DANIL HAMMOUDI.MD

SINOE MEDICAL ASSOCIATION

 

USMLE QUESTIONS:

 

 

volume of distribution: Vd= TOTAL AMOUNT OF DRUG IN BODY

                              [] OF DRUG IN THE PASMA

 

-WARFARIN EXERTS ITS ANTICOAGULANTS EFFECT BY:

            ***INHIBITING THE CARBOXYLATION OF PRO-CLOTTING FACTORS

WARFARIN BLOCKS THE VIT K-DEPENDENT STEP IN THE SYNTHESIS OF CLOTTING FACTORS BLOCKING THE STEP OF VIT K REGENERATION BY AN EPOXIDE REDUCTASE REQUIRING NADH.

-THE THERAPEUTIC EFFECT OF SODIUM WARFARIN IS DEPENDENT ON THE HALF LIVES OF ALL THE FOLLOWING COAGULATION FACTORS:

                  ***II

                  ***VII

                  ***IX

                  ***X

·         SODIUM WARFARIN IS THE PROTOTYPE OF THE COUMARIN DERIVED ANTICOAGULANTS.

·         8-12 HOURS ARE REQUIRED FOR ACTION .

·         IT IS 99% BOUND TO PLASMA ALBUMIN

·         METABOLIZED IN THE LIVER-EXCRETED IN THE URINE AND FECES.

·         FACTORS AFFECTING ACTIVITY:

      ***CONDITIONS THAT INCREASE THE RESPONSE TO ANTICOAGULANTS INCLUDE :

                  +++VIT K DEFICIENCY

                  +++HYPERMETABOLIC STATES,SUCH HYPERTHYROIDISM.

                  +++DEBILATING STATES, SUCH CONGESTIVE HEART FAILURE

                  +++AGE: THE OLDER THE PATIENT, THE GREATER THE RESPONSE TO THESE COAGULANTS.

      ***WARFARIN INDUCE MICROSOMIAL ENZYMES

      ***EXCESSIVELY REDUCED LEVELS OF PROTHROMBIN WILL RESULT IN HEMORRHAGE.

      ***DURING PREGNANCY, VIT K DEPENDANT FACTORS ARE INCREASED, RESULTING IN DECREASED RESPONSIVENESS TO ORAL ANTICOAGULANTS.

      SINCE HEPARIN DOES NOT CROSS THE PLACENTA, IT IS CONSIDERED SAFE FOR THE FETUS.

 

THERAPEUTIC USES: ***SECONDARY PROPHYLACTIC TRT OF VENOUS THROMBOSIS

                                                    PULMONARY EMBOLISM.

                  PREVENT THE RECURRENCE OR EXTENSION OF VENOUS THROMBUS FORMATION .

      -SINCE ORAL ANTOCOAGULANTS HAVE NO EFFECT ON PLATELETS, THEY ARE NOT USED IN THE TRT OF TROMBOTIC DISEASE IN THE ARTERIAL SYSTEM.

 

ADVERSE EFFECTS:  -WARFARIN NECROSIS =PAINFULL ERYTHEMATOUS PATCH ON THE SKIN ,WHICH CAN PROGRESS TO GANGRENE. 3-10DAYS OCCURS OF STARTING WARFARIN THERAPY.

      THROMBI OCCUR IN THE VASCULATURE OF AFFECTED TISSUE.

                  - A PURPLE TOE SYNDROME CAN OCCUR 3-8 WEEKS AFTER STARTING WARFARIN THERAPY . IT IS CAUSED BY CHOLESTEROL EMBOLI FROM ATHEROMATOUS PLAQUES, FOLLOWING BLEEDING INTO THE PLAQUES.

                  - WARFARIN IS CONTRE INDICATED IN PREGNANCY BUT NOT FOR THE NURSING MOTHER SINCE IT IS NOT EXCRETED IN MILK.

 

REVERSAL ANTICOAGULANT EFFECTS:

VIT K1 [PHYTONADIONE] WILL ENHANCE TO RECOVERY

FOR SEVERE HEMORRHAGE , PHYTONADIONE IS GIVEN INTRAVENOUSLY . PT RETURN TO NORMAL 6-12 HOURS.


 

DRUGS INTERACTIONS WITH ORAL ANTICOAGULANTS

DRUGS                   EFFECT ON RESPONSE TO ANTI COAG                            MECHANISM

acetylsalicylic acid                i                            decreased ADP release by platelets ,IMPAIRING PLATELET AGGREGATION

BARBITURATES-                       D                            INDUCE DRUG MICROSOMAL METABOLIZING SYSTEM

GLUTHEMIDE

CHOLESTYRAMINE                      D                             DECREASE HYPOPROTHROMBINEMIA; INCREASE PLASMA CLEARANCE OF DRUG.

CIMETIDINE                          I                               UNKNOWN

CLOFIBRATE                          I                             DECREASE PLATELET ADHESIVENESS

                                                                 INCREASE TURNOVER OF VITAMIN K-DEPENDENT FACTORS

DISULFIRAM-METRONIDAZOLE            I          

 


·         HEPARIN:

·         ANTITHROMBIN FACTOR

·         IT IS AN ANTIPLATELET DRUG

·         IT HAS NO EFFECT ON THE SYNTHESIS OF BLOOD COAGULATION FACTORS

·         DOES NOT BLOCK PROTHROMBIN SYNTHESIS IN THE LIVER AS DO THE ORAL ANTICOAGULANTS

·         IHIBITS CONVERSION OF PT

·         INTERFERE WITH FORMATION OF FIBRIN.

·         . PT RET

 

 

 

MORE ON ANTIGOAGULANTS COMING UP SOON

Monday, May 14, 2001