Parkison's Disease Flashcards by TRISHA JOY BASILLE RODRIGUEZ

what is the 2nd most prevalent neurodegenerative disorder?

parkison’s disease

How well did you know this?

Not at all

Perfectly

what are the diff pathogenesis of parkisons?

impaired degradatio of proteins, intracellular protein accumulation & aggregation, oxidative stress, mitochondrial damage, inflammatory cascades, apoptosis
Prion diseaes -> presence of Lewy bodies
Genetic factors
Environmental & endogenous toxins

How well did you know this?

Not at all

Perfectly

what are the 2 parts of substantia nigra & their functions?

pars reticulata = receives signals from another part of the basal ganglia (stratum)
pars compacta = sends messages to the striatium

How well did you know this?

Not at all

Perfectly

what is the structure that receives nadequat eamount of nigrate cells which impairs person’s ability to control movement?

striatum portion of basal gangli

How well did you know this?

Not at all

Perfectly

what is the pathophysiology of parkinons dis?

loss of dopaminergic neurons in substantia nigra
presence of Lewy body
Cholinergic & serotenergic deficits

How well did you know this?

Not at all

Perfectly

what are important neurotransmitters affected in Parkinsons disease?

Dopamine
Acetylcholine

How well did you know this?

Not at all

Perfectly

what will happen if there is no dopamine?

excess muscle tone, tremors, & rigidity

How well did you know this?

Not at all

Perfectly

when will symptoms of PD show?

if there is >60-80% dopamine lost

How well did you know this?

Not at all

Perfectly

what are motor & non-motor symptoms of parkinsons disease?

Motor symptoms
* resting tumor
* rigidity
* bradykinesia
* postural instability

Non-motor symptoms
* autonomic: GI, urinary, & sexual, orthostatic hypotension, hyperhidrosis
* sleep disorders
* cognitive decline
* sensory problems (pain, visual)
* neuropsychiatric comorbidity (depression, dementia, psychosis)

How well did you know this?

Not at all

Perfectly

what are other symptoms of PD?

“pill-rolling” tremor = repetitive invluntary rubbing of the thumbn and index finger
rigidity
stooped posture
expressionless, mask-like face

How well did you know this?

Not at all

Perfectly

what is the tx goal of PD?

alleviate motor and nonmotor symptoms
limit complications
slow down, stop, or modify disease progression

How well did you know this?

Not at all

Perfectly

what is used to see if there are any improvements in the drug efficacy and symptom control?

rating scales: Hoehn & Yahr scale & Unified Parkinson’s disease rating scale

How well did you know this?

Not at all

Perfectly

what is the simplest treatment of PD?

Dopamine

however, it cannot cross the BBB

How well did you know this?

Not at all

Perfectly

what are the different dopamine receptors?

D1 reeptors: D1 & D 5
D2 receptors: D2, D3, D4

How well did you know this?

Not at all

Perfectly

What happens with stimulation of D2 receptors?

Antiparkinsonism

How well did you know this?

Not at all

Perfectly

What dopamine receptors are targeted by drugs?

D2
D1
D3

How well did you know this?

Not at all

Perfectly

What are the 4 pathways for production of Dopamine?

Nigostrial pathway
Mesolimbic and mesocortical pathways
Tuberoinfundibular pathway

How well did you know this?

Not at all

Perfectly

What are the 4 pathways for production of Dopamine?

Nigostrial pathway
Mesolimbic and mesocortical pathways
Tuberoinfundibular pathway

How well did you know this?

Not at all

Perfectly

What are the functions of these pathways of Dopamine production?

Nigostrial pathway = responsible for movement & coordination
Mesolimbic & Mesocortical pathway = controls motivation, emotion, desire
Tuberoinfundibular pathway = inhibits the secreiton of prolactin

How well did you know this?

Not at all

Perfectly

What is the intendd target pathway for Anti-parkinson medication?

Nigostrial pathway

How well did you know this?

Not at all

Perfectly

what are diff drugs used to tx motor sympotoms in px with parkinsons diseases?

Levodopa = dopamin precursor
Dopamine precursor combination
Dopamine receptor agonists
Monoamine oxidase B inhibitors
COMT inhibitors
Anticholinergics
Others: Amantadine, Apomorphine

How well did you know this?

Not at all

Perfectly

What is the gold std for Parkisons dis?

Levodopa

IT CAN CROSS THE BBB

How well did you know this?

Not at all

Perfectly

what phenomenon has symptoms of rigidity and hypokinesia improve when they take the med but effects wear of AFTER 1-2 HRS?

wearing-off phenomenon

How well did you know this?

Not at all

Perfectly

what phenomenon has off periods of marked akinesia alternate over the course of few hrs with on-periods of improve mobility but often marked dyskinesia?

On-off phenomenon

How well did you know this?

Not at all

Perfectly

what are important AEs of Levodopa?

* dyskinesias (chronic use) -> apomorphine (emergency drug tx for overdose) * depression, anxiety, agitation

what are are the clinical uses for Levodopa?

* used during first few yrs * motor features of PD, bradykinesia

what are C/Is of Levodopa?

* not for psychotic px * peptic ulcer disease

what happens to the effects of Levodopa admin from early stages to chronic use?

* early stage = almost complete improvement * advanced stage of the disease = partial imprtovement of motor symptoms * longer stage = partial improvement with dewveloping dyskinesia

what happens if DOPA decarboxylase exits outside the CNS?

INC dopamine levels in the rest of the body -> nausea, vomiting, anorexia, and orthostatic hypotension

what is the more problematic side effect of L-dopa?

can cause tachycardia and arrhythmia

what are advantages of Levodopa combinations?

* prevents peripheral side effects (nausea, vomiting) * more Levodopa available for use byu the brain * GI effects are less bothersome * CV effects are reduced

what are the diff Levodopa combinations?

* Sinemet (Levodopa + Carbidopa) * Stalevo (Levodopa + Carbidopa + Entacapone)

what is a DOPA decarboxylase inhibitor of Sinemet?

Carbidopa | does not enter CNS

What is Entacapone in Stalevo?

COMT inhibitor | reduyces metabolism of L-dopa

What is Entacapone in Stalevo?

COMT inhibitor | reduyces metabolism of L-dopa; prolonging action of the drug

what are alternative first line drugs of PD?

Dopamine receptor agonsits

what are advantages of Dopamine receptor agonists?

* reduced risk of dykinesias & motor fluctuations * indicated for those who cannot tolerate high doses of L-dopa

what is the MOA of Dopamine receptor agonsits?

* diretly asks on postsynaptic dopamine reeptors * no toxic metabolites * do not compete

what are important AEs of Dopamine receptor agonsits?

* impulse control disorders are enhanced * GI: anorexia, nausea, vomiting * CV: postural hypotension, painless digital vasospasm * Dyskinesias * Mental: hallucinations, delusions, impulse control * Bromocriptine: nasuea, vomiting, somnolence, pulmonary fibrosis * Pergolide: valvular heart disease

what are ergot derivatives that can be used in Dopamine receptor agonists?

Bromocriptine: D2 agonist Pergolide: D1 & D2 agonists

What are C/Is of Dopamine receptor agonists?

* Ergot derivatives = peripheral vascular disease * Pergolide = valvular <3 disease

what are diff tx for motor symptoms?

* levodopa * levodopa combinations * dopamine receptor agonists * COMT inhibitors * Monoamine oxidase inhibitors * acetylcholine blocking agents * Amantadine

what are the 2 Monoamine oxidase inhibitors used for PD?

Selegiline Rasagiline

what are the MOA of Selegiline & Rasagiline?

* retards breakdown of dopamine * enhances effect of LD * reduce on-off phenomenon

what are important AEs?

* Selegiline = insmonia & hallucinations * MAO-A or MAO-B = tachycardia, vomiting, headache

what drugs are not supposed to be taken w/ MOAIs?

* Meperidine * Tramadol * Methadone * Propoxyphene * Cyclobenzaprine * St. John's wort * Dectromethorphan

What are other COMT inhibitors?

Tolcapone Entacapone

what do these COMT inhibitors do?

* prevent peripheral enxyme from degrading L-dopa * More L-dopa to get into the brain * only Tolcapone can cross BBB * given as adjunct

what are AEs of COMT Inhibtors?

* dyskinesia * nausea * confusion * diarrhea * abdominal pain * orthostatic hypotension * sleep disturbances * orange discoloration of urine * Tolcapone

what PD drugs are used to improve tremor and rigidity more than bradykinesia?

Acetylcholine blocking agents

What are the diff Ach Blocking agents?

Benzotropine Biperiden Trihexyphenidyl HCl

what are significant AEs?

* dry mouth * blurred vision * difficulty with micturition/constipation

what is the clinical use of Ach blocking agents?

monotherapy later on as adjunct therapy

what is an antiviral agent that has potentiate dopaminergic functions that influence synthesis, release and reuptake of dopamine?

Amantadine

what are important AEs of Amantadine?

Restlessness confusion irritability insomnia depression hallucinations confusion seizures

what are other treatment approaches?

* neurosurgery: Pallidotomy & deep brain stimulation * neuroprotective therapy * gene therapy * deep brain stimulation

what tx approach involves an implantable device that directly sends elecrtical signals to the basal ganglia and coutneract the signaling in PD?

Deep brain stimulation

what is used as tx for Dementia?

Rivastigmine

What is used as tx for Psychosis?

Atypical antipsychotics = Clozapine, Quetiapine | DO NOT USE TYPICAL ANTIPSYCHOTICS

What is used as tx for Psychosis?

Atypical antipsychotics = Clozapine, Quetiapine | DO NOT USE TYPICAL ANTIPSYCHOTICS

What is the tx for mood disorders?

antidepressants

what is the tx for sleep disorders?

Melatonin

what are txs for Autonomic dysfunction?

* avoid preceipitating factors of orthostatic hypotension (sudden changes in posture, large meals, vasodilators)

what are general rules in prescribing levodopa?

* use of this should be delayed until there is signficant disability * to delay long-term side effects -> dopamine agonist or a slow-release levodopa

what are other anti-PD used if there is functional impairment?

* anticholinergic = for tremors * Amantadine = drug-induced dyskinesias * Apomorphine = freezing "off" episodes or "on-off" phenomenon

what anti-PD is given if age is >60yo or <60yo?

* <60 yo = Dopamine receptor agonists * >60 yo = Levodopa

Parkison's Disease Flashcards

(66 cards)