Movement disorders durgs

Question 1

First line treatment of PD?

Answer 1

Levodopa + Carbidopa

Question 2

Why is L-dopa usually given in combination with carbidopa?

Answer 2

L-Dopa is converted to DA by DOPA decarboxylase in the brain
–> Carbidopa Inhibits DOPA decarboxylase in
peripheral tissues but does not cross BBB – increases formation of DA in brain
at the periphery.

Question 3

Why is L-Dopa used instead of DA to treat PD?

Answer 3

beacause Dopamine has low bioavailability and does not readily cross the BBB

Question 4

Drugs used as precursor of DA in PD?

Answer 4

Levodopa + Carbidopa

Question 5

drugs (Agonist) used to Directly stimulate DA receptors for PD?

Answer 5

1) Bromocripton (D2 agonist)
2) Pramipexole (D3 > D2 receptor agonist)

Question 6

Drugs that inhibit the breakdown of DA?

Answer 6

1) Selegiline
2) Rasagiline

Question 7

Drugs that block muscarinic activity: ↓ Cholinergic activity?

Answer 7

Benzotropin

Question 8

COMT inhibitors

Answer 8

Entacapone, Tolcapone

Question 9

Clinical signs of Parkinson’s disease

Answer 9

RAFT:
Rigidity of skeletal muscles, Akinesia (or bradykinesia), Flat face & Tremor at rest.

Question 10

Parkinsonism is characterized by?

Answer 10

Loss of DA neurons in this tract –> excessive ACh activity –> extrapyramidal dysfunction

Question 11

Indication of Levodopa

Answer 11

First line treatment of PD
–> used in combination with Carbidopa

Question 12

MoA of levodopa

Answer 12

• It is converted to DA by DOPA decarboxylase in the brain.
• Contraindicated in psychosis patients.
• Not a cure to PD– management drug.

Question 13

PK of Levodopa

Answer 13

1. half-life of levodopa is prolonged, lower doses of levodopa are effective, and there
   are fewer peripheral side effects.
2. ↓ signs of parkinsonism (e.g.
   bradykinesia)
3. Not a cure for parkinsonism & ↓
   responsiveness with time.

Question 14

what is the Respons to levodopa
treatment?

Answer 14

1) Fluctuations in clinical outcome – related to timing of levodopa dosing
2) On-off phenomena – off-periods of akinesia may alternate over a few hours with on-periods of improved mobility but often with
dyskinesias.
–> Can be used as an adjuvant with other pharmacological agents.

Question 15

Adverse Effects of Levodopa and Carbidopa

Answer 15

1. GI effect:
   –> anorexia, nausea, emesis.
2. Postural hypotension.
3. Cardiac effect:
   –> asystole, tachycardia, cardiac arrhythmias (rare)
4. Dyskinesias + choreoathetosis of face
   and extremities.
5. Behavioral effect:
   –> anxiety, hallucinations (Therfore it is contraindicated in Psychosis patients)

Question 16

MoA of Carbidopa

Answer 16

Inhibits DOPA decarboxylase in peripheral tissues but does not cross BBB – increases formation of DA in brain at the periphery.

Question 17

MoA of Bromocriptine

Answer 17

D2 agonist (not commonly used)

Question 18

Indication of Bromocriptine

Answer 18

1. Individual drug in patients who cannot tolerate levodopa.
2. Can be an adjuvant to levodopa

Question 19

Administration route of Bromocriptine / Pramipexole

Answer 19

orally

Question 20

Adverse effects of Bromocriptine and Pramipexole

Answer 20

1. Anorexia.
2. Nausea.
3. Vomiting.
4. Dyskinesias.
5. Postural hypotension.

Behavioral effect –> common with
bromocriptine – confusion + hallucination.

Question 21

PK of Pramipexole

Answer 21

short half-life & renal elimination.

Question 22

MoA of Pramipexole

Answer 22

D3 > D2 receptor agonist
–> increases dopamine activity on nerves of striatum and substantia nigra.

Question 23

Administration route of Selegiline and Rasagiline

Answer 23

orally.
(Half-lives permit bid dosing.)

Question 24

Adverse effects of Selegiline and Rasagiline

Answer 24

1. Insomnia.
2. mood changes.
3. Dyskinesias.
4. GI distress.
5. Hypotension.

Question 25

Indication of Selegiline

Answer 25

Give adjunctively with L-dopa

Question 26

Indication of Rasagiline

Answer 26

1. Monotherapy in early PD. 2. Can be used in combo with L-dopa

Question 27

MoA of Selegiline and Rasagiline

Answer 27

Inhibit MAOB receptors --> which are responsible for the metabolisim of DA

Question 28

Administration of Benztropine

Answer 28

orally –limited to one pill a day.

Question 29

AE of Benztropine

Answer 29

1. Serotonin syndrome with meperidine and possibly SSRI’s and TCA’s 2. CNS toxicity.

Question 30

MoA of Benztropine

Answer 30

↓ excitatory actions of cholinergic neurons on cells in the striatum by blocking muscarinic receptors.

Question 31

Indication of Benztropine

Answer 31

1. Adjunctively used in parkinsonism. 2. Used to alleviate the reversible extrapyramidal symptoms caused by antipsychotic drugs.

Question 32

what PD symptoms does Benztropine improve?

Answer 32

tremor and rigidity not bradykinesia.

Question 33

MoA of Entacapone and Tolcapone

Answer 33

Inhibit COMT enzyme which converts L-dopa to 3-O-methyldopa (3OMD)

Question 34

Administration route of Entacapone and Tolcapone

Answer 34

orally.

Question 35

Adverse effects of Tolcapone and Entacapone

Answer 35

1. Dyskinesias. 2. Postural hypotension. 3. Sleep disturbances. 4. Orange discoloration of urine.

Question 36

Indication of Entacapone and Tolacapone

Answer 36

Used for the purpose of prolonging L-dopa actions

Question 37

Physiologic and Essential tremor: Characterized by postural tremor ---> accentuated by anxiety, fatigue, and certain drugs (bronchodilators, tricyclic antidepressants, and lithium) Are treated with?

Answer 37

1) β- blocking drugs (e.g. propanolol) - Anti-epileptic drugs (e.g. gabapentine) - IM injection of Botulinum toxin.