Week 6: Stroke, Sleep Flashcards
What is a Transient Ischemic Attack (TIA)
cerbral ischemic event lasting less than 24 hours (typically only minutes without apparent parmanent neurologic deficit)
What is Completed Stroke-
cerebral ischemic acute event with deficit that persists
Other types of ischemic strokes
a)Hemispheric Infarct
b)Lacunar Infarct
c)Microvascular Ischemic White Matter Lesions
a) stroke, usually caused by occlusions of carotid artery, leading to infarct of entire hemispheres of the brain. can be
b) blockage of arteries that supply deeper portions of the brain
c) occlusion of very small blood vessels in white matter. Pts. often times can be asymptomatic. treatment is controversial
Treatable Risk factors for Stroke
HTN
hypercholesterolemia
heart disease (espatrial fibrillation)
DM
cigarette smoking
excessive alcohol intake
phsyical inactivity
obesity
carotid bruit
Untreatable risk factors for stroke
age
sex
race
prior stroke
stroke pathophysiology
thrombus formation
1. asymptomatic atherosclerotic plaque
- platelet deposition
- occlusive thrombus formation
- plaque fissure-> red thrombus->embolism
a.primary hemostasis-platelet plug
b-coagulation->fibrin clot->thrombus
cardiogenic embolus-blood stasis->thrombus->ejected to brain
Clinical presentation of stroke/TIA
Carotid territory
unilateral weakness
unilateral sensory symptoms
aphasia- difficulty understanding peech or speaking, or both
monocular visual loss
transient global amnesia
Clinical presentation of stroke/TIA
vertebrobasilar territory
bilateral weakness, sensory, and/or visual complaints
- diplopia, ertigo, ataxia w.o weakness, dysphagia (difficulty swallowing)
hard to distinguaish a vertebrobasilar stroke from other differential diagnosis. one distinguishing factor is the rapidity of symptoms for a vertebrovascular stoke.
General SS of stroke
unilateral weakness
unilateral sensory symtpms
dysphasia
dysarthria (slurred speech)
vision disturbances
sudden confusion/mental status changes
facia droop
seizures (rare)
ataxia
loss of balance
verigo
dizziness
dysphagia
headache
vomiting
Phases of stroke care
Primary prevention
acute management of stroke
secondary prevention
primary prevention of stroke
modifiable risk factors
a. HTN, HLD, smoking, DM, a. fib, cad, obesity, post menopausal hormone therapy
nonmodiafiable risk factors:
a.age>55, race (black,hispanic), male gender, family hx of stroke/TIA, personal hx of stroke/tia
Who are at highest risk for having a stroke
patients who have had a previous stroke
General Treatment of an intial cerebrovacular event
ANTIPLATELET THERAPY
*small vessel lacunar
*Large Vessel Embolic
*Large Vessel thrombotic
WARFARIN THERAPY
Cardioembolic
General Platelet cascade in thrombus formation
fissure in lipid plaque recongnized by the body as injury activates platelets, adhere to fissure, followed by platelet aggregation on fissure.
recruit fibrin and RBC, causing a clot
Mechanism of Action of Anti-platelet Agents
a)Ticlopidine/Clopidogrel/ Praugrel: IRREVERSIBLY Block ADP receptors, inhibiting platelet aggregation
b)Aspirin: IRREVERSIBLY inhibits COX enxyme and thromboxane(potent activcator of platelet aggregation), leading to inhibition of platelets
c) Dipyridamole: REVERSIBLY increases plasma adenosine and inhibits platelet phosphodiesterase, causing inhibition of platelet activation and aggregation
Secondary stroke ppx
ASA
Ticlopidine
Clopidogrel
Prasugrel
Ticagrelor
ASA/ER dipyrdamole
Notes on PK of aspirin
~18-25% decreased risk of having another stroke
- inhibition of plt. aggregation require ~97% of COX-1 inhibition
*in ~70% of pts. this is achieved with an aspirin dose of 80-100 mg
*older age and obese patient may require higher doses of aspirin to produce effect
*inhibition of thromboxane occurs pre-systemically in portal circulation
*enteric coated products are erratically absorbed from the GI tract
Ticlopidine vs. Aspirin
additional 21% risk reduction of having another stroke in comparison to aspirin
fatal toxicity risks, including diarrhea, rash, nausea, and gastritis, ulcer, GI bleeding
Clopidogrel vs Aspirin
CAPRIE study shows that clopidogrel has ~7% additional risk reduction of having another stroke, which is not statistically significant.
only statisticlaly significant finding from CAPRIE study was that clopidogrel had 23.8% relative risk reduction of PAD over aspirin
Dipyridamole ER vs. Aspirin
Dipyridamole ER (which has ~ same RRR as aspirin) not available in the US, only IR
ESPS2 study showed that inorder to achieve same time conc. of Dipyridamole ER with IR, pt must take IR 100 mg QID for the rest of their life, which would drastically increase risk of pt noncompliance.
Aggrenox vs. Aspirin
Aggrenox is Dipyridamole ER+ASA combo
ESPS 2 study showed 36.8% RRR vs placebo and 23% RRR vs ASA.
HOWEVER, PROFESS study showed there is no difference btw. aggrenox and clopidogrel
Overall, how to pick an antiplatelet agent best for the patient
Since there are no significant differences btw. anti-plt. choices, anti-plt agents used is based on whats best for individual patient.
A)base it on pt specific needs
consider..
side effect profile relative to your pts hx
(ex. Aggrenox can cause vascular headache, can cause GI problems->caution in GI problems..etc.)
the agent that produces an inhibition of aggregation in your specific patients (ex: some pts can be aspirin reisstant due to genetics)
can be used in lowest effective dose to reduce risk of bleeds
b) will aparticular agent be less than optimal for a particulr pt
*ex: ASA allergy
*pts on clopidogrel may have DDI w. agents that inhbit CYP2C19 such as CCBs, PPI’s etc.
*aggrenox therapy andmigraine hx
*aggrenox therapy and spastic colon or IBS
c)does your patient warrent dual anti-plt therapy
*Clopidogrel + ASA only has increased anti-plt effects in firt 30-90 days, then risk of bleeding outweighs beenfit
*coronary artery stenrs and new cerbral ischemia
*a. fib not able to take coumadin
d) are your pt plt. responding to their anti-plt agent
*ex: ASA or Plavix resistance
Individualized pharmacotherapy for anti-plt. choice
urgency of needing full antiplt. therapy
agent least likely o produce adverse effects
*headache hx
*spastic coloitis or ulcerative colitis/chrons
*gastric ulcer hx
*true aspirin alergy
agent least likely for drug interactions
*need for chronic NSAID, PPI, or CCB use
dual anti-plt therapy
*failure of monotherpay
*first 3-6 mo post troke w. high risk factors
*a. fib w. CI for anticoagulation
approach to ASA resistance
assurance compliance
*urinary salicyates
remove drugs that compromise ASA effects
*NSAIDS other than celecoxib(celebrex)
*some herbal supplements
change from EC to chewable ASA or alka seltzer
*particularly in older women
*change ASA dose where appropriate
approach to plavix resistace
minimize use of other drugs that inhibit cyp3a4 AND CYP2C19
SUBSTITUTE DRUGS THAT HAVE LESSOR EFFECT ON THESE p450 is iso enzymes
add meds that can induce CYP enzyme activity
common meds that influence CYP3A4 or CYP2C19
statins other than Rosuvastatin (crestor)
CCBs, not BB, ACE, or ARBS
*NOTE: IF CCB + clopidogrel is an issue in a pt, before switching the CCB, be sure pt is on CCB for htn and not rate control. if ccb used for rate control is changed, might do more harm in pt.
Ambien, Lunesto (Sonata least likely)
Gliburide, not glipizide or metformin
Enablex, Ditropan, not detrol or sanctura
PPI’s
what to do if pt is truly resistant to both aspirin and clopidogrel
- ticagrelor
*prasugrel
BOTH OF THESE NOT FDA approved.
*max ASA dose 100 mg daily w. ticagrelor
Signs and symptoms of sleep disorders
excessive daytime sleepiness (EDS)
impaired daytime funcitoning
irregular breathing
increased movement during sleep
irregular sleep and wake cycle
difficulty falling asleep
common types of sleep disorders
insomnia
sleepapnea
narcolepsy
circadian rhythm disorders
parasomnia
restless leg syndrome
What is insomnia
most common reported sleep disorder
difficulty falling asleep, maintaining sleep, or non restorative sleep