Pharmacology of Drugs Used

in Ischemic Stroke

Group 1
 ● Firdha Aprillia W 465464
Group 1 ● Aida Udhiyati 465449
● Sundas Ejaz 457462
Members
Stroke Pharmaceutical
Therapy
Fibrinolytic Drugs
Classification of Fibrinolytic Drug by Generation

Streptokinase

First Generation

Urokinase
Fibrinolytic Agent

Tissue type plasminogen

activator

APSAC

Second Generation

scuPA
Classification of Fibrinolytic Drug by Generation

Reteplase

Third Generation

Tenecteplase
Fibrinolytic Agent

Staphylokinase

Other Fibrinolytic
Classification by Specificity
★ Fibrin Specific Agent → A R T
○ Alteplase
○ Reteplase
○ Tenecteplase
★ Fibrin non-Specific Agent → U S A
○ Urokinase
○ Streptokinase
○ Anistreplase
Non Fibrin Specific vs Fibrin Specific
★ Non Fibrin Specific Agent → U S A
★ Binds equally to circulating and non-
circulating plasminogen
★ Produces breakdown of clot (fibrinolysis) and
circulating fibrinogen (fibrinogenolysis) →
systemic fibrinolytic state leading to
bleeding
★ Fibrin specific agent → A R T
★ Selective in action or clot specific fibrin
★ Binds preferentially to plasminogen to
fibrin surface (non-circulating) rather than
circulating plasminogen
★ Less risk of bleeding than non-specific agents
Schematic Mechanism of
Fibrinolytic
Streptokinase
Streptokinase is a nonenzymatic protein of
-hemolytic streptococci. It activates the fibrinolytic
system indirectly by forming a 1:1 stoichiometric
complex with plasminogen, which then activates
plasminogen, converting it to the active enzyme
plasmin.

Unlike tPA, it does not bind preferentially to clot-

associated fibrin and therefore binds equally to
circulating and non-circulating plasminogen.
Therefore, SK produces significant fibrinogenolysis
along with clot fibrinolysis.

Because SK is derived from streptococci, patients who

have had recent streptococci infections can require
significantly higher doses of SK to produce
thrombolysis.
Urokinase
Urokinase is a trypsin-like serine
protease composed of two polypeptide
chains connected by a disulfide bridge.
It activates plasminogen directly,
converting it to the active enzyme
plasmin.
APSAC - Anistreplase
Acylation of plasminogen (APSAC) protects the
molecule from autodigestion and also prevents its
inactivation by circulating plasma inhibitors, resulting
in a half-life of approximately 100 minutes. These
features permit bolus dosing.

It is a complex of purified human plasminogen and

bacterial streptokinase that has been acylated to
protect the enzyme's active site. When the drug is
administered, the acyl group gets hydrolyzed, thereby
freeing the activator complex. It converts plasminogen
to plasmin, which in turn degrades fibrin (
blood clots) to fibrin split products.
Rateplase
Genetically engineered, smaller derivative of
recombinant tPA. It is an unglycosylated single chain t-
PA deletion variant produced in E. coli K12 in the form of
insoluble inclusion bodies. The loss of the kringle 1
domain in r-PA increased the half-life of this molecule
from 4 to »15 min with mainly renal form of
elimination.

However, its fibrin binding affinity is 5-fold lesser than

alteplase because of the absence of the fibrin-binding
finger domain. Despite of the presence of the kringle 2
domain in the molecule that is known to interact with
fibrin and stimulate the activity, the fibrinolytic activity
of r-PA is 4- fold lower than alteplase.
Tenecteplase
Recombinant tPA, has longer half life and greater
binding affinity for fibrin than Alteplase.

TNK-tPA is a multipoint mutation of the parent tPA

molecule. In its mutant form, T103N, N117Q, KHRR
(296–299), AAAA, threonine 103 has been changed to
asparagine 103, creating a new glycosylation site
(and a longer half-life)). The change as ASP117 (to
glutamine) also contributes to the molecule’s
prolonged half-life (18 minutes).

The molecule also possesses 14-fold enhanced fibrin

specificity than t-PA but comparable fibrin-binding
affinity and plasma clot lysis activity in vivo.
tPa
Relative fibrin specificity of tPA, made the clot
dissolution occurs with less breakdown of
circulating fibrinogen than occurs with SK and UK.

Although tPA is relatively selective for clot-bound

plasminogen, it still activates circulating plasminogen
thereby releasing plasmin, which can lead to the
breakdown of circulating fibrinogen and cause an
unwanted systemic fibrinolytic state.

In summary, although tPA is relatively selective for

clot-associated fibrin, it can produce systemic lytic
state and undesirable bleeding.

Has a low affinity for free plasminogen in the plasma,

but it rapidly activates plasminogen that is bound to
fibrin in a thrombus or a hemostatic plug → fibrin
selective at low doses

Approved for MI, massive PE, and AIS

Mechanism of tPa and Its Recombinant
Loss of tPA Fibrin-Specificity?
Comparison of the Pharmacokinetic Properties
Urokinase Reteplase

Tenecteplase

Alteplase
Pharmacokinetic and Pharmacodynamic Comparison of
Fibrinolytic Agent
Comparison of t ½ and Specificity
Comparison of Characteristic Fibrinolytic Therapy
Streptokinase Trials
rt-PA Trials
Antiplatelets
1. ASPIRIN

Mechanisme of
Action
Pharmacodynamics/kinetics: ASPIRIN

Onset : 30 minutes

Duration : 4-6 hours

Absorption : Rapid

Distribution : Vd: 10 L; readily into most body fluids and tissues; 49& plasma protein bound

Metabolism : Hydrolyzed to salicylate (active) by esterases in GI mucosa, red blood cells,

synovial fluid, and blood; metabolism of salicylate occurs primarily by hepatic
conjugation; metabolic pathways are saturable

Bioavailibility : 50% to 75% reaches systemic circulation

Half-life elimination : Parent drug: 15-20 minutes; Salicylates (dose dependent): 3 hours at lower doses
(300-600 mg), 5-6 hours (after 1 g), 10 hours with higher doses

Time to peak, serum : ~1-2 hours

Excretion : Urine (75% as salicyluric acid, 10% as salicylic acid)

Clinical Use:
- The drug is used extensively to prevent transient ischemic attacks (TIAs), ischemic
stroke, and other thrombotic events.
- Acute ischemic stroke: Oral: 150-325 mg once daily, initiated within 48 hours (in
patients who are not candidates for alteplase and not receiving systemic
anticoagulation)
- Stroke/TIA (noncardioembolic; secondary prevention): Oral: 50-325 mg once daily
(Adams, 2008)

Trevor, A., Katzung, B., Knuidering-Hall, M., 2015. Katzung & Trevor’s
Pharmacology Examination and Board Review,11th Edition.
2. GLYCOPROTEIN IIb/IIIa RECEPTOR INHIBITORS

Mechanisme of
Action
Pharmacodynamics/kinetics: ABCIXIMAB

Onset : 10 minutes (<20% baseline)

Duration : 72 hours

Metabolism : Through proteolytic cleavage

Platelet binding : Remains bound for 15 days

Time to peak : 30 minutes (platelet inhibition)

Half-life : 30 minutes
Pharmacodynamics/kinetics: EPTIFIBATIDE

Onset : within 1 hour

Duration : Platelet function restored ~4 hours following discontinuation

Protein Binding : ~25%

Half-life elimination : 2,5 hours

Excretion : Primarily urine (as eptifibatide and metabolites); significant renal impairment may
alter disposition of this compound
Clearance: Total body: 55-58 mL/kg/hour; Renal: ∼50% of total in healthy subjects
Pharmacodynamics/kinetics: TIROFIBAN

Distribution : 35% unbound

Metabolism : Minimally hepatic

Half-life elimination : 1,5 - 2 hours

Excretion Urine (65%) and feces (25%) primarily as unchanged drug

Clearance: Elderly: Reduced by 19% to 26%
Clinical Use:
- Prevent restenosis after coronary angioplasty and are used in acute coronary
syndromes (eg, unstable angina and non-Q-wave acute myocardial infarction).
- The efficacy of IV tiforiban and eptifibatide is not well established for AIS.
- The administration of other glyvopretein IIb/IIIa receptor antagonist, including
abciximab, in the treatment of AIS is potentially harmful and should not be
performed.

Trevor, A., Katzung, B., Knuidering-Hall, M., 2015. Katzung & Trevor’s
Pharmacology Examination and Board Review,11th Edition
Poers et al., 2018. Guidelines for Management of Acute Ischemic Stroke
3. ANTAGONIST OF ADP RECEPTORS

Mechanism of
Action
Pharmacodynamics/kinetics: CLOPIDOGREL

Onset : Inhibition of platelet aggregation detected: 2 hours after 300 mg

administered; after second day of treatment with 50-100
mg/day. At steady-state with 75 mg/day, the average inhibition level
observed was 40% to 60%.

Peak effect: 50-100 mg/day: Bleeding time: 5-6 days; Platelet function: 3-7
days

Absorption : Well absorbed

Protein binding : Parent drug: 98%; metabolite: 94%

Metabolism : Extensively hepatic via hydrolysis; biotransformation primarily to carboxyl

acid derivative (inactive). The active metabolite that
inhibits platelet aggregation has not been isolated.

Half-life elimination : ~8 hours

Time to peak, serum : ~1 hours

Excretion Urine (50%); feces (46%)

Pharmacodynamics/kinetics: TICLOPIDINE

Onset : ~6 hours

Peak effect: 3-5 days; serum levels do not correlate with clinical antiplatelet
activity

Absorption : Well absorbed

Protein binding : Parent drug: 98%; <15% bound to alpha1-acid glycoprotein

Metabolism : Extensively hepatic; has at least 1 active metabolite

Half-life elimination : 13 hours

Time to peak, serum : ~2 hours

Excretion : Urine (60%); feces (23%); with only 2% excreted unchanged in urine.
Clinical Use:
- Clopidogrel and ticlopidine are effective in preventing TIAs and ischemic strokes,
especially in patients who cannot tolerate aspirin.
- Clopidogrel is routinely used to prevent thrombosis in patients who have received a
coronary artery stent
- Clopidogrel PO for reduction of stroke, MI, or vascular death 75 mg once daily. A
loading dose of 300 mg on the first day is often used to hasten the onset of action.
- Ticlopidine PO for thrombotic stroke reduction in patients with stroke or stroke
precursors, patients with unstable angina, or those undergoing coronary artery bypass
graft or coronary angioplasty 250 mg bid.

Trevor, A., Katzung, B., Knuidering-Hall, M., 2015. Katzung & Trevor’s
Pharmacology Examination and Board Review,11th Edition.
4. INHIBITORS OF PHOSPHODIESTERASE 3

Mechanisme of
Action
Pharmacodynamics/kinetics: CILOSTAZOL

Onset : 2-4 weeks; may require up to 12 weeks

Protein binding : Cilostazol 95% to 98%; active metabolites 66% to 97%

Metabolism : Hepatic via CYP3A4 (primarily), 1A2, 2C19, and 2D6; at least one
metabolite has significant activity

Half-life elimination : 11-13 hours

Excretion : Urine (74%) and feces (20%) as metabolites

Pharmacodynamics/kinetics: DYPIRIDAMOLE

Onset : 24 minutes

Duration : 3 hours

Protein bound : 91-99%

Distribution : Vd: 2-3 L/kg

Metabolism : Liver

Clearance : 2,3-3,5 mL/min/kg

Excretion : Feses
Clinical Use:
- Dipyridamole is approved as an adjunct to warfarin in the prevention of thrombosis
in those with cardiac valve replacement and has been used in combination with
aspirin for secondary prevention of ischemic stroke.
- Cilostazol is used to treat intermittent claudication, a manifestation of peripheral
arterial disease

Trevor, A., Katzung, B., Knuidering-Hall, M., 2015. Katzung & Trevor’s
Pharmacology Examination and Board Review,11th Edition.
Anticoagulants
Definition:

● An anticoagulant is substance that prevents coagulation or clotting of blood via its action on
clotting factor.
● Anticoagulants are the mainstay of treatment for stroke and systemic embolism prevention in
patients with atrial fibrillation (AF) or flutter.
● They can be used as well for prevention and treatment of venous thromboembolism (VTE) and
treatment of thrombus formation in other places.
Classification according to route of administration:
Heparin and low molecular weight heparins (LMWH)
Heparin is an injectable, rapidly acting anticoagulant that is often used acutely to
interfere with the formation of thrombi. Heparin occurs naturally as a macromolecule
complexed with histamine in mast cells, where its physiologic role is unknown. It is
extracted for commercial use from porcine intestinal mucosa.
Unfractionated heparin is a mixture of straight-chain, anionic glycosaminoglycans with
a wide range of molecular weights. It is strongly acidic because of the presence of sulfate
and carboxylic acid groups. The realization that low molecular weight forms of heparin
(LMWHs) can also act as anticoagulants led to the isolation of enoxaparin, produced by
enzymatic depolymerization of unfractionated heparin. Other LMWHs include dalteparin
and tinzaparin.The LMWHs are heterogeneous compounds about one-third the size of
unfractionated heparin
Mechanism of action: Heparin

● Heparin acts at a number of molecular targets, but its anticoagulant effect is a

consequence of binding to antithrombin III, with the subsequent rapid
inactivation of coagulation factors. Antithrombin III is an α globulin that inhibits
serine proteases of thrombin (factor IIa) and factor Xa.
● In the absence of heparin, antithrombin III interacts very slowly with thrombin
and factor Xa. When heparin molecules bind to antithrombin III, a conformational
change occurs that catalyzes the inhibition of thrombin about 1000-fold.
● LMWHs complex with antithrombin III and inactivate factor Xa (including that
located on platelet surfaces) but do not bind as eagerly to thrombin.
Heparin accelerates inactivation of coagulation factors by antithrombin
Heparin and low molecular weight heparin (LMWH)–mediated inactivation
of thrombin or factor Xa
Therapeutic use:

Heparin and the LMWHs limit the expansion of thrombi by preventing fibrin formation.
These agents are used for :
➢ The treatment of acute venous thromboembolism (DVT or PE).
➢ Prophylaxis of postoperative venous thrombosis in patients undergoing surgery (for
example, hip replacement) and those with acute MI.
➢ These drugs are the anticoagulation of choice for treating pregnant women, because
they do not cross the placenta, due to their large size and negative charge.
➢ LMWHs do not require the same intense monitoring as heparin, thereby saving
laboratory costs and nursing time.
➢ These advantages make LMWHs useful for both inpatient and outpatient therapy.
Pharmacokinetics:
● Heparin must be administered
● The LMWHs are administered
subcutaneously or intravenously, because
the drug does not readily cross membranes. subcutaneously.

● Whereas the anticoagulant effect with ● The anticoagulant effect of the

heparin occurs within minutes of IV LMWHs occurs about 4 hours after

administration (or 1 to 2 hours after subcutaneous injection.

subcutaneous injection) ● It is usually not necessary to monitor

coagulation values with LMWHs because
the plasma levels and pharmacokinetics
of these drugs are more predictable.
Pharmacokinetics (Cont..)

● However, in renally impaired, pregnant, and

obese patients, monitoring of factor Xa levels
● The inactive metabolites, as well as some of
is recommended with LMWHs.
the parent heparin are excreted into the
● The inactive metabolites (LMWH) are
urine.
excreted into the urine.
● The half-life of heparin is approximately 1.5
● Renal insufficiency prolongs the half-life of
hours. LMWHs. Therefore, the dose of LMWHs
should be reduced in patients with renal
impairment.
● The half-life of the LMWHs is longer than
that of heparin, ranging from 3 to 12 hours.
Route of administration & fate:
ADRs
● The chief complication is Bleeding.
● Excessive bleeding may be managed by discontinuing the
drug or by treating with protamine sulfate.
● Possible adverse reactions include: chills, fever, urticaria, and
anaphylactic shock.
● Heparin-induced thrombocytopenia (HIT) is a serious condition, in
which circulating blood contains an abnormally low number of
platelets. This reaction is immune-mediated and carries a risk of
venous and arterial embolism. Heparin therapy should be
discontinued when patients develop HIT or show severe
thrombocytopenia.
 ● In cases of HIT, heparin can be replaced by another anticoagulant, such as argatroban.

● In addition, osteoporosis has been observed in patients on long-term heparin therapy.

Contraindications:

● Heparin and LMWHs are contraindicated in patients who have hypersensitivity to heparin,

bleeding disorders, alcoholism, or who have had recent surgery of the brain, eye, or spinal

cord.

[Note: LMWHs can have cross-sensitivity and are not recommended in HIT.]
Argatroban
Introduction & Pharmacokinetics:
Argatroban is a synthetic parenteral anticoagulant that is derived from l-arginine. It is a direct
thrombin inhibitor.

Metabolism: By Liver. Because argatroban is metabolized in the liver, it may be used in patients
with renal dysfunction, but it should be used cautiously in patients with hepatic
impairment.

Half-life: 39 to 51 minutes

Monitoring: aPTT, hemoglobin, and hematocrit.

ADRs: Bleeding

Uses: prophylaxis or treatment of venous thromboembolism in patients with HIT, and also
in patients who have or are at risk for developing HIT.
Bivalirudin and Desirudin
 Pharmacokinetics & Pharmacodynamics:
Bivalirudin and desirudin are parenteral anticoagulants that are analogs of hirudin, a thrombin
inhibitor derived from medicinal leech saliva.

MOA: These drugs are selective direct thrombin inhibitors that reversibly inhibit the
catalytic site of both free and clot-bound thrombin. Bivalirudin is an alternative to
heparin in patients undergoing PCI (Percutaneous Coronary Intervention) who have or are
at risk for developing HIT (Heparin-induced thrombocytopenia) and also in patients with
unstable angina undergoing angioplasty.

Half-life: Bivalirudin = 25 minutes. Adjust dose in renally impaired patients.

Uses: Desirudin is indicated for the prevention of DVT in patients undergoing hip
replacement surgery.

ADR: Bleeding
Fondaparinux
Introduction & Pharmacology
Fondaparinux is a pentasaccharide anticoagulant that is synthetically derived.

MOA: Selectively inhibits only factor Xa. By selectively binding to antithrombin III,
fondaparinux potentiates (300- to 1000-fold) the innate neutralization of factor Xa
by antithrombin III.

Uses: In the treatment of DVT and PE and for the prophylaxis of venous
thromboembolism in the setting of orthopedic and abdominal surgery.

Absorption: well absorbed from the subcutaneous route with a predictable pharmacokinetic
profile and, therefore, requires less monitoring than heparin.

Elimination: Fondaparinux is eliminated in the urine mainly as unchanged drug

 ● HIT is less likely with fondaparinux than with heparin but is still a possibility.
● Fondaparinux should not be used in the setting of lumbar puncture or spinal cord surgery.

Half-life: 17 to 21 hours.

Contraindication: in patients with severe renal impairment.

ADR: Bleeding

Antidot: There is no available agent for the reversal of bleeding associated with
fondaparinux.
Dabigatran etexilate
Pharmacokinetics

Mechanism of action: Dabigatran etexilate is the prodrug of the active moiety dabigatran,
which is an oral direct thrombin inhibitor. Both clot-bound and free thrombin are
inhibited by dabigatran.

Therapeutic use: It is approved for the prevention of stroke and systemic embolism in
patients with nonvalvular atrial fibrillation.

Alternative: Because of its efficacy, oral bioavailability, and predictable pharmacokinetic

properties, dabigatran may be an alternative to enoxaparin for thromboprophylaxis in
orthopedic surgery.
Route: Administered Orally.

Elimination: Eliminated renally.

Metabolism: The CYP450 system does not play a role in

metabolism of dabigatran. Instead, dabigatran is
a substrate for P-glycoprotein (P-gp)

Adverse effects: Bleeding.

Caution Should be used with caution in renal

impairment or in patients over the age of 75, as
the risk of bleeding is higher in these groups.
Antidot: There is no approved antidote for reversing bleeding associated with dabigatran.

Monitoring: Dabigatran does not require routine monitoring of the international normalized ratio
(INR) and has fewer drug interactions as compared to warfarin.

GI adverse effects are common with this drug and may include dyspepsia, abdominal pain,
esophagitis, and GI bleeding.

Abrupt discontinuation should be avoided, as patients may be at increased risk for thrombotic events.

Contraindication: This drug is contraindicated in patients with mechanical prosthetic heart valves
and is not recommended in patients with bioprosthetic heart valves.
Rivaroxaban and Apixaban
Mechanism of action:

Rivaroxaban and apixaban are oral inhibitors of factor Xa. Both agents bind to the active site of
factor Xa, thereby preventing its ability to convert prothrombin to thrombin.

Therapeutic use:

● Rivaroxaban is approved for treatment and prevention of DVT and Pulmonary Embolism and
for the prevention of stroke in nonvalvular atrial fibrillation.
● Apixaban is used for stroke prevention in nonvalvular atrial fibrillation.
 ADRs

● Bleeding is the most serious adverse effect for the factor Xa inhibitors. As both drugs are
eliminated renally, declining kidney function can prolong the effect of the drugs and, therefore,
increase the risk of bleeding.
● Neither drug should be used in severe renal dysfunction (creatinine clearance less than 15
mL/min).

Antidot: There is no antidote available to reverse bleeding caused by rivaroxaban or apixaban.

● Abrupt discontinuation of these agents should be avoided.

Warfarin
Introduction:
● The coumarin anticoagulants owe their action to the ability to antagonize the cofactor
functions of vitamin K.
● Initially used as a rodenticide, warfarin is now widely used clinically as an oral anticoagulant.
● The INR is the standard by which the anticoagulant activity of warfarin therapy is
monitored.
● The goal of warfarin therapy is an INR of 2 to 3 for most indications, with an INR of 2.5 to
3.5 targeted for some mechanical valves and other indications.
● Warfarin has a narrow therapeutic index. Therefore, it is important that the INR is
maintained within the optimal range as much as possible, and frequent monitoring may be
required.
Mechanism of action:
Factors II, VII, IX, and X require vitamin K as a cofactor for their synthesis by the liver. These factors
undergo vitamin K–dependent post translational modification, whereby a number of their glutamic acid
residues are carboxylated to form γ-carboxyglutamic acid residues.

The γ-carboxyglutamyl residues bind calcium ions, which are essential for interaction between the
coagulation factors and platelet membranes. In the carboxylation reactions, the vitamin K–dependent
carboxylase fixes CO2 to form the new COOH group on glutamic acid. The reduced vitamin K cofactor is
converted to vitamin K epoxide during the reaction.

Vitamin K is regenerated from the epoxide by vitamin K epoxide reductase, the enzyme that is inhibited by
warfarin. Warfarin treatment results in the production of clotting factors with diminished activity (10% to
40% of normal), due to the lack of sufficient γ-carboxyglutamyl side chains.

Unlike heparin, the anticoagulant effects of warfarin are not observed immediately after drug administration.
Instead, peak effects may be delayed for 72 to 96 hours, which is the time required to deplete the pool of
circulating clotting factors. The anticoagulant effects of warfarin can be overcome by the
administration of vitamin K. However, reversal following administration of vitamin K takes approximately
24 hours (the time necessary for degradation of already synthesized clotting factors).
Warfarin MOA:
 Therapeutic uses:

● Warfarin is used in the prevention and treatment of DVT, stroke prevention,

stroke prevention in the setting of atrial fibrillation and/or prosthetic heart
valves, protein C and S deficiency, and antiphospholipid syndrome.
● It is also used for prevention of venous thromboembolism during orthopedic
or gynecologic surgery
Pharmacokinetics (WARFARIN)

Absorption: Rapidly absorbed after oral administration (100% bioavailability).

Protein Binding: Warfarin is highly bound to plasma albumin, which prevents its
diffusion into the cerebrospinal fluid, urine, and breast milk.

Half-life: 40 hours (variable among individuals)

Metabolism: Metabolized by the CYP450 system

Excretion: After conjugation to glucuronic acid, the inactive metabolites are

excreted in urine and feces.

Placental barrier: Warfarin readily crosses the placental barrier.

Drugs affecting the anticoagulant
effect of warfarin.

Drug Interactions: Warfarin has numerous

drug interactions that may potentiate or
attenuate its anticoagulant effect.
Adverse effects
● The principal adverse effect of warfarin is hemorrhage, and the agent has a black box warning for
bleeding risk.
● Therefore, it is important to frequently monitor the INR and adjust the dose of warfarin. Minor
bleeding may be treated by withdrawal of the drug or administration of oral vitamin K1 ,but
severe bleeding may require greater doses of vitamin K given intravenously. Whole blood, frozen
plasma, and plasma concentrates of blood factors may also be used for rapid reversal of warfarin.
● Skin lesions and necrosis are rare complications of warfarin therapy. Purple toe syndrome, a rare,
painful, blue-tinged discoloration of the toe caused by cholesterol emboli from plaques, has also
been observed with warfarin therapy.
● Warfarin is teratogenic and should never be used during pregnancy. If anticoagulant therapy is
needed during pregnancy, heparin or LMWH may be administered.
Interactions with
Anticoagulants
REFERENCE
● Anderson, P., Knoben, J., Troutman, W., 2001. Handbook of Clinical Drug Data, 10th edition. ed. McGraw-Hill Medical, New
York.
● Hankey, G.J., Eikelboom, J.W., 2003. Antiplatelet drugs. Med. J. Aust. 178, 568–574.
https://doi.org/10.5694/j.1326-5377.2003.tb05361.x
● Lacy, C.F., Armstrong, L.L., Goldman, M.P., Lance, L.L., 2008. Drug Information Handbook 17th Edition. Lexi-Comp.
● Trevor, A., Katzung, B., Knuidering-Hall, M., 2015. Katzung & Trevor’s Pharmacology Examination and Board Review,11th
Edition, 11th edition. ed. McGraw-Hill Education / Medical, New York
● Bivard, A., Lin, L., & Parsonsb, M. W. (2013). Review of stroke thrombolytics. Journal of stroke, 15(2), 90–98.
https://doi.org/10.5853/jos.2013.15.2.90
● Mohammadi, E., Seyedhosseini-Ghaheh, H., Mahnam, K., Jahanian-Najafabadi, A., & Mir Mohammad Sadeghi, H. (2019).
Reteplase: Structure, Function, and Production. Advanced biomedical research, 8, 19. https://doi.org/10.4103/abr.abr_169_18
● Huang X, Moreton FC, Kalladka D, Cheripelli BK, MacIsaac R, Tait RC, Muir KW. Coagulation and Fibrinolytic Activity of
Tenecteplase and Alteplase in Acute Ischemic Stroke. Stroke. 2015 Dec;46(12):3543-6. doi: 10.1161/STROKEAHA.115.011290.
Epub 2015 Oct 29. PMID: 26514192.
● Aikens, G. B., Osmundson, J. R., & Rivey, M. P. (2014). New oral pharmacotherapeutic agents for venous thromboprophylaxis
after total hip arthroplasty. World Journal of Orthopaedics, 5(3), 188–203. https://doi.org/10.5312/wjo.v5.i3.188
Thank you for your
attention
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