fibrinolytic drugs (thrombolytic drugs ) by prof. hanan hagar

Fibrinolytic Drugs Fibrinolytic Drugs

(Thrombolytic Drugs )(Thrombolytic Drugs )

By Prof. Hanan HagarBy Prof. Hanan Hagar

Definition: are Definition: are Drugs that cause lysis of Drugs that cause lysis of already formed thrombusalready formed thrombus

Fibrinolyic drugsFibrinolyic drugs

1. 1. Streptokinase.Streptokinase.

2. Anistreplase.2. Anistreplase.

3. Urokinase3. Urokinase

4. Tissue plasminogen activators ( t -PA).4. Tissue plasminogen activators ( t -PA).

Mechanism of ActionMechanism of Action acts directly or indirectly to convert acts directly or indirectly to convert

plasminogen to plasmin within the thrombusplasminogen to plasmin within the thrombus Plasmin degrades fibrin clots and other Plasmin degrades fibrin clots and other

plasma proteins (non-fibrin specific)plasma proteins (non-fibrin specific)

UsesUses

1.1. Acute myocardial infarction.Acute myocardial infarction.

2.2. Acute thrombotic stroke.Acute thrombotic stroke.

3.3. Peripheral artery occlusion.Peripheral artery occlusion.

4.4. Pulmonary embolism.Pulmonary embolism.

5.5. Deep venous thrombosis.Deep venous thrombosis.

PrecautionsPrecautions Should be given as soon as possible.Should be given as soon as possible. Fibrinolytics are given intravenously.Fibrinolytics are given intravenously.

Bleeding can occur (Systemic fibrinolysis).Bleeding can occur (Systemic fibrinolysis).

ContraindicationsContraindications PregnancyPregnancy

Cerebrovascular diseaseCerebrovascular disease Uncontrolled hypertension.Uncontrolled hypertension.

Peptic ulcerPeptic ulcer

StreptokinaseStreptokinaseIs a protein synthesized by B-hemolytic Is a protein synthesized by B-hemolytic

streptococci.streptococci.

Mechanism of ActionMechanism of Action acts indirectly by forming plasminogen-acts indirectly by forming plasminogen-

streptokinase complex which converts inactive streptokinase complex which converts inactive plasminogen into active plasmin.plasminogen into active plasmin.

It is the least expensive.It is the least expensive. T 1/2 = half an hour.T 1/2 = half an hour.

I.V. Infusion (250,000U then 100,000U/h for I.V. Infusion (250,000U then 100,000U/h for 24-72 h). 24-72 h).

Side effectsSide effects1.1. Bleeding due to Bleeding due to activation of circulating activation of circulating

plasminogenplasminogen2.2. Hypersensitivity due to antigenicity Hypersensitivity due to antigenicity (rash, (rash,

fever, allergic reaction).fever, allergic reaction).3.3. Hypotension.Hypotension.4.4. not used in patients with streptococcal not used in patients with streptococcal

infections (have antistreptococcal antibodies infections (have antistreptococcal antibodies and may develop fever, allergic reactions and and may develop fever, allergic reactions and resistance upon treatment with streptokinase).resistance upon treatment with streptokinase).

Anistreplase ( APSAC )Anistreplase ( APSAC ) Anisoylated plasminogen-streptokinase Anisoylated plasminogen-streptokinase activator complex activator complex Is a complex of purified human plasminogen Is a complex of purified human plasminogen + bacterial streptokinase that rendered + bacterial streptokinase that rendered inactive by introducing anisoyl group at its inactive by introducing anisoyl group at its active site.active site. It is a It is a prodrugprodrug, de-acylated in circulation into , de-acylated in circulation into the active plasminogen-streptokinase complex the active plasminogen-streptokinase complex ((acts directly to convert plasminogen into acts directly to convert plasminogen into plasminplasmin).).

Advantages Advantages

Longer duration of action (Longer duration of action (TT1/2 1/2 is is 70-120 min70-120 min).).

Given as a bolus I.V. (30 U over 3 - 5 min.).Given as a bolus I.V. (30 U over 3 - 5 min.).

DisadvantagesDisadvantages(less than streptokinase alone).(less than streptokinase alone).

1. Expensive.1. Expensive.2. Antigenic.2. Antigenic.

3. Allergic reactions.3. Allergic reactions.4. Bleeding due to minimal fibrin specificity 4. Bleeding due to minimal fibrin specificity

UrokinaseUrokinaseHuman enzyme synthesized by the kidney, Human enzyme synthesized by the kidney,

obtained from either urine or cultures of human obtained from either urine or cultures of human embryonic kidney cells.embryonic kidney cells.

acts directly converting plasminogen to active acts directly converting plasminogen to active plasmin.plasmin.

given by intravenous infusiongiven by intravenous infusion DoseDose 300,000U over 10 min then 300,000U/h for 300,000U over 10 min then 300,000U/h for

12h.12h.

DisadvantagesDisadvantages 1. Expensive.1. Expensive. 2. Systemic lysis. 2. Systemic lysis.

Advantages Advantages 1. Not antigenic.1. Not antigenic.

2. No Hypotension.2. No Hypotension.

Tissue Plasminogen Activators ( t - PA )Tissue Plasminogen Activators ( t - PA )

AlteplaseAlteplase

- - AlteplaseAlteplase ( Single Chain ). ( Single Chain ).- Reteplase Reteplase ( Deleted Form ).( Deleted Form ).

- TenecteplaseTenecteplase• All are recombinant human t - PA.All are recombinant human t - PA.

• Synthesis by recombinant DNA Synthesis by recombinant DNA technology.technology.

AdvantagesAdvantages

1.1. Clot specific ( fibrin specific ).Clot specific ( fibrin specific ). activate fibrin-bound plasminogen rather activate fibrin-bound plasminogen rather

than free plasminogen in blood.than free plasminogen in blood.

2. Limited systemic fibrinolysis.2. Limited systemic fibrinolysis.

3. Non–antigenic (Can be used in patients 3. Non–antigenic (Can be used in patients with antistreptococcal antibodies).with antistreptococcal antibodies).

Alteplase Alteplase very short half life (5 min.)very short half life (5 min.)

(60 mg i.v. bolus + 40 mg infusion over 2 h).(60 mg i.v. bolus + 40 mg infusion over 2 h).

Reteplase Reteplase (two I.V. bolus of 10 U ).(two I.V. bolus of 10 U ).

Contraindications to thrombolytic therapyContraindications to thrombolytic therapy

Absolute contraindications include:Absolute contraindications include: Recent head trauma or caranial tumorRecent head trauma or caranial tumor Previous hemorrhagic shockPrevious hemorrhagic shock StrokeStroke Active internal bleedingActive internal bleeding Major surgery within two weeksMajor surgery within two weeks Relative contraindications include:Relative contraindications include: Active peptic ulcer, diabetic retinopathy, Active peptic ulcer, diabetic retinopathy,

pregnancy, uncontrolled hypertensionpregnancy, uncontrolled hypertension

Antiplasmin Antiplasmin (Antifibrinolytics)(Antifibrinolytics)

inhibit plasminogen activation and thus inhibit plasminogen activation and thus inhibit fibrinolysis and promote clot stabilization.inhibit fibrinolysis and promote clot stabilization.

Tranexamic Acid.Tranexamic Acid.Aminocaproic AcidAminocaproic Acid

Aprotinin.Aprotinin.

Aminocaproic Acid & tranexamic acidAminocaproic Acid & tranexamic acid Synthetic Synthetic

It competitively inhibits plasminogen activationIt competitively inhibits plasminogen activation Given orallyGiven orally

Aprotinin Aprotinin It acts by blocking plasmin.It acts by blocking plasmin.

Uses Uses Can be taken orally or I.V.Can be taken orally or I.V.

1. Adjunctive therapy in hemophilia.1. Adjunctive therapy in hemophilia.2. Antidote for fibrinolytics.2. Antidote for fibrinolytics.