Pharma Flashcards
Why not higher doses of asa and what trial helped with this?
Higher dose is higher bleeding risk seen w cure trial
Vorapaxar moa and when is it given why not used more widely
Reduction in ischemic endpoints but sig bleeding with asa Studied in its with cad and pad Moa is par inhibitor and thromboxane a2 Traced acs was asa + plavix+ vorapaxar stopped early bc of ich Trap 13 percent reduction in ischemic events with a 66 percent increase in bleeding risk
3 steps to platelt mediated thrombosis and pharma targets?
- Adhesion - Vwf, endothelial damage, collagen (no approved antiplt agents in this category 2. activation - ADP (most antiplts), TXA2, TXA 3. Aggregation - GIIb/IIIa links together - this is the final common pathway so is very potent.
why are GIIb/IIIa so potent
final common pathway for clotting so very potent.
ASA trials need to know
- Lancet 1988 with stemi ASA + SK 8% vasc death comared to 13% in placebo and 10.7% w asa a;pme amd 1-/4 wotj SL a;pme/ 2/ Caorms MEJM in 1985 50% RRR with ASA over no ASA in MI or cardiac death.
PCI w/o ASA
meta-analysis 2013 worse ischemica events (not looking at other adjunctive therapies)
Stemi load ASA
325 chewed. load
MOA of P2Y12 differnt MOAs ****
- Clopidogrel - P2y12 2 step esterification and then oxiadtion with CYP45 3A 2. Prasugrel one step oxifation to active form 3. Ticag CPTP active drug All block ADP from binding P2Y12 and starting the Gi@ coupled receptor to activate platelets.
MOA of the 3 P2Y12 differnt MOAs ****
- Clopidogrel - P2y12 2 step esterification and then oxiadtion with CYP45 3A 2. Prasugrel one step oxifation to active form 3. Ticag CPTP active drug All block ADP from binding P2Y12 and starting the Gi@ coupled receptor to activate platelets.
General MOA of P2Y12/CPTP
block ADP inteactoin with P2Y12 recpetor preventing platelet activation.
first p2y12 study
STARS - (leon MB) ticlopidine + asa ten either asa alone or asa + warfarin in reducing ST after BMS. rate of 30 day STent trhombosis. 2.9 with ASA alone, 2.7 with ASA + coumadin, 0.5 with asa + ticlopidine.
STARS trial
0.5 % with ticlopidine + ASA , 2.9 % ASA alone, 2.7% with ASA + Coumadin
1st clopidogrel trial
CURE and PCI-cure reduction with clopidogrel.
cyp for clopidogre
cyp450 3a
current oasis 7
600 with UA/NSTEMI or STMEI and early invasive very slight reduction in CV death/MI stroke after PCI
Prasugrel Trial ST Bleeting?
Triton timi 38 2.4 % vs. 1.1% ST (definite 0.8 vs 2.0% p < 0.0001) 12K pts. increased bleeding and black box warning > 75, low body weight < 60 g , hx of stroke (and 7 days of surgery
3 times when cant use prasugre
increased bleeding and black box warning > 75, low body weight < 60 g , hx of stroke (and 7 days of surgery
Prasugrel 5?
trilogy ACS , 75 years of age (same as clopidogrel if allergy)
- Why dyspnea with ticagrelor?
- Frequency of dyspnea plavix vs. ticag
- daily asa dose
- bc of adenosine reuptake is blocked by ticagrelor.
- 7.8% vs. 13,8%
- 81 mg, ticag used this to explain the North american group
Delayed absorption of antiplatets in STEMI
up to 6 hours even with the more potent agents, exacerbated by opiates.
Guidline strength for patients not at high risk for bleeding w/ ticag and prasugrel over clopidogrel
IIa
Updated guidelines 2016/2017 for duration of dapt
SIHD?
ACS?
SIHD - 6 month HBR 3 mo
ACS 12 mon HBR 6 mo
Does PCI complexity favor longer dapt
What are the complex features?
Yes if complex features consdier >=12 mo DAPT
3:2:1 (3 vessels,3 stents, 3 lesions, bifurcation with2 stents, length greater than 60 or cto
3 vessels treated
>= 3 stents placed
>= 3 lesions
Bifurcation with 2 stents
stent lenght > 60 mm
CTO
After CABG if ACS event what is dapt rec
Non ACS CABG DAPT
Should have plavix added to complete 12 mo of dapt.
IIb for clopidogrel after SIHD CABG
3 mo dapt when based on guidelines
HBR and SIHD
Plavix binding to P2Y12
Clopidogrel is first or second gent
Abs CI for Prasugrel
irreversible
seocnd I guess
prior TIA or stroke
when load with tigcag in setting of cangrelor
crushed ticag/prasugrel
any time bc both reversible
beneficial
Broad classification of vasodilators
endothelium dependent–> need to bind to a receoptor leading to the release of Nitric oxide—> Ach, serotonin,
endothelium independent –> Nitroprusside, nitroglycerine (needs o2)
Draw basic pathway of NO synthesis
Nitric diffuses across cell or endothelial dependent vasodilators bind recepto to rellease NO—> GTP —> G-cyclase–> cGMP –> relaxation
How dose ACh work
binds muscarinic receptor–> if healthy vasodil effect, if diseased vasoconstr can be used to assess endothelial dysfunction (research tool)
3 common drugs for no reflow
- Verapamil
- Adenosine
- Nitroprusside
Pressor summary chart based on pressor type
DA Alpha1, beta 1 , DA
Dobutamine b1, B2
Epi Alpaa, B1, B2
Isoproternol B1, B2
pehnyl Alpa
Vasopressin v1 v2 on smooth muscle and vaodilate
vasoreceptors and function
DA vasodil kidney
Alpha vasoconstrict peripheral
B1 increases heart rate and onctractility
B2 vasolilates sm in lung
V1 vasocon periperhal v2 free water retention
trail of CV shock
SOAP II de backer nejm NE betther than DA (also the case in septic shock)
DA more arrhtythmia.
concious sedation def
drug induced depression of consciousness during which patients respond purposefully to verbal commands either along or accomanied by tactile stim
ASA class?
Benzos and opiates have ____ effects
Minimum recovery time after concious sedation
Approprate for 1-3
Class I is normal and health,
Class II is mild systemic dz
Class III is severe systemic dz, nondecomp
Class IV severe systemic dz, decompensated
Class V moribund, survival unlikel
Synergistic
2 hours.
Reversal agents and dosages
Naloxone (Narcan) 0.4 mg duration 30 min
Flumazenil 1 mg duration 30 min
Severe MS awaiting procedure and bp drops what medication do you give
Phenyl (works rapdily and dont want to increase HR which will worsenen the gradients)
Two class one medications for monoVT
bb and amio (also good for polymorphic)
Gusto mod bleeding HR
Gusto Severe (5g)
~2
3.2
RR reduction for heparin + asa in ACS
0.67 HR (so 1/3 RR or 30%)
Metanalysis of medical rx heparin vs. enox
STEEPLE
Synergy
20% RRR combination of Essence and timi 11b
Lovenox in elective PCI (IV) vs. heparin, Montalescot et al NEJM 2006 no difference with higher bleeidng in heparin.
STEMI/NSTEMI loaded with heparin vs. enox –> no difference but if switched it was bAD
study showing if switched from lovenox to heparin it was bad
Synergy trial
***What do guidelines say about those receiving lovenox prior to PCI
if only had one dose of neox or received dose 8 to 12 hours prior to pci then give 0.3 mg/Kg IV at the time of PCI.
It also says dont switch to UFH if received lovenox (no one listens to this).
Patient had 2 doses of enox with last dose 7 hours prior do you need to give more IV
no. Need to give 0.3 mg/kg IV if 8 to 12 hours from last dose and only had one dose. This is some bs that will be on the test.
- Heparin, LMWH, fonda all act on what
- All bival trials basically show what?
- Exception
basically Xa (via thrombin 3)
vs. Heparin + GPI no diff in ischemia with much less bleeding
Except in ISAR react 3 which shwoed no differ in either but was vs heparing alon as GPIs were left off.
More recent Bival vs. Heparin trials and prolems (3)
EUomax Heat PPCI, Matrix
increased ST
problem with bival recnt trials compared to heparin
more ST.
ATLAS II TIMI 51
ACS added riva (to whatever rx on for ACS), 2.5 mg or 5 mg–> reduction in MACE at 2 years…. (still 20% reduction, with 3x riksk of bleeding and 4x increased risk for 5 mg–> FDA did not give an indiaction for this which is why we dont really do.
- Study of riva added to DAPT
- If patient come to lab after receivn fonda in ED what do you give as far as UFH
Atlas timi 51 –> 2x increased risk of bleeding.
85 IU/kg heparin IV and only 60 IU/kg if on IIb/IIIa
Anticoagulation with lysis key points
- UFH 1.5 to 2 x upper limit of lab x 48 hrs or until revasc
- Enoxaparin admin according to age weight and cr clearance given as an iv bolus followed in 15 min by SC dose, continue up to 8 days or revasc
- fonda admin with inital IV dose followed in 24 hours by daily SC injuectio as long as GFR > 30 continue up to 8 days or revasc
Bival dosing in PCI
for those who had UFH wait 30 min the 0.75 g/kg lad then 1.75 mg/kg.h infusion
if already on the infusion give an additional 0.5 mg.gkand increase infusion to 1.75 mg/kg/h
Goal ACT heparin
hepain load
250-300 hemotc and 300-350 hemochron unless on GPI then go for 200-250 on hemotec
no GPI 70-100 /kg
GPI 50-70 U/kg
If use fibrinolsysi need ___ x 48 hours or if….
incidence of hit in LMWH
Severe bleeding incidence in current trials (gusto maj hb 5 untis
antithrombotic x 48 hours or if go to cath lab and reperfuse can stop.
<1% in LWMH
<1 %
- 3 IIB/IIIa inhibitors
- Mol weight
- potency
- clearance
- t/12
eptifibatide (integralin) - comnetitive, 800, 1/2, renal, 2 hrs
tirofibran (aggrestate) competifiv, 500, 1/2, renal, 2 hrs
abciximab reopro - high affinity, 50,000, 1/2, proteolysi, 24 hrs
Which GIIb/IIIat type gives disaggregation of clots
dosing?
all of them.
Abciximab - 0.5mg. kg then 0.125 mg/kg/min for 12 hours after PCI no renal adju
Tirofiban aggrestat 25 mcg (10 mcg bolus in a trial was inferior so increased) maintenc 0.1 for 18 hours need to dose reduce by 50% if GFR < 60). one with the high bolus
Eptibifibatide (extrasylabal so double bolus) 180 mcg/kg followed by 180 mcg/kg bolus followed by a maintence dose of 2.0 mcg/kg. min reduce by 50% 18-24 hours
Worst SE of GPIIb/IIA
How long to stop prior to surgery
When give IIB/IIIa guidelines
tCP worse with abcicimab (can transfuse bc irrevs.)
4hrs for small mol 24 hours for apiximab
if not preloaded class I, otherwise only the highest risk for Mi.
Type I indicationfor IIb/IIIa
none
Cangrelor binds?
Board question
CTPT direct P2Y12 agonist. superior to clopdiogrel in 1 trial (champion pheonix)
if preloaded doesnt help. (not discussed in guidelnies)
Give clopdiogrel/prasugrel at end of infusion. pro drug short half life so will get metobolized off. (irreversible)
dont give bival w/
gibb/iiia
GL recommendation on preloading in NSTEMIU?
Why ticlopdinine go away
says to do it.
agranulocytosis (needed cbc q2weeks)
PRU associated with adverse outcomes
other association with this ?
What polymorpms is assocaited with stnet thrombosis
general recommendations for testing
> 208
Bleeding is less.
homeozygote for cyp2c19 –> note the carrier status is common *2–>east asian–> black box warning for this.
not really recommended even thought its a moraker of fecresed risk.
trial looking at PPI
Genetic testing Guidlines
cogent was negative (liberal) –> use pantoprazole
IIb or C.
FDA recs for length of rx for dapt stoppage prior to sugery?
prasugrel 7 days
Ticag 5 days
plavix 5 days
3 surgeries were bleeding risk too high for DAPT operation
intracranial
spinal
post chamber eye
