Dopaminergic Drugs Flashcards
Dopamine in the CNS
dopaminergic and cholinergic striatal interneurons modulate GABA-ergic output to the substantia nigra
DA and ACh in Parkinsons
the DA balance is missing while the ACh is functioning normally, overall unbalanced
DA Pathophysiology
loss of DAergic neurons in Sub. Niag. leads to DA depletion in striatum, leads to lack of stimulation and loss of inhibition
Cardinal Features of Parkinsons
T-R-A-P: tremor, unilateral to start, rigidity (stiffness), Akinesia (slowness of mvmt), Postural instability (easily loses balance)
MPTP
meperidine derivative, neurotoxic to dopaminergic neurons in substantia nigra
MAO-B
metabolize DA only, blocks breakdown of DA, ADE: nausea, dizziness, abdominal pain MEDS: Selegiline / Rasagiline
Amantadine
antiviral agent, MOA idiopathic, ADE: restlessness, insomnia, dry mouth, vivid dreams (induces livedo reticularis)
Anticholinergics
restore balance between DA and ACh, Artane(trihexyphenidyl)
Cogentin(benztropine)
Akineton(biperiden), most useful in younger patients with tremor, ADE: drying, cognitive impairment
Dopamine Agonists
Parlodel (bromocriptine)
Permax (pergolide)
Non-ergot derived: pramipexole and ropinerole (effective as monotherapy early in PD)
DA agonist ADE
nausea, hypotension, sudden onset of sleep (rare), compulsive behaviors, effects on mesolimbic pathway
Apomorphine
Apokyn, injectable DA agonist, tx of hypomobility, Significant NV
Levodopa
precursor of DA, can’t give DA b/c it wont cross BBB
Levodopa Kinetics
GI absorption depends on rate of gastric emptying and pH, food delays absorption, given with carbidopa (dopa-decarboxylase inhibitor) to facilitate mvmt. to CNS
Levodopa ADE
NV, hypotension, syncope, tachycardia, arrhythmias, depression/anxiety, wearing off effect, dyskinesias (involuntary body movements), precursor to melanin (may cause malignant melanoma)
COMT Inhibitors (catechol-o-methyltransferase inhibitors)
block conversion of levodopa, extend duration of levodopa effect, ineffective if used alone, Tasmar (tolcapone) Comtan (entacapone) Stalevo (sinemet and comtan)
