Parkinson's, Headache, Dementia Flashcards
neuroanatomical and neurochemical processes leading to parkinsons
dopamine deficiency
loss of dopaminergic cells
formation of lewy bodies
main symptoms of parkinsons
bradykinesia, rigidity, resting tremor, postural instability
slowness and difficulty initiating voluntary movement
bradykinesia
resistance to passive range of motion
rigidity
occurs at rest abolished by movement but can progress to action
tremor
motor symptoms of parkinsons
freezing, slow turning, decreased dexterity
MOA of benztropine & trihexyphenidyl
anticholinergic- blocks acetylcholine at muscarinic receptors
AEs of anticholinergics
possible link to cognitive impairment and decline***
mydriasis, dry mouth/skin, urinary retention, constipation, fever, mental change, flushed skin
gold standard for parkinsons treatment that is a building block of dopamine
levodopa
contraindications to l-dopa
breastfeeding, closed angle glaucoma, melanoma
dopa-decarboxylase inhibitor that blocks peripheral l-dopa metabolism and is always given with l-dopa
carbidopa
AEs of l-dopa
dopaminergic CNS/GI
dyskinesia, on-off, decreased effect w/ time, psych disturbances, vivid dreams, nausea, orthostatic hypotension, falls, urine/sweat/saliva discoloration, NMS w/ abrupt d/c (taper)
DDIs of l-dopa
da antagonists, nonselective maois, high protein, iron salts, b6
carbidopa dose needs to be maintained at what per day
at least 70-100 mg/day
onset of effect with ER sinemet is
delayed
intestinal gel form of l-dopa
duopa
powder for inhalation form of l-dopa
Inbrija
AEs of inbrija
blackens saliva and nasal secretions **
somnolence, hallucinations, dyskinesia, cough, URTI, nausea
when is inbrija not recommended
asthma, COPD, other lung disease
contraindications of inbrija
nonselective maoi within 2 weeks
when is inbrija used
intermittent for off episodes, DOES NOT REPLACE PO
reversible selective inhibitors of COMT that prevent breakdown of l-dopa and extend its effects
entacapone, tolcapone, opicapone
are COMT inhibitors monotherapy or adjust
ADJUNCT ONLY- no effect in absence of L-dopa
DDIs with COMT inhibitors
nonselective MAOIs*, drugs metabolized by COMT
when is entacapone administered
with each dose up carb/levo up to 8x a day
AE of entacapone
brown/orange urine
major AE/CI of tolcapone
risk for hepatocellular injury
CI with hepatic disease
opicapone dosing
once daily QHS
how is opicapone absorption affected by food
decreased absorption with high fat/calorie meals
noncompetitive, selective antagonists of MAO-B that decrease breakdown of DA and free radical production
selegiline
rasagiline
safinamide (xadago)
AEs of selegiline
insomnia, jitteriness*
HA, dopaminergic, HTN crisis, serotonin syndrome, etc.
caution with MAOI-B agents and foods containing
tyramine
is selegiline mono or adjunct
labeled adjunct, can be mono early
which MAO-B has 3 active amphetamine metabolites
selegiline
which MAO-B can be disease modifying
rasagiline
is rasagiline mono or adjunct
either
AEs of rasagiline
orthostasis, dopaminergic, HA, arthralgia, GI
most MAO-B agents have DDI with
nonspecific MAOIs, serotonergic drugs, sympathomimetics, tyramine foods
is safinamide (xadago) mono or adjunct
adjunct for wearing off
AEs of safinamide
dopaminergic, daytime somnolence, withdrawal NMS syndrome, retinal
CI to safinamide
child pugh C
agents that directly activate post synaptic DA receptors
pramiprexole
ropinrole
rotigotine
apomorphine
are DA agonists mono or adjunct
mono in healthy/young patients, or adjunct in case of deterioration in response to L-dopa
which type of AEs are more common with dopamine agonists? examples? in who?
nonmotor in older/frail
impulsive behaviors, psychosis, vivid dreams, daytime sedation
major DI of ropinrole with substrates of
CYP1A2
CI of ropinrole
abrupt d/c, hepatic disease
route of admin of rotigotine (neupro)
patch
rotigotine AEs
CNS, GI, peripheral edema, application site rxn*
caution with what when using rotigotine
heat & MRIs, allergy potential
when is apomorphine used
advanced PD PRN adjunctive treatment if unpredictable off or nonresponsive to other therapy
how is apomorphine initiated
test dose under supervision pretreated with an antiemetic
major DDI/CI of apomorphine
5HT3 antagonists increase hypotensive effects
AEs of apomorphine
dopaminergic, dizziness, falls, somnolence, chest pain
agent with poorly understood mechanism that increases endogenous DA
amantadine
effects of amantadine
decreases l-dopa induced dyskinesia*, and other parkinsons sx
ER amantadine (Gocovri) is only indicated for
l-dopa induced dyskinesia
amantadine needs dose adjustment for
renal impairment
AEs of amantadine
orthostatic hypotension, dizzy, falls, hallucinations, etc.
DIs of amantadine
LAIV, quinine/quinidine, HCTZ & triamterene
agent than blocks adenosine A2A receptor for parkinsons
istradefylline
is istradefylline used mono or adjunct
combo with carb/levo for patients with off episodes
when does istradefylline need dose adjustment
smokers
hepatic impairment
3 steps for management of PD psychosis
- evaluate hypoxemia, infection, electrolyte disturbances
- simplify drug regimen
- add atypical antipsychotic
agents used for mild to mod migraine
NSAIDs, APAP, caffeine combos
agents used for mod to sev or refractory migraine
triptans, DHE, gepants, ditans
agents for refractory mod to sev migrain
triptan + NSAID, gepants, ditans, combo of analgesics with codeine or tramadol, opioids
2 oral solution NSAIDs for migraine TREATMENT
diclofenac potassium (Cambia)
celecoxib (elyxyb)
caffeine combo products with risk for dependence for migraine TREATMENT
butalbital/APAP/caffeine (Fioricet)
butalbital/ASA/caffeine (Fiorinal)
major AE of fioricet and fiorinal
risk for med overuse headache when taken >3 days/month
5HT1D AND 5HT1B selective agonists that cause vasoconstriction and reduce neurogenic inflammation…. for migraine TREATMENT
triptans
when & how are triptans best administered
early in course of attack, limit use to <10 days/month to prevent med overuse HA
AEs of triptans
flushing, chest pain, palpitations, dizziness, fatigue, xerostomia, serotonin syndrome
when are triptans avoided
CV or cerebrovascular conditions
which triptans have longest half lives
frovatriptan > naratriptan
which triptan has a lower AE incidence and is more tolerable
almotriptan
which triptan has the quickest onset of action
intranasal and SQ sumatriptan
which triptan has a higher AE incidence
sumatriptan
formulations of rizatriptan
PO, ODT, oral film
formulations of sumatriptan
PO, IN spray and powder, SQ
formulations of zolmitriptan
PO, ODT, IN
5HT1F agonist for migraine TREATMENT, CV
lasmiditan (reyvow)
administration key point for lasmiditan
must wait 8 hours between dosing and operating heavy machinery or driving
major AE of lasmiditan
CNS depression**
also serotonin syndrome, dec HR, inc BP, palpitations, etc.
small CGRP receptor antagonists for headache TREATMENT
gepants
rimegepant
ubrogepant
zavegepant
what is rimegepant (nurtec) indicated for
acute treatment and prophylaxis
nurtec dosing for prophylaxis
1 tab PO every other day
dosing of ubrogepant (ubrelvy)
1 tab once, can repeat after 2 hours
activate 5HT1D AND 5HT1B receptors on intracranial blood vessels and activates 5HT1D on sensory nerve endings for headache TREATMENT
ergots
ergotamine
dihydroergotamine
BBW for ergots
CI with potent 3A4 inhibitors (protease inhibitors, macrolides, -azoles).
major ergot AEs
cardiac valvular fibrosis, ergotism
when should ergots not be used
pregnant, breastfeeding, within 24 hours of triptans, other serotonin agonists, or ergotamine containing/ergot like agents
ergotamine AEs
NV (may worsen migraine associated NV), ECG changes, HTN, ischemia, etc.
additional CI for dihydroergotamine
ischemic heart disease, angina pectoris, MI hx, etc (other CV issues)
ergot other CI
pregnancy, PVD, CAD, hepatic/renal impairment, uncontrolled HTN, sepsis
options for migraine PROPHYLAXIS
nurtec
topiramate, valproic acid
beta blockers
TCAs, venlafaxine
qulipta (atogepant)
CGRP MAbs
nerve block
AEs of topiramate
cognitive dysfunction, CNS effect, nephrolithiasis, metabolic acidosis, angle closure glaucoma, oligoidrosis, hyperthermia, suicidal ideation, weight loss, paresthesia
counseling point for topiramate and when to avoid
important to stay hydrated
avoid in pregnancy
CI for valproic acid
prevention of migraine in pregnant women and women of childbearing potential who are not using effective contraception
dosing and AEs of TCAs for migraine prevention
lower doses than used for MDD
AE anticholinergic, cardiac conduction abnormalities
gepant used only for migraine prophylaxis taken once daily
atogepant (qulipta)
CGRP MAbs for migraine prevention
eptinezumab (vyepti)
erenumab (aimovig)
fremanezumab (ajovy)
galcanezumab (emgality)
which CGRPs bind the ligand? receptor?
ligand- vyepti, ajovy, emgality
receptor- aimovig
admin & AEs of vyepti
IV Q3M
infusion rxn, nasopharyngitis, nausea, inc. risk for Ab development
admin & AEs of aimovig
SQ QM
injection site rxn, constipation
amin & AE of ajovy
SQ QM or Q3M
injection site rxn
admin and AE of emgality
SQ QM
injection site rxn
alternative options for migraine prophylaxis
magnesium
B2
feverfew
butterbur
AEs of magnesium, how to manage
diarrhea, NV – titrate dose
AE and when to avoid feverfew
GI AEs
avoid in pregnancy
AE and when to avoid butterbur
AE: GI, drowsy, fatigue, rash, hepatotoxicity
avoid products that aren’t PA free
when is botox used
for chronic migraine
AE and BBW for botox
AE injection site pain, neck pain, myalgia, facial paresis
BBW spread of toxin effect
preferred agents for menstrual migraines
frovatriptan, naratriptan
when should estrogen containing CHCs be avoided
migraine with aura- stroke risk
first line for migraine in pregnant patients
APAP
major counseling point for tension HA
medication overuse HA
gold standard for prevention of cluster HA
verapamil
gold standard for hemicrania continua
indomethacin
2 types of thunderclap headaches that require immediate referral to the ED
reversible cerebral vasoconstriction syndrome
subarachnoid HA
max days/month for ergots, triptans, and opioids
<10
max days/month for non opioid analgesics
15 days
max days/month for butalbital
<4
which gene can increase risk for alzheimers
APOE4
what major neurotransmitter is decreased in alzheimers
acetylcholine
2 major things seen in the brain indicative of dementia
beta-amyloid plaques
neurofibrillary tangles
general pathophysiologic process of dementia
brain atrophy
ventricular enlargement
neuronal degeneration
low Ach
beta amyloid
tangles
what drugs could potentially increase dementia risk? examples?
cumulative anticholinergic use
antihistamines, TCAs, oxybutynin
drugs that block acetylcholinesterase therefore blocking metabolism of ACh
acetylcholinesterase inhibitors
donepezil
rivastigmine
galantamine
AEs of AChE inhibitors
sialorrhea, lacrimation, urination, defecation, GO, emesis (SLUDGE), bradycardia
major DDI/CI for AChEi drugs?
CI with baseline bradycardia or conduction system issues
DDI with drugs that induce bradycardia or alter AV node conduction
how to counsel if someone says their AChEi disrupts sleep? nausea?
sleep – move dose to AM/earlier
nausea – take with food or at bedtime
which AChEi have 2D6 and 3A4 metabolism
donepezil, galantamine
where can the rivastigmine patch be applied
back, chest, and arms only
poor absorption elsewhere
major AE of rivastigmine
GI disturbances
when should donepezil be taken (if tolerated)
bedtime
NMDA receptor antagonist
memantine
what is the combo pill with memantine ER?
+ donepezil
Namzaric
AEs of memantine
confusion (mild, transient), constipation, diarrhea
caution taking memantine if??
when does dose need adjusting??
caution if seizures or CV disease
lower dose if CrCl <30
anti-amyloid agents
lecanemab (Leqembi)
donanemab (Kisunla)
what is required to initiate an anti-amyloid
presence of amyloid beta pathology must be confirmed
major BBW for anti-amyloids
what increases risk
ARIA
increased risk with APoE4 carriers
lecanemab dosing
can it be d/c with improvement?
IV Q2W
no
donanemab dosing
can it be d/c with improvement?
IV Q4W
yes with threshold reduction of amyloid plaques
monitoring for anti-amyloid drugs
MRIs before and during treatment
antipsychotic indicated for agitation associated with dementia due to alzheimers
brexpiprazole (rexulti)
