Anticoagulant drugs dicoumarol

Dicoumarol The anticoagulant drug dicoumarol is identified and synthesized. 

It has been known since 1921 that cattle eating spoiled sweet clover hay often would die from uncontrollable bleeding after suffering a very minor injury. This discovery and other subsequent findings eventually led to the isolation of bishydroxycoumarin (i.e., dicoumarol) in 1934 by Link and Campbell and its use in humans in 1954 as the first orally active anticoagulant drug (21). 

Information is very sparse and limited to dicoumarol and warfarin, but the interaction seems to be established. Be alert for other coumarins to behave similarly. Anticipate the need to alter the anticoagulant dosage if ethchlorvynol is started or stopped. The benzodiazepines may be a useful non-interacting alternative to ethchlorvynol, see Coumarins + Benzodiazepines and related drugs, p.391. 

Some drugs can alter thyroid status as an unwanted effect, and this will also alter the response to the oral anticoagulants. For example, amiodar-one , (p.363) can cause thyrotoxicosis, which decreases warfarin requirements. Also, use ofdextrothyroxine for hypercholesterolaemia decreased the required dose of warfarin and dicoumarol, presumably because it has weak thyroid activity. 

Not understood. One suggestion is that the tricyclic antidepressants inhibit the metabolism of the anticoagulant (seen in animals with nortriptyline or amitriptyline and warfarin, but not with desipramine and acenocoumarol ), but tricyclics are not established known inhibitors of the metabolism of any drug so this seems unlikely. Another idea is that the tricyclics slow gastrointestinal motility thereby increasing the time available for the dissolution and absorption of dicoumarol. ... 

---