Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Unit 3 B&L > BL 02-27-14 11am-Noon Pharmacology of Anticoagulation Therapy - Leslie > Flashcards

BL 02-27-14 11am-Noon Pharmacology of Anticoagulation Therapy - Leslie Flashcards

1
Q

Classes of antithrombotic drugs:

A
  1. Heparin and oral anticoagulants (prevent clots)
  2. Fibrinolytic agents (clot busters)
  3. Anti-platelet agents (prevent clots)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Heparin and oral anticoagulants

A
  • interfere w/ coagulation cascade

- prevent formation of thrombin, which converts fibrinogen to fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Fibrinolytic agents

A
  • promote lysis of clots by increasing formation of plasmin, a serine protease that degrades fibrin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Anti-platelet agents

A
  • inhibit formation of platelet products or block

platelet adhesion, thus preventing platelet aggregation and clot formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Antithrombotic drugs affect & caution

A
  • Antithrombotic drugs disrupt hemostasis.
  • Therefore, fine balance btwn efficacy *& toxicity
  • Pts on anti-coagulant therapy must be carefully monitored to avoid hemorrhage.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Heparin - type of drug, source

A

= an anticoagulant
- occurs naturally in granules of mast cells
- extracted from porcine intestine or bovine lung for therapeutic use
-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Heparin - 3 types

A

Unfractionated Heparin

Low molecular weight heparins (LMWH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Unfractionated Heparin

A

= Proteoglycan containing covalently-linked sulfated
polysaccharide chains of varying length
- Mean MW of 12,000 daltons
- Has the highest negative charge density of any known macromolecule –> poor pharmacokinetcs & bioavailability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Low molecular weight heparins (LMWH)

A
  • lovenox, enoxaparin, dalteparin, nadroparin

- Produced by chemical or enzymatic depolymerization of heparin to 1/3 the size of heparin (~4500 Daltons)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Fondaparinux (Arixtra)

A
  • Synthetic pentasaccharide corresponding to the minimal sequence in heparin for binding antithrombin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Heparins are used for treatment and prevention of:

A
  1. Venous thrombosis & pulmonary embolism (rapid onset of action )
    - – Used w/ oral anticoagulants & fibrinolytic drugs (heparin as initiation therapy, then switch to warfarin, etc.)
  2. Unstable angina or acute MI
  3. During & after coronary angioplasty or stent placement.
  4. During surgery requiring cardiopulmonary bypass.
  5. Kidney dialysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Toxicity of heparins

A
  • Bleeding
  • Heparin-induced thrombocytopenia syndrome (HIT)
  • Allergic events
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Bleeding w/heparin

A
  • Anticoagulant effect of heparin disappears w/in hours of discontinuation of drug
  • If life-threatening hemorrhage occurs, effect of heparin (and LMWH) can be reversed w/ protamine sulfate (+charged compound that neutralizes heparin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Heparin-induced thrombocytopenia syndrome (HIT)

A
  • Platelet count decreases (>50%) in 3-5% of patients 5-10 days after heparin
  • Caused by development of Abs to platelet factor 4/heparin complexes
  • These Abs bind to & activate platelets resulting in a prothrombotic state (venous thromboembolism, arterial thrombosis, MI, stroke)
  • Thrombocytopenia is less common with LMWH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Treatment of HIT (heparin-induced thrombocytopenia syndrome)

A

Direct thrombin inhibitors:

  • Argatroban (Novastan) - small molecule inhibitor
  • Lepirudin (Refludan) - Recombinant form of hirudin, the anticoagulant from leeches
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Allergic events w/ heparin

A
  • Due to contaminant oversulfated chondroitin sulfate (rarely if ever found in nature).
  • Activation of contact system (production of bradykinin & complement activation).
  • Development of improved screening methods
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Warfarin (coumadin)

A
  • the most commonly used oral anti-coagulant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Source/structure of Warfarin

A

= a derivative of dicumarol, which was discovered as a component in spoiled sweet clover responsible for a hemorrhagic disease in cattle
- Warfarin (Wisconsin Alumni Research Foundation) initially was made (1948) for rodent control
= a vitamin K analogue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Action of Warfarin

A

= inhibits enzymes that use vitamin K as a
cofactor (acts as VitK cofactor)
- Several coagulation proteins (II, VII, IX & X) undergo vitamin K-dependent gamma carboxylation of N-terminal glutamates
- Vitamin K undergoes oxidation/reduction during the rxn

  • Recycling of vitamin K to reduced form by reductases is inhibited by warfarin
  • –> depletion of vitamin K
  • Coagulation proteins lacking gamma carboxylation cannot bind calcium and are non-functional.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Pharmacokinetics of warfarin

A
  • rapidly absorbed (90 min)
  • good bioavailability
  • long half-life (36-48 hr).

Full antithrombotic effect of warfarin not achieved until existing coagulation factors in circulation are removed (requires 2-3 days), then they can be replaced by the inactivated factors
—> takes time (3-5 days til action)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Warfarin is used to prevent:

A
  • Venous thromboembolism (in combo w/ heparin, which acts more rapidly)
  • Systemic embolism in patients w/ prosthetic heart valves or atrial fibrillation
  • Stroke, recurrent infarction, or death in pts w/ acute MI
22
Q

Adverse effects of Warfarin

A

Hemorrhage

  • Drug is stopped & vitamin K is administered (takes 24-48 hr for reversal since coagulation factors have to be resynthesized)
  • Can transfuse plasma to replace coagulation factors

Teratogenic
- Cannot be used during pregnancy since it crosses the placenta & is teratogenic

23
Q

Drug and food interactions with Warfarin: Increasing Warfarin affect

A
  • Drugs that inhibit platelet function (aspirin).
  • Drugs that decrease vitamin K synthesis by intestinal microbes (antibiotics).
  • Drugs that displace warfarin from plasma proteins, effectively increasing [active free drug] (clofibrate, phenytoin)
  • Drugs that reduce metabolism & elimination of warfarin in liver (cimetidine, amiodorone, phenylbutazone).
24
Q

Drug and food interactions with Warfarin: Decreasing Warfarin affect

A
  • Drugs that increase the metabolism by inducing metabolic enzymes in the liver (barbiturates, rifampin).
  • Drugs that decrease warfarin absorption from the GI tract (cholestyramine).
25
Q

New oral anticoagulants - Direct thrombin or Factor Xa inhibitors - Advantages

A
  • Rapid onset of action
  • Absence of food interactions
  • Do not require monitoring (though this is being rethought)
26
Q

New oral anticoagulants - Direct thrombin or Factor Xa inhibitors - Disadvantages

A
  • Contraindicated w/ kidney disease
  • Greater GI bleeding than w/ warfarin
  • Short half-life (2 per day –> compliance issues)
  • Cost (20X>warfarin)
  • No antidote available to reverse effects
27
Q

Dabigatran etexilate (Pradaxa)

A
  • new oral anticoagulant
  • direct thrombin inhibitor
  • FDA approved 2010 in atrial fibrillation
  • Oral prodrug converted to dabigatran, a potent, direct inhibitor of thrombin.-
  • Lower rates of stroke & systemic embolism than with warfarin
  • Less intracranial hemorrhage (but increased MI)
  • Should not be used in pts w/ prosthetic heart valves (inferior to warfarin)
28
Q

Apixaban (Eliquis)

A
  • new oral anticoagulant
  • Factor Xa inhibitor
  • FDA approved 2012 for atrial fibrillation
29
Q

Rivaroxaban (Xarelto)

A
  • new oral anticoagulant
  • Synthetic anti-coagulants that directly inhibit Factor Xa
  • FDA approved 2011, 2012 for atrial fibrillation, VTE
  • Superior to warfarin in preventing strokes & emboli for treatment of atrial fibrillation
30
Q

Fibrinolytic Agents - action

A

Convert plasminogen to plasmin, a protease that degrades fibrin clots

31
Q

Tissue plasminogen activator (t-PA) (Alteplase)

A
  • a fibrinolytic agent
  • Serine protease produced by recombinant DNA technology
  • Newer modified forms can be given as bolus injections & have prolonged half-life (retoplase, lanoteplase, tenecteplase)
  • The t-PA type fibrinolytic drugs bind fibrin, which increases cleavage of plasminogen to plasmin.
32
Q

Urokinase (u-PA) (Abbokinase)

A
  • a fibrinolytic agent
  • Enzyme obtained from renal cells in culture that
    converts plasminogen to plasmin
  • Does not bind fibrin
33
Q

Streptokinase (Streplase)

A
  • a fibrinolytic agent
  • Non-enzymatic protein obtained from β-hemolytic
    streptococci (less expensive than t-PA)
  • Forms complex w/ plasminogen, which becomes activate and converts to plasmin
34
Q

Fibrinolytic agents are used for treatment of…

A
  • Acute MI (AMI) - Used in combo w/ aspirin, ASAP after MI (or else not effective)
  • Ischemic stroke - Effective if given w/in 3 hr after
  • DVT - Used in conjunction w/ heparin / warfarin treatmen
  • PE
35
Q

Adverse effects of Fibrinolytic agent

A
  • Hemorrhage from lysis “physiologic thrombi” at sites of vascular injury
  • Induces systemic lytic state due to increased formation of plasmin which destroys other coagulation factors (V,VIII).
  • Allergic rxn & formation of Abs to streptokinase
36
Q

Antiplatelet Drugs - use

A
  • Platelets provide initial hemostatic plug at sites of vascular injury & contribute to pathological thrombi
  • Antiplatelet drugs treat acute coronary syndrome (angina, MI) characterized by atherosclerotic plaque rupture & platelet-mediated thrombosis
37
Q

Three classes of anti-platelet drugs

A
  1. inhibit formation of platelet products (aspirin)
  2. prevent activation/aggregation (ADP receptor antagonists)
  3. block adhesion proteins (glycoprotein
    IIb/IIIa inhibitors)
38
Q

Aspirin (acetylsalicylic acid)

A
  • anti-platelet drug
  • Irreversibly inactivates COX, preventing thromboxane A2 formation by platelets
  • Since platelets cannot synthesize new proteins (i.e. COX) the effect is permanent, lasting the life of the platelet (7-10 days)
  • used in combination w/ thrombolytic therapy after AMI & thrombotic stroke
  • Used for prevention of AMI & stroke in high-risk pts with atherosclerosis
39
Q

ADP receptor antagonists

A
  • Thienopyridines (clopidogrel (Plavix), ticlopidine (Ticlid), prasugrel
  • Ticagrelor (approved 2010)
40
Q

Thienopyridines - examples

A 
= ADP receptor antagonists
Examples:
- clopidogrel (Plavix)
- ticlopidine (Ticlid)
- prasugrel.
41
Q

Thienopyridines - action

A

= Oral antiplatelet agents that bind to ADP receptor (P2Y12) on platelets

  • block platelet activation by ADP, which inhibits secretion of alpha granules & blocks expression of adhesion proteins GPIIb/IIIa
  • binds irreversibly to platelets —> effect lasts for platelet life span (7-10 days)
42
Q

Thienopyridines - pharmacokinetics

A
  • rapidly absorbed
  • BUT have slow onset of action (max effect in 5-7
    days) b/c prodrugs (metabolized in liver to active
    intermediate –> variable patient responses)
43
Q

Thienopyridines - uses

A
  • Prevention of cardiac events in pts w/ atherosclerosis & unstable angina in combo w/ aspirin
  • Pts w/ aspirin intolerance
  • Clopidogrel has fewer adverse effects but Prasugrel is most potent (shown in clinical trails to be better than clopidogrel in preventing death & MI (increased risk of bleeding & cancer))
44
Q

Ticagrelor - action

A
  • Oral ATP analogue that binds reversibly to ADP receptor P2Y12
45
Q

Ticagrelor - use/pharmacokinetics

A
  • More rapid action than thienopyridines since it does not require metabolic activation
  • Greater platelet inhibition than clopidogrel.
  • in treatment of acute coronary syndrome, ticagrelor reduced rate of death w/out an increase in overall major bleeding (compared to clopidogrel)
46
Q

Glycoprotein IIb/IIIa (GPIIb/IIIa; αIIbβ3)

A

= an adhesion protein (integrin) on the surface of platelets that is a receptor for fibrinogen

47
Q

Glycoprotein IIb/IIIa (GPIIb/IIIa; αIIbβ3) inhibitors - action

A

= block receptor for fibrinogen (Glycoprotein IIb/IIIa) on surface of platelets —> prevent platelet aggregation

48
Q

Glycoprotein IIb/IIIa (GPIIb/IIIa; αIIbβ3) inhibitors - examples

A

Abciximab (Reopro)

Eptifibatide (Integrilin)

49
Q

Abciximab (Reopro)

A

= Monoclonal antibody fragment against glycoprotein receptor, GPIIb/IIIa

  • used following coronary angioplasty & for unstable angina
  • Prevents restenosis, recurrent AMI & death when used w/ aspirin & heparin
  • Also used in combo w/ thrombolytic drugs for AMI.
  • Given IV, inpatient use only
50
Q

Eptifibatide (Integrilin)

A

Cyclic peptide inhibitor of binding site on GPIIb/IIIa that is used for unstable angina & during angioplasty

51
Q

Tirofiban (Aggrastat)

A

Small molecule inhibitor used for treatment of unstable angina & MI

52
Q

Adverse effects of Glycoprotein IIb/IIIa inhibitors

A
  • bleeding & thrombocytopenia

- can be reversed by platelet infusions

Unit 3 B&L (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions