Dopaminergic Drugs

Question 1

Dopamine in the CNS

Answer 1

dopaminergic and cholinergic striatal interneurons modulate GABA-ergic output to the substantia nigra

Question 2

DA and ACh in Parkinsons

Answer 2

the DA balance is missing while the ACh is functioning normally, overall unbalanced

Question 3

DA Pathophysiology

Answer 3

loss of DAergic neurons in Sub. Niag. leads to DA depletion in striatum, leads to lack of stimulation and loss of inhibition

Question 4

Cardinal Features of Parkinsons

Answer 4

T-R-A-P: tremor, unilateral to start, rigidity (stiffness), Akinesia (slowness of mvmt), Postural instability (easily loses balance)

Question 5

MPTP

Answer 5

meperidine derivative, neurotoxic to dopaminergic neurons in substantia nigra

Question 6

MAO-B

Answer 6

metabolize DA only, blocks breakdown of DA, ADE: nausea, dizziness, abdominal pain MEDS: Selegiline / Rasagiline

Question 7

Amantadine

Answer 7

antiviral agent, MOA idiopathic, ADE: restlessness, insomnia, dry mouth, vivid dreams (induces livedo reticularis)

Question 8

Anticholinergics

Answer 8

restore balance between DA and ACh, Artane(trihexyphenidyl)
Cogentin(benztropine)
Akineton(biperiden), most useful in younger patients with tremor, ADE: drying, cognitive impairment

Question 9

Dopamine Agonists

Answer 9

Parlodel (bromocriptine)
Permax (pergolide)
Non-ergot derived: pramipexole and ropinerole (effective as monotherapy early in PD)

Question 10

DA agonist ADE

Answer 10

nausea, hypotension, sudden onset of sleep (rare), compulsive behaviors, effects on mesolimbic pathway

Question 11

Apomorphine

Answer 11

Apokyn, injectable DA agonist, tx of hypomobility, Significant NV

Question 12

Levodopa

Answer 12

precursor of DA, can’t give DA b/c it wont cross BBB

Question 13

Levodopa Kinetics

Answer 13

GI absorption depends on rate of gastric emptying and pH, food delays absorption, given with carbidopa (dopa-decarboxylase inhibitor) to facilitate mvmt. to CNS

Question 14

Levodopa ADE

Answer 14

NV, hypotension, syncope, tachycardia, arrhythmias, depression/anxiety, wearing off effect, dyskinesias (involuntary body movements), precursor to melanin (may cause malignant melanoma)

Question 15

COMT Inhibitors (catechol-o-methyltransferase inhibitors)

Answer 15

block conversion of levodopa, extend duration of levodopa effect, ineffective if used alone, Tasmar (tolcapone) Comtan (entacapone) Stalevo (sinemet and comtan)

Question 16

Drug induced PD

Answer 16

DA antagonist may induce parkinsons-like symptoms, haloperidol, metoclopramide, dose dependent, resolves upon d/c

Question 17

RLS Pathophysiology

Answer 17

unclear, maybe due to Central DA and GABA abnormalities, Fe status important (low Fe associated with RLS symptoms

Question 18

RLS Diagnosis

Answer 18

urge to move limbs, motor restlessness, sx worsen at rest, present in evening and at night

Question 19

RLS Treatment

Answer 19

is is daily or intermittent, DA-agonist for daily symptoms, levodopa for intermittent sx, gabapentin or Fe

Question 20

Essential tremor

Answer 20

pathologic tremor affecting mainly the upper extremities, head, and voice, involvement of GABA and adrenergic systems

Question 21

Essential tremor

Answer 21

hallmark symptom is bilateral action tremor in upper extremity, second most affected anatomical site is head (then tongue)

Question 22

Tx of essential Tremor

Answer 22

B-Blockers, Primidone, BZ, Alcohol