EXTRINSIC SYSYTEM
INTRINSIC SYSTEM
EXTRINSIC SYSTEM
DAMAGED TISSUE
TISSUE FACTOR
(VII)
INTRINSIC SYSTEM
VESSEL WALL
DAMAGE ( XII, XI)
THROMBIN
FIBRINOGEN
FIBRIN
COAGULANTS
VITAMIN K - K1 PHYTONADIONE
K2 MENAQUINONE
K3 SYNTHETICMENADIONE
MISCELLANEOUS- FIBRINOGEN
ANTIHEMOPHILIC
FACTOR
ADRENOCHROME
ETHAMSYLATE
50-100g/ day
USES
1. Hemorrhage or threatened bleeding due to
coumarin or inandione anti coagulants
2. Hypoprothrombinemia of the premature infant
administration of phytomenadione to mother 1-5
mg, 4 to 24 hrs before delivery or 0.3 mg/kg im to
the baby
3 Hypoprothombinemia due to intestinal
malabsorption
4 Aspirin overdosage
TOXICITY
FIBRINOGEN
This is given in hemophilia , auto afibrinogenemic states
0.5 g is infused iv
ANTI HEMOPHILIC FACTOR
Concentrated anti hemophilic globulin is used for
hemophilia
It is short acting . Action lasts for 1-2 days 5-10 IU /kg
iv repeated 6-12 hourly
ADRENOCHROME MONO SEMICARBAZONE
Reduces Capillary Fragility
Controls Oozing From Raw Surfaces
Prevents microvessel bleeding
Used in epistaxis
hematuria
micro retinal hemorrhage
secondary hemorrhage from wounds
ETHAMSYLATE
Reduces capillary bleeding when platelets are adequate.
Used in prevention and treatment of bleeding in menorrhagia,
after abortion, epistaxis, malena, hematuria,
SIDE EFFECTS
Nausea, Rash ,Fall In Bp,
Headache
ANTICOAGULANTS
1.
USED IN VITRO
A. HEPARIN
B. CALCIUM COMPLEXING
AGENTS
Sodium citrate,
Sodium oxalate,
Sodium edetate
2. USED IN VIVO
A. HEPARIN & HEPARINOIDS
B. ORAL ANTICOAGULANTS
COUMARIN- WARFARIN,DICUMAROL
INANDIONE-PHENINDIONE (not
used)
ANTICOAGULATION
Acts instantly, used in vivo and in vitro.Acts
indirectly by activating plasma anti thrombinIII
The complex then binds to the clotting factors
of the intrinsic and common pathways and
inactivates them. Inhibition of factor Xa as
well as the thrombin mediated conversion of
fibrinogen to fibrin.
Low concentrations prolong aPTT but the high
concentrations prolong both aPTT and PT
ANTIPLATELET ACTION
High dose inhibits platelet aggregation and prolongs
bleeding time
LIPEMIA CLEARANCE
Injection of heparin clears the post prandial lipemic
plasma in vivo. Heparin releases a lipoprotein lipase
from the vessel wall and tissues. This converts the
triglycerides of chylomicrons and vldl to free fatty
acids.
Heparin is not absorbed orally . It does not cross the
blood brain barrier or the placenta. not given im. as
it accumulates between muscle fibres causing
hematoma formation
1. Bleeding
2. Thrombocytopenia
3. Osteoporosis
4. Skin necrosis
5. Transient alopecia
6. Hypersensitivity
HEPARIN IS ANTAGONISED BY
PROTAMINE SULPHATE
NEUTRALISES HEPARIN WEIGHT BY
WEIGHT. 1MG IS NEEDED FOR EVERY
100IU OF HEPARIN. MAXIMUM DOSE
USED IS 50MG. GIVEN BY SLOW IV
INFUSION.
CONTRAINDICATIONS
1.
BLEEDING DISORDERS
2.
SEVERE HYPERTENSION
3.
4.
5.
CHRONIC ALCOHOLICS
6.
CIRRHOSIS
7.
RENAL FAILURE
8.
USES
1. Prophylaxis Of DVT And Pulmonary
Embolism
2. Maintains the Patency Of Cannulae and
Shunts In Dialysis Patients
ORAL ANTICOAGULANTS
HISTORY
In 1924 a hemorrhagic disease was
described in the cattle. The cattle were
feeded on spoiled sweet clover hay. This
contained a chemical bishydroxycoumarin
It was initially used as rat poison
MODE OF ACTION
Used only in vivo
Behave as competitive antagonists of
vitamin k
Interfere with the vitamin k dependent
clotting factors in the liver
Descarboxyprothrombin
Vitamin K (hydroquinone)
NAD
Prothrombin
vitamin K (epoxide)
NADH
TREATMENT OF OVERDOSAGE
1. PREGNANCY
2. NEPHROTIC SYNDROME
3. GENETIC WARFARIN RESISTANCE
COMPARISON
HEPARIN
WARFARIN
Mucopolysaccharide
Coumarin
Iv, sc
oral
Immediate action
delayed action
3-6 days
Invivo
Protamine sulphate
Vitamin k
Blocks X, thrombin
synthesis of clotting
factors inhibited
FIBRINOLYTICS ( THROMBOLYTICS)
These are drugs used to lyse thrombi or clot to recanalyse
occluded blood vessels.
PLASMINOGEN
ACTIVATORS
INHIBITORS
PLASMIN
FIBRIN
FIBRIN
DEGRADATION
PRODUCTS
ACTIVATORS
TISSUE PLASMINOGEN ACTIVATOR
UROKINASE
STREPTOKINASE
INHIBITORS
EPSILON AMINO CAPROIC ACID
TRANEXAMIC ACID
APROTININ
STREPTOKINASE
From the hemolytic streptococcus group C
Antigenic, can cause anaphylaxis or
hypersensitivity
UROKINASE
Nonantigenic
ALTEPLASE
Nonantigenic
Very expensive
RETEPLASE
USES
1.
2.
3.
4.
ANTIFIBRINOLYTICS
Inhibit plasminogen activator and dissolution of clot
Epsilon amino caproic acid is the specific antidote
of fibrinolytic agents
Tranexamic acid occupies the site on the fibrin at
which plasminogen is bound
USES:
Overdosage of fibrinolytics after tonsillectomy or
prostrate surgery
Tooth extraction in hemophiliacs
ANTIPLATELET DRUGS
Prostacyclin inhibit platelet aggregation
Thromboxane promotes platelet aggregation
DRUGS
1.
ASPIRIN
2.
DIPYRIDAMOLE
3.
SULFINPYRAZOLE
4.
TICLOPIDINE
ASPIRIN
Inhibits cyclooxygenase and thromboxane
synthesis
Inhibits release of ADP from platelets
1.
2. DIPYRIDAMOLE
3. SULFINPYRAZONE
Uricosuric drug. Cyclooxygenase inhibitor.
Decreases thromboxane and prostacyclin
synthesis
4. TICLOPIDINE
Interacts with the platelet membrane
It is relatively new drug
RECENT ADVANCES
Biochemical manipulation of streptokinase and
plasminogen mixtures have resulted in
therapeutic agents
Eg acetylation of active site serine of streptokinaseplasmin complex forms compound BRL26921
It binds fibrin in inactive form and only becomes
activated slowly due to slow deacylation of the
active site
MANAGEMENT OF HEMORRHAGE
1.
2.
3.
4.
WHITEHEADS VARNISH
Consists of the following
Benzoin
10 parts
Storax
7.5 parts
Balsam of tolu
5 parts
Iodoform
10 parts
Solvent ether up to 100 parts
Half inch ribbon gauze is soaked in whiteheads
varnish. It is remove in 48 hours or it may give to
dry socket
DRUG INTERACTIONS
Thrombolytic agents + nsaids, sulfinpyrazone,
anticoagulants, platelet inhibitors increases
hemorrhage
Anticoagulants+ ACE inhibitors= hyperkalemia
NSAIDS, ethacrynic acid cephalosporins valproic acid
propylthiuracil + anticoagulant drugs results in
bleeding
Nitroglycerine antagonises the anticoagulant effect of
heparin
Chlorthalidone, Chlordiazepoxide,Haloperidol,
spirinolactone, Rifampicin decrease anticoagulant
activity
Amiodarone, Disulfiram, Halothane increase warfarin
activity
Various antibiotics affect the anticoagulation of
warfarin by altering bacterial synthesis of vitamin k in
the GI tract eg cephalospoins, Chloramphenicol
,Metronidazole, Tetracyclines
Vitamin E in high doses inhibits vitamin K
Garlic produces antiplatelet effect
REFERENCES
THANK YOU