Parkinson's Drugs

Question 1

L-dopa: MOA

Answer 1

Intracellular precursor to dopamine. L-dopa CAN cross BBB.

Question 2

L-dopa is administered with? Why?

Answer 2

Carbidopa. Carbidopa cannot cross BBB and prevents conversion of L-dopa to dopamine in periphery (inhibits the enzyme). It minimizes side effects: N/V and orthostatic hypotension.

Question 3

L-dopa indications

Answer 3

PD (L-dopa and carbidopa)
Effective for bradykinesia, tremor, rigidity. NOT POSTURAL INSTABILITY.

Effective for Parkinsonian sx in other neurodegenerative diseases (e.g. Lewy Body dementia).

Effective for Restless Leg Syndrome

Question 4

L-dopa side effects

Answer 4

Dose dependent side effects: N/V, orthostatic hypotension, psychosis (all because conversion of L-dopa to dopamine in periphery)

Motor complications of long-term L-dopa use: 50% of patients on levodopa for five years experience motor fluctuations and dyskinesia.

Question 5

L-dopa metabolism

Answer 5

L-dopa is converted to dopamine intracellularly. Dopamine is metabolized to homovanillic acid mostly via enzyme monoamine oxidase.

Question 6

L-dopa drug interactions

Answer 6

L-dopa plus MAO inhibitor can lead to dopamine toxicity resulting in psychosis, N/V, cardiovascular problems.

Question 7

What are the dopamine agonists?

Answer 7

Bromocriptine, pramipexole, ropinirole.

Question 8

Dopamine agonists: MOA

Answer 8

Post-synaptic mimicry of naturally occurring dopamine

Question 9

Dopamine agonists: Indications

Answer 9

Bromocriptine suppresses prolactin secretion (prolactinoma)

Restless Leg Syndrome and PD. Started early in course of PD before L-dopa and later used as adjunctive therapy to reduce dyskinesias and motor fluctuations.

Question 10

Dopamine agonists: Side effects

Answer 10

N/V, orthostatic hypotension, visual hallucinations.

Bromocriptine is associated with heart valve fibrosis.

Prramipexole/ropinirole can cause sleep attacks.

Question 11

Dopamine agonists: Metabolism

Answer 11

Hepatic CYP1A2 is enzyme responsible for metabolism of ropinirole.

Inhibitors of CYP1A2 can lead to ropinirole toxicity due to its decreased breakdown. Example: CIPROFLOXACIN (watch out for elderly patients with UTIs and PD).

Question 12

MAO-B inhibitors?

Answer 12

Selegiline and Rasagiline

Question 13

MAO-B inhibitors: MOA

Answer 13

Prevent breakdown of dopamine by inhibiting MAO-B. Monamine NTs: Dopamine, norepinephrine, epinephrine, + serotonin.

Question 14

MAO-B inhibitors: Indication

Answer 14

Benefit for symptoms of early PD

Question 15

MAO-B inhibitors: Side effects

Answer 15

Nausea and headache. Selegiline can cause confusion (esp. in elderly) and insomnia due to its amphetamine metabolites.

Question 16

MAO-B inhibitors: Drug interactions

Answer 16

MAOIs should NOT be administered with either SSRIs or with tricyclic antidepressants due to risk of serotonin syndrome.

Question 17

A drug with mixed gluatmate and dopamine effects?

Answer 17

Amantadine

Question 18

Amantadine: MOA

Answer 18

NMDA glutamate antagonist. Increases dopamine release and blocks dopamine re-uptake.

Question 19

Amantadine: Indication

Answer 19

Early tremor predominant PD. Add on therapy late in PD to treat dyskinesias and motor fluctuations.

Question 20

Amantadine: Side Effects

Answer 20

Ankle edema, confusion, insomnia

Question 21

COMT inhibitors?

Answer 21

Tolcapone and entacapone

Question 22

COMT inhibitors: MOA

Answer 22

Outside CNS, L-dopa is metabolized to dopamine via decarboxylation. Secondary pathway: L-dopa converted to 3-O-methyldopa by COMT. Blocking COMT increases half-life of L-dopa and ameliorates motor fluctuations late in course of PD.

Question 23

COMT inhibitors: Indication

Answer 23

Treats patients with L-dopa associated motor fluctuations who are experiencing end-of-dose “wearing off” periods. Ineffective without carbidopa/L-dopa.

Question 24

COMT inhibitors: Side effects

Answer 24

Can potentiate L-dopa side effects–nausea, orthostasis, psychosis. Can also cause diarrhea and hepatotoxicity (tolcapone).

Question 25

Anticholinergics?

Answer 25

Trihexyphenidyl and benztropine

Question 26

Anticholinergics: MOA

Answer 26

Dopamine and ACh normally in balance in basal ganglia. In PD, dopamine depletion produces state of cholinergic sensitivity. Anticholinergic meds can improve PD symptoms.

Question 27

Anticholinergics: Indications

Answer 27

Used for early tremor-predom PD in YOUNG people; or as add-on treatment in patients with Parkinsonian sx secondary to antipsychotics.

Question 28

Anticholinergics: Side effects

Answer 28

Elderly and cognitively impaired patients susceptible to memory impairment, confusion, hallucinations and SHOULD NOT RECEIVE THESE DRUGS.

Peripheral anti-muscarinic side effects: dry mouth, orthostatic hypotension, blurred vision, constipation, nausea, urinary retention, impaired sweating, tachycardia. Caution advised in patients with known prostatic hypertrophy or closed-angle glaucoma.