NEUROLOGY: SEIZURE, PARKINSON, PAIN Flashcards
defined epilepsy and status epilepticus
epilepsy: 2 or more unprovoked seizure occurring >24 hours apart or 1 unprovoked with high probability of reoccurrence >60%
epilepticus: seizure lasting >5 mins or seizures occurring close together where patient doesn’t recover in between episodes
focal seizures
partial (affects one side of the brain)
simple: no impairment of awareness
complex : impairment of awareness, lasting longer (1-2 mins)
three types of generalized seizures
absence ( petit mal)
generalized tonic clonic ( grand mal)
atonic
myoclonic
absence seizure
impaired consciousness
features: staring
generalized tonic clonic grand mal
impaired consciousness rigid muscle (tonic) followed by jerking of muscles ( clonic), jerking muscle possible tongue biting, incontinence
atonic
impaired consciousness
loss of muscle tone ( drop attacks)
myoclonic
no impairment consciousness
brief bilateral “shock-like” jerks or jerking of ground of muscles
1st and 2nd line for generalized tonic clonic seizure
first line: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine valproic acid/divalproex 2nd: clobazam, perampanel, phenytoin, topiramate
1st and 2nd line for absence seizure,
1: ethosuximide
2: Lamotrigine
valproic acid/divalproex
1st and 2nd line for myoclonic and atonic?
1: VPA
2: brivaracetam clobazam
lamotrigine
stiripentol[d]
topiramate
first line for focal (partial)
carbamazepine
lamotrigine
levetiracetam
oxcarbazepine
most common AE of AED?
CNS and GI effects (dose dependent)
idiosyncratic: skin rash ( occur within 6 weeks of therapy)
chronic: low bone density and fractures
most common AED to be associate with skin rashes?
lamotrigine, CBZ, phenytoin
which AED is enzyme inducing
carbamazepine
eslicarbazepine
oxcarbazepine
perampanel (8 mg daily or higher)
phenobarbital
phenytoin
primidone
rufinamide
topiramate (200 mg daily or higher)
which AED that is non enzyme inducing
brivaracetam
clobazam
ethosuximide
gabapentin
lacosamide
lamotrigine
levetiracetam
valproic acid
vigabatrin
which AED that is non enzyme inducing
brivaracetam
clobazam
ethosuximide
gabapentin
lacosamide
lamotrigine
levetiracetam
valproic acid
vigabatrin
what drug interaction is significant with lamotrigine
lamotrigine + COC
lamotrigine levels can be expected to drop by at least 50% after a COC is started.
consider doubling the dose of lamotrigine
MOA of barbiturates
and AE
phenobarbital and primidone
potentiates GABA effects on GABA receptor, increasing Cl- channel activity
AE: behaviour and cognitive problems, mood changes, sedation, depression
which BZD is used as AED?
what are its main disadvantages?
clobazam
, Tolerance (initial good response followed by loss of seizure control).
Valproic acid MOA and AE
increased GABA activity, Na+ and K+ channels
AE:
CNS ( drowsiness), tremor, WEIGHT GAIN, menstrual cycle abnormalities
main advantage of VPA and disadvantage
broad spectrum
no hepatic enzyme induction
disadvantage: teratogenic, avoid in women of childbearing potential
Gabapentin AE
CNS, tremors, vision changes
Main disadvantages of Vigabatrin
Reports of visual field defects have severely limited use of this drug.
which drug is ONLY indicated for absence seizure
ethosuximide
MOA of phenytoin and ae
GABA, inhibits NA + CI- channels
AE: sedation, rash, hyperplasia gingival, body hair
Long-term cosmetic adverse effects ( acne, skin thickening)
Dosing complicated by saturation kinetics (nonlinear pharmacokinetics).
main disadvantage of phenytoin
main disadvantage:
Long-term cosmetic adverse effects ( acne, skin thickening)
Dosing complicated by saturation kinetics (nonlinear pharmacokinetics).
drug inducing
MOA of CBZ? AE?
blocks voltage gated Na+ cHANNELS
CNS, GI, RASH, anemia, exfoliative dermatitis, hypoantremia, hepatic toxicity
disadvantage of CBZ?
worsen absence seizures, exacerbate/ produce myoclonus
oxcarbazepine: higher risk of hypoantremia compared to CBZ and eslicarbazepine ( lowest risk of hypoantremia
both oxcarbazepine and eslicarbazepine have minimal enzyme induction
hepatoxicity, avoid use in patient with active liver disease, elderly
Ethosuximide MOA and AE?
inhibits t-type calcium channels
AE: CNS and GI upset
what are the advantages and disadvantages of levetiracetam
ad: BID dosing, broad spectrum, no drug interactions, rapid titration
dis: Psychiatric side effects, irritability, depression.
avoid if abuse potential or history of mental illness , may increase or decrease breast milk
main disadvantage of lacosamide
PR interval prolongation; caution in patients with cardiac conduction abnormalities.
what s the evidence for perampanel? main AE / disadvantages?
strong evidence to support efficacy for drug-resistant primary generalized tonic-clonic seizure
AE: CNS. serious psychiatric effects in patients with or without history of psychiatric conditions
avoid use with alcohol
what is the main limitation in using topiramate
cognitive effects limits its use
when should we complete BMD?
after 5 year of AED use and before starting AED in postmenopausal women
when to stop AED
AED are typically lifelong but favour successful discontinuation are: seizure free for 2-4 years complete seizure control within 1 year onset of seizure between 2-35 normal neurological exam normal ECG
will patient required AED after first seizure
Many patients will not require AED treatment after a single seizure
what is the role of AED in provoke seizure
there is no role for AEDs in patients with acute symptomatic (provoked) seizures, such as those provoked by metabolic derangements (e.g., hypoglycemia, hyponatremia) or withdrawal from drugs or alcohol.
time frame to monitor for reduce or elimination of seizure
1-4 weeks
parkinson’disease is defined as
movement disorder caused by loss of dopamine
(symptoms do not occur until loss of 70-80% of dopaminergic production in the substania nigra
4 cardinal clinical symptoms of parkinson
resting tremor
bradykinesia
rigidity
postural instability
list drug that can cause drug induced parkinsonism
antipsychotic: phenothiazine, butyrophenones, risperidone
antiemetics: metoclopramide, prochlorperazine
reserpine
valproic acid, lithium: tremor
antidepressants: TCA, SSRI
is non pharmacotherapy only adequate to properly manage PD?
no, need pharmacotherapy
pharmacological options for mild/eldery PD and moderate/severe PD?
mild: MAO-B inhibitor ( rasagiline, selegiline)
dopamine precursor+ DOPA decarboxylase inhibitor
dopamine agonist: NOT ERGOT-derived as first line
moderate/ severe PD: combination therapy with above classes
COMT inhibitor: may be added in advance PD
amantadine: may not be effective in early PD, use in later stages
difference between selegiline and rasagiline
selegiline: amphetamine metabolite
non-selective MAO-B inhibitor ( tyramine drug interaction)
available as orally disintegrating tablet ( increasing bioavailability)
rasagiline: longer duration of action ( once daily dosing)
selective MAO-B inhibitor
benefit of MAO-B inhibitor
used for early stage PD ( mild)
rasagiline is more potent and can be used for wearing off symptoms ( advance disease)
AE of MAO-B inhibitor
headache, insomnia, nausea, orthostatic hypotension
selegiline specific: sympathomimetic effects ( due to interactions involving tyramine): HTN, tachycardia, jitteriness
MOA of anticholinergics, what is the benefit of anticholinergics in PD?
Benztropine, trihexyphendiyl, procyclidine, ethoproprazine
counteracts increased cholinergic activity ( decreasing dopamine) which contributes to tremor
benefits against resting tremor but no effects on bradykinesia, improves dystonic symptoms
AE of anticholinergic?
confusion, memory impairment, hallucinations, dry mouth, blurred vision, urinary retention, constipation and somnolence.
precautions for anticholinergics and contraindication
avoid due in elderly patient due to S/E
contraindicated in glaucoma, BPH, patient with dementia ( due to cognitive impairment)
benefit of amantadine and AE?
useful in later stages to reduce choleric movement ( L-Dopa induced dyskinesia)
AE: hallucinations, confusion, nightmares, insomnia, leg edema, nausea, dry mouth, lived reticularis ( diffuse mottling skin)
which agents are ergot agents and which is non ergot
ergot: bromocriptine and pergolide
non-ergot: pramipexole, ropinorole, rotigotine
what is the difference between ergot agents
pergolide is 13x more potent than bromocriptine
differences b/w non-ergot agents
pramipexole: interacts with drugs that are secreted by cationic transport system ( cimetidine, ranitidine, verapamil and diltiazem)- up to 20% decreased clearance
ropinorole: interacts with drugs that inhibit/ induce CYP1A2
what is the disadvantage of non-ergot
although it has favourable S/E profile, non ergot can caused compulsive behaviour ( gambling or shopping)
*
what is benefit/ role of dopamine agonist?
- useful in wearing off symptoms
- younger patient who do not want to start on levodopa
- less motor complication long term compared to levodopa
- patient who cannot tolerate high doses of levo-dopa
AE of dopamine agonist?
Nausea, diarrhea, somnolence, daytime drowsiness, orthostatic hypotension, hallucination, confusion
unique AE of bromocriptine?
pulmonary fibrosis
why does levodopa need too be in combination with decarboxylase inhibitor ( carbidopa, benserazide?
to cross BBB
advantages and disadvantages of levodopa/carbo
advantages: everyone will need, use it in older adults due to greater AE with other agents and older patient may not live long enough to experience motor complications
disadvantages:
earlier onset of dyskinesia (peak dose effects )
wearing off
delayed response may be seen with SR formulations
AE of levodopa
N/V/D, orthostatic hypotension, cardiac arrhythmias, restlessness
administration requirement for levodopa
separate from meals ( decrease bioavailability
drugs that are COMT inhibitors
entacapone
what is the role of COMT-I
use with L-DOPA to extends duration of therapy to manage “wearing off”
extends L-Dopa effect ( 1-2.5 hrs)
important counselling points for entacapone
discoloured your urine ( brownish orange)
L-DOPA is given how often
TID
adverse effects of COMT-I
dopamine effects ( dyskinesia, psychoses, diarrhea, abdominal pain)
managing delayed “on” response
chew or crush tablets and drink full glass of water
use regular tablet formulation ( NOT SR)
reduce protein intake with levodopa administration
managing “wearing off”
increased levo dosing or dosing frequency
add dopamine agonist ( pramipexole or ropinirole)
add rasagiline
administer levo CR or dopamine agonist HS
add entacapone
SQ short acting apomorphine ( rapid onset of action)
management of “freezing”
non-pharm: physiotherapy
medication changes are not helpful
management of “off period” dystonia
bedtime administration of controlled-release
baclofen use
selective chemical denervation with injections of botulinum toxin
administering l-dopa with entacapone
decreased L-DOPA by 15-30%
antipsychotic that can be used for psychosis in patient is parkinson
quetiapine, clozapine
managing vomiting/nausea in PD
use domperidone
avoid metoclopramide
managing depression in PD
avoid SSRI, SNRI, bupropion if on MAO-B
motor complications in patient taking levodopa will occur in — years
5 years
which dopamine agonist are available in patch
Rotigotine
role of apomorphine?
dopamine agonist that has fast onset of action, used in “wearing off”
significant GI upset ( need 3 days pretreatment with domperidone)
treatment for REM behaviour disorder in PD
clonazepam and melatonin
does dopamine therapy need to be taper
yes, Parkinsonism-hyperpyrexia syndrome (similar to neuroleptic malignant syndrome) is a potentially fatal complication of PD treatment usually associated with abrupt reduction or discontinuation of dopaminergic drugs
1) how should you treat status epilepticus
2) you are the emergency room pharmacist at the local hospital. After 10-15 minutes of administration of diazepam IV, you suggest the following drug for status epilepticus?
1) lorazepam 4mg IV
2) Phenobarbital 1,500 mg IV administered 50-75 mg/min.
What is the usual maintenance dose of gabapentin?:
900-3600 mg/day divided Q6-8H
what the serum drug concentration for valproic acid
50-100 mcg/ml
indication for lacosamide
Adjunctive therapy in the management of partial-onset seizures in adult patients with epilepsy who are not satisfactorily controlled with conventional therapy.
which drug can cause side effects of hyper sexual behaviour and pathologic gambling
) Dopamine agonists such as pramipexole, and drugs that convert to dopamine such as levodopa can cause impulse control disorders such as hypersexual behaviour and pathologic gambling in about 15% of patients.
which drug can used side effects of hyper sexual behaviour and pathologic gambling
Correct answer: b) Dopamine agonists such as pramipexole, and drugs that conver to dopamine such as levodopa can cause impulse control disorders such as hypersexual behaviour and pathologic gambling in about 15% of patients.
What is the typical starting dose of Levodopa / Carbidopa combination?
50/12.5 mg BID
what dose of amantadine
100mg BID
Amantadine side effects
Live do reticularis
Which anticonvulsant can cause menstrual cycle abnormalities in female patient
Valproate
