McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

Pharmacokinetics Heparin is injected IV or subcutaneously (SC) and has an almost immediate onset of action. It is excreted in urine. Warfarin, apixaban, dabigatran and rivaroxaban are used orally. All other drugs in this class (heparin, antithrombin, fondaparinux and bivalirudin) are given parenterally. Warfarin is readily absorbed through the GI tract, metabolised in the liver and excreted in urine and faeces. Warfarin’s onset of action is about 3 days; its effects last for 4 to 5 days. Because of the time delay, warfarin is not the drug of choice in an acute situation, but it is convenient and useful for prolonged effects. Because antithrombin is an exogenous form of a naturally occurring anticoagulant, the body handles it in the same way that it handles naturally occurring antithrombin. Fondaparinux is absorbed quickly from SC sites and metabolised and excreted by the kidneys. Bivalirudin is given IV and is excreted through the kidneys. Contraindications and cautions The anticoagulants are contraindicated in the presence of known allergy to the drugs to avoid hypersensitivity reactions . They also should not be used with any condi­ tions that could be compromised by increased bleeding tendencies , including haemorrhagic disorders, recent trauma, spinal puncture, GI ulcers, recent surgery, intrauterine device placement, tuberculosis, presence of indwelling catheters and threatened abortion. Warfarin is contraindicated in pregnancy because fetal injury and death have occurred ; in breastfeeding, because of the potential risk to the baby ; and in renal or hepatic disease, which could interfere with the metabolism and effectiveness of these drugs. Although some adverse fetal effects have been reported with its use during pregnancy, heparin does not enter breast milk, and so it is the anticoagulant of choice if one is needed during breastfeeding. Dabigatran is renally cleared and accu­ mulates in people with poor renal function. Therefore, • Tell any doctor, nurse or other healthcare provider involved in your care that you are taking this drug. You should carry or wear medical identification stating that you are taking this drug to alert emergency medical personnel that you are at increased risk for bleeding. • Avoid situations in which you could be easily injured— for example, engaging in contact sports or games with children or using a straight razor. • Report any of the following to your healthcare provider: unusual bleeding (when brushing your teeth, excessive bleeding from an injury, excessive bruising); black or tarry stools; cloudy or dark urine; sore throat, fever or chills; severe headache or dizziness.

• Keep this drug, and all medications, out of the reach of children. • Avoid the use of over-the-counter medications while you are taking this drug. If you feel that you need one of these, consult with your healthcare provider for the best choice. Many of these drugs can interfere with your anticoagulant. • Schedule regular, periodic blood tests while you are taking this drug to monitor the effects of the drug on your body and adjust your dose as needed.

dabigatran must not be given to people with a creatinine clearance (CrCl) of less than 30 ml/minute. Caution should be used in people with heart failure (HF), thyrotoxicosis, senility or psychosis because of the potential for unexpected effects and in individuals with diarrhoea or fever, which could alter the normal clotting process by, respectively, loss of vitamin K from the intestine or activation of plasminogen . Caution should be used in pregnancy with anticoagulants other than warfarin because of the potential for adverse effects ; benefit should outweigh potential risks. Adverse effects The most commonly encountered adverse effect of the anticoagulants is bleeding, ranging from bleeding gums with tooth brushing to severe internal haemorrhage. Individuals will need teaching about administra­ tion, disposal of the syringes and signs of bleeding to watch for. Periodic blood tests will be needed to assess the effects of the drug on the body. Clotting times should be monitored closely to avoid these problems. Table 48.2 reviews clotting studies that should be monitored. The person should also be monitored for warfarin overdose. Serious adverse effects may occur when adding or taking away a drug from the regimen of a person receiv­ ing warfarin without careful monitoring and adjustment of the warfarin dose (see Clinically important drug– drug interactions). Warfarin has been associated with alopecia and dermatitis, as well as bone marrow depression and, less frequently, prolonged and painful erections. The Focus on safe medication administra­ tion discusses treatment of heparin overdose. Nausea, GI upset, diarrhoea and hepatic dysfunction also may occur secondary to direct drug toxicity. Clinically important drug–drug interactions Increased bleeding can occur if heparin is combined with oral anticoagulants, salicylates, penicillins or