Antiparkinson Drugs

Question 1

cardinal features of parkinsons

Answer 1

resting tremor, muscular rigidity, bradykinesia, gait impairment

Question 2

principal metabolite of dopamine

Answer 2

HVA - homovanillic acid

Question 3

what do the D1 and D2 receptors do

Answer 3

• D1: activated adenylyl cyclase

- D2: inhibits adenylyl cyclase, opens K+ channels, suppresses Ca2+ currents

Question 4

classification of drugs used to treat parkinsons

Answer 4

AAIDD

Amantadine
Antimuscarinics
Inhibitors of Dopamine Metabolism: COMT and MAO
Dopamine Precursors
Dopamine Receptor Agonists: Ergot and Non-ergot dopamine agonists

Question 5

what is the dopamine precursor drug

Answer 5

Levodopa

Question 6

mechanism of levodopa

Answer 6

transported into the brain by facilitative L transport system –> converted to dopamine in the brain using DOPA decarboxylase

Question 7

what drug is given with levodopa and why

Answer 7

Carbidopa - Dopa decarboxylase inhibitor

• it does not cross into the brain but works in the periphery by preventing conversion to dopamine in the periphery so that most of the L-DOPA can cause into the brain
• also conversion to dopamine in periphery –> nausea, vomiting, cardiac arrhythmias, hypotension

Question 8

what is Sinemet

Answer 8

preparation containing carbidopa and L-DOPA in fixed preparation

Question 9

what is levodopa’s metabolite

Answer 9

homovanillic acid (HVA)
dihydroxyphenylacetic acid (DOPAC)

Question 10

what happens with long term use of levodopa

Answer 10

it is only effective for 3-5 years then responsiveness becomes lost completely

Question 11

AE of levodopa

Answer 11

GI effects (dopamine agonists cause nausea and vomiting)
CNS effects (Visual and auditory hallucinations and dyskinesia)
CVS effects (dopamine stimulates heart -- tachycardia)

Question 12

what is the on-off phenomenon seen with levodopa

Answer 12

-off periods of marked akinesia alternate over on periods of improved mobility but often marked dyskinesia

Question 13

contraindications of levodopa

Answer 13

HAV PAMP

• Hypertensive crisis with Phenelzine or Tranylcypromine (MAOI)
• Angle closure glaucoma
• Vitamin B6 (co factor for L-dopa decarboxylase)
• Psychotic patients esp if on Antipsychotics
• Arrhythmias in cardiac patients
• Melanoma
• Peptic ulcers

Question 14

what are the dopamine receptor agonists

Answer 14

Ergot derivatives: Bromocriptine

Non ergot derivatives: PARR
Pramipexole
Apomorphine
Ropinirole
Rotigotine

Question 15

mechanism of bromocriptine and what is it used to treat

Answer 15

D2 agonist

Parkinsons
Hyperprolactinemia

Question 16

mechanisms of the non ergot derivatives dopamine agonist

Answer 16

Pramipexole: preferential affinity for D3 receptors
Apomorphine: dopamine agonist
Ropinorole: purely D2 receptor agonist
Rotigotine: transdermal formulation that is dopamine agonist

Question 17

AE of the nonergot dopamine agonists (minus apomorphine)

Answer 17

GI effects (nausea and vomiting)
CVS effects
Dyskinesia
Mental disturbances: hallucination etc
Somnolence

harder ones to reason out:
Pulmonary Infiltrates
Pleural and Retroperitoneal Fibrosis
Erythromelalgia

Question 18

long term complication of ergot derivatives dopamine agonist

Answer 18

painless digital vasospasm

Question 19

when is apomorphine usually used

Answer 19

in off periods of akinesia in patients on dopaminergic therapy

Question 20

since apomorphine is highly emetogenic, what pre treatment is usually used

Answer 20

Trimethobenzamide

Domperidone

Question 21

contraindication of apomorphine

Answer 21

5-HT3 antagonist -> profound hypotension and loss of consciousness

Question 22

AE of apomorphine

Answer 22

QT prolongation

Question 23

what are the inhibitors of dopamine metabolism

Answer 23

MAO inhibitors: Selegiline and Rasagiline

COMT inhibitors: Tolcapone and Entacapone

Question 24

what are the MAOIs used for in treatment of parkinson

Answer 24

• Selegeline: selectively inhibits MAO-B so prevents breakdown of dopamine and enhances effect of levodopa (little chance for hypertensive crisis)
• Rasagiline: prolongs effects of levodopa-carbidopa in parkinson patients

Question 25

what is Selegiline metabolized to and its importance

Answer 25

Methamphetamine and Amphetamine --> insomnia if taken after midafternoon

Question 26

what occurs when carbidopa is used together with levodopa (name the COMT inhibitors)

Answer 26

Tolcapone and Entacapone -firstly inhibition of dopa decarboxylase by carbidopa --> increased in COMT in order to metabolized levodopa --> increases plasma 3-O-methyldopa (3-OMD) --> competes with levodopa for a carrier hence the levodopa that aren't bound are not useful since they don't get into the brain

Question 27

what is mechanism of COMT inhibitors

Answer 27

Tolcapone and Entacapone decrease metabolism of levodopa decreased 3-O-methyldopa (3-OMD) increased uptake of levodopa higher concentration of dopamine in the brain

Question 28

where do the COMT inhibitors exert their effect

Answer 28

Tolcapone in the central and periphery | Entacapone only periphery

Question 29

why is Entacapone preferred over Tolcapone

Answer 29

- not associated with hepatotoxicity (TOLCAPONE LEADS TO HEPATIC NECROSIS) - available as fixed dose with levodopa/carbidopa

Question 30

AE of COMT inhibitors

Answer 30

Entacapone and Tolcapone - increased levodopa: dyskinesias, nausea, vomiting - fulminating hepatic necrosis with Tolcapone (every 2 week monitoring of liver function) - Orange discoloration of urine

Question 31

mechanism of amantadine in parkinsons

Answer 31

increase synthesis, release, or re-uptake of dopamine from surviving neurons

Question 32

AE of amantadine

Answer 32

Livedo Reticularis (lace like purplish discoloration of skin)

Question 33

contraindications/caution that should be taken in patient taken amantadine

Answer 33

caution in patients with history of seizures and heart failure

Question 34

antimuscarinics used in treatment of parkinsons

Answer 34

Benztropine | Trihexyphenidyl

Question 35

AE of the antimuscarinics

Answer 35

benztropine and trihexyphenidyl xerostomia, pupillary dilation, dry mouth, other effects associated with anticholinergics

Question 36

contraindication of antimuscarinics

Answer 36

benztropine and trihexyphenidyl Glaucoma Prostatic Hypertrophy Pyloric Stenosis

Question 37

most effective symptomatic treatment of Parkinsons

Answer 37

Levodopa with Carbidopa

Question 38

reduce motor fluctuations in patients with advanced disease

Answer 38

MAOI and COMT-I

Question 39

used for control of tremor and drooling

Answer 39

antimuscarinics