Anticoagulants absorption

Dicoumarol, warfarin + coleslyramine Anticoagulant absorption is reduced and slowed (25% lower blood levels) Binding to colestyramine Space doses by 2-3 h... 

This case is isolated, but it shows that herbal preparations of this kind might affect anticoagulation. Absorption through the skin appears to be enough to upset the anticoagulant control. 

Use of the macrolides increases serum levels of digoxin and increases the effects of anticoagulants. Use of antacids decreases the absorption of most macrolides. The macrolides should not be administered with clindamycin, lincomycin, or chloramphenicol a decrease in the therapeutic activity of the macrolides can occur. Concurrent administration of the macrolides with theophylline may increase serum theophylline levels. 

Concurrent use of the fluoroquinolones with theophylline causes an increase in serum theophylline levels. When used concurrently with cimetidine, the cimetidine may interfere with the elimination of the fluoroquinolones. Use of the fluoroquinolones with an oral anticoagulant may cause an increase in the effects of the oral coagulant. Administration of the fluoroquinolones with antacids, iron salts, or zinc will decrease absorption of the fluoroquinolones. There is a risk of seizures if fluoroquinolones are given with the NSAIDs. There is a risk of severe cardiac arrhythmias when the fluoroquinolones gatifloxacin and moxifloxacin are administered with drains that increase the QT interval (eg, quini-dine, procainamide, amiodarone, and sotalol). 

When administered with cholestyramine or colestipol there is a decreased absorption of the oral thyroid preparations. These drugs should not be administered within 4 of 6 hours of the thyroid hormones. When administered with the oral anticoagulants there is an increased risk of bleeding. It may be advantageous to decrease the dosage of the anticoagulant when a thyroid preparation is prescribed. There is a decreased effectiveness of the digitalis preparation if taken with a thyroid preparation. 

Dispositional antagonism occurs when one drug alters the pharmacokinetics (absorption, distribution, biotransformation, or excretion) of a second drug so that less of the active compound reaches the target tissue. Tor example, phenobarbital induces the biotransformation of warfarin, reducing its anticoagulant activity... 

Parenteral Anticoagulant-induced prothrombin deficiency hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K (eg, obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, regional enteritis) drug-induced hypoprothrombinemias due to interference with vitamin K metabolism (eg, antibiotics, salicylates) prophylaxis and therapy of hemorrhagic disease of the newborn. 

Absorption/Distribution - Heparin is not adsorbed from the Gl tract. An IV bolus results in immediate anticoagulant effects. The duration of action is dose-dependent. Peak plasma levels of heparin are achieved 2 to 4 hours... 

Drug/Food interactions Vitamin K-rich vegetables may decrease the anticoagulant effects of warfarin by interfering with absorption. Minimize consumption of vitamin K-rich foods (eg, spinach, seaweed, broccoli, turnip greens) or nutritional supplements. Mango has been shown to increase warfarin s effect. 

WARNING Systemic absorption of oral route may cause neuro/oto/nephrotox may result resp paralysis possible w/ any route of administration Uses Hepatic coma, bowel prq) Action Aminoglycoside, poorly absorbed PO -1- GI bacterial flora Dose Adults. 3-12 g/24- h PO in 3-4 doses Peds. 50-1 (X) mg/kg/24 h PO in 3-4 doses Caution [C, /-] Renal failure, neuromuscular disorders, hearing impair Contra Intestinal obst Disp Tabs, PO soln SE Hearing loss w/ long-term use rash, NA EMS Use neuromuscular blockers w/ caution, reduced dose may be necessary t bleeding risk w/ concurrent anticoagulant use OD May cause neuromuscular block and kidney failure calcium salts can be used to revise neuromuscular block... 

Hypoprothrombinemia may occur in malabsorption syndromes and also the use of broad-spectrum antibiotics may produce a hypoprothrombinemia that responds readily to small doses of vitamin K. In premature infants and in infants with hemorrhagic disease of the newborn the use of vitamin K may be indicated. However, the main indication for the use of vitamin K is to antagonize the anticoagulant activity of coumarins. Oral absorption of phytonadione and the menaquinones is by the lymph while menadione and its water-soluble derivatives are absorbed directly. The absorption of phytonadione is energy-dependent and saturable. Intravenous administration of phytonadione has produced flushing, dyspnea, chest pains, and cardiovascular collapse. 

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. 

Barbiturates and rifampin cause a marked decrease of the anticoagulant effect by induction of the hepatic enzymes that transform racemic warfarin. Cholestyramine binds warfarin in the intestine and reduces its absorption and bioavailability. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

Uses Acute chronic gout Action X Renal tubular absorption of uric acid Dose 100-200 mg PO bid for 1 wk, T PRN to maint of 200—400 mg bid max 800 mg/d take w/ food or antacids plenty of fluids avoid salicylates Caution [C (D if near term), /-] Contra Renal impair, avoid salicylates peptic ulcer blood dyscrasias, near term PRG, allergy Disp Tabs, caps SE N/V, stomach pain, urolithiasis, leukopenia Interactions T Effects OF oral anticoagulants, oral hypoglycemics, MTX X effects W/ ASA, cholestyramine, niacin, salicylates, EtOH X effects OF acetaminophen, theophylline, verapamil EMS T Effects of anticoagulants and oral hypoglycemic X effects of verapamil OD May cause N/V, loss of coordination, dyspnea, Szs symptomatic and supportive... 

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