Brainscape's Knowledge GenomeTM

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


See full index

12. Pharmacology > Anticoag/thrombotic drugs > Flashcards

Anticoag/thrombotic drugs Flashcards

1
Q

Goal of tx

A

protect against risk of bleeding
o Coronary endothelial damage → feature of ischemic heart disease
 Constant risk of antiaggregatory forces < proaggregatory forces
 Risk of further vascular damage → thrombosis

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

3 main types of agents

A

o Platelet inhibitors
o Anticoagulants
o Fibrinolytic agents

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

4 steps of thrombus formation

A

a) Exposition of subendothelial tissue factor (endothelial damage)
b) Activation of coagulation factors → generate thrombus
o Conversion of fibrinogen → fibrin
c) Platelet adhesion, activation, aggregation → action of thrombin
o Platelet activation: shape and conformational changes
o Activated platelet R → promote aggregation → formation of primary platelet plug
o Thrombin generated by platelets and coag factors
 Stimulate further platelet activation/aggregation
 Forms fibrin → stabilized platelet plug
o Platelet release substances further promoting activation and aggregation
d) Thrombus formation
o Fibrin forms polymer cross-link
o Aggregated platelets tightly combine

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

Essential components of thrombus formation

A

Tissue factor
Thrombin
Von Willebrand factor

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

What is tissue factor

A

Cell surface glycoprotein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Tissue factor expression is increased w/

A

 ↑ expression in damaged endothelial cells and exposed subendothelial cells
 Derived from microparticles released in plaque rupture

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

Tissue factor activation leads to

A

o Form a complex/activate factor VII
 Factor VIIa → activate directly factor X and indirectly by factor IX
 Factor Xa convert prothrombin → thrombin

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

Role of thrombin and effect

A

o Thrombin activate protease activated R on platelets → rapid platelet activation
o Positive feedback on coag pathway → activate factor V, VIII, XI, XIII
 XIIIa: necessary for full stabilization of fibrin clot

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

Role of intrinsic pathway

A

o Start with activation of several factors: XII, XI, IX, X
o Xa: Acts on prothrombin to form thrombin
 Convergence of intrinsic and extrinsic pathways → common pathway

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

Von Willebrand factor: normal

A

o Normally present in high levels but inactive in plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Von willebrand factor activation

A

o Immobilized and activated at site of injury
 Interact with platelet R glycoprotein Ib-α (GpIbα)
* Tether platelets to the site of injury
 Release Ca2+ from endoplasmic reticulum
* Helps activate platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Propagation of clot mechanism: other substances

A

o Secretion of plasminogen activator inhibitor (PAI-1)
 ↑ clot resistance to lysis
o Secretion of thromboxane A2 (TXA2)
 Vasoconstriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Platelet activation

A

o Transition from low to high affinity binding state
 Inside-outside activation
o Thrombin: potent activator
 Release of more thrombin by platelets
 Release of adenosine diphosphate (ADP)
 Release of TXA2
o Bind to respective platelet-R → promote further activation = self amplification
 Activated-R bind more vWF, subendothelial collagen and fibrinogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Platelet shape change

A

o Activated platelets have activated contractile prots
o Formation of new actin filaments
o TXA2 + thrombin R binding → activation of MLCK → platelet conformation change
 ↑ surface membrane available for platelet activation
 Promotion of R conformational change → further activate platelets
 Release of ADP, TXA2, thrombin → activate other platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens w/ platelet intracell Ca2+

A

o ↑ intracell [Ca2+] during activation
 Stimulate formation of TXA2
 Activate platelet contraction/shape change
* Conformational activation of GpIIb/IIIa
* Adhesive prot + fibrinogen interlink platelets
 ↑ADP release from platelet granules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Platelet rapid propagation

A

o ↑ local [thrombin] → local fibrin → polymerize in end-to-end or side-to-side reaction → fibrin clot
 Changes factor XIII → XIIIa which cross link fibrin units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Antiplatelet agents

A

Aspirin
Clopidogrel/ticlopidine
Dipyridamole
Sulfinpyrazone
Prasugrel
Ticagrelor
Cangrelor
Vorapaxar
Atopaxar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Aspirin: molecule

A

acetylsalicylic acid

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

Aspirin: MOA

A

Irreversible acetylation of cyclooxygenase (COX)
o Isoform COX-1 inhibition
 ↓ TXA2 synthesis → ↓ thrombin formation
 No strong effect on COX-2 → prostaglandin production pathway
* Contribute to inflammatory response
o Inhibition for complete life span of platelet: 8-10 days
 Effective until new platelets form
o Vascular COX: can be reformed w/I hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Aspirin: side effects

A

o Bleeding = most serious
o GI side effects: indigestion, nausea, vomiting
 Gastric irritation and ulcerations → related to dose
* Can give w food or coated to ↓ risk (may also ↓ bioavailability)
* H+ pump inhibitors: ↓ risk of side effects

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

Aspirin resistance

A

o Defined as: failure of suppression of TXA2 generation
 ↑urinary TXA2 metabolite
 Recurrent vascular event despite adequate tx dose
* 50% of cats after 1st vascular event
o 5-20% of patients will experience recurrence of thrombotic event
 Continuous spectrum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Aspirin resistance mechanisms

A

 Platelet Gp polymorphism
 Activation of platelets by pathways other than COX
 ↑ inflammatory activity from ↑ COX-2 expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Aspirin: clinical uses

A

o Prophylaxis: after previous myocardial infarction or stroke
o Effort unstable angina
o Coronary artery bypass sx

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Aspirin: CI

A

o Aspirin tolerance
o Hx of GI bleeding/peptic ulcer
o Renal disease: retard urine excretion of create and uric acid
o Hemophilia: not absolute if strong CV indication
o Relative: gout, indigestion, iron-deficiency anemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Aspirin: drug interactions

A

o Warfarin: ↑ risk of bleeding
o NSAIDs with dominant COX-1 activity
 Ibuprofen and naproxen: ↑ risk of GI bleeding
o Corticosteroids: ↑ risk of GI bleeding
o ACEi: opposite effects on renal hemodynamics
 Aspirin inhibit vs ACEi promote vasodilatory PGs
o Phenobarbital, phenytoin, rifampin: ↓ efficacy by induction of hepatic enzymes
o Thiazides: ↓ urinary excretion of uric acid → ↑ risk of gout

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Clopidogrel/Ticlopidine: molecule

A

o Thienopyridine derivatives
 1st generation = ticlopidine
 2nd generation = clopidogrel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Clopidogrel/Ticlopidine: MOA

A

o Irreversible binding to the P2Y12 R
 ADP released by platelets during activation → interact with
* P2Y1 R → platelet shape change + GpIIb/IIIa activation
* P2Y12 R → perpetuate GpIIb/IIIa activation + stabilize platelet aggregation
* Activate IV tissue factor indirectly
 Inhibition of P2Y12 R =prevent transformation and activation of GpIIb/IIIa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

PharmacoK ticlopidine

A

 ↓ clearance on repeated dosing
 4-7 days to achieve max inhibition of platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Metabolism ticlopidine

A

 Metabolism: liver, excretion: kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Clopidogrel: pharmacoK, onset of action

A

 Onset of action: hrs after oral dose
* Steady state inhibition requires 3-7 days
* ↓ clearance with repeated dosing
 Takes 5 days to generate new platelets and reduce bleeding after stopping
 Variation in platelet reactivity to clopidogrel: can cause clinical resistance
* ↑ compared to newer drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Clopidogrel: metabolism

A

 Hepatic or intestinal metabolism: activation by cytochrome CYP3A4 and 2C19
* Atorvastatin and omeprazole inhibit hepatic activation → ↓ effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Clopidogrel side effects

A

 Low rate of myelotoxicity (0.02% of cases)
 ↓ GI bleeding compared to aspirin
 Major side effect: ↑ major bleed w/o ↑ intracranial bleed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Ticlopidine side effects

A

rarely used because of side effects compared to clopidogrel
 Neutropenia: 1st 3mo of tx (2.4% of cases)
 Liver abnormalities
 Thrombotic thrombocytopenic purpura

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Clopidogrel: drug interaction

A

o Statin and H+ pump inhibitors (omeprazole)
 Inhibit hepatic activation (theory, not proven by studies)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Dipyridamole: MOA

A

bind prostacyclin R on platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Dipyridamole: MOA

A

prosthetic mechanical valves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Dipyridamole: drug interaction

A

adenosine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Sulfinpyrazone MOA

A
  • Mechanism: inhibit COX
    o Similar effect to aspirin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Newer anti platelet drugs

A
  • Prasugrel
    Ticagrelor
    Cangrelor
    Vorapaxar
    Atopaxar
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Pasugrel: molecule

A

o Newer generation thienopyridine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Pasugrel: MOA

A

o Mechanism: Irreversible/noncompetitive inhibition of P2Y12 R
 5-9x more potent vs clopidogrel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Pasugrel: pharmacoK

A

 Prodrug: hydrolyzed in GI → thiolactone → converted in liver by CYP3A4 and CYP2B6
* CYP inhibitors (diltiazem, verapamil): not alter activity but ↓ peak [plasma]
 Onset of action 5-10 days
 ½ life = 7h

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Pasugrel: side effects

A

risks of serious bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Ticagrelor: molecule

A

o Cyclopentyl-triazolopyrimidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Ticagrelor: MOA

A

reversible binding/noncompetitive inhibition of P2Y12 R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Ticagrelor: pharmacoK

A

 More rapid/consistent onset of action → 3-4 days
* ½ life = 12h
 More rapid offset of action
 No hepatic activation needed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Ticagrelor: drug interaction

A

 Amlodipine, statins, diltiazem, verapamil: inhibit CYP3A → ↑ levels and reduce speed of offset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Ticagrelor: side effects

A

 Bleeding
 Dyspnea
 ↑ frequency of ventricular pauses
 ↑ uric acid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Cangrelor: MOA

A

Potent competitive inhibitor of P2Y12 R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Cangrelor: pharmacoK

A

 Rapid acting: IV effect in 20min → 85% inhibition of ADP induced platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Vorapaxar MOA

A

o Mechanism: potent competitive PAR-1 antagonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Atopaxar MOA

A

o Mechanism: reversible protease activated R-1 thrombin R antagonist
 Interfere in platelet signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Vorapaxar side effects

A

o Significant ↑ risk of major bleeding, including intra cranial

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Dual anti-platelet therapy

A
  • Aspirin + clopidogrel
    o 20% reduction in ↓ vascular events
    o Different mechanism of action → should create strong combination
  • Aspirin + newer anti platelet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Glycoprotein IIb/IIIa R-antagonist MOA

A

inhibition of platelet adhesion R GpIIb/IIIa
o Block final platelet activation and cross-linking by fibrinogen and vWF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Glycoprotein IIb/IIIa R-antagonist: side effects

A

acute thrombocytopenia and ↑ risk of delayed thrombocytopenia
o Risk range from 0.3 to 6%
o Secondary to drug dependent anti bodies

57
Q

Glycoprotein IIb/IIIa R-antagonist: CI

A

o Bleeding or ↑ risk for bleeding
o Thrombocytopenia

58
Q

Glycoprotein IIb/IIIa R-antagonist: drugs

A

Abciximab
Tirofiban
Eptifibatide

59
Q

Abciximab: molecule

A
  • Monoclonal antibody against platelet GpIIb/IIIa R
60
Q

Abciximab: pharmacoK

A

o IV: maximal platelet aggregation inhibition at 2h
o Duration 12h
o ½ life 10-30min
o Remain platelet bound in circulation for 15 days

61
Q

Abciximab: how to reverse action

A
  • Reverse action by platelet transfusion
62
Q

Abciximab: side effects

A

bleeding, thrombocytopenia, hypersensitivity

63
Q

Tirofiban: molecule

A
  • Highly specific nonpeptide peptidomimetic GpIIb/IIIa inhibitor
    o Inhibition of fibrinogen and vWF binding to R
    o ↓ risk of hypersensitivity to monoclonal antibody
64
Q

Tirofiban: pharmacoK

A

acute onset, ½ life 2h
o 35% unbound in circulation
o Clearance: 65% renal, 25% fecal

65
Q

Tirofiban: side effects

A

bleeding, renal disease, thrombocytopenia

66
Q

Eptifibatide: molecule

A
  • Synthetic cyclic heptapeptide
    o Structural differences w Tirofiban
    o Bind at different site on GpIIb/IIIa R → same end result
     Lower affinity compared to others
67
Q

Eptifibatide: pharmacoK

A

½ life 2-3h, renal clearance 30%

68
Q

Eptifibatide: side effects

A

bleeding, renal disease, thrombocytopenia

69
Q

Oral anticoag: drugs

A

Warfarin

70
Q

Warfarin: MOA

A
71
Q

Warfarin: pharmacoK

A

o PO: high plasma albumin bound

72
Q

Warfarin: onset

A

2-7 days, 1/2 life = 37h

73
Q

Warfarin: metabolism

A

hepatic cytochrome CYP2C9 and vit K epoxide reductase (VKORC1)
 Inactive metabolites → excreted in urine and stools
 Genetic variation in enzymes → individual dosage variability

74
Q

Warfarin: decrease dose if

A
  • CHF or liver failure
  • Malnutrition (↓vit K)
  • Thyrotoxicosis: ↑ vit K catabolism
  • Renal failure
75
Q

Warfarin: monitoring tx

A

international normalized ration (INR) → aim is moderate intensity
o High intensity warfarin (INR 3-4) → more effective vs aspirin
 More bleeding associated and close monitoring needed
o Moderate intensity warfarin (INR 2-3) → ↓ bleeding risks, better vs aspirin

76
Q

Warfarin: side effects

A

few
o Over anticoagulation: bleeding, risk of intracranial hemorrhage
 Highest in 1st 1-3mo (10x ↑)
o Skin necrosis: rare

77
Q

Warfarin: drug interaction

A

many drugs
o Barbiturates, phenytoin → accelerate degradation by liver
o Allopurinol, amiodarone, cephalosporins → potentiate effects by inhibiting vit K formation
o Antibiotics (ie metronidazole and others) → ↓ warfarin degradation → ↑ anticoag effect
o Aspirin, clopidogrel, NSAID may potentiate bleeding

78
Q

Warfarin: CI

A

o Recent stroke
o Uncontrolled hypertension
o Hepatic cirrhosis
o Potential GI/genitourinary bleeding points: hiatus hernia, peptic ulcer, gastritis, gastric reflux, colitis…
o Renal impairment
o Pregnancy

79
Q

Acute anticoagulant: drugs

A

Heparin (unfractionated heparin)
Low molecular weight heparin
Enoxaparin
Dalteparin
Bivalirudin
Fondaparinux

80
Q

Heparin: molecule

A
  • Heterogenous mucopolysaccharide: molecular weight = 5000-30000 Da
81
Q

Heparin: MOA

A

Interact w antithrombin and thrombin (factor IIa)
o Binds to antithrombin (Penta saccharide segment of heparin molecule)
 Heparin-antithrombin → inhibit factor Xa > factor XIa
o Binds to thrombin by 13 additional saccharide units
 Inhibit thrombin induced platelet aggregation
o Binds to variety of plasma proteins, endothelial , macrophages
 Some inactivation of molecule

82
Q

Heparin: dosage

A

IV infusion or SQ BID to TID → MAX 24h

83
Q

Heparin: dose effect relationship

A

o Dose-effect relationship hard to predict
 Heterogeneous group of molecules extracted by variety of procedures
 Strength varies from batch to batch

84
Q

Heparin: dose adjustment

A

o Dose adjusted based on aPTT
 Should be 1.5 to 2.5x normal (higher ↑ risks of cerebral bleeding)
 Monitored at 6, 12, 24h
 Some patients are resistant → high doses, monitor q4h

85
Q

Heparin: side effects

A

o Risks of thrombocytopenia (3-5% of patients): IM
 4T’s clinical score
* Thrombocytopenia: <50% count drop
* Timing: 5-10days after initiation
* New thrombosis
* Other causes of thrombocytopenia
 Thrombocytopenia-thrombosis syndrome: prothrombotic condition
* Immunoglobulin bridge platelets causing ↓ counts and thrombosis
o ↑ risk of hemorrhage: subacute bacterial endocarditis, hematologic disorders (hemophilia, hepatic diseases), GI ulcerations
o Allergic reactions: derived from animal tissue

86
Q

Heparin: advantages compared to LMWH

A

o Effect stops rapidly after discontinuing the drug
o Completely reversed by protamine
o Not cleared by kidneys → safe with renal failure

87
Q

Low molecular weight heparin: molecule

A
  • 1/3 of heparin molecular weight = mean 5000Da
    o Heterogenous size
88
Q

Low molecular weight heparin: MOA

A
  • Mechanism: bind to
    o Antithrombin (factor IIa) activity
    o Anti factor Xa activity
    o Some direct inhibition of thrombin (less powerful than heparin)
89
Q

Low molecular weight heparin: pharmacoK

A

o > bioavailability
o > ½ life = 4h

90
Q

Low molecular weight heparin: dosage

A

SQ SID to BID

91
Q

Low molecular weight heparin: side effect

A

bleeding
o ↓ but not completely reversible with protamine
o Residual anti-Xa activity remains

92
Q

Low molecular weight heparin: advantages vs UFC

A

 < expensive
 No need for monitoring
* Can measure antiXa levels if renal failure, severe obesity, pregnancy
 Lack of complete antidote: partially reversible w protamine
 Inability to monitor degree of anticoagulation

93
Q

Enoxaparin: MOA

A

inhibit factor Xa
o Some degree of thrombin inhibition

94
Q

Enoxaparin: dosage

A

1mg/kg SQ injection q12h

95
Q

Enoxaparin: drug combination

A

Can be combined with aspirin/clopidogrel or GpIIa/IIIb inhibitor

96
Q

Enoxaparin: metabolism

A

o Renal excretion

97
Q

Dalteparin: dosage

A

deep SQ

98
Q

Bivalirudin: molecule

A
  • Molecular weight = 2180Da
99
Q

Bivalirudin: MOA

A

direct binding to thrombin (factor IIa)
o Inhibit thrombin induced conversion fibrinogen → fibrin
 Both soluble and clot bound thrombin
o Inhibit thrombin induced platelet aggregation

100
Q

Bivalirudin: pharmacoK

A

o Linear kinetic
o ½ life 25min
o Not protein bound → few drug interactions
o Elimination: proteolytic cleavage > renal excretion (20%)

101
Q

Bivalirudin: dosage

A

IV infusion
o No reversal agent but coagulation time normalize 1h after discontinuation

102
Q

Bivalirudin: monitoring

A

aPTT, ACT → correlated w [plasma]

103
Q

Fondaparinux: molecule

A
  • Molecular weight = 1728Da
    o Similar to antithrombin-binding sequence in heparin
104
Q

Fondaparinux: MOA

A

specific conformational change in antithrombin
o High affinity reversible binding to antithrombin → promote antithrombin inhibition of factor Xa
o Strong and selective inhibition of factor Xa

105
Q

Fondaparinux: pharmacoK

A

o SQ injection: 100% bioavailability
o ½ life 17h

106
Q

Fondaparinux: reversal

A

rVIIa is partial antagonist

107
Q

Fondaparinux: dosage

A

SQ SID
o ↓ dose in older/ renal impair
o No monitoring needed

108
Q

Fondaparinux: CI

A

o Renal clearance < 30ml/min
o BW <50kg

109
Q

Direct thrombin inhibitors: drugs

A

Dabigatran

110
Q

Anti factor Xa agents: drugs

A

Rivaroxaban
Apixaban

111
Q

Dabigatran: MOA

A
  • Mechanism: direct competitive thrombin inhibitor
    o Thrombin → conversion fibrinogen → fibrin
    o Effective on free and clot-bound thrombin
    o Inhibit thrombin induced platelet aggregation
112
Q

Dabigatran: pharmacoK

A

o Bioavailability 6.5
 Dabigatran etexilate mesylate absorbed as ester → hydrolyzed → dabigatran
 Maximal [plasma] w/I 1h
 ½ life 12-17h
o Excretion: 80% kidneys

113
Q

Dabigatran: side effects

A

gastric discomfort

114
Q

Dabigatran: CI

A

age, ↑ bleeding risk

115
Q

Dabigatran: advantages vs warfarin

A

o Rapidly effective
o Not interact w food or drugs
o Not require monitoring
o ↓ risk of ischemic stroke or intracranial bleed

116
Q

Rivaroxaban: MOA

A

oral inhibitor of factor Xa

117
Q

Rivaroxaban: pharmacoK

A

o Bioavailability: 100%
 No metabolites
 Rapid absorption, maximal [plasma] after 2-4h
 ½ life = 5-13h
 High plasma protein bounding: 92-95%
o Metabolism: hepatic by CYP3A4 and CYP 2J2
o Excretion: 2/3 liver, 1/3 kidneys

118
Q

Rivaroxaban: dosage

A

once daily
o Major advantage

119
Q

Apixaban: MOA

A

direct factor Xa inhibitor

120
Q

Apixaban: pharmacoK

A

o Bioavailability: 50%
 Max [plasma] after 3-4h
 ½ life 8-15h
o Metabolism: liver 75% by CYP3A4
 25% excreted unchanged in urine
o Dosage: BID

121
Q

Fibrinolytic/thrombolytic therapy goals

A
  • Thrombolytic therapy goal: formation of plasmin → clot lysis
    o Plasminogen activator system: form plasminogen → bind clot surface → clot lysis
    o Plasminogen activator inhibitor (PAI-1): inhibit plasmin formation
     Made by adipose tissue
  • Fibrinolysis: goals is to achieve early reperfusion and patency = critical 1st 2-3h
    o ↑ myocardial salvage
    o Preserve LV fct
    o ↓ mortality
122
Q

Fibrinolytic/thrombolytic therapy: drugs

A

Alteplase/tissue plasminogen activator (tPA)
Tenecteplase (TNK)
Reteplase (rPA)
Streptokinase (SK)

123
Q

Plasmin inhibitors: drugs

A

Tranexamic acid

124
Q

Activation of coagulation: drugs

A
  • Recombinant factor VIIa
  • Prothrombin complex concentrate (PCC)
125
Q

Indication Recombinant factor VIIa

A

hemophilia

126
Q

Prothrombin complex concentrate (PCC) indication

A

o Reverse anticoagulant effect of rivaroxaban

127
Q

Tranexamic acid effect

A
  • Reduced bleeding when administered w/I 3h after trauma
128
Q

Alteplase/tissue plasminogen activator (tPA): molecule

A
  • Natural enzyme
129
Q

Alteplase/tissue plasminogen activator (tPA): MOA

A

bind to fibrin
o > affinity vs strepto/urokinase
o Once bound: convert plasminogen → plasmin

130
Q

Alteplase/tissue plasminogen activator (tPA): pharmacoK

A

short ½ life <5min, duration 90min

131
Q

Alteplase/tissue plasminogen activator (tPA): indication

A

acute thrombotic event

132
Q

Alteplase/tissue plasminogen activator (tPA): side effect and CI

A

related to hemorrhage

133
Q

Tenecteplase (TNK): molecule

A
  • Mutant of native tPA: amino acid substitutions at 3 sites
134
Q

Differences tPA vs TNK

A

o ↓ plasma clearance and longer ½ life
o ↑ fibrin specificity
o ↑ resistance to PAI-1

135
Q

Reteplase (rPA): molecule

A
  • Mutant of alteplase:
    o Deletion of kringle-1, finger and epidermal growth domain
    o Carbohydrate side chains
136
Q

Reteplase (rPA): pharmacoK

A
  • Prolonged plasma clearance
137
Q

Streptokinase (SK): MOA

A
  • Original thrombolytic agent
  • Mechanism: bind plasminogen to form 1:1 complex
    o No direct effect on plasminogen
    o Complex → become active enzyme convert plasminogen → plasmin
    o Can ↑ levels of activated prot-C → ↑ clot lysis
138
Q

Streptokinase (SK): side effects

A

hypersensitivity, hypotension, bleeding

12. Pharmacology (10 decks)

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