LIYANA SAFITRI

1800077
D3 – 3B
TROMBOLITIC MEDICATION
1. Streptokinase
Mechanism of Action: Streptokinase activates plasminogen indirectly
by first joining plasminogen to form an activator complex. Furthermore,
the activator complex catalyzes the change of free plasminogen to
plasmin.
indications: deep venous thrombosis, pulmonary embolism, acute
myocardial infarction, acute / subacute peripheral thrombosis.
Contraindications:
High blood antistreptokinase levels.
Dose. IV:
Adult dose for acute myocardial infarction is recommended a total dose
of 1.5 million IU by infusion for 1 hour. For acute venous thrombosis,
pulmonary embolism, acute arterial thrombosis or embolism can be
given a loading dose of 250,000IU infusion for 30 minutes followed by
100,000 IU / hour (usually for 24 hours in pulmonary embolism
patients, 24-72 hours in patients with arterial thrombosis or embolism
and up to 72 hours in patients with deep vein thrombosis).
Side effects:
Bleeding, head and back pain, temporary rise in temperature,
anaphylactic reaction.
2. Urokinase
Mechanism of Action: Unlike streptokinase, urokinase directly activates
plasminogen. In addition to pulmonary embolism, urokinase is also
used for thromboembolism in arteries and veins. Like streptocination
this drug does not work specifically against fibrin, causing systemic lysis
(fibrinogenolysis and destruction of other blood clotting factors). The
use of urokinase with heparin causes a greater incidence of bleeding
(45%) compared to heparin alone (27%). Should not be given to
patients with pulmonary embolism who are older than 50 years,
patients with a history of cardiopulmonary disease or severe
hemostatic disorders.
indications: intravenous thrombosis of the arteries and intravenous
cannula, thrombolysis of the eye, deep vein thrombosis, pulmonary
embolism, periverial vascular occlusion.
Contraindications: Urolithiasis
dosage: 1000-4500 IU / kgBB loading dose IV followed by IV infusion of
4400 IU / kgBB / hour.
Side effects: Bleeding, head and back pain, temporary rise in
temperature, anaphylactic reaction.
3. Tissue plasminogen activator (t-PA)
Mechanism of Action: Endogenous plasminogen is also activated by an
activator of tissue plasminogen alteplase and reteplase which is an
activator of human tissue plasminogen and is produced by DNA
engineering techniques.
This drug works more selectively in activating plasminogen that binds
to fibrin than free plasminogen in the blood. Therefore, t-PA works
more selectively against blood clots / fibrin.
indications: thrombolytic treatment of acute myocardial infarction, acute
massive pulmonary embolism with unstable hemodynamics, and acute
ischemic stroke.
contraindications: damage to the central nervous system and neoplasms,
advanced liver disease, endocarditis infections, pregnancy.
dose: STEMI: bolus 15 mg iv, then 0.75 mg / kg for 30 minutes, then 0.5 mg /
kg for 60 minutes. total dose of no more than 100 mg.
Pulmonary embolism: 10 mg intravenous injection for 1-2 minutes, followed
by 90 mg intravenous infusion for 2 hours, a maximum of 1.5 mg / kg in
patients weighing less than 65 kg.
acute stroke: intravenous infusion of 0.9 mg / kg (maximum 90 mg) for 60
minutes, 10% of the dose given by intravenous injection, elderly. not
recommended for ages> 80 years.
Side effects: Bleeding, temporary temperature rise.
 Antiplatelet
Antiplatelet is a drug that can inhibit platelet aggregation so that
thrombus formation is inhibited, which is especially often found in the
arterial system which works to prevent adhesion of platelets with the
walls of injured blood vessels or with other platelets, which is the first
step in the formation of thrombus
 classification of antiplatelet drugs
1. Aspirin
Mechanism of Action: Aspirin inhibits the synthesis of thromboxane A2
(TXA2) in platelets and prostacyclin (PGI2) in blood vessels by
irreversibly inhibiting the enzyme cyclooxygenase (but cyclooxygenase
can be reshaped by endothelial cells). Inhibition of cyclooxygenase
occurs because aspirin acetylates the enzyme. Small doses of aspirin
can only suppress the formation of TXA2, resulting in a reduction in
platelet aggregation.
Dosage: As an antiplatelet effective dose of aspirin 80-320 mg per day.
Indications: To relieve pain, especially headaches and dizziness,
toothache, and muscle aches and reduce fever.
Contra Indications: Patients with peptic ulcers and are sensitive to
salicylic acid derivatives, sufferers of asthma and allergies. Patients who
have or often experience bleeding under the skin, patients who are on
therapy with anticoagulants, patients with hemofolia and
thrombocytopenia.
Side effects: nausea, and gastrointestinal bleeding can usually be
avoided if the daily dose is no more than 325 mg. The use of antacids or
H2 antagonists can reduce these effects. These drugs can interfere with
hemostasis in surgery and when given with heparin or oral
anticoagulants can increase the risk of bleeding.
2. Dipiridamol
Mechanism of Action: Dipyridamole inhibits adenosine uptake and
metabolism by erythrocytes and blood vessel endothelial cells, thereby
increasing its level in plasma. Adenosine inhibits platelet function by
stimulating adenylate cyclase and is a vasolidator. Dipyridamole also
increases the antiaggregation effects of prostacyclin.
Dosage: For long-term prophylaxis in patients with artificial heart valves
400 mg / day along with warfarin. To prevent platelet activation during
by-pass surgery the dose is 400 mg starting 2 days before surgery.
Contraindication: Hypersensitivitas
Indications: increase intracellular cAMP levels by inhibiting cyclic
nucleotide phosphodieterase. This inhibits the synthesis of
thromboxane A2 and can strengthen the effects of prostacyclin (PGI2)
to fight platelet adhesions and hence reduce platelet adhesions on
thrombogenic surfaces.
Side effects: headaches, When used for patients with angina pectoris,
dipyridamole sometimes worsens symptoms due to coronary steal
phenomena. Other side effects are dizziness, syncope, and
gastrointestinal disorders.
3. Tyclopidine
Mechanism of Action: Tyclopidine inhibits platelet aggregation induced
by ADP. Maximum inhibition of platelet aggregation is only seen after 8-
11 days of therapy.
dose: 1 tab given 1-2x / day (250-500 mg / day).
Indications: Reducing the risk of thrombotic stroke in patients who have
had a precursor to a stroke or having had a stroke is an option if there is
an intolerance to aspirin.
Contraindications: Changes in blood picture, bleeding tendency,
pregnancy, lactation and children.
Side effects: Common are nausea, vomiting, and diarrhea. The most
dangerous is severe neutropenia in about 1% of patients.
4. Clopidogrel
Mechanism of Action: As an antagonist ADP inhibits the binding of ADP
to its platelet receptor selectively and also activates the GP IIb / IIIa
receptor complex mediated by the ADP so that prevention of blood
plates occurs.
Dosage: Generally 75 mg / day with or without a loading dose of 300
mg.
Indications: Use of prophylactic therapy secondary to brain and cardiac
infarction in patients who are not acid resistant or have attacks while
using acid.
Contraindications: Changes in blood picture, severe liver failure,
bleeding tendencies, pregnancy.
Side effects: GIT bleeding, nasal bleeding, hematoma, changes in blood
picture, GIT complaints.
5. Glycoprotein IIb / IIIa inhibitors
Absiximab is a mice / human monoclonal antibody.
Mechanism of action: Absiximab works by blocking the glycoprotein
IIb / IIIa receptors thereby inhibiting platelet aggregation. Absiksimab is
used with asspirin and heparin for patients undergoing angioplasty and
atherectomy.
Indications: Use of non-stable angina pectoris therapy, percutaneous
coronary intervention
Contraindications: Active bleeding, major surgery or trauma in the last
2 months, vascular malformations, bleeding tendencies, malignant
hypertension, thrombocytopenia, severe liver disorders,
cerebrovascular complications in the last 2 years.
Side effects: Bleeding, back pain, hypotension, nausea and vomiting,
chest pain, headache, bradycardia, fever, formation of human antisimer
antibodies.
Tirofiban is a small molecular nonpeptide compound that acts as an
inhibitor of αIIbβ3 which is eptifibatid.
Mechanism of action: Specific inhibition of fibrinogen binding to GP-IIb /
IIIa receptors of platelets.
indications: Indications Prevent blood clots or heart attacks.
Contraindications: Active bleeding, major surgery or trauma in the last 2
months, vascular malformations, bleeding tendencies, malignant
hypertension, thrombocytopenia, severe liver disorders, cerebrovascular
complications in the last 2 years.
Side effects: Bleeding, back pain, hypotension, nausea and vomiting, chest
pain, headache, bradycardia, fever, formation of human antisimer
antibodies.
Anticoagulant
Anticoagulants are used to prevent blood clots by inhibiting the
formation or inhibiting the function of several blood clotting factors. On
this basis anticoagulants are needed to prevent the formation and
spread of thrombus and embolism. Oral and heparin anticoagulants
inhibit fibrin formation and are used prophylactically to reduce the
incidence of thromboembolism especially in veins. Both types of
anticoagulants are also useful for the treatment of arterial thrombosis
because they affect the formation of fibrin that is needed to maintain
platelet clots. In a thrombus that has formed, anticoagulants only
prevent the enlargement of the thrombus and reduce the chance of an
embolism, but do not reduce the thrombus.
 ANTI-COAGULANT DRUGS

Heparin Other Anti

Coagulants
LMWH Hirudin
Direct Thrombin
Fondaparinux Danaparoid
Inhibitor
Enoxaparin Drotrecogin alfa
Warfarin Dabigatran –
Parnaparin
etexilate
Dalteparin
Ximelagatran
Nadroparin
 1. Heparin
Heparin
Heparin has an anticoagulation effect, this is because heparin increases
anti-thrombin activity, on the contrary decreases thrombin activity and
coagulation factors.
I : Treatment of DVT and pulmonary embolism, unstable angina pectoris,
myocardial infarction I, in DIC patients, and prevention of
thromboembolism for those at high risk.
Ki : Hemophilia and other hemorrhagic disorders, thrombocytopenia,
gastric ulcers, cerebral hemorrhage that just happened. Severe
hypertension, severe cardiac disease (including esophageal varices),
kidney failure, after severe injury or surgery, hypersensitivity to heparin.
ES : Hemorrhage, skin necrosis, thrombocytopenia, hypercalcemia,
hypersensitivity reactions (urticaria, angiodema, and anaphylaxis).
D: Acute myocardial infarction: Bolus IV 60 U / KGBB, maximum dose of
4000 U. IV infusion of 12 U / KGBB for 24-48 hours with a maximum
dose of 1000 U / h Target APTT 1.5-2x control.
DVT and pulmonary embolism: 5,000 units of bolus (I.V) followed by
1,200-1,600 units every D hours through an infusion pump until
reaching an APTT value of 1.8-2.5 times that of the control (APTT is
checked every 6 hours). The duration of administration depends on the
severity of the case. Thromboembolic prophylaxis in patients
undergoing surgery: 5,000 units subcutaneously 2 hours before surgery
and continued 5,000 units every 12 hours until the patient is discharged
from the hospital.
DVT and pulmonary embolism: 5,000 units of bolus (I.V) followed by
1,200-1,600 units every D hours through an infusion pump until
reaching an APTT value of 1.8-2.5 times that of the control (APTT is
checked every 6 hours). The duration of administration depends on the
severity of the case. Thromboembolic prophylaxis in patients
undergoing surgery: 5,000 units subcutaneously 2 hours before surgery
and continued 5,000 units every 12 hours until the patient is discharged
from the hospital.

S: 5,000 IU / ml Injection (generic Heparin. Inviclot, Vaxcel Heparin

Sodium)
2. Low Molecular Weight gelatin ( LMWH)
The mechanism of action of MWH as an anti-coagulant is:
- Inhibits factor Xa.
- Increase Tissue Factor Pathway Inhibitors (TFPI) from endothelium.
- TFP will bind to the Xa factor & inhibit the Vila complex tissue factor.
Inhibiting the incorporation of factor Xa with platelets.
Indications and side effects of LMWH are the same as heparin.
The advantages of LMWH over Heparin are:
1. Have a more predictable pharmacokinetic profile that allows the
use of subcutaneous doses based on body weight without requiring
rigorous laboratory monitoring.
2. Has a lower incidence of thrombocytopenia than heparin .
3. Has a lower risk of bleeding.
4. The frequency of administration is less than ordinary heparin. Basic
Pharmacology Notes
Fondaparinux
I: Prevention of venous thromboembolic events (VIE) in patients
undergoing major orthopedic surgery on limbs in the section below and
in patients at risk of thromboembolic complications, treatment of acute
deep vein thrombosis (DVT). 3D treatment of acute pulmonary
embolism (PE), treatment of unstable angina or non-ST elevation
segments of myocardial infarction (UA / NSTEMI). additional treatment
of ST segrnen myocardial infarction elevation (STEMI) in patients who
are on treatment with thrombolytic.
KI: hypersensitivity, active bleeding. acute bacterial endocardits. Severe
kidney disorders (creatinine clearance
ES : Anemia, bleeding, from bositopenia. purpura, abnormafunction
liver test results, edema.
D : Myocardial infarction: 2.5 mg per day subcutaneously. Prevention of
venous thromboembolic events (VTE): 2.,5 mg once daily given
subcutaneously after surgery, the initial dose should be given at least 6
hours after surgery is complete. Treatment is continued for 5-9 days
Treatment of deep veln thrombosis (DVT) and pulmonary embollage:
dose 5 mg for BW 100 kg. subcutaneous dibenchon treatment for at
least 5 days, treatment with vitamin K anfagonists begins as soon as
possible within 72 hours.

S : Prefiled-syringe (for subcutaneous injection) 2.5mg / 0.5ml: Arictra

Enoxaparin
I : Venous thrombous obstruction associated with orthopedic surgery
or general surgery, treatment of venous thrombosis in patients treated
for acute ocular disease including cardiac insufficiency, respiratory
failure, severe failure, severe infections, rheumatic diseases during
hemodialysis: prophylaxis of deep vein thrombosis in patients treated
for acute angina including cardiac insufficiency, respiratory failure,
severe failure, severe infections, rheumatic diseases during
hemodialysis: prophylaxis of deep venous thrombosis non-Qwave,
taken together with salicylic acetic acid: prevention of thrombus in
extracorporeal circulation.
KI : History of thrombocytopenia during therapy with enoxaparin.
bleeding tendencies, organic lesions that tend to bleed, acute bacterial
endocarditis KI, major stroke blood clotting disorders, acute
gastrointestinal ulcers, hypersensitivity.

ES : Symptoms of bleeding, thrombocytopenia. Rarely hematomas &

skin necrosis at the injection site, skin allergic. and systemic allergic
reactions.
D : Myocardial Infarction: 1 mg / kgBB subcutaneous injection is
administered every 12 hours. Prophylaxis of deep venous thrombosis,
(subcutaneous injection) In patients at risk of sedong 20 mg (2000
units) 2 hours before surgery, then 20 mg (2000 units) every 24 hours
for 7-10 days: O In patients at high risk: 40 mg ( 4000 units) 12 hours
before surgery, then 40 mg (4000 units) every 24 hours per day 710
days Treatment of deep vein thrombosis through subculant injection.
Img / kgsa (100 units / kg88) for every 12 hours of bioseed during not 6
hours until oral anticoogulant is achieved.
S : - Profiled-synnge 20 mg/02ml: lovenox
- Prefiled-syringe 40 ml/0.4 ml : lovenox
- prefille – syiringe 60 mg/0,6 mm : lovenox
 3. Warfarin
Warlarin is an oral anticoagulant. This drug inhibits coagulation by
preventing enzymatic reduction of vitamin K in the liver. Vitamin K (in
the form of reduction) is a cofactor responsible for activation of blood
clotting factors il, Vil, IX. and X. proteins C. S and Z. Oral anticoagulants
prevent reduction of oxidized vitamin K so that activation of blood
clotting factors is interrupted or does n day ot occur. Warfarin
indications are the same as heparin and are usually given after heparin
administration, Warfarn is also used as a systemic preventative drug for
patients with acute myocardial infarction, prolonged bed rest. heart
failure, atrial fibrillation, patients with prosthetic valves, the use of
wortarin for CHD patients is still reaping the pros and cons so that this
drug has not been included in the protocol for CHD therapy.
Warfarin Na
I: Prophylactic embolization in rheumatic heart disease and
prophylactic atrial fibrillation after valve fitting prosthetic heart:
prophylaxis and treatment of venous thrombosis and pulmonary
embolism: transient cerebral ischemic attacks.

KI : Pregnancy, peptic ulcer, severe hypertension, bacterial

endocarditis.
ES : decreased, skin necrosis, purple toes, jaundice, liver dysfunction;
nausea, vomiting, pancreatitis.

D : The dosage is individual. Initial dose 5-10 mg / day for 2 days.

Dosage adjustments made according to the results of INR in the range
of 2-3 are already considered therapeutic doses. Maintenance dose 2-
10 mg /day.

S : Tablet 1 mg: Warfarin Eisai Tablet 2 mg: Simarc-2, Coumadin, Notisil

 4. Direct Thrombin Inhibitor
Dabigatran etexilate: Is an oral direct thrombin inhibitor that selectively
inhibits free thrombin and thrombin that bind to blood clots. Several
studies have shown dabigatran is effective in reducing the risk of
venous thromboembolism in orthopedic surgery. Example trademark:
Pradaxa

Ximelagatran: Ximelagatran is as effective as warfarin in preventing

strokes and thromboembolic events in atrial fibrillation patients. The
advantage of this drug compared to warfarin is that it has a more stable
pharmacokinetics and the variation per individual is also not large so
that it can be given with foxed dose without the need for checking
blood coagulation.