Drugs Used in Parkinsonism Flashcards
4 Ways to Address Pathology of Parkinsonism
Increase level of Levodopa
Dopamine Agonist
Increase availability by Inhibiting Degrading Enzymes
Curb the Cholinergic Excess
The pathological hallmark of Parkinson’s disease
loss of the pigmented neurons of the substantia nigra pars compacta
Intracellular inclusions in Parkinson’s disease
LEWY BODIES
Principal component of the Lewy bodies
a-synuclein
Primary signs of Parkinson’s Disease
TRAP
Tremor
Rigidity
Akinesia - loss of ability to move your muscles voluntarily
Postural instability
Occurrence of reversible Parkinsonian symptoms in patients taking the ff drugs
TYPICAL antipsychotic drugs - dopamine antagonist
RESERPINE - depletes catecholamine stores
MPTP (methylphenyltetrahydropyridine) - protoxin damaging dopaminergic neurons
Drug Induced Parkinsonism
DOC for Parkinson’s Disease
Levodopa-Carbidopa (SINEMET)
Inhibits peripheral metabolism via DOPA DECARBOXYLASE
Carbidopa
Alternating periods of improved mobility and akinesia occurring over a few hours to days during treatment
UNRELATED TO TIMING OF DOSES
On-Off Phenomena
Deterioration of drug effect in between medication doses
d.t. progressive destruction of nigrostriatal neurons that occurs w/ disease progression
RELATED TO TIMING OF DOSES
Wearing-Off Phenomena
DOPAMINE AGONISTS
PRAMIPEXOLE ROPINIROLE APOMORPHINE ROTIGOTINE BROMOCRIPTINE
Partial agonists at dopamine D2 receptors in brain
D2 agonism – inhibition of prolactin release
BROMOCRIPTINE
Pergolide
Cabergoline
Piribedil
Partial agonists at dopamine D2 receptors in brain and D3 receptors
PRAMIPEXOLE (D2)
ROPINIROLE (D3)
MOA of APOMORPHINE (Opioids)
AGONIST at dopamine D2 receptors
ANTAGONIST of 5-HT and alpha adrenoreceptors
Used for RESCUE TREATMENT for off periods of Parkinson’s disease
APOMORPHINE
Premedicate w/ TRIMETHOBENZAMIDE to prevent severe nausea
COMT (-)
block L dopa metabolism by (-) COMT
for ON and OFF phenomena
ENTACAPONE - blood only
TOLCAPONE - blood and brain
SE - hepatotoxicity (tolcapone)
orange urine
MAO-B (-)
RASAGILINE
SELEGILINE
SAFINAMIDE
MOA of SELEGILINE
selective inhibitors of monoamine oxidase type B (MAO-B) – decreased degradation of dopamine
does NOT cause CHEESE effect (hypertensive crisis seen with ingestion of tyramine rich food (CHEESE) while taking a nonselective MAO (-)
Adjunct for WANING EFFECT treatment to Levodopa of Parkinson’s disease, wearing off or on-and-off phenomenon
Selegiline
Rasagiline
Occurs when MAO-B (-), SSRIs, TCA and Meperidine are used simultaneously
Serotonin syndrome
MOA of AMANTADINE
Potentiate dopaminergic function by influencing the synthesis, release or reuptake of dopamine
Antagonizes the effects of adenosine at adenosine A2a receptors
Adverse Effect of Amantadine
LIVEDO RETICULARIS
Antimuscarinic Agents (Anticholinergics) Parasympatholytic
BENZTROPINE
BIPERIDEN
TRIHEXYPHENIDYL
PROCYCLIDINE
MOA of ROTIGOTINE
Dopamine agonist
