Anticoagulant drugs oral administration

Heparin is prescribed on a unit (lU) rather than milligram basis. Tlie dose must be determined on an individual basis. Heparin is not absorbed after oral administration and therefore must be given parenterally. Intravenous administration results in an almost immediate anticoagulant effect. There is an approximate 2-hour delay in onset of drug action after subcutaneous administration. Intramuscular injection of heparin is to be avoided because of unpredictable absorption rates, local bleeding, and irritation. Heparin is not bound to plasma proteins or secreted into breast mUk, and it does not cross the placenta. 

Disposition in the Body. Well absorbed after oral administration. The 5-enantiomer is stated to be considerably more potent as an anticoagulant than the R-form but there appears to be little difference in pharmacokinetic properties. Phenprocoumon is thought to be excreted almost entirely as a glucuronide conjugate with less than 10% of the dose as unchanged drug. 

Drug interactions Concurrent administration of ReoPro with oral anticoagulants is contraindicated. Limited experience with the concurrent use of ReoPro and low molecular weight dextran during a PTCA procedure has also shown an increased risk of a major bleeding episode. Concurrent administration of ReoPro and heparin may also increase the risk of bleeding, but ReoPro is intended for use with aspirin and heparin and has only been studied in that setting. ReoPro has... 

Susceptibility factors previous heparin therapy, co-administration of antiplatelet drugs or oral anticoagulants... 

In the neonate with hemorrhagic disease of the newborn, the administration of vitamin K raises the concentration of these clotting factors to the level normal for the newborn infant and controls the bleeding tendency within -6 hours. The routine administration of 1 mg phylloquinone intramuscularly at birth is required by law in the U.S.. This dose may have to be increased or repeated if the mother has received anticoagulant or anticonvulsant drug therapy or if the infant develops bleeding tendencies. Alternatively, some clinicians treat mothers who are receiving anticonvulsants with oral vitamin K prior to delivery (10-20 mg/day for 2 weeks). 

The pKa values of the N-arylanthranilic acids (4.0-4.2) resemble those of the arylalkanoic acids thus, it is not surprising that they are strongly bound to plasma proteins and that interactions with other highly protein bound drugs are very probable. The most common interactions reported are those of mefenamic acid and meclofenamic acid with oral anticoagulants. Concurrent administration of aspirin results in a reduction of plasma levels of meclofenamic acid. 

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