Which MAO i are used as adjuncts for levodopa treatment?

Answer 19

selegiline - deprenyl
and
(new one, not listed in antidepressant lec) =
Rasagiline

GILINES

Question 20

What is a concern about the metabolism of selegilin

Answer 20

metabolized to metamphetamine and amphetamine so can cause insomnia if take late in the day

Question 21

Justify the use of Tolcapone (gangster) and Entacapone

Answer 21

Tolcapone and Entacapone inhibit COMT –> thus levodopa is not metabolized to 3-o-methyl dopa so there is no compeition for uptake of levodopa to the BBB or the intestine; when you use carbidopa it causes increase shunting of levodopa to its metabolite

Question 22

Describe site of action of tolcapone and entacapone

Answer 22

tolcapone - in bbb and intestine

entacapone - periphery (enterocytes ie enta @ gut)

Question 23

~*~A/se of tolcapone

Answer 23

fulminating hepatic necrosis; entacapone doesnt cause this so preferred.

Question 24

~*~Antiviral with antiparkinsonism effects?

Answer 24

Amantadine

Question 25

MOA Amantadine

Answer 25

a) increases synthesis, release or reuptake of DA from **surviving neurons

Question 26

Bolded side effect of Amantadine

Answer 26

Levido reticularis - clears spontaneously after 1 month of cessationg of tx

Question 27

What good are antimuscarinics for Parkinson?

Answer 27

improve tremor and rigidity but not relaly bradykinesia (more central and due to DA… maybe)

Question 28

When should you not use antimuscarins

Answer 28

glaucoma
prostatic hyeprtrophy
pyloric stenosis

Question 29

Describe the first line regimen for Parkinson.

Answer 29

levodopa + carbidopa

Question 30

Decribe what you’d give for second line treatment of Parkinson

Answer 30

dopamin agonist
ergot - bromocriptine
nonergot - pramipexole, ropinirole, rotigotine

Question 31

Why would you add a COMT inhibitor or an MAOB inhibitor to levodopa?

Answer 31

to reduced motor fluctations for peopel with advanced disease

COMT inhibitors are teh CAPTONES
MAo-b are the GILINES

Question 32

Why would you add an antimuscarinic to the treatment regimen @ parkinson?

Answer 32

control of tremor and drooling.

Question 33

If I say CAPTONE you say?

Answer 33

COMT inhibitors
control of adcanced disease
fulminating hepatic necrosis

Question 34

If I say GILINE you say?

Answer 34

MAO-B inhibitor
control of advanced disease
dont take late in the day because of the meth metabolism ;)