lecture for post gradutes

1. DR. N. K .AGRAWAL
PROFESSOR
JNMC, SAWANGI

2.  HEMOSTASIS IS THE ARREST OF BLEEDING
FROM DAMAGED BLOOD VESSELS

3.  Fibrinolysis is lysis of thrombus to restore
blood flow

4. Decrease in coagulation and/or increase in
fibrinolysis –
 bleeding
Increase in coagulation and/or decrease in
fibrinolysis is –
 Thrombosis,
 Thromboembolism,
 DIC

5.  IN NORMAL CONDITION THE ENDOTHELIUM
POSSESS-
ANTIPLATELET,
ANTICOAGULANT,
PRO FIBROLYTIC EFFECT
WHICH PREVENT CLOTTING

6.  NEGATIVELY CHARGED ENDOTHELIUM HAVE
ANTI PLATELET ACTIVITY WHICH RELEASES—
PROSTACYCLIN AND NITRIC OXIDE

7. ADENOSINE DIPHOSPHATASE (ADPASE)
SYNTHESIZED BY VASCULAR ENDOTHELIAL
CELLS DEGRADES ADENOSINE DIPHOSPHATE
(ADP), ANOTHER POTENT PLATELET
ACTIVATOR.

8.  NATURALLY OCCURING HEMOSTASIS
INHIBITORS ARE –
 THROMBOMODULIN ( thrombin inhibitor )
 GLYCOAMINOGLYCANS ( natural heparin )

9.  - ADHESION
 -ACTIVATION
 -AGGREGATION

11.  When injury occurs, the platelets adhere to
the injury site
 Exposure of sub endothelial matrix protein
like Collagen, vWF, glycoprotein leads to
adhesion of platelets

12.  ALPHA GRANULES- V , VIII, vWF
 DENSE BODIES- ADP, ATP,
 Ca
 serotinin
 histamine
 epinephrine

13.  The activation leads to newly active
glycoprotein II b/III a receptors on platelets
surface bind fibrogen leads to aggregation of
platelets

14.  DAMAGE TO VASCULAR ENDOTHELIAL CELL
 EXPOSE EXTRA CELLULAR MATRIX (ECM)
 EXPOSED ECM ACTIVATES COAGULATION
 GENERATE FIBRIN AND CLOT

15.  THROMBIN
 HYPOXIA
 HIGH FLUID SHEAR STATE INDUCES
 PROTHROMBATIC VASCULAR STATE LEADS TO
THROMBOSIS -POST OPERATIVELY

16.  PRINCIPALLY ENZYMATIC FIBROLYSIS AGENT
PLASMIN –
GENERATED BY INACTIVE PLASMINOGEN

17.  Coagulant
 Anticoagulant
 Anti platelets
 Fibrinolytic
 Fibrinolysis inhibitors I

18.  Direct acting-
 Thrombin
 Fibrinogen
 Calcium gluconate
 Calcium chloride
 Gelatina medicanilis

19. Indirect acting-
 Vitamin K
 Vikasolum

20.  THROMBIN –
 ACTIVE COMPOUND OF COAGULATION
SYSTEM WHICH HELP IN ARREST OF BLEEDING
FROM SMALL VESSELS
 MAY BE USED TOPICALLY OR I.V.
 FIBRINOGEN-
 NON ACTIVE COMPOUND USED FOR BLEEDING
FROM BIGGER VESSELS

21.  CALCIUM GLUCONATE AND CHLORIDE –
USED TO STIMULATE ACTIVATION FACTORS
 GELATINA MEDICANILIS-
STABLIZES VESSEL WALL,
INCREASES VISCOSITY,
USED FOR BLEEDING FROM BIGGER VESSELS

22.  SYNTHETIC WATER SOLUBLE VIT K
 INDIRECT ACTING
 MAY BE GIVEN ORALLY, IM, IV
 ACTION IN 12- 18 HOURS
 TAKES PART IN SYNTHESIS OF CLOTTING
FACTORS IN LIVER

23.  USED IN REPEATED BLEEDING DISORDERS,
LIVER DISEASES, CHRONIC BLEEDING
 RADIATION SICKNESS
 OVERDOSE OF ANTI COAGULANT

24.  DIRECT ACTING- (vivo and vitro )
 HEPARIN
 FRAXIPARIN
 SODIUM CITRATE

25.  WARFARIN
 NEODUCUMARINUM
 PHENYLINUM

26.  DEBIGATRAN
 RIVAROXABAN
 APIXABAN

27.  NATURAL OCCURING SUBSTANCE
 PRODUCED BY MAST CELLS
 HIGH CONCENTRATION IN LUNGS AND WALLS
OF INTESTINE
 IS A ACIDIC MUCOPOLYSACCHRIDE

28. CAN BE GIVEN IV, IM, SC OR TOPICALLY
 IV –IMMEDIATELY 4-6 HRS
 IM-15-30 MIN 6-8 HRS
 SC-30-60 MIN 8-12 HRS
 METABOLISED IN LIVER
 EXCRETED IN URINE

29.  Heparin binds to anti-thrombin III " conformational
change " rapid inactivation of
 thrombin and inhibition of fibinogen conversion to
fibrin.
 Heparin has negative charge "is absorbed on blood
cells " increase in negative charge
 on platelets " decrease in platelet aggregation and
adhesion.
 Heparin releases lipoprotein lipase from endothelial
cells

30.  strong rapid decrease in all stages of blood
coagulation
 decrease in platelet aggregation
 improve of microcirculation and coronary
circulation
 decrease in lipids concentrations in blood
serum
 decrease in inflammation
 decrease in immunity

31.  increase in synthesis of surfactant in lungs
 decrease in blood pressure (in higher doses)
 decrease in glucose level in blood serum (in
higher doses)
 increase in diuresis (in higher doses)

32. 1. - Acute thrombosis and thrombo embolism
2. - Myocardial infarction
3. -Ischemic insult
4. - Prevention of thrombus formation after
surgeries
5. - During haemodialysis or blood transfusion
6. - Thrombophlebitis

33.  - Syndrome of disseminated blood coagulation
 - Atherosclerosis
 - Autoimmune diseases
 - Chronic non-specific diseases of lungs
 - Paradontitis, stomatitis (topically)
 The time of bleeding or the time of blood
coagulation should be controlled

34.  1. Bleeding
 2. Hematomas
 3. Micro and macro hematuria
 4. Thrombocytopenia
 5. Allergy
 6. Osteoporosis
 7. Silvering of the hair
 8. Severe diseases of liver and kidney

35.  1. Haemorrhages
 2. Haemorrhagic diathesis
 3. Leukaemia
 4. Anaemia
 5. Malignant diseases
 6. Gastric ulcer
 7. Hypertension
 8. Severe diseases of liver and kidney

36.  It is low molecular weight heparin
 is administered SC once a day; has bigger
bioavailability, longer duration of action
 less binding with plasma proteins
 depress activated Stuart-Prauers factor more
than prothrombin
 is used for treatment of thromboflebitis,
prevention of thrombus formation after surgery

37.  Vitamin k epoxide reductase
 Half life-40 hrs
 Peak - 72-96 hrs
Antidote- vit K

39.  It is indirect acting anticoagulant, cumarine
derivative

40.  . is administered orally
 · is absorbed in GI tract
 · is bound with proteins in plasma
 · is metabolized in liver

41.  begins to act 2-3 hr after administration
 · maximal action after 12-30 hr after
administration
 · action lasts up to 48 hours after the end of
treatment
 · is excreted by urine

42.  Mechanism of action of Neodicumarinum,
warfarin and other indirect-acting
anticoagulants is
 block of epoxide reductase in the liver " block
of creation of active form of vitamin K “
 inhibition of synthesis of clotting factors.

43.  . Decrease in blood coagulation
 · Increase in fibrinolysis
 · Decrease in lipids concentration in blood

44. - Acute thrombosis (together or after of heparin’s
usage)
 - Myocardium infarction
 - Ischemic insult
 - Thrombo-embolism
 - Thrombophlebitis
 - Prevention of thrombus formation after
surgeries
 Index of prothrombin should be controlled !

45.  Side-effects/ Contraindications
 1. Bleeding
 2. Formation of hematomas
 3. Haematuria
 4. Dyspepsia
 5. Suppression of liver function
 6. Allergy
 7. Bleeding gums and petechia in mucous
membrane of oral cavity

46.  1. Haemorrhage
 2. Hemorrhagic diathesis
 3. Gastric ulcer
 4. Malignant diseases
 5. Diseases of liver and kidney
 6. Pregnancy
 For treatment of overdose – Vikasolum !

47.  · It is indirect-acting anticoagulant; indandione
derivative
 · mechanism of action is the same of
Neodicumarinum
 · start of action is slower, duration of action is
more
 · may cause pink colour of urine resulting from
excretion of drug and its metabolites

48. Classification
1. COX-inhibitors
 Acetylsalicylic acid (Aspirin)
2. Inhibitors of phosphodiesterase
 Dipyridamole
3. Inhibitors of ADP-mediated aggregation
 Ticlopidine

49. ANTI-PLATELET ACTION OF ASPIRIN
 Aspirin irreversibly inhibits platelet cyclooxygenase-
 1"prevention of synthesis of thromboxane A
2 " decrease in platelet aggregation.
 This effect occurs in lower doses ( less than 0.5gm
per day) and last more than 48 hr.
 In higher doses aspirin also inhibits synthesis of
prostacycline.

50. ANTI-PLATELET ACTION OF DIPYRIDAMOLE
 Dypiridamole inhibits adenosine desaminase
and phosphodiesterase in platelets “
 increase in cAMP concentration in cells "
inhibition of thromboxane A2 synthesis “
 decrease in platelet aggregation. It also
increases prostacycline level.

51. ANTI-PLATELET ACTION OF TICLOPIDINE
 Ticlopidine irreversibly blocks purinergic
receptors for ADP in platelet membranes
 Inhibition of ADP-induced expression of
glycoprotein (GP)IIb/ IIIa receptors in platelet
membrane decreases platelet aggregation.

52.  INDICATIONS TO ANTI-PLATELET DRUG USAGE
 - prevention of thrombosis and re-thrombosis
(as discontinuation of anticoagulant therapy)
 - prophylaxis of myocardial infarction and insult
 - prophylaxis of thrombosis after surgeries
 - angioplasty
 - prevention of thrombosis in patients with
prosthetic cardiac valves
 - thrombophlebitis

53.  Classification
 1.Fibrinolytic drugs
 a) direct-acting
 Fibrinolysin
 b) indirect-acting (activators of profibrinolysin)
non-selective
 Streptokinase
 Streptoliase
selective
 Alteplase

54. 2.Inhibitors of fibrinolysis
a) direct –acting
 Contrykal
b) indirect- acting
 Amben
 Aminocaproic acid

55.  It is protein from donors’ plasma, the active
factor of fibrinolysis
 is administered by IV infusion
 has direct action on fibrin and dissolves
fibrin clot in the first hours after thrombosis
 is used for treatment of acute thrombosis,
acute myocardial infarction.

56.  thrombophlebitis
may cause bleeding resulting from increase in
fibrinolysis, allergy, anaphylaxis, arrhythmia,
hypotension
contraindications:
 bleeding, cerebral vascular accident, recent
trauma of brain surgery, uncontrolled
hypertension.

57.  It is the proteolytic enzyme from haemolytic
streptococcus.
 It acts indirectly, inhibits the conversion of
plasminogen to plasmin " degradation both
 of fibrin and fibrinogen " systemic activation of
fibrinolysis and dissolving of thrombus.
 Plasma half-life is 23 min; is administered by IV
infusion (intracoronary infusion in
myocardial infarction).
 It is more active than fibrinolysin, does not
cause arrhythmia

58. ALTEPLASE (ACTILISE)
 is tissue plasminogen activator, product of
biotechnology
 half-life is 5 min, is administered by IV
infusion
 has high affinity for fibrin and selectively
acts only on plasminogen, bound with
thrombus

59.  INHIBITORS OF FIBRINOLYSIS
CONTRICAL (Aprotinin)
 is direct acting inhibitor of fibrinolysis and
proteolysis
 is administered IV slowly or by IV infusion
 binds with plasmin and inactivates it, inhibits
activity of trypsin and kallikrein

60.  inhibits fibrinolysis and decreases bleeding
caused by activation of fibrinolysis; inhibits
proteolysis and inflammation
 INDICATIONS: bleeding resulting from activation
of proteolysis, myocardial infarction, acute
pancreatitis, prophylaxis of proteolytic
complications after surgeries on pancreas,
thyroid glands, prevention of proteolysis
activation after the surgery on bigger salivary
glands;
 paradontitis (topically)
 SIDE-EFFECTS: allergy, nausea, vomiting,
hypotension, tachycardia

61.  is indirect-acting inhibitor of fibrinolysis
 is administered orally and by IV infusion, acts
during 4-6 hr, is not metabolized
 excreted with urine

62.  interacts with plasminogen and inhibits its
transformation into plasmin, particularly
inhibits plasmin; inhibits proteolytic enzymes
and kallikcrein
 inhibits fibrinolysis and decreases bleeding
caused by the activation of fibrinolysis

63.  inhibits fibrinolysis and decreases bleeding
caused by the activation of fibrinolysis;
 oppresses proteolysis, decreases
inflammation, has anti-allergic action,
stimulates
 antitoxic function of the liver
 indications are similar to the same to
contrykal and also syndrome of disseminated

64. intravascular coagulation, obstetrics
pathology (ablation placenta, uterine
haemorrhages), liver diseases, hypo plastic
anaemia
 in dentistry, it is applied topically to treat
parodontitis and to stop bleeding from dental
root channels
 SIDE-EFFECTS: dizziness, hypotension,
bradycardia, arrhythmia, skin rash, vomiting
and nausea

65.  dizziness
 hypotension
 bradycardia
 arrhythmia
 skin rash
 vomiting
 nausea

66.  ORAL ANTI THROMBIN INHIBITOR
 HALF LIFE 14-17 HRS
 PEAK EFFET-2 HRS
 DOSE-150 mg OD

67.  ORAL
Xa inhibitor
 Half life- 5-9 hrs
 Peak - 2-4 hrs
 Dose - 10mg/qid

68.  ORAL
Xa INHIBITOR
 HALFLIFE- 10-14 HRS
 PEAK - 3-4 HRS
 DOSE - 5mg/bd

69.  RETEPLASE
 STAPHYLOKINASE
 TETNECTPLASE