Anti-Platelet Drugs, Anticoagulants and Thrombolytics (Stewart)

Drugs Used in Clotting Disorders

To reduce clotting:
o Anticoagulants
o Thrombolytics
o Antiplatelet drugs
To facilitate clotting
o Plasminogen inhibitors
o Replacement factors
Anticoagulants (reduce clotting)
Indirect Thrombin Inhibitors
Drug

MOA

Preparations

Heparin

Increases
proteolytic
actions of
antithrombin
resulting in
reduced
activity of
clotting factors
XIIa, Xia, IXa,
Xa and IIa
(thrombin)

High molecular
weight (UFH)
- Inhibits
thrombin (IIa),
IXa, and Xa
- Has to be
monitored via
activated
partial
thromboplastin
time (aPTT or
PTT)
Low molecular
Weight
(enoxaparin)
- Inhibits Xa (less
effect on
thrombin)
- Monitored only
in pregnancy,
obesity and
patients with
renal
insufficiency
Route of
administration: IV
or SC

Clinical Uses

Side Effects

-Venous
thrombosis
-Pulmonary
embolism
-Anticoagulatio
n (coronary
surgery,
stent
placement)
-Does not cross
placenta

- Bleeding
- Thrombocyto
penia (HIT)
- Osteoporosis
- Alopecia
- Hypersensitiv
ity

Notes
- Mixture
of sulfated
mucopolys
accharides
*Activity
reversed
by
protamine
sulfate

Direct Thrombin Inhibitors

Drug

MOA

Preparations

Hirudin

Irreversible
thrombin
inhibitor

- Derived from
leech saliva

Clinical Uses

Side
Effec
ts

Notes
Cleared by kidneys

- Recombinant
form
lepirudin
Bivalirudi
n
Dabigatra
n

- Inhibits platelet
activation
- Rapid
onset/offset
- Rapid
onset/offset
- Substrate for Pglycoprotein
efflux pump

- IV
- IV

- Oral

Used to prevent
stroke and
systemic
embolism in
atrial fibrillation
(alternative to
warfarin)

- 20% cleared by
kidney
- 80% metabolic
clearance
- Renal impairment
reduces clearance
- Concomitant use
of ketoconazole,
amiodarone,
quinidine, and
clopidogrel
increases
dabigatrans effect

Inhibitors of Clotting Factor Synthesis

Drug

MOA

Preparations

Warfarin
(Coumadi
n)

- Inhibits
vitamin K
synthesis
- Blocks vitamin
K mediated
gamma
carboxylation of
multiple
coagulation
factors
- 8 12 hr. delay
in warfarin
action

- Racemic
mixture of Swarfarin and Rwarfarin
- Over 99%
bound to
plasma albumin
- Long half life in
plasma
- Oral

Clinical
Uses
Thrombosis
Pulmonary
embolism

Side Effects

Notes

- Crosses the
placenta (fetal
hemorrhage
disorder and
abnormal bone
formation)
- Cutaneous
necrosis

- Monitoring

prothrombin
time (PT) or
INR


Factor
Xa

inhibitors
Drug

MOA

Rivaroxaba
n

- Rapid onset
of action
- Oral

Apixaban

- Rapid onset
of action
- Oral

Drug

Preparati
ons

Clinical Uses

Side Notes
Effec
ts
- Prevent venous
- Not for use in
thrombosis
patients with
following hip/knee
severe renal or
surgery
hepatic
- Prevent embolic
impairment
stroke in patients
- No monitoring
with nonvalvular
required
atrial fibrillation
- Half life less
- Treat venous
than warfarin
thromboembolic
- Prevent stroke in
- Not for use in
nonvalvular atrial
patients with
fibrillation
severe renal or
hepatic
impairment
- No monitoring
required
- Half life less
than warfarin

Thrombolytics (to reduce clotting)

*thrombolytics lyse thrombi by catalyzing plasmin formation
MOA

Preparati

Clinical Uses

Side

Notes

ons
Streptokina - Indirectly
se
promotes
plasmin
formation
Forms
stable
complex
with
plasminoge
n
Complex
catalyzes
plasminoge
n plasmin
Anistreplas
e

- Protein
produced
in
Streptococ
cus

Effects
- Pulmonary
embolism with
hemodynamic
instability
- Deep vein
thrombosis
- Ascending
thrombophlebi
tis
- Arterial
thrombosis or
embolism
- Acute MI

- Bleeding
Antigenicit
y

- no longer
available in
the U.S.

- IV
- Acyl group
hydrolyzed in
vivo
- Plasminogenstreptokinase
complex
catalyzes
formation of
plasmin
- IV

- Complex
of human
plasminoge
n and
bacterial
streptokina
se
- active
site
acylated
(prevents
activation)
Tissue
- Serine
- Alteplase
Plasminoge protease
is
n Activator - Converts fibrin- recombina
(tPA)
bound
nt form of
plasminogen to
tPA
plasmin
- other
recombina
nt forms
include
replase
and
tenectepla
se

- Pulmonary
- Bleeding
embolism with
hemodynamic
instability
- Deep vein
thrombosis
- Ascending
thrombophlebi
tis
- Arterial
thrombosis or
embolism
- Acute MI
- Acute
ischemic
stroke
4

Urokinase

Aminocapr
oic Acid

- Enzyme that
directly converts
plasminogen
plasmin
- Competitive
inhibitor of
plasminogen
activation

- Enzyme
synthesize
d in kidney

- Pulmonary
embolism

- Bleeding

- Synthetic
inhibitor of
fibrinolysis

- Bleeding due
to
thrombolytic
therapy
- Adjunctive
therapy to
hemophilia
- prevent
rebleeding
from
intracranial
aneurysms

intravascul
ar
thrombosis
hypotensio
n
- myopathy
- diarrhea
- nasal
stuffiness
Abdominal
discomfort

* Contraindications to thrombolytic therapy

o Surgery within 10days
o Serious GI bleeding within 3 months
o Hypertension
o Active bleeding/hemorrhagic disorder
o Previous stroke

Antiplatelet Drugs (to reduce clotting)

Drug

MOA

Aspirin

Ticlopidine

Prepara
tions

Clinical Uses

Side Effects

- COX inhibitor
reduced TXA2 and
prostaglandin
synthesis
- Oral

- MI (low dose)
- Analgesia
- Antipyretic
- Antiinflammatory
(high dose)

- Irreversible ADP
receptor inhibitor
- Reduce platelet
aggregation

- Prevention of
stroke (in
patients that
cant tolerate

- Bleeding
complications
- Hypersensitive
reactions
- Gastric
intolerance
- Renal toxicity
- Liver toxicity
- uricosuric effect
- Nausea
- Dyspepsia
- Diarrhea
- Hemorrhage
5

Not
es

Clopidogre
l

Same as
ticlopidine

Abciximab

- Monoclonal
antibody against
GP IIb/IIIa
complex and
vitronectin
receptor
- IV
- Blocks binding
of ligand to GP
IIb/IIIa receptor
Inhibits
receptor
activation
Reduces
platelet
aggregation
IV

Epitifibatid
e

Dipyramid
ole

- Vasodilator
- Blocks platelet
function
- Inhibits
adenosine uptake
and cGMP
phosphodiesteras
e activity
- Oral

- Note
requires
activatio
n by
CYP2C19

aspirin)
- Prevention of
coronary stent
thrombosis
(combo rx with
aspirin)
- Unstable
angina
- MI (STEMI or
NSTEMI)
- Recent MI,
stroke or
peripheral
artery disease
- Percutaneous
coronary
intervention
- Acute coronary
syndrome

- Leukopenia
- Thrombotic
thrombocytopeni
c purpura
- Fewer than
ticlopidine
- Neutropenia
and GI side
effects (rare)
- Thrombotic
thrombocytopeni
c purpura
Thrombocytopeni
a

-Acute coronary
syndromes
- Percutaneous
coronary
intervention

- Prevent
cerebrovascular
ischemia (with
aspirin)
- Prophylaxis:
thromboemboli
in patients with
prosthetic heart
valves (with
warfarin)

To Facilitate Clotting: