17094800-Anticjoagulant-Presentation.ppt

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1. Classes of AnticoagulantsClasses of Anticoagulants
•Indirect-acting: Indirect-acting: the coumarin derevatives
drugs (e.g. warfarin) take about 72 h to
become fully effective, act for several
days, are given orally or by injec..
•Direct-acting: Direct-acting: heparin and LMW heparin
are rapidly effective, and available
parenterally.

2. Indirect-actingIndirect-acting
Warfarin is a synthetic derivative of coumarin,
it is a Vitamin K antagonists. it is readily
absorbed from the GIT and more than
90% bound to plasma protein.

3. Mechanism of actionMechanism of action
It is structurlly similar to vit K & competitively
inhibit epoxide reductase that is
responsible for the reactivation of vit K to
form coagulant factors(2,7,9,10 &
anticoagulant protein c & s).
**Vit K interfere with the carboxylation of glutamic
acid residues in clotting factors II, VII, IX and X..

4. Mechanism of actionMechanism of action
In active factors 2,7,9,10,& protein c & s.
Activated clotting factors
Reduced Vitamin KOxidized Vitamin K
NADHNAD
Warfarin
epoxide
reductase

5. Onset of action of warfarinOnset of action of warfarin
The effect takes several days to develop because
of the time taken for degradation of
preformed carboxylated clotting factors. The
onset of action thus depends on the
elimination half-lives of the relevant factors.
Factor VII, with a half-life of 6 hours, is
affected first, then IX, X and II, with half-lives
of 24, 40 and 60 hours, respectively

6. Dose of warfarinDose of warfarin
There is much inter-individual variation in dose
requirements. The usual dose to initiate
therapy is 5-10 mg daily for 2 da ys, with the
maintenance dose then adjusted according to
the INR.
•1. INR 2.0-2.5 Prophylaxis of deep vein
thrombosis
•2. INR 2.0-3.0 treatment of DVT & pulmonary
embolism.
•3. INR 3.0-4.5 recurrent DVT & pulmonary
embolism .

7. MONITORING OF ANTICOAGULANT MONITORING OF ANTICOAGULANT
THERAPYTHERAPY
MONITORING OF ANTICOAGULANT
THERAPY by INR ( international
normalized ratio ), which is the ratio of
prothrombin time in the patient to that in a
normal (un-anticoagulated) person.

8. Adverse effects of warfarin Adverse effects of warfarin
1. Bleeding (4-8%).
2. Cutaneous reactions: apart from purpura and
ecchymoses, in those who are excessively
anticoagulated; & skin necrosis due to a
mixture of haemorrhage and thrombosis
occurs rarely where induction of warfarin
therapy is abrupt and/or the patient has a
genetically detemined deficiency of the
anticoagulant protein c & s .

9. Adverse effects of warfarin …cont.Adverse effects of warfarin …cont.
3. Warfarin used in early pregnancy may
injure the fetus (other than by *bleeding).
It causes *skeletal disorder (5%) (bossed
forehead, sunken nose) and *absence of
the spleen.
*CNS abnormalities are reported with
warfarin used at any stage of pregnancy
and are presumed to be due to
intracranial hemorrhage.

10. Adverse effects of warfarin …cont.Adverse effects of warfarin …cont.
4. Another rare complication that may occur
early during warfarin treatment (usually
within 3 to 8 weeks) is purple toe syndrome.
This condition is thought to result from small
deposits of cholesterol breaking and flowing
into the blood vessels in the skin of the feet,
which causes a blueish purple color and may
be painful.

11. Management of bleeding caused by Management of bleeding caused by
warfarin warfarin
•Blood replacement, prothrombin complex
concentrate(containing factor II, IX9 and X,
and given i.v. as 50 units per kg of factor
IX) or fresh frozen plasma. If full reversal
of anticoagulation is judged necessary, 5
mg of Vit. K is then given by slow i.v.
injection.

12. ManagementManagement of bleeding caused by warfarin….CONT. of bleeding caused by warfarin….CONT.
•for lesser bleeding, warfarin should be
withheld and 0.5-2 mg of Vit.K may be
given by slow i.v. injection.
•INR> 7 but with out bleeding. Correct by
withholding warfarin, and given 0.5 mg OF
Vit.K by slow i.v. injection if judged
appropriate.
•INR 4.5-7.0 manage by with holding
warfarin for 1-2 days and then reviewing
the INR.

13. Drug InteractionsDrug Interactions
Increase risk of hemorrhage:
1- Decrease metabolism by amidarone , metronidazole , ciprofloxacin,
erythromicine , cimetidine , INH & flouxitine .
2- Displacement from protein binding sites caused by loop diuretics and valproate.
3- Relative deficiency of vit K.
4-Excessive use of alcohol is also known to affect the metabolism of warfarin
5- Low concentration of coagulation factors as in
-Hepatic failure -Hyperthyroidism
-Congestive heart failure

14. Drug InteractionsDrug Interactions
*Decrease anticoagulant effect
1- Decrease absorption by cholystiramine in
GIT.
2- Increase metabolism by barbiturate,
carbamazepine, rifampicin.
3- There is a decreased response to warfarin in
conditions (e.g. pregnancy) where there is
increased coagulation factor synthesis.
Similarly, the effect of oral anticoagulants is
lessened in hypothyroidism.

15. MONITORING OF MONITORING OF
ANTICOAGULANT THERAPYANTICOAGULANT THERAPY
•The activated partial thromboplastin time
(APTT) used for detecting abnormalities in
blood clotting,

and to monitor the treatment
effects with heparin. indicator measuring the
efficacy of the "intrinsic“ pathway.

16. Adverse affects of heparinAdverse affects of heparin
1.Bleeding
2.The syndrome of thrombocytopenia (HIT
syndrome) with arterial thromboemboli and
hemorrhage which occurs in about 2-3٪ of
patients who receive heparin for a week or
more.
3.Warfarin should be substituted, if the platelet
count falls when a patient receives heparin.
4.Osteoporosis.
5.Hypersensivity reactions and skin necrosis
may occur but are rare.

17. Adverse affects of heparin…cont.Adverse affects of heparin…cont.
6. The other complication is hyperkalemia,
which occurs in 5 to 10% of patients receiving
heparin, and is the result of heparin-induced
aldosterone suppression.

18. LMW heparins LMW heparins
•Are as effective and safe as conventional
(unfractionated) heparin at preventing venous
thrombosis.but They are eliminated mainly by renal
excretion, and unfractionated heparin is preferred in
renal failure.
e.g. :
-Dalteparin .
- Dnoxaparin.
- demiparin.

19. LMW heparins …contLMW heparins …cont
Low-molecular-weight heparins are given
subcutaneously. They have a longer half-life
than unfractionated heparin, so the effects
are more predictable and dosing less frequent
(once or twice a day). LMWHs do not prolong
the APTT; unlike unfractionated heparin, the
effect of a standard dose is sufficiently
predictable that monitoring is not required
routinely.

20. Heparin LMWHs
•15 - 100 monosaccharides
per molecule
•High affinity for plasma
proteins
•30% bio-availability after
subcutaneous injection
•4 - 40 monosaccharides per
molecule
•Low affinity for plasma
proteins
•90% bio-availability after
subcutaneous injection

21. Surgery in patients receiving Surgery in patients receiving
anticoagulant therapyanticoagulant therapy
For elective surgery warfarin may be withdrawn
about 5 days before the operation and resumed
about 3 days after if condition seems
appropriate, low-dose heparin may be used in
the intervening period. In patients with
mechanical prosthetic valves, heparin is
substituted at full dosage 4 days before surgery
and restarted 12-14h after the operation.
Warfarin is restarted when the patient resumes
oral intake.

22. The use of anticoagulants in The use of anticoagulants in
pregnancypregnancy
Women on long term warfarin should be advised
not to become pregnant while taking the drug.
Heparin should be substituted prior to conception
and continued through the first trimester, after
which warfarin should replace heparin, as
continued exposure to heparin may cause
osteoporosis. Warfarin should be discontinued
near term as it exacerbates neonatal
hypoprothrombinaemia .