Parkinson's, essential tremor, and spasticity drugs

Question 1

What is the mechanism of action of levodopa and carbidopa (sinemet)?

Answer 1

• L-dopa is transported across the blood brain barrier and then into remaining SN DA secreting neurons and converted to DA by aromatic amino acid decarboxylase (AADC)
• Carbidopa blocks peripheral AADC and is always combined with levodopa to allow more L-dopa to reach remaining DA neurons in SN (reduces peripheral AEs)

Question 2

What is levodopa/carbidopa used for treating?

Answer 2

Parkinson’s disease

Question 3

What are side effects of levodopa/carbidopa (sinemet)?

Answer 3

N/V, somnolence, headache, dizziness, orthostatic hypotension, cardiac arrhythmias, hallucinations, agitation, confusion, psychosis, dyskinesia, motor fluctuations, discolored urine/sweat/saliva

Question 4

COMT inhibitors mechanism of action

Answer 4

• Both inhibit peripheral COMT, preventing metabolism of L-dopa to inactive metabolite –> allows more L-DOPA to reach remaining DA neurons in SN
• Combined with L-DOPA/Carbidopa

Question 5

COMT inhibitors mechanism of action

Answer 5

• Both inhibit peripheral COMT, preventing metabolism of L-dopa to inactive metabolite –> allows more L-DOPA to reach remaining DA neurons in SN
• Combined with L-DOPA/Carbidopa

Question 6

What two drugs are COMT inhibitors?

Answer 6

Entacapone and tolcapone

Question 7

What are COMT inhibitors used for?

Answer 7

Added onto therapy for parkinson’s disease (useful extenders w therapy in patients that have motor fluctuations)

Question 8

What are side effects of COMT inhibitors?

Answer 8

Increases side effects of L-DOPA and causes hepatotoxicity (tolcapone only)

Question 9

What is the mechanism of action for dopamine agonists?

Answer 9

Stimulate DA receptors in the stiatum (bypasses DA input from the remaining SN neurons)

Question 10

What two drugs are dopamine agonists?

Answer 10

Pramipexole and ropinirole

Question 11

What are side effects for dopamine agonists?

Answer 11

• Similar to L-DOPA/Carbidopa but some are less frequent (less n/v, orthostatic htn, motor fluctuations and dyskinesias) or more frequent (adverse behavioral side effects, somnolence)
• Watch out for disorders of impulse control: gambling, shopping, eating, sex

Question 12

What is the mechanism of action of muscarinic antagonists?

Answer 12

Block muscarinic receptors in striatum

Question 13

What are dopamine agonists used for?

Answer 13

Parkinsons disease (can be used alone or added tx)

Question 14

What two drugs are muscarinic antagonists?

Answer 14

Trihexyphenidyl and benztropine

Question 15

What are muscarinic antagonists used for?

Answer 15

Parkinson’s disease- useful for younger patients who have resting tremor as a predominant finding and preserved cognitive function

Question 16

What are side effects of muscarinic antagonists?

Answer 16

Xerostomia, blurry vision, constipation, urinary retention, impaired sweating, tachycardia, confusion, impairment of recent memory, hallucinations, delusions

Question 17

What are some contraindications for muscarinic antagonists?

Answer 17

BPH, narrow angle glaucoma, older patients or patients with congnitive impairment

Question 18

What is the mechanism of action of MAO-B inhibitors?

Answer 18

Irreversible selective inhibition of MAO-B which decreases the oxidative metabolism of DA; Neuroprotective effects unclear

Question 19

What two drugs are MAO-B inhibitors?

Answer 19

Selegiline and rasagiline

Question 20

What are side effects of MAO-B inhibitors?

Answer 20

Nausea, orthostatic hypotension, headache, confusion, hallucinations, insomnia

Question 21

What are MAO-B inhibitors used for?

Answer 21

Mild symptomatic benefit and often used w L-DOPA/carbidopa and/or DA receptor agonists for treatment of parkinson’s disease

Question 22

What is the mechanism of action for NMDA receptor antagonists?

Answer 22

Uncertain but blocking NMDA receptors may decrease glutaminergic transmission in BG (reduce L-DOPA dyskinesias) and may increase dopamine release, block DAT, or stimulate DA receptors

Question 23

What is an example of a NMDA receptor antagonist?

Answer 23

Amantadine

Question 24

What are side effects of amantadine?

Answer 24

Orthostatic htn, dizziness, confusion, hallucinations, insomnia, n/v, livedo reticularis

Question 25

What are NMDA receptor antagonists used for?

Answer 25

Weak parkinsons disease drug with low toxicity that is most useful short-term in early mid PD or later to help with dyskinesias from L-DOPA/carbidopa

Question 26

What is the mechanism of action for essential tremor drugs?

Answer 26

Enhance neurotransmission at the GABA-A receptor

Question 27

What drugs are used for essential tremor?

Answer 27

1. Primidone (barbiturate)
2. Topiramate (also prolongs inactivation of Na voltage gated channels and blocks CA)
3. Gabapentin (binds ca vg channels and increase gaba + decrease glutamate transmission)
4. Alprazolam (benzo)
5. Propanolol (bb)

Question 28

What is the mechanism of action of tizanidine?

Answer 28

alpha 2 agonist and enhances inhibition of muscle stretch reflex

Question 29

What are side effects of tizanidine?

Answer 29

skeletal muscle weakness, hypotension, bradycardia, drowsiness, xerostomia

Question 30

What is tizanidine used for?

Answer 30

Spasticity

Question 31

What is baclofen’s mechanism of action?

Answer 31

GABA-B agonist and enhances inhibition of muscle stretch reflex

Question 32

What are side effects of baclofen?

Answer 32

skeletal muscle weakness (more than tizanidine), dizziness, drowsiness, depression, fatigue

Question 33

What is diazepams mechanism of action?

Answer 33

Increases GABA-A activity by enhancing inhibition of muscle stretch reflex

Question 34

What are side effects seen with diazepam?

Answer 34

Sedation, motor impairment, amnesia, tolerance, physical dependance

Question 35

What is diazepam used to treat in this case?

Answer 35

Spasticity