Anticoagulants Flashcards

(41 cards)

1
Q

Anticoagulants

A

Heparin, Enoxaparin, Lepirudin, Dabigatran, Rivaroxaban, Warfarin

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2
Q

Fibrinolytics

A

Streptokinase, Alteplase

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3
Q

Antithrombotics

A

Aspirin, Clopidogrel, Vorapaxar, Abciximab

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4
Q

Thrombogenesis

A

Immediate hemostatic response of a damaged vessel, Vasospasm
Within seconds, Platelets stick to the exposed collagen of the damaged endothelium, Platelet adhesion
& then to each other, Platelet aggregation
Platelet plug quickly arrests bleeding
Must be reinforced by fibrin for long-term effectiveness

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5
Q

White thrombus

A

Forms in high-pressure arteries & decreases arterial flow, Stasis triggers fibrin formation → Stroke, MI

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6
Q

Red thrombus

A

Can form around a white thrombus or in low-pressure veins, Platelets form a long tail consisting of a fibrin network in which RBC are enmeshed → DVT → PE

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7
Q

Blood Coagulation

A

Blood coagulates by the transformation of soluble fibrinogen → insoluble fibrin
At each step of this cascade, a clotting factor, i.e., zymogen undergoes limited proteolysis & becomes an active protease, VII is activated to VIIa
Protease activates the next clotting factor, Until a solid fibrin clot is formed

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8
Q

Regulation of Coagulation & Fibrinolysis

A

Blood coagulation must be confined to the smallest possible area to achieve local hemostasis in response to bleeding, Without causing disseminated coagulation or impaired blood flow

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9
Q

Blood contains ________ that rapidly inactivate the coagulation proteins as they leave the site of injury, e.g.,

A

protease inhibitors; antithrombin

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10
Q

Critical step in fibrinolysis

A

Conversion of inactive plasminogen into the proteolytic enzyme plasmin

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11
Q

Heparin

A

about 50 monosaccharides in a chain
Greatly increases the rate of activity of antithrombin, Heparin (-) binds with antithrombin (+) which inhibits serine protease clotting enzymes

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12
Q

Heparin inhibits

A

Inhibits clotting factors IIa (thrombin) & Xa, (IXa, XIa, & XIIa)

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13
Q

Heparin uses

A

Thrombosis/Embolism: Prophylaxis (e.g., after major surgery) & active Treatment (e.g., PE, DVT)
Disseminated Intravascular Coagulation (DIC)

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14
Q

Heparin side effects

A

Hemorrhage (<10%) anywhere in the body (e.g., GI)
Allergy (chills, fever, urticaria)
Thrombocytopenia (HIT) (Heparin induces antibodies which destroy platelets, also attack the lining of blood vessels which can trigger a coagulation cascade
HIT can cause stroke & other thrombotic complications which can be life threatening)

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15
Q

Heparin antidote/Hep’s activity measured by

A

protamine; aPTT

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16
Q

Heparin drug interactions

A

Cephalosporins, penicillins, NSAIDs (ex aspirin)

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17
Q

Enoxaparin mech of action

A

(smaller version of heparin) more sensitive for Xa than IIa

18
Q

Enoxaparin therapuetic uses

A

DVT prophylaxis
DVT Tx (+/- PE)
Unstable angina/Non-Q-wave MI

19
Q

Enoxaparin side effects/drug interactions

A

similar effects to heparin, also hematomas; interacts w/ same drugs as heparin

20
Q

Rivaroxaban mech of action; thera uses

A

Direct Xa inhibitor; Atrial fibrillation: Prevent → Stroke, Systemic embolism
Prophylaxis of DVT: Knee, Hip replacement

21
Q

Rivaroxaban side effects and pharmacodynamics

A

Hemorrhage: Spinal or Epidural anesthesia or puncture; CYP3A4, P-gp
Severe renal & hepatic impairment (↑AUC)

22
Q

Lepirudin; thera use

A

Polypeptide analog of hirudin → Hirudo medicinalis (leech); Heparin-induced thrombocytopenia

23
Q

Lepirudin, Argatroban, Dabigatran mech of act

A

Inhibits thrombin (IIa) by binding to it (1:1 stoichiometry)

24
Q

Lepirudin side efect; pharmocokinectics

A

Allergy- Antibody inhibition b/c of yeast expression; Adjust dose with hepatic function

25
Dabigatran; Therapeutic uses
Prodrug; Atrial fibrillation: Prevent systemic embolism, Stroke
26
Dabigatran side effects; pharmaco
Hemorrhage (intracranial bleeding), Less bleeding with dabigatran vs. warfarin, GI (dyspepsia, gastritis); Adjust dose with renal function, Rifampin (P-gp)
27
Warfarin
Racemic mixture, S-enantiomer 4 x more potent; Therapeutic efficacy, Measured by international normalized ratio (INR), Therapeutic range, 2.0 to 3.0
28
Warfarin mech of action and therap uses
Vitamin K analog & thus blocks the gamma-carboxylation of several glutamate resides in clotting factors II, VII, IX & X; Venous thrombosis: prophylaxis & treatment Atrial fibrillation: prevent embolization
29
Warfarin side effects
``` Hemorrhage Necrosis (gangrene of the skin) Hypercoagulation (transient) Warfarin blocks the biosynthesis of protein C which inactivate clotting factors Va, VIIIa (via proteolysis), Because of the slow onset of anticoagulation with warfarin therapy, Heparin tx is used for the 1st 5 days Birth defects (facial, CNS) Abortion ```
30
treatment of warfarin hemorrhaging
D/C warfarin, Give Vitamin K1 (phytonadione), Give Plasma, Give Factor IX concentrate
31
warfarin drug interactions
Bleeding PK: Amiodarone, Metronidazole, Fluconazole Sulfamethoxazole/Trimethoprim, Clopidogrel PD: Aspirin, Ceftriaxone, Ginkgo biloba Clotting PK: Phenobarbital, Rifampin, Carbamazepine, St. John’s Wort, Cholestyramine PD: Vitamin K, Hydrochlorothiazide
32
mech of action of Streptokinase, Alteplase
Converts plasminogen into plasmin which degrades fibrin & fibrinogen
33
thera uses Streptokinase, Alteplase
``` Acute myocardial infarction (S,A) Pulmonary embolism (S,A) Deep vein thrombosis (S) Arterial thrombosis & embolism (S) Occluded arteriovenous cannulae (S) Acute ischemic stroke (A) ```
34
side effects Streptokinase, Alteplase
Hemorrhage Lysis of fibrin at vascular injury Systemic plasmin inhibits factors V & VIII Allergy (anaphylaxis, S)
35
aspirin mech of action
Inhibits the synthesis of thromboxane A2, Irreversible acetylation of COX-1/2, Anuclear platelet, Can’t synthesize more COX during its 10-day lifetime Thromboxane A2 function: platelets c shape, release granules, & aggregation
36
aspirin uses, side effects
1o prophylaxis of MI & TIA ; | Bleeding, GI Ulcers
37
Clopidogrel mech of action and therapeutic use
P2Y12 receptor antagonist, therefore it interferes with platelet membrane function by inhibiting ADP-induced platelet-fibrinogen binding & subsequent platelet-platelet interaction ; Arterial thromboembolism prophylaxis: Prevent Myocardial infarction, Stroke
38
Clopidogrel side effects and pharmacodynamics
Thrombocytopenia, Leukopenia, Thrombotic Thrombocytopenic Purpura; Bioactivated 1o by CYP2C19 & Inhibitor of CYP2C9
39
Vorapaxar mech of action and thera use
Mechanism of action: Protease-activated receptor-1 (PAR-1) antagonist, Inhibits thrombin mediated activation of platelets Therapeutic use: Myocardial infarction, Peripheral artery disease, ↓ thrombotic cardiovascular events, With ASA + Clopidogrel
40
Vorapaxar side effects and drug interactions
Hemorrhage: contraindicated in patients with 1. active bleeding conditions, 2. history of TIA, 3. stroke & 4. intracranial bleeding, Anemia, Retinopathy (diplopia); CYP3A4 substrate, Anticoagulants (e.g., NSAIDs, SSRIs, warfarin)
41
Abciximab mech of action, thera use, side effect
Mechanism of action Inhibits the glycoprotein IIb/IIIa receptor of platelets → ↓ platelet aggregation w/ fibrinogen & vWF Therapeutic use Acute coronary syndrome: percutaneous coronary intervention (PCI) used with aspirin &/or heparin Side Effect Thrombocytopenia