Parkinson's meds Flashcards
sxs of Parkinson’s result from loss of what in where?
dopamine-secreting (dopaminergic) cells in the pars compact region of the substantia nigra
primary defect in parkinson’s?
loss of dopamine in nigrostriatal pathway
4 pathways of dopamine?
nigrostriatal, mesocortical, mesolimbic, mtuberoinfundibular
disruption of dopamine along non-striatal pathways results in what ssxs?
depression, dementia, psychosis
major sxs of parkinsons? other sx?
tremor at rest
rigidity
bradykinesia and akinesia
postural instability - slow and reduced amplitude gait w/small, rapid, stutter-steps forward
stooped or flexed posture is common
can also impair nerve endings in the heart that regulate the release of NE which could cause an abrupt drop in BP (orthostatic hypotension and bradycardia)
masked facies/drooling
speech problems - vocal cords can be affected causing monotonous, whispery, soft speech qualities
difficulty swallowing
micrographia
urinary incontinence typically occurs late in dz progression
fatigue
depression
anxiety or panic attacks
dementia is a later development in 20-40% of all Parkinson’s pts
gravitational line and what does it encourage?
ear to acromion to greater trochanter to calcaneus which tilts us forward so its easier to walk
first MC sx of parkinson’s?
tremor
can start in one finger and spread over time to involve entire arm
often rhythmic, 4-5 cycles per second, frequently causes pill-rolling action
can occur when limb is at rest of when held in a stiff unsupported position
disappear during movement and do not occur during sleep
how does dementia present in Parkinsons?
typically starts w/slowing of mentation, progressing to difficulties w/abstract thought, memory and behavioral regulation
what can you see in the brain in Parkinson’s?
Lewy bodies = clusters of alpha-synuclein protein
accumulate inside the neurons
tremor usu begins where?
beings in upper extremities and are usu UL or asymmetrical at onset of dz
if metabolic cause of a tremor, how will it present?
will be BL, whereas Parkinson’s will be a UL tremor
cause of Parkinson’s?
idiopathic for the most part - not clear what causes the death of neurons and subsequent dopamine loss
small portion have an identifiable genetic defect
possible environmental role in Parkinson’s development?
environmental toxins, infxns and other triggers can provoke excessive production in the body of ROS and free radical damage which may lead to nerve cell death
what %age of dopamine has to be gone before usu see sxs?
75% of dopamine in substantia nigra and corpus striata have usu been lost before see sxs of Parkinson’s
main drug to tx Parkinson’s? long term complications?
levodopa - a dopamine precursor
long term complications: motor fluctuations, dyskinesias, mental status changes
why can’t you just give dopamine?
b/c it can’t cross the BBB
main SE of levodopa? what do you combine it with to avoid that SE?
levodopa + carbidopa to prevent the nausea that comes with levodopa tx
chief SEs of levodopa/l-dopa? via what MOA? secondary SEs are from what?
chief: N/V, anorexia induced by stimulation of dopamine receptors in the GI tract and chemotrigger receptor zone in the brain
secondary SEs from drug not working anymore - hypotension, choreiform movements, insomnia, anxiety
what is levodopa usu co-administered with?
combined w/peripheral dopa-decarboxylase inhibitor such as carbidopa or benserazide in order to prevent it from being broken down prematurely and converted into dopamine in the adrenal glands or other peripheral tissues = more levodopa for the brain
3 MC used meds which contain levodopa w/a peripheral dopa-decarboxylase inhibitor?
levodopa + carbidopa/sinemet
levodopa + benserazie/prolopa
levodopa + carbidopa and entacapone/stalevo
(entacaopne is a COMT inhibitor)
2 benefits of entacapone?
when administered in conjunction w/L-dopa the bioavailability of L-dope is increased and it’s passage across the BBB is increased
most common SE of entacapone?
dyskinesia
also N/V, diarrhea, abd pn
MC SEs of dopaminergic drugs?
nausea, sleepiness, dizziness, chorea
how long will L-dopa tx be beneficial?
proves effective for a short period of time, on average approximately 5 years
longer you take the meds the wider the trough will be between when you take the drug and how long it will decrease sxs for
as the disease progresses and the longer someone has been on L-dopa, what can happen?
so called “wearing off period” where pts will develop unpredictable fluctuations btw mobility and immobility (“on and off effect”)
what happens after 5-8 yrs of L-dopa tx?
most pts have dose related clinical fluctuations and dose related dyskinesias
as dz progresses what levodopa resistant motor and non-motor problems will appear?
motor: difficulties w/balance, gait, speech, swallowing
non-motor: autonomic, cognitive, psychiatric problems
what can you never use with L-dopa? why?
MAOI b/c can lead to HTN crisis
what pt population should avoid using L-dopa and why?
pts w/psychiatric conditions b/c could worsen psychotic sxs
class of L-dopa w/carbidopa/sinemet? indications? MOA? how to give and how many times a day?
class: dopamine precursor w/peripheral dopamine decarboxylase inhibitor
indications: Parkinson’s dz
MOA: increases dopamine levels in the brain, esp in substantia nigra
give PO, TID-QID
when needing to increase L-dopa + decarboxylase inhibitor, which do you increase 1st?
increase the decarboxylase inhibitor first then the L-dopa
SEs of L-dopa w/carbidopa/sinemet?
prior to addition of carbidopa, nausea was the MC SE, but now SEs are more hallucinations, nightmares, dyskinesias, serpentine like movements
what tx can be utilized to delay using L-dopa? how can you utilize it if you are going to start L-dopa tx?
dopamine agonists
can also be added at the same time as L-dopa in an effort to keep L-dopa dose as low as possible
5 dopamine agonists?
bromocriptine/parlodel carbergoline/dostinex pergolide/permax (no longer used b/c increased risk of cardiac valve dysfxn) pramipexole/mirapex ropinirole/requip
class of bromocriptine/parlodel? indications? MOA? how to give? cross BBB? used to delay or augment what?
class: dopamine agonist
indications: parkinson’s, prolactin secreting adenomas and acromegaly
MOA: mimics dopamine in stimulation of dopamine receptor sites
give PO, crosses BBB
used to delay L-dopa tx or augment L-dopa therapy
to minimize SEs of bromocriptine/parlodel, how do you give? max dose/day?
tx is generally initiated at a very low dose and slowly increased over 4-6 wks as needed
max dos is 100 mg/d
SEs of bromocriptine/parlodel? how do these SEs limit its use?
nausea, HTN, hypotension, confusion, hallucinations, H/A, depression, dyskinesia, possible seizures, pulmonary fibrosis (at high doses, why dose is limited to 100 mg/d)
because of large range and severity of SEs, the usefulness is limited
effect of bromocriptine on glutamate? insulin? BP?
inhibits release of glutamate by reversing glutamate GLT1 transporter
BP needs to be monitored
severe H/A, HTN, seizures, stroke and MI have occurred as well
use of anticholinergics?
used in certain surgical and emergency procedures to help decrease secretions from the throat, lungs or GI
anticholinergics can be used to tx what?
antidote to tx poisoning dt organic phosphorous and poisoning by nerve gas
most commonly give atropine
SEs of anticholinergics? how are these useful in tx’ing Parkinson’s?
dry mouth, constipation, urinary retention, confusion (anti-SLUD)
want anticholinergic effects in Parkinson’s b/c usu drooling, urinary incontinence
anticholinergics are useful in tx’ing what sxs of Parkinson’s?
tremor and/or drooling but less useful in tx’ing bradykinesia and rigidity
anticholinergic drugs we use to tx parkinson’s? 4
benzotropine/cogentin
ethosopropazine/parsitan
procyclidine/kemadrim
trihexyphenidyl/artane
class of benztropine/cogentin? indications? MOA?
class: anticholinergic
indications: Parkinson’s dz, esp when tremor or drooling are prominent sxs, appears to also help with cognitive sxs, can also diminish SEs of antipsychotic drugs
MOA: anticholinergic antagonist at muscarinic receptor sites
how to give benztropine/cogentin? can it be used as a single therapy to tx Parkinson’s? SEs?
give PO
used as single therapy or as an added adjunct to other meds
as a single agent it has minimal efficacy
SE: dry mouth, blurred vision, urinary retention, constipation, confusion, drowsiness, disorientation, memory impairment, visual hallucinations, possible exacerbation of pre-existing psychotic sxs, CNS depression
what will reverse anticholinergic overdose?
physostigmine SC or IV
will reverse sxs of anticholinergic intoxication
drug that acts as an anti-Parkinson’s and antiviral (influenza A) drug? supposed MOA? ssxs of overdose?
amandatine/symmetrel
MOA: appears to be related to antagonism of N-methyl-D-aspartate receptors
overdose ssxs: N/V, anorexia, CNS effects , can cause death, urinary retention
effect of amandatine on ssxs of Parkinson’s?
modest symptomatic benefit in tremor, rigidity and bradykinesia
antagonism of NMDA appears to do what? what drug utilizes this MOA? when can it be used to tx Parkinson’s?
diminish dopamine reuptake which may be the chief mechanism that accounts for beneficial effects of amandatine in tx of Parkinson’s
can be used alone to tx early PD or used as an adjunct in later stages usu in pts w/levodopa related dyskinesia
class of amandatine/symmetrel? indications? MOA? how to give? when to use?
class: anti-parkinson, anti-viral agent
indications: PD, influenza A
MOA: unclear but probable NMDA receptor antagonism accounts fro anti-PD effects
give PO
chiefly use din attempt to delay onset of time of initiating PD therapy w/L-dopa
SEs of amandatine/symmetrel?
lightheadedness, confusion, drowsiness, nightmares, dry mouth, constipation, urinary retention, N/V
benefits of therapy are short-lived w/pts exhibiting diminished or absent response to amandatine after 6 mos or less
order of efficacy of meds used to tx PD?
L-dopa to bromocriptine to amandatine to anticholinergics
if minimal motor disability and cognitive is normal what can you start with?
MAO-B1
if mild/moderate disability and cognition is normal and less than 60 yo what do you start with?
dopamine agonist
if moderate/severe disability and cognition is abn what do you start with?
levodopa
why are MAOI-Bs used more often than MAOI-As?
b/c MAOI-Bs do not show the HTN and excess catecholamine release problems as a consequence of eating tyramine-rich foods such as aged cheeses or raisins
