Antithrombotic pharmacotherapy Flashcards
for each disease, name the thorombus location:
- atrial fibrillation
- myocardial infarction
- DVT/PE
- Stroke
-Critical limb ischemia
- atrial fibrillation: atrial appendage
- myocardial infarction: coronary artery
- DVT/PE: deep vein (femoral)/ pulmonary artery
- Stroke: CNS circulation
-Critical limb ischemia: peripheral circulation (legs)
What are two critical elements in thrombus formation? what element is critical for thrombolytics? List the drugs for each.
Fibrin–> anticoagulants:
- heparin
- warfarin
- direct thrombin inhibitors
- factor 10 inhibitors
Activated platelets –> antiplatelets
- aspirin
- ADP blockers
- IIb/IIIa inhibitors
- PDE inhibitors
Thrombolytics
-tPA
Different disorders = different Rx
Acute MI:
antigocagulants:
heparin, direct thrombin inhibitors
antiplatelets:
aspirin, IIb/IIIa
** Thrombolytics **
Different disorders = different Rx
A fib
anticoagulant: heparin
Different disorders = different Rx
Stroke
Anticoagulants: heparin
Antiplatelets: aspirin
thrombolytics
Different disorders = different Rx
DVT/PE
anticoagulant: heparin
thrombolytics
Different disorders = different Rx
limb ischemia
anticoagulant: heparin
thrombolytics
Different disorders = different Rx
chronic/prevention
coronary disease
antiplatelet: aspirin
Different disorders = different Rx
Chronic/prevention
A fib
Anticoagulant: warfarin
Different disorders = different Rx
Chronic/prevention
Stroke
antiplatelet: aspirin, clopidogrel (ADP blockers)
anticoagulant: warfarin
Different disorders = different Rx
chronic/prevention
DVT/PE
anticoagulant: warfarin
Different disorders = different Rx
chronic/prevention
Peripheral vascular disease
antiplatelet: aspirin
“white” vs “red” thrombus
Red: more fibrin than platelets
venout clots (DVT, PE) —> antithrombotics
White: more platelets than fibrin
arterial clots (MI, Stroke) –> antiplatelets
extrinsic vs intrinstic pathway
extrinsic: need to add tissue factor (factor VII)
intrinsic: TF exposed to bloodstream when endothelial damage (silica added, starts with factor X)
drugs related to the factor that converts prothrombin (II) to thrombin (IIa)
Factor X related drugs:
- unfractionated heparin (indirect)
- low molecular weight heparin (indirect)
fond aparinux
rivaroxaban (direct inhibitors po)
apixaban (direct inhibitor, po)
What do indirect Factor X related drugs target?
activate/amplify anti thrombin III
anti thrombin III blocks prothrombin and factor Xa activation
direct thrombin inhibitors and uses
hirudin, lepirudin, bivalirudin
uses: pt with heparin-induced thrombocytopenia (HIT) or A fib
If you administer someone with UF heparin and the PPT does not elevate as it should, what is a possible expalantion? (recall PTT measures intrinsic pathway)
Anti-thrombin deficiency –blunted response to heparin
(UF heparin activates AT III)
UF Heparin:
- administration of drug
- action, effect
- uses
- side effects
- IV drug, acute onset
- increases PTT
- lots of binding to plasma proteins, cells
- highly variable response, dose must be adjusted to reach goal PTT
- acute management: DVT/PE, Mi, stroke, prophylaxis for DVT in hospitalized pts
- side effects: bleeding, thrombocytopenia, osteoporois, mild increased AST/ALT
Heparin Induced Thrombocytopenia
severe- immune mediated reaction, binds platelet factor 4
LMWH (low molecular weight heparin), Enoxaparin
-similarities/differences to UFH
- works just like UFH
distinction: does NOT inhibit 2–>2a (note that UF heparin and LMWH activate AT III, which inhibits 10–>10a and 2—>2a) - more predictable effects (dose based on weight, no titrating, reduced binidng to plasma proteins and cells)
- given subcutaneously
- not reverseible, meanwhile UFH is
protamine
reverses effects of UF heparin
what do you check if monitoring LMWH?
anti-10a levels (obesity and renal failure pts can have variable response)
3 drugs that block deactivated platelet conversion to activated platelet
- aspirin
- ADP receptor blockers
- PDE inhibitors
action of aspirin, uses, side effects
- irreversibly inhibits cox
- 7-10 day clearance
- uses: acute MI, acute stroke, MI/stroke preventions
side effects: gastric ulcers, tinnitus, reye’s syndrome
Reye’s Syndrome
- effect
- symptoms
- mechanism
- encephalopathy, liver failure, fatty infiltration
- vomiting, confusion, seizures, coma
- caused by diffused mitochondrial insult
- follows viral illness (varicella, influenza)
- associated wiht aspirin use in children (never give ASA to children, exception is Kawasaki disease)
Ticlopidine, Clopidrogrel, Prasugrel
- mechanism
- uses
- side effects
ADP receptor blockers (antiplatelets)
- irreversible (5 day clearance)
- uses: when allergy to aspirin, added to aspirin after coronary stenting or for stroke prevention
- side effects: ticlopidine-thrombotic thrombocytopenic purpura
Cilostazol, Dipyrimadole:
- mechanism
- use
- side effects
PDE inhibitors (antiplatelet)
- inhibits PDE III —–| cAMP + platelets
- uses
cilostazol: claudication, improves leg pain
dipyrimiadel + aspirin (aggrenox): stroke prevention
-side effects: vasodilation –> nausea, headache, flushing, hypotension, abdominal pain
Abciximab, Eptifibatide, Tirofoban
- type of drug + mechanism
- uses
- side effects
- antiplatelets - IIb/IIIa (glue) inhibitors
- uses: unstable angina, acute MI, after stent implantation
- side effects: thrombocytopenia
Vitamin K factors:
2, 7, 9, 10 (1972)
Warfarin
- mechanism
- uses
- side effects
- antagonist Vit K, lowers all levels of Vit K factors
- takes DAYS to reach effective dose
- dose ajusted to reach target PT/INR
- level affected by diet, drugs (antibiotics increase INR)
- crosses placenta
- side effects: bleeding, skin necrosis
- uses: stroke prevention, chronic/preventitive A fib, mechanical heart valves, prior DVT/PE
Treatment with this drug causes initial protein C deficiency
Warfarin -
protein C (anticlotting factor) is also vitamin K dependent
-causes brief increased risk of clotting, very low risk, eventually other factors fall
For active clot disorders (PVT/PE), always start _____ first for its acute onset
one exception: start _____ by itself first for A fib
Heparin first
warfrin for A-fib, no active clot, just risk
Indications for Chronic Oral Anti-coagulation (3)
- A-fib
- mechanical heart valve
- Prior DVT/PE
(Prior standard: warfarin –low cost but required montly blood draws for INR checks)
Dabigatrant, Bivalarudin
Direct thrombin inhibitors
Novel Oral anticoagulants (NOACs)
warfarin alternatives:
- factor 10a inhibitors
- direct thrombin inhibitors
pros: no INR checks, consistent dose
cons: $$, no reversal angets, only provein effect in A-fib
Thrombolytics
increase plasmin activation
(plasminogen –> plasmin —> breaks down fibrin into degradation products
tPA, streptokinase, urokinase
*powerful clot busters- use for acute MI, stroke, but serious bleeding risk
Lab tests to monitor drug effects:
Intrinsic
Extrainsic
INR
2 rare measurements
Intrinsic: activated partial thrombolastin time (PTT)
- add plasma to negative charged silica
- time to form clot (nl = 30 sec)
Extrinsic: Prothrombin Time (PT)
- add plasma to TP
- time to form clot (nl = 10 sec)
INR = patient PT/control PT (nl = 1, therapeutic = 2-3, higher # = slower clot time)
**2 rare measurements: **
thrombin time, bleeding time
which test measures heparin? which one measures warfarin?
PTT (intrinsic) = heparin
PT/INR (extrinsic) = warfarin
Drug reversal treatment
and INR protocol
- fresh frozen plasma (FFP)
- Vitamin K
- INR 3-5: hold warfarin*
- INR 5-9: hold warfarin, oral Vit K*
- INR > 9: IV Vit K, FFP*
