Treatment Of Parkinson

Question 1

Precursor of dopamine that crosses the blood brain barrier

Answer 1

L-dopa

Question 2

It is the major drug used to decrease rigidity, tremors and other symptoms of parkinson

Answer 2

L-dopa

Question 3

Has extremely short half life 1-2 hours which causes fluctuations in plasma concentration

Answer 3

L-dopa

Question 4

Dopamine is the major peripheral product of ————— and is responsible for most of the peripheral adverse effects

Answer 4

L-dopa

Question 5

What are the adverse effects of Levodopa?

Answer 5

1. Dyskinesia ( involuntary movements) —-> due to an overactivity of dopamine at receptors in the basal ganglia
2. On -off effects:
   Due to fluctuating plasma concentrations of Levodopa
3. Nausea, vomiting,and anorexia —> due to stimulation of chemoreceptor trigger zone of medulla
4. Tachycardia and arrhythmia:
   Due to dopaminergic action on the heart —> receptor found in the atria
5. Behavioral changes such as confusion, hallucinations, and other effects as seen in schizophrenia
   —-> due to increased dopamine activity in the brain ( affects all parts of the brain not just basal ganglia) —> nigrostriatal pathway

Question 6

Because levodopa has a short duration of action we need to optimize it with other drugs what are the examples of other drugs ?

Answer 6

1. Carbidopa
2. Peripherally acting dopamine receptor antagonists—> Domperidone
3. Monoamineoxidase inhibitors —» selegiline
4. COMT inhibitors —> Entacapone and opicapone
5. Dopamine recptor agonist:
   Ropinirole
   Rotigotine
   Apomorphine
   Amantadine

Question 7

Is a drug that was released in a self-injectable form

It is now used as “rescue” drug for advanced PD and Severe off episodes

Answer 7

Apomorphine ( dopamine receptor agonist)

Question 8

Dopamine receptor agonist that is formulated as once daily transdermal (skin) patch that is changed every 24 hr

Answer 8

Rotigotine

Question 9

Notes about rotigatine

Answer 9

Most common side effect —> skin irritation

Clinical trials have shown rotigotine is just as effective as oral dopamine agonists : pramipexole and ropinirole

Has some actions on the D1 receptors which might confer some additional benefits

Question 10

Initially developed as an antiviral medication to treat influenza
Used to treat dyskinesia in late disease through:
Antiglutamaterguc activity
Block dopamine reuptake
Stimulate release of endogeneous dopamine
Mild anticholinergic effect

Answer 10

Amantadine

Question 11

Usually given with carbidopa-levodopa therapy during the later stages of parkinson’s disease to control involuntary movements (dyskinesias ) induced by carbidopa-levodopa

Answer 11

Amantadine

Question 12

A drug that has
purple mottling of the skin
Ankle swelling
Restlessness

Answer 12

Amantadine

Question 13

Potent agonist at the dopamine (D2) receptors in the CNS

Answer 13

Ropinirole

Question 14

Often added to levodopa when levodopa alone doesn’t adequately prevent symptoms or when patients experience severe on-off fluctuations

Answer 14

Ropinirole

Question 15

Stimulates D2 recptors in other areas

Leading to uncotrolled shopping / gambling / eating and secual urges

Answer 15

Ropinirole

Question 16

What is the benefit of dopamine receptor agonists?

Answer 16

1. Duration of action longer than that of levodopa
2. Can be used effectively as single agents in the early stages of PD or in combination with levodopa / carbidopa in the later stages of disease
3. Effective in the early treatment of the motor symptoms of PD and plays an important role in controlling motor fluctuations in response to levodopa
4. Initial therapy with the newer drugs is associated particularly with less risk of developing dyskinesias and motor fluctuations when compared with patients starter levodopa therapy

Question 17

Inhibitors of catechol-o-methyltransferase are the newest drugs

Answer 17

Entacapone

Opicapone

Question 18

Used to increase central levodopa levels by preventing the metabolism of Levodopa to 3-o-methyldopa

Answer 18

Entacapone

Opicapone

Question 19

What is the benefit of COMT inhibitors ?

Answer 19

Reduce the symptoms of the wearing off phenomena seen in patients on levodopa-carbidopa —> help maintain a constant dose

Question 20

Peripheral dopa decarboxylase inhibitors

Answer 20

Carbidopa

Question 21

Peripherally acting dopamine receptor antagonist?

Answer 21

Domperidone

Question 22

It is a drug that acts as peripherally acting dopamine receptor antagonist
It doesnt cross the blood brain barrier
However it works in the chemoreceptor trigger zone (outside the blood brain barrier) but does not gain access to the basal ganglia
And usefull in preventing nausea and anorexia

Answer 22

Domperidone

Question 23

It is a MAO inhibitor that selectively block it and can be used to inhibit dopamine metabolism in the brain

Answer 23

Selegilline

Question 24

It is metabolized into amphetamine and methamphetamine and so can cause insomnia if administered later than midafternoon

Appears to slow progression of disease in newly diagnosed patients -neuroprotective

Answer 24

Selegilline

Question 25

It is a muscrinic acetylcholine recptor anatgonists and less peripheral effects than atropine

Answer 25

Benzotropine

Question 26

What are side effects of benzotropine?

Answer 26

Adverse effects: 
Dry mouth 
Constipation 
Impaired vision 
Urinary retention

Question 27

It is a drug due to its troublesome side effects, these are rarely used except to treat parkinsonian symotoks in patients recieving antipsychotic drugs (which are dopamine antagnoists and thus nullifying the effect of levodopa )

Answer 27

Benzotropine

Question 28

It is an A2A adenosine receptor antagonist

Answer 28

Istradefylline

Question 29

Used once daily for treatment of off episodes

Answer 29

Istradefylline

Question 30

Because of the potential risk of exacerbating psychosis, patients with a major psychotic disorder should bot be treated with ——

Answer 30

Istradefylline