Antiparkinson Drugs

Question 1

PD causes, risk facotrs, cardinal symptoms

Answer 1

95% idio patic…5% familia

Positive - age, heredity, sex, toxic

Negative - coffee, tobacco, NSAIDs

Resting tremor - pill rolling
Muscular cogwheel rigidity
Bradykineia - slowness and restricteed movement

Question 2

Pathology, why survival time, and reflex vs. coluntary

Answer 2

Loss of dopamanergic in SN
Hallmark lewy bodies
>80% loss before symtoms

Mitchondrial dysfunction, ROS, excititoxic glutamate exposure

3-5 yrs untreated
5-10 yrs tx

Reflexes intact but voluntayr slower

Question 3

PD subtypes

Answer 3

PD - less common…tremor main complaint…younger patients…slower

PDD - postural imabalance and gait…>70 y/o at diagnosis…akinesia, rigidity…rapid decline

Question 4

Parkinsonism

Answer 4

Drug induced PD symptoms (due to DA antagonists like antipsychotics)

Question 5

MPTP

Answer 5

MPTP protoxin taken up by DAergic neurons via transporter…converted to MPP+ by MAOB in astrocytes…MPP+ interferes with mitochondria…free radical uidup and death

Question 6

Levodopa/L-Dopa mech and rationale

Answer 6

DA does not cross BBB

Prodrug has no action…crosses the BBB (unlike DA)…decarboxylated ti DA in ingrostriatal neurons…seuqestered in vesicles avaiable for release into DA deprived striatum

Question 7

Dopamine creation

Answer 7

Tyroosine to L-dopa to dopamine

Question 8

L-DOPA therapeutics

Answer 8

Gold standard
Efficacy decreases as disease progresses
NEver given alone

Question 9

L-DOPA kinetics

Answer 9

AA in diet compete iwht L-DOPA for transport

Metabolized to HVA and DOPAC

1-3% into CNS

Question 10

Clinical use and side effects of LDOPA

Answer 10

On target effects weaken and side effects strengthen as dz progresses…best early

Peripheral (because of L-DOpa to DOpa conversion)…GI distrubrances because of DOPA decarboylase in gut…tachycardia and hypotension

Central - wearing off (associated with dosing schedule), on/off(NOT associated with dosing scheudle), abnormal involuntary movements, psychotomimetic

Question 11

L-Dopa interactions and contraindiciations

Answer 11

Vit B6 (enhances metabolism) or within 2 weeks of MAOA (hypertensive crisis)

Psychosis, glaucoma, cardiac dz, peptic ulcers, melanoma

Question 12

Carbidopa

Answer 12

L-DOPA given with
DOes not cross BBB
Reduces Nausea and CV effects
IMproves delivery to CNS

DOpa decarbozylase inhibitors

Question 13

Rationale of COMT inhibitors

Answer 13

Inhibiting peripheral DOPA decarbozylase upregulates COMT…converts L-DOPA to 3OMD…competes with L-DOPA for BBB transport to CNS

Question 14

Entacapone, stalevo with side effects

Answer 14

Preferred…does not cross BBB
Entacopone + carbidopa+L-DOPA

Organge colored urine is main one

Question 15

Dopamine agnosits advantage and disadvantages

Answer 15

Do not require nigrostriatal neurons or metabolic conversion
Longer duration
Selective for D2 subtype
Do not conpete for trnapsort 
Can be monotherapeutic 

Not under neuronal control
Off target

Question 16

Dopamine agnost side effect

Answer 16

N/V, sleepiness, insomnia, AIMs

Question 17

Bromocriptine

Answer 17

Absorbed in gut 
Peak in 1-2 horus 
Excreted in bile and feces 
Ergot based
Newer, non-ergot DA agnoists are preferred

Question 18

Pramipexole

Answer 18

Antioxidant free radical svaneger
May be neuroprotective
Excreted by kindey
Renal insufficiency could be problem

Question 19

Ropinirole

Answer 19

Metabolized by CYP1A2…competing could slow clearance

Question 20

Pramiprexole and ropinirole are both

Answer 20

DA2 type agnosits
Slow titration needed
Monotherapy for mild

Question 21

Rotigotine

Answer 21

One daily pathc
Binds D3 more strongly
DA2>DA1

Question 22

APomorphine mech, indicaion, pharmacokinetics, side effects

Answer 22

Potent non selective DA agonist
Relief of the off state
Delivered subq…lasts 2 hours…quick acting
Nausea

Question 23

DA agonist side effects and contraindications

Answer 23

GI (N/V constipation)
CV (hypotension with vasospasm)
Dyskinesia
Mental disturbance

Psychosis, MI, peripheral ascular dz (for ergot)

Question 24

MAOI rationale

Answer 24

MAOB inhibition will increase DA avialbility and lower ox strsss

Question 25

Selegiline mech and side effedcts

Answer 25

Selective and irreversible MAOB

Modd elevating, N/V, dry mouth

Question 26

Amantadine

Answer 26

Rduces dyskinesia late in PD progression
Adjunct iwht sinemet
Worry about renal dz
Similar to L-DOPA side effects

Contra with history of seizure or heart failure

Question 27

Muscarinic antagonist

Answer 27

Reducing Ach can balance Ach:DA ration

No effect on brady kinesia but can reduce tremor and rigidity

Start low and tritrate up

Question 28

Trihexyphenidyl

Answer 28

Muscarinic antagonist