Fibrinolytics & antifibrinolytics

FIBRINOLYTICS &

ANTIFIBRINOLYTICSBy Dr.Elza Emmannual

FIBRINOLYTICS

Drugs used to lyse thrombi to recanalize occluded blood vessels

Works by activating the natural fibrinolytic system

NATURAL FIBRINOLYTIC SYSTEM

PLASMINOGEN

FIBRIN FRAGMENTS

FIBRIN

PLASMIN

ACTIVATORSt-PA, Kallikrein,Factor Xa

INHIBITORSα2 Antiplasmin

α2 Macroglobulin

• Venous thrombi lysed more easily

• Recent thrombi respond better

• Little effect on thrombi >3 days old

Clinically important fibrinolytics are,

• Streptokinase

• Urokinase

• Alteplase (rt PA)

• Reteplase

• Tenecteplase

Streptokinase• Source:β haemolytic streptococci group C

• Inactive as such

• Combines with circulating plasminogen forms activator complex proteolysis of plasminogen Active plasmin

• Cheap,widely used in India

Disadvantages1.Activates both circulating & fibrin bound plasminogenDepletion of circulating plasminogen → bleeding

2. Antistreptococcal Abs from past infections inactivate considerable fraction of initial dose , loading dose needed

3.AntigenicHSR & anaphylaxis when used for 2nd time

4.Repeat doses less effective due to neutralisation by Abs

Urokinase• Isolated from human urine ,now from cultured human

kidney cells

• Activates plasminogen directly

• Moderately specific to fibrin bound plasminogen

• Nonantigenic

• Indicated in whom streptokinase has been used for an earlier episode

Alteplase Produced by recombinant DNA technology

•Nonantigenic

•Short t1/2 so given as slow IV infusion

•ExpensiveReteplase Produced by

recombinant DNA technology

•Modified form of rt-PA

•Long acting

•So given as bolus dose repeated in 30 min

Tenecteplase

Produced by r DNA technology

•Mutant variant of rt-PA•Long duration of action•Single IV bolus

USES1.Acute MI –

– chief indication,alternate to emergency percutaneous coronary intervention with stent placement

– Golden period-1hr,Better results- within 3hrs

– Timelag in starting infusion is critical in • Reducing area of necrosis• Preserving ventricular function• Reducing mortality

2.Deep vein thrombosis

3.Pulmonary embolism

4.Peripheral arterial occlusion

5.Stroke- – rt-PA –approved for treatment of ischaemic stroke– treated within 3 hours of onset– intracranial hemorrhage has to be ruled out

CONTRAINDICATIONS• All situations where the risk of bleeding is increased– Recent trauma– Surgery– Biopsy– Hemorrhagic stroke– Peptic ulcer– Severe hypertension– Aneurysms– Bleeding disorders– Diabetes– Acute pancreatitis– pregnancy

ANTIFIBRINOLYTICS

Drugs which inhibit plasminogen activation & dissolution of clot

EPSILON AMINO-CAPROIC ACID(EACA)

• Analogue of lysine

• Binds to lysine binding sites of plasminogen & plasmin so that it cannot bind to fibrin & lyse the clot

USES

• Overdose of fibrinolytics

• To prevent recurrence of G.I & subarachnoid hemorrhage

• Certain traumatic & surgical bleedings like prostatectomy,tooth extraction in haemophiliacs

• Abruptio placentae,PPH & menorrhagia

Adverse Effects• In hematuria –ureteric obstruction by the unlysed clots

• Intravascular thrombosis

• Hypotension,bradycardia,arrhythmias

• Caution in impaired renal function

• Myopathy

TRANEXAMIC ACID• MOA-similar to EACA• 7 times potent than EACA• Preferred drug for bleeding due to– Fibrinolytic drugs– Cardiopulmonary bypass surgery– Tonsillectomy,prostatic surgery,tooth extraction in

haemophiliacs– Menorrhagia– Recurrent epistaxis,hyphema due to ocular

trauma,peptic ulcer

Adverse Effects

• Nausea• Diarrhoea• Thromboembolic events• Disturbed colour vision• Allergic reactions• Thrombophlebitis

PLASMINOGEN

FIBRIN FRAGMENTS

FIBRIN

PLASMIN

ACTIVATORS

INHIBITOR

• Streptokinase• Urokinase• Alteplase• Reteplase• Tenecteplase

• EACA• Tranexaemic acid

THANK YOU