Parkinson's and Seizures Flashcards
(60 cards)
1
Q
definition of parkinson’s disease
A
- slowly progressive degenerative dz affecting mostly the extrapyramidal motor system in the CNS
- one of the most common neurodegenerative movement disorders
- 4 cardinal sxs: bradykinesia, postural instability/gait disturbance, resting tremor, rigidity
2
Q
movement disorders
A
- Parkinson’s dz (idiopathic, drug-induced)
- Huntington’s dz
- RLS
- Tics
- Tremors
3
Q
parkinsonism
A
- Parkinson’s dz is the most common cause
- neurodegenerative diseases can cause this (we often call this secondary parkinsonism)
4
Q
Parkinson’s ds epidemiology
A
- onset usually 4th decade of life
- males more than females 2:1
5
Q
etiology of parkinson’s
A
- true etiology unknown
- combination of aging (degeneration of neurons), genetic constitution (oxidative stress), environmental factors (pesticide exposure)
- degeneration of dopaminergic neurons in the nigrostriatal pathway
6
Q
pathophysiology of PD
A
- loss of dopaminergic neurons in the substantia nigra (motor features not detectable until 70-80% loss)
- imbalance: dopaminergic and cholinergic pathways
7
Q
symptoms of PD
A
-usually worsen over time
8
Q
upper extremity tremor at rest
A
- present in males predominantly
- eliminated with intentional movement
9
Q
bradykinesia
A
- slowness of movement
- difficulty with initiation
- freezing
- festinating gait
- postural instability (advanced PD, increased risk of falls)
10
Q
rigidity
A
- upper and lower extremities
- increased muscular resistance to passive range of motion
- cogwheel/ratchet-like quality of tremor is present in affected extremity
- facial muscles may be involved (flat affect and some people may not be able to smile and respond - hypomimia)
11
Q
Motor symptoms of PD
A
TRAP
- tremor at rest (pill rolling)
- rigidity (stiffness and cogwheel rigidity)
- akinesia or bradykinesia (slowness of movement in both initiation and execution)
- Postural instability and gait abnormalities (shuffling, short stepped gait, forward leaning, stooped posture, difficulty turning while standing and laying, tendency to fall backwards, decreased arm swing with walking
12
Q
Non-motor symptoms of PD
A
- Sleep disturbances: insomnia, rapid eye movement, restless leg syndrome
- Other: nausea, fatigue, speech, pain, dysethesias, seborrhea
- Autonomic: drooling, constipation, sexual dysfunction, urinary problems, sweating, orthostatic hypotension, dysphagia
- Psychological symptoms: anxiety, psychosis, cognitive impairment, depression
13
Q
drug induced parkinsonism
A
- antipsychotics (typical and atypical)
- antinausea medications (metoclopramide, prochlorperazine, promethazine)
- toxins
- reserpine
- halipoeridol, metoclopramide, phenothiazines
- methyldopa
- valproate
- verapamil
- risperidon
14
Q
tx of PD
A
- restoration of dopamine balance in CNS
- selection of first line agent directly related to targeted symptoms
15
Q
Goals of PD tx
A
- minimize sxs
- maximize function and QOL
- minimize medication related SE
- maximize safety and reduce fall risk
- improve cognitive impairment, depression, fatigue, sleep disorders
16
Q
PD - anticholinergics
A
- benztropine
- trihexyphenidyl
17
Q
PD - COMT inhibitors
A
- entacapone
- tolcapone
18
Q
PD - dopamine
A
-levodopa
19
Q
PD - dopamine agonists
A
- apomorphine
- bromocriptine
- pramipexole
- ropinirole
20
Q
PD - MAO-B inhibitor
A
- rasagiline
- selegiline
21
Q
pharmacologic tx of PD
A
- restore the balance
- increase dopamine levels in the brain
- decrease Ach levels
- initiate with levodopa or DA agonist (DA agonist may result in less motor benefit and greater risk of hallucinations or somnolence
- anticholinergics, amantadine, or MAO-B inhibitors can be used as initial tx for mild cases of PD (not as effective as DA agonist)
- start at low doses and titrate slowly
22
Q
ADR: end of dose wearing off
A
- increasing loss of neuronal DA storage capability, increased dependence on exogenous levodopa
- options: increase Ldopa frequency, change to long-acting formula, add short-acting dose to long-acting regiment, add DA agonist, MAO-B inhibitor, or COMT inhibitor
23
Q
ADR: drug-resistant off periods
A
- “delayed on” or “no on” response
- due to delayed gastric emptying or decreased GI absorption - should be given on empty stomach so that you get as much in the system as possible
- options: give on empty stomach, crush tablet or take ODT formulation, avoid CR formulation
24
Q
treatment of response fluctuations - PD
A
- keep extra dose while away from home in case medication wears off
- longer acting medications
- maximize on time
- minimize off time
- minimize wearing off periods
- minimize dyskinesia with on time
- provide treatments to decrease freezing episodes
- schedule activities for on time
25
PD: wearing off
- return of parkinsonian symptoms before the next dose is due
- add MAO-B inhibitor
- add COMT inhibitor
- add dopamine agonist
- adjust dosing interval if carbidopa/levodopa
26
PD: on-off phenomenon
- unpredictable return of parkinson's symptoms without respect to dosing interval
- add entacapone, rasagiline, pramipexole, ropinirole, or selegiline
- redistribute dietary protein and space med 2 hrs from this meal
27
Seizure definition
- excessive, hypersynchronous discharge of cortical neuron activity
- measured by electroencephalogram (EEG)
- may involve changes or disturbances in sensory motor systems, subjective well-being, and objective behavior
- may or may not involve loss of consciousness
28
convulsion definition
-involuntary contractions of the voluntary muscles; a type of seizure
29
epilepsy
- medical disorder or group of disorders, classified by recurrent, unprovoked seizure activity
- usually recur unpredictably in the absence of a consistent provoking factor
30
epileptogenesis
-the disease process by which epilepsy develops after brain insults or as a result of genetic mutations
31
occurrence of first seizure
peaks in newborns and young children and then again in pts >65 yo
32
predisposing factors for seizure
genetics, head trauma, stroke, malignancy, infection, substance abuse, degenerative disease
33
seizure classification
-new basic seizure structure is based on 3 key features: where seizures begin in the brain, level of awareness during a seizure, other features of seizures
34
Generalized seizure
- involve both hemispheres, LOC, may be convulsive or non-convulsive:
- Absence (petit mal): sudden onset, interruption of ongoing activities, blank stare, generally occur in young children through adolescence
- Tonic-clonic (grand mal): convulsive seizure, both tonic and clonic phases
- myoclonic: brief, shock-like sudden muscle contraction
- atonic: sudden loss of muscle tone
35
pathophysiology of seizures
- imbalance between excitatory and inhibitory currents in brain
- neuronal circuits (axonal conductance: propagation of action potentials along neuronal axons; synaptic transmission: between neurons; both employ ion channels)
- we will focus on GABA and glutamate
36
ion channels
- membrane spanning proteins
- selective pores for Na, K, Cl, or Ca
- movement of ions across neuronal membrane (determines electrical membrane potential, generates action potential)
- ATP-dependent Na/K pump (maintains resting membrane potential at -70mV; concentration gradient: K inside, Na outside; when opened Na moves in and K moves out
37
voltage gated ion channels
- activated by changes in membrane potential
- alters conformation state; allows passage of charged ions (Na and Ca channels depolarize cell membrane (excitatory); K channels hyperpolarize cell membrane (inhibitory)
38
Ligand gated ion channels
- opened by neurotransmitter binding
| - example neurotransmitters: glutamate (excitatory), GABA (inhibitory)
39
Pharmacotherapeutic goals - AE
- decrease seizure frequency
- decrease risk of death
- decrease risk of injury
- complete suppression balanced with ADRs
- improve QOL
- psychosocial
- leisure activities
40
How do AEDs work (generally)
- do NOT prevent or reverse pathological process that underlies epilepsy
- do NOT prevent development of epilepsy
- do NOT have disease modifying effects that prevent/reverse medication resistant epilepsy
41
when to start therapy - AE
- first seizure in high risk patients
| - all patients with second seizure
42
drug selection - AE
- seizure type, seizure control, and side effects
| - medication not considered ineffective unless unacceptable adverse effects with continued seizures
43
evaluation of seizure control
- no change in seizure frequency → maximize dose
| - when switching agents → ALWAYS VIA TAPER
44
Reduction in seizure frequency, seizures still occur
- maximize dose
| - add second agent: if controlled, may consider tapering 1st drug
45
drugs used for partial onset (+/- secondarily generalized)
Carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramet, zonisamide, lacosamide
46
primary generalized
ethosuximide (absence only), lamotrigine, levetiracetam, topiramate, valproate, zonisamide
47
elderly with focal epilepsy
lamotrigine, levetiracetam
48
women of childbearing potential - AEDs
lamotrigine, levetiracetam, zonisamide
49
drugs to avoid with primary generalized
gabapentin, pregabalin, tiagabine, vigabatrin
50
drugs to avoid in women of childbearing potential - AED
valproate
51
status epilepticus
- any seizure lasting >30mins +/- LOC
- recurrent seizures with no intervening period of consciousness between
- may be convulsive or non-convulsive
52
treatment for status epilepticus
supportive therapy to minimize brain damage (O2, preservation of cardiorespiratory function)
Eliminate epileptiform activity:
- Benzos: IV push Lorazepam, diazepam (higher doses used in status epilepticus)
- PHT/fosphenytoin IV loading dose followed by PO maintenance therapy (alternative = PB)
53
Steps to cross taper AEDs
- start new drug at low initial dose and gradually increase over several weeks
- once the new drug is at a minimally effective dose, gradually taper the drug to be discontinued while continuing to increase the new drug to the target dose
54
when to consider stopping therapy - AEDs
- no seizures >2 years
- control achieved on monotherapy
- no previous unsuccessful attempts at drug discontinuation
- normal neurologic examination (IQ)
- consider risk vs. benefit
must meed 5 criteria:
- no seizure for 2-5 years
- normal neurologic examination
- normal IQ
- single type of partial or generalized seizure
- normal EEG with tx
55
favorable conditions for a good outlook with AEDs
- complete control w/in 1 year of onset
- onset after age of 2yo and before 35yo
- normal neuro exam and EEG
56
AEDs for women of childbearing years
- should receive monotherapy whenever possible
| - should use a formulation that contains at least 50mcg of ethinyl estradiol or mestranol
57
management during/after pregnancy AEDs
- continue pharmacotherapy that best controls seizures prior to conception
- if medication withdrawal is planned, it should occur at least 6 months before conception
- do not abruptly discontinue AEDs
- use monotherapy and lowest dose possible whenever possible
- monitor AED serum concentrations every month
58
Lactation and AEDs
- many AEDs cross through the placenta or into the breast milk in measurable concentrations
- clinical consequences to infant largely unkown
- known transfers to breast milk: lamotrigine, primidone, levetiracetam, gabapentin, topiramate
59
Geriatrics and AEDs
- more pronounced reactions to the sedetave and cardiorespiratory effects of AEDs
- weight may be overestimated - be careful with loading doses
- consider smaller doses
- evaluated for renal and hepatic insufficiency
- adherence
- drug interactions
- some AEDs associated with increased fracture risk
60
Driving and AEDs
- all states have driving restrictions
| - some require mandatory physician reporting to the DOT
