seizures and parkinson Flashcards
parkinson’s is the loss of dopamine continuing neurons in the _____ where they
substantia nigra inhibit the firing of cholinergic neurons
three broad mechanisms of parkinsons drugs
dopamine replacement
dopamine agonist therapy
anticholinergic
all of which aim to correct the imbalance of the cholinergic neurons in the striatum
this drug is a metabolic precursor of dopamine that crosses the bbb
levodopa
why are large doses of levodopa necessary in tx
what is the problem with this
because the drug is decarboxylated to dopamine in the periphery
this causes side effects
carbidopa
dopamine decarboxylated inhibitor that does not cross the BBB
this reduced the peripheral metabolism of levodopa and increases the amount that reaches the brain
Selegiline/deprenyl MOA
inhibitor of monoamine oxidase
this is the enzyme that metabolizes dopamin in the CNS
Rasagiline
newer monoamine oxidase inhibitor similar to selegiline
this drug is known for disabiling response fluctuations over time
levadopa
mnemonics for parkinson’s tremor
MAIN- bradykinesia (slowness)
TRAP-motor
tremor at rest
rigidity
akinesia
postural stability
SOAP-non motor
sleep disturbances
other: nausea fatigue, speech
autonomic
psychologic
two classes of medications that cause parkinsonism
anti-psychotics
anti-nausea
both result in the loss of dopamine
7 categories of anti parkinsons drugs
Anticholinergic Amantadine COMT Dopamine Dopamine agonists MAO-B inhibitors
name the two anithcholinergic drugs used for parkinsons
benztropine
trihexyphenidryl
COMT inhibitors
entacapone
tolcapone
dopamine agonsits
apomorphine
bromocriptine
praipexole
ropinirole
MAO inhibitors
rasagiline
selegiline
what are the PK issues with levadopa
do not take with high protein meal because its absorption is affected by the diet
LAAD inhibitor
L-amino acid decarboxylase inhibitor
carbidopa
CI or carvidopa levodopa
narrow angle glaucoma
non-selective MAOIs- hypertensive cris
drug resistant off periods with levodopa carbidopa are due to
delayed gastric emptying or decreased GI absorption
GIVE ON EMPTY STOMACH
try to avoid control released products
what drugs would you not want to give with a pt on levodopa
dopamine antagonists: antipsychotics and antiemetic
non-selective MAOI
buproprion:increased side effects
protease inhibitors:toxcitiy
phenytoin, ion: reduce the IO-dope efficacy
AE to levodopa
GI effects common: nausea vomiting
postural hypotension and unstable balance
arrhythmias (low incidence)
sedation/vidi dreams/
why do we see the end of dose effect with levodopa
what can you do to help prevent this
increasing loss of neuronal dopamine storage
relying on exogenous source (med)
can increase dosing frequency
change to long acting
add short acting regimen to long acting
add other durgs
COMT
methylates levadopa
entacapone and
tolcapone both target what pathway
COMT methylation of L dopa
how doe tolcapone differ from decarboxylase inhibitors
blocks COMT in the brain and helps to increase the levlels of dopamine and
tolcapone SE
cna increase liver enzymes causing failure
how does MOA B differ from antidepressants
selective targets dopamine degradation therefore MOABI like selegiline and rasaligine slectively target this and prevent degradation in the CNS
these durgs only have minor effects when given alone and are used mostly in conjungtion with levadopa
MOA of ropinarole
D2 receptor agonist similar to bromocriptine
paramipexole (D3)
viral agetn that increase dopamine release and uptake and can be used for parkinson’s
amantadine
benztropine
trihexyphenidryl
how do thye work
benztropine
trihexyphenidryl
antimuscarninic agent
help restore balance of dopamernergic and cholinergic activity
centrally acting antimuscarinic that effect tremor but not effect of brady
help with parkinsonism effects of drugs
used if tremor is a big side effect
vomiting before abdominal pain think
medical
pain before vomiting think
surgical
but be prepared for either or both
if you see hmg drop by
more than a point in a week you check occult blood three time
sometimes the bleeding is proxismal
SIRS
criteria that they
defined as at least 2
heart rate >90
RR >20 <32
temperatrue <96.8 (36) or >38 > 100.4
WBC>12 or <4 or with >10% bands
SE with parmipexole ropinorle and bromocriptine
common nausea confusion hallucinations light headedness LE edema
postural hypotension
sedation
serious: compulsive behavior physchosis, sleep attacks, pleuropulmonary fibrosis
what is a side effect that is exclusive to ergot derivatives
pleuropulmonary fibrosis
drug interactions with bromocriptine
w/ bromocriptine
azole
antifungals
protease inhibitors
erythromyocin
increase bromocriptine
DI with ropinirole
altered metbaolism with CYP1A2 inducers and inhibitors
this drugs provides rapid effective temporary relief of off period akinesia
apomorphine
apomorphine
effective temporary relief of off period akinesia
SI
N/V
premedicate with trimethobenzamide
trimethobenzamide
used for N/V associated with apomorphone (off period akinesia)
can cause dizziness hallucinations an ink site irritation
trimethobenzamide CI
5HT3 receptor blockers
rotigotine
row to go tin
dopamine agonist patch also used in RLS
what is special about apomorphine
the first dose of apomorphine must be given in a clinic setting. The patient should not take apomorphine if he is allergic to metabisulfite.
The dose should be re-titrated if he has not taken apomorphine for 1 week.
Apomorphine causes severe nausea and vomiting.
two COMT inhibitors and the differences between their side effects
entacapone: peripheral SE
tolcapone: central and peripheral
of the two COMT I which one can cause hepatotoxcity
tolcapone:
COMT
degrades dopamine in periphery AND CNS
if the pt is taking levodopa and about to start a COMT what should be done first
reduced levodopa by 30% in first 48 hours to avoid ADE
other than hepatotoxicty with tolcapone what SE would we expect to see with COMT I
orange brown urine delayed onset diarrhea
COMT I interact with
NONSELECTIVE :
MOAIs
the uses of COMTI
reduced off time and increase l-dopa AUC by 35%
allow for reductions in L-dopa
1st line for managing motor fluctuations with pts on L dopa
entacapone
when would we used tolcapone
reserved for pts with fluctuations that are not responding to other therapies
MAOB inhibitors work selectively in the
CNS
increases dopamine in the brain
MAOBI
rasagiline
safinamide
selegiline
safari
and giline MOUSE
when would we use MAOBI transdermal patch
depression only
Adverse effects of selegiline
SILLY rat
the same as everything else
+ DIZZINESS HA
rare: atrial fibb
Adverse effects of rasagiline
red rat
same as every other parkinsonian drug
+vomiting
depression
dyskinesia
orthostatic hypotension
rare: GI hemorrhage
Adverse effects of safinaminde
safari rat
same as other PD drugs except for fall
rare: hypertension and hallucinations
what kind of drugs are CI with MAOB
other MAOIS Isocarboxazid (Marplan) Phenelzine (Nardil) Selegiline (Emsam) Tranylcypromine (Parnate)
and opiods and OTC cold meperidine methadone tramadol porpoxyphene dextromethrophan
what should you advise a pt ot MAOI
avoid all OTC cold prep
don’t take with other MAOIS
Serotonin syndrome :use in caution with pts on antidepressants
avoid NON SELECTIVE MAO inhibitors -hypertensive crisis life trhreatening
(accumulation of NE )
which MOA B I can be used as monotherapy
rasagiline
this is thought to be the MOA of amantainde
may potentiate dopaminergic function
NDMA antagonis–> anti-dyskinetic
why don’t we use amantadine regualrly
short lived
less effective than l-dopa
amantadineSE
most of the mental
depression irritability excitability agitation confusion
livedo reticularis
reversible duffuse skin mottling and often LE edema
seen with amantadine
these types of medications are used for symptomatic control of tremors only
anticholinergics
bextropine (cogentin)
trihexyphenidyl (artane)
trihex benz car aretan
what population do you want to be weary of with anticholinergics
geriatric lower doses and titrate slowely
worried about confusion
constipation
dry mouth
urinary retention
what is your first approach to the pt with IPD
non pharmacologic: education, exercise, nutrition, psychosocial
or consider rasagiline
what do you do for a pt on rasagiline who needs additional tremor control
if under 65 anticholinergic or amantadine
if over 65 amantadine
what do you do for a pt on rasagiline who continues to experience symptoms of bradykinesia rigidity or tremor
add amantadine
DA agonist
or Carbidopa L-dopa
delayed onset fluctuations seen as bradykinesia at the beginning of dosing intervals is known as
delayed onset
what is peak-dose dyskinesia
involuntary movement at peak levodopa levels
how do you treat response fluctuations
keep extra dose with you in case meds wear off while out
longer acting meds
maximize on time
minimize off time
what can you do for a pt that experiences wearing off
ass MAO BI
ADD COMT I
ADD DOPAMINE AGNOSIT
ADj dosing
what to do for on-off phenomenon
add entacapone rasagiline pramipexole ropinirole or selegiline
redistribute dietary preotein and space meds 2 hours from a meal
focal seizures are defined as
what are the three categories
arising from localized regions of the brain and can be
simple (focal aware)
complex (focal impaired awareness)
secondary generalized (focal to bilateral)
generalized seizures definition and categories
involve both hemispheres LOC and may be convulsive or non-convulsive
absence (petit mal)
tonic-clonic (grand mal) : both phases
myoclonic
atonic (loss of muscle tone)
ion channel phsyiology in seixures
selective pores for Na, K, Cl, Ca
ATP dependent Na/K pump that maintains resting membrane potential at -70 mV
concentration gradient: K inside Na outside
when opened Na movies in and K moves out
charges change confirmational state of voltage gated chanels and Na and Ca depolarize the membrane
four broad classifications for the MOA of anti seizure drugs
(1) modulation of voltage-gated sodium, calcium, or potassium channels
2) enhancement of fast GABA-mediated synaptic inhibition
(inhibitory GABA)
(3) modification of synaptic release processes
(4) diminution of fast glutamate-mediated excitation.
when would you start therapy for individuals experiencing seizures
first seizure for high risk pts
all pts at seocnd seizure
when pt is still experiencing seizures despite medication regimen
if not decreasing in frequency
switch to second med with taper
if decreasing in frequency
maximize dose
add second agent
could potentially taper first
seizure medication options for pregnant women
oxclamotrigine, levetiracetam, zonisamide
seizure medication options for elderly with focal epilepsy
levetiracetam, lomotrigine
primary generalized med options
ethosuximide (absence only)
levetiracetam, lomotrigine, topiramate, valproate, zonisamide
partial onset (focal) with or w/ot secondary generalized properties meds
topiramate, levetiracetam, lomotrigine, oxclamotrigine, zonisamide
carbamazepine
oxacarbazepine
lacosamide
drugs to avoid in primary generalized
gabapentin
pregabalin
tiagabine
vigabatrin
what would you never want to use in a woman of childbearing potential
valproate (d) Phenytoin Carbamezapine Oxcarbazepine Phenobarbital
ALL category D
CBZ
carbamazepine
carbatrol epitol equetro tegretol tegretol-XR
PB
phenobarbital
PHT
phenytoin
dilantin
phenytek
VPA
VPA -valproate
depacon depakaene depakote SPRINKLES Stavzor
ESM
zarontin
ethosuximide
PB MOA
enhances GABA evoked Cl- currents
barber taking up GABA
PHT MOA
blocks Na channels
towing car and carba both throwing out salty chips
CBZ
blocks Na channels
VPA
Valerie wearing her sprinkle coat is not about to eat salty chips either
or tea flavored ice cream
VPA blocks Na channels and T type Ca channels
ethosuximide/ESM MOA
aaron trying to be zaro still sux
he isn’t eating tea ice cream either and he is skinny af
major drug old epi drug approved for JME
PB
which drug can be used off label for post-taumatic seizures following TBI
PHT
what is the main older epi med that can be used for status epi
PHT
phenytoin
my care is dying tow me call and check the STATUS of the tow truck
usual dosage of PB
Dzz-Mzz (100-300)
normal dosage and initial dosage of CBZ
Dzz-Nzz (100-200 BID)
800-1200 max
Fuzz- thinzz
see d think
2
see m think
3
8
F V
1
t or d
ESM dosage
Ethosuxamide
Start LESS of Aaron like half (250-500)
At the max you have to Tells him
TELSS 1500
VPA dosage
dL
15mg
max
shes
mx: 60
PB dose adj
hepatic and renal
barbershop with the kidney and the liver
PHT adjustments needed
need to monitor free unbound levels for liver
CBZ need what adjustment
use caution in liver
CrCL<10
dz
VPA adjustments
hepatic adjustment for moderate to severe
NO RENAL
val likes to drink but her kidneys are fine
ESM dosage adjustments
use caution in liver and kidney
which anti seizure meds are CYP inducers
PB
PHT
CBZ
cbz cns DEPRESSION se
Diplopia and drowsiness
dose related SE CBZ
HA
N/V
idiopathic SE CBZ
Rashes
hyponatremia
bloody dyscrasias
VPA CNS SE
somnolence
VPA Dose-related SE
weight gain
N/V
alopecia
throbocytopenia
Val is gaining wait and bald playing the trombone
ESM CNS SE
drowsiness
aaron is tired
ESM dose related SE
anorexia
weight loss
abd cramps
ESM Idiopathic SE
leukopenia eosinophilia psychiatric sleep disturbances aggression
VPA idiopathic SE
drug rashes
hepatotox
pancreatitis
thrombocytopenia
drinking
playing the trombone epigastric pain
rash
what are some common ASE shared between
PB PRM PHT CBZ VPA and ETH
drowsiness
GI
hepatic dose
all renal dose except: VPA and PB
VPA most significant adverse SE
thrombocytopenia
ESM most significant SE
aggression
when to draw blood for PHT
whats the range
about every 2 weeks
MS (30) you’re getting towed
you want to be between TOSS and NICE
CBZ therapeutic range
R - tin
greater than
TL you’re done
VPA range
L- TNL
5-125
Over TNS 150 not good
CBZ blood draw
4-6
RaaSH
LTG
lamotrigine
lamictal
GBP
gabapentin
neurontin
TPM
Topiramate
topamax
LEV
levetiracetam
keppra
OXC
oxcarbazepine
trileptal
PGM
pregablin lyrica
ZNS
zonisamide
conegram
LTG MOA
blocks Na channles
GBP MOA
Unknown but probably increases gaba synth
TPM
blocks Na channels
PGB MOA
modulates the influx of Ca by binding to presynaptic voltage gated channels
gabling lyrica is fucking with the wires on the ice cream truck
OXC MOA
blocks Na channels
ZNS MOA
blocks Na and T-type Ca
similar to VPA
Lacosamide MOA
vimpat
binds to collapsing response mediated protein 2 to enhance inactivation of Na
Waco pat isn’t letting the potato chip truck arrive
LTG is indicated for
partial
GTC
LGS
off label absence
when would you use GBP
ADJ for partial
rare and severe kind of epilepsy that starts in childhood
LGS
what two drugs can you use for LGS
GBP
LTG
what new epi meds can be used as an adjunct for children under the age of two
OXC
PGM and ZNS are both used as
partial adjunct
what new epi drugs would you see dose related weight gain with
GBP
PGB
what new epi drugs would you see dose related weight loss
ZNS
TPM
N/V are common with every single new epi drug except
GBP ‘
only SE are somnolence and weight gain
acute angle glaucoma is a idiopathic SE of what antiepi med
TPM
TPM idiopathic SE
glaucoma
acute-angle glaucoma
oligohydrosis
hyperthermia
systemic life threatening rash and hepatic failure are idiopathic SE of this antiepi drug
LTG
what anti epi drugs would you see associated with blood dyscrasias
CBZ and OXC
peripheral edema and thrombocytopenia are associated with this new antiepi
PGB
this new anti epi is associated with sulf allergies
ZNS
all newer antiepi casue drowsiness except
lacosamide
all new epi cause GI effects except
GBP and PGB
all new anti epi drugs require hepatic dose adj except for
GBP
PGB
LEV
ALL REQUIRE RENAL
slowing psychomotor disturbances and significant CI are all associated with what newer ant epi
TPM
mood changes are associated with what newer epi
LEV/ keepra
status epilepticus
any seizure lasting longer than 30 minutes with or without LOC
recurrent seizures with no intervening period of consciousness
may be convulsive or non-convulsive
tx of status
oxygenation preservation of cardioresperatory function
Benzos: IV push of lorazepam or diazepam
or
PHT/fosphenytoin IV loading dosed followed by PO maintenance
alt: PB
Monitoring needed for PB
CBC w/ diff and LFTs anually
serum Ca and bone scan periodically
PHT monitoring
ALBUMIN huge deal and LFT anually
CBC with differential every 6 -12 mo
Ca and vitamins levels as well as DEXA scan
monitoring with CBZ and VPA
CBC with differential and platelets q3mo and then every 6 mo
LFTs
for CBZ also need CMP every 6 mo
when should you consdier stopping therapy
no seizure >2 years
IQ, neurological test
no previous unsuccessful attempts at drug discontinuation
normal neurologic examination
consider risk vs benefits
normal EEG
single type of partial or generalized with mixed there is a heightened ris
what is the major teratogenic drug we worry about anti-epileptics
valproate
as well as CBZ PB PHT TPM
LMT
these drugs have known transfers to breast milk
LMT primidone LVT GBP TPM
common AE with clonazepam
disinhibition
ataxia
severe
respiratory depression
physical dependence
these two antiepis have decreased clearance in geri population
CBZ
LMT
decreased protein binding seen with these two anti epi in geri populations
PHT
VPA
increased half life in geriatrics with this antiepi med
Diazepam
fewer AED in geriatic pop with this drug
LMT
low dose TPM
GBP
and LCT
poly
oligo
normal
AFI
8-18 = normal
, AFI ≤5 cm = oligohydramnios,
AFI ≥24 = POLY
causes of oligp
Urethral obstruction (e.g., posterior urethral valves)
Bilateral renal agenesis
Autosomal recessive polycystic kidney disease (ARPKD)
Chromosomal aberrations (e.g., trisomy 18)
Intrauterine infections (e.g., congenital TORCH infections)
In multiple pregnancies: twin-to-twin transfusion syndrome
Late or post-term pregnancies (> 42 weeks of gestation) Placental insufficiency Preeclampsia Premature rupture of membranes Idiopathic
PCN allergy GBS treatment
cephazolin
super severe PNC ampicillin allergy
clinda
vanco
Tx for mom with hep b
C section to avoid maternal mixing of blood
need to give baby hep B ivig and hep B vaccine (first day of life)
ideally you vaccinate mom prior to pregnancy
HIV
baby cares about viral load increase in viral loas means increase in infectious risk
CD4 count–> risk of opportunistic infection (think TORCH)
DOES NOT CROSS PLACENTA
Is mom immune to hep B or infected
Antigen wins –> infexted
INFECTED
e–> INFECTIOUS
ab–> immune
surface ab—> immune through vaccination of exposure
diagnoses in HIV
ELISA
viral blot
if she shows up with no testing
2+1
2 NTRI+1 NNRTI
1PI
NNRTI
nevirapine (c)
protease inhibitor
atazanavir (b)
When can you delivery vaginally with HIV
delivery VL<1000 and on HARRT
don’t know mom’s HIV status
AZT
AZT (zidovudine),
charcot’s triad sx
Most patients have fever, jaundice, and right upper quadrant pain (Charcot triad).
