Parkinson's Drugs Flashcards
L-dopa: MOA
Intracellular precursor to dopamine. L-dopa CAN cross BBB.
L-dopa is administered with? Why?
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.
L-dopa indications
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
L-dopa side effects
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.
L-dopa metabolism
L-dopa is converted to dopamine intracellularly. Dopamine is metabolized to homovanillic acid mostly via enzyme monoamine oxidase.
L-dopa drug interactions
L-dopa plus MAO inhibitor can lead to dopamine toxicity resulting in psychosis, N/V, cardiovascular problems.
What are the dopamine agonists?
Bromocriptine, pramipexole, ropinirole.
Dopamine agonists: MOA
Post-synaptic mimicry of naturally occurring dopamine
Dopamine agonists: Indications
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.
Dopamine agonists: Side effects
N/V, orthostatic hypotension, visual hallucinations.
Bromocriptine is associated with heart valve fibrosis.
Prramipexole/ropinirole can cause sleep attacks.
Dopamine agonists: Metabolism
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).
MAO-B inhibitors?
Selegiline and Rasagiline
MAO-B inhibitors: MOA
Prevent breakdown of dopamine by inhibiting MAO-B. Monamine NTs: Dopamine, norepinephrine, epinephrine, + serotonin.
MAO-B inhibitors: Indication
Benefit for symptoms of early PD
MAO-B inhibitors: Side effects
Nausea and headache. Selegiline can cause confusion (esp. in elderly) and insomnia due to its amphetamine metabolites.
MAO-B inhibitors: Drug interactions
MAOIs should NOT be administered with either SSRIs or with tricyclic antidepressants due to risk of serotonin syndrome.
A drug with mixed gluatmate and dopamine effects?
Amantadine
Amantadine: MOA
NMDA glutamate antagonist. Increases dopamine release and blocks dopamine re-uptake.
Amantadine: Indication
Early tremor predominant PD. Add on therapy late in PD to treat dyskinesias and motor fluctuations.
Amantadine: Side Effects
Ankle edema, confusion, insomnia
COMT inhibitors?
Tolcapone and entacapone
COMT inhibitors: MOA
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.
COMT inhibitors: Indication
Treats patients with L-dopa associated motor fluctuations who are experiencing end-of-dose “wearing off” periods. Ineffective without carbidopa/L-dopa.
COMT inhibitors: Side effects
Can potentiate L-dopa side effects–nausea, orthostasis, psychosis. Can also cause diarrhea and hepatotoxicity (tolcapone).
Anticholinergics?
Trihexyphenidyl and benztropine
Anticholinergics: MOA
Dopamine and ACh normally in balance in basal ganglia. In PD, dopamine depletion produces state of cholinergic sensitivity. Anticholinergic meds can improve PD symptoms.
Anticholinergics: Indications
Used for early tremor-predom PD in YOUNG people; or as add-on treatment in patients with Parkinsonian sx secondary to antipsychotics.
Anticholinergics: Side effects
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.
