Pharm Ch48 Drugs Affecting Blood Coagulation

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Blood Coagulation

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Blood in fluid state in closed system
Injury (cut, puncture or capillary destruction)
Fluid could leak – causing system to lose pressure and possibly shut down
Liquid blood turns solid – clot – plugs hole in system (coagulation)
Need to unclot or reverse coagulation to keep blood flowing
Drugs in coagulation work in different steps in the clotting and dissolving processes to restore balance

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Blood Vessel Injury

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Local vasoconstriction seals off small injury
Platelet aggregation forms a platelet plug
Hageman factor is activated (XII)
Intrinsic pathway converts prothrombin to thrombin to seal system
Extrinsic pathway clots the blood that has leaked out of the vascular system

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Clot Resolution

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Anticlotting substances released
Plasmin or fibrinolysis dissolves clots
Precursor is plasminogen
Converts to plasmin – affected by other factors
Keeps blood vessels open and functional
High levels found in lungs and uterus

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Types of Blood Disorders Thromboembolic disorder

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Conditions that predispose a person to the formation of clots and emboli

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Types of Blood Disorders Hemorrhagic disorder

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Condition in which excess bleeding occurs

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Drugs Affecting Clot Formation Anticoagulants

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Interfere with the clotting cascade and thrombin formation

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Drugs Affecting Clot Formation Antiplatelets

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Alter the formation of the platelet plug

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Drugs Affecting Clot Formation Thrombolytic drugs

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Break down the thrombus that has been formed by stimulating the plasmin system

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Antiplatelets Action

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Inhibit platelet adhesion and aggregation by blocking receptors sites on the platelet membrane
Anagrelide: blocks the production of platelets in the bone marrow

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Antiplatelets Indications

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Reduce risk of recurrent TIAs or strokes; reduces death or nonfatal MI; MI prophylaxis; anti-inflammatory, analgesic, and antipyretic effects

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Antiplatelets Pharmacokinetics

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Well absorbed and bound to plasma proteins
Metabolized in the liver and excreted in the urine

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Antiplatelets Contraindications

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Allergy, pregnancy, and lactation

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Antiplatelets Caution

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Bleeding disorder, recent surgery, closed head injury

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Antiplatelets Adverse effects

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Bleeding
Headache, dizziness, and weakness
GI distress

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Antiplatelets Drug-to-drug interaction

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Other blood-clotting drugs

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Anticoagulants and Their Indications Warfarin (Coumadin)

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Maintains a state of anticoagulation when the patient is susceptible to potentially dangerous clot formation. Interferes with Vit K clotting factors

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Anticoagulants and Their Indications Heparin (generic)

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Inhibits the conversion of prothrombin to thrombin

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Anticoagulants and Their Indications Antithrombin (Thrombate III)

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Used for hereditary antithrombin III deficiencies and replacement therapy in congenital antithrombin III deficiency

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Anticoagulants and Their Indications Argatroban (Acova)

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Used to treat thrombosis in heparin-induced thrombocytopenia

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Anticoagulants and Their Indications Bivalirudin (Angiomax)

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Used with aspirin to prevent ischemic events in patients undergoing transluminal coronary angioplasty

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Anticoagulants Action

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Interfere with the normal cascade of events involved in the clotting process

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Anticoagulants Pharmacokinetics

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Vary based on the drug

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Anticoagulants Contraindications

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Allergy and conditions that could be compromised by increased bleeding tendencies
Pregnancy, renal, and hepatic disorders

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Anticoagulants Cautions

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CHF, thyrotoxicosis, senility, and psychosis

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Anticoagulants Adverse effects

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Bleeding
GI upset
Hepatic dysfunction
Alopecia, dermatitis, bone marrow suppression, and prolonged and painful erection

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Anticoagulants Drug-to-drug interactions

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Heparin and oral anticoagulants, salicylates, penicillins, and cephalosporins
Heparin and nitroglycerine
Warfarin: number of documented interactions

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Disseminated Intravascular Coagulation (DIC)

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Bleeding and clotting at same time disorder
Severe infection, septic shock, traumatic childbirth or missed abortion and massive injuries
Must treat underlying problem
Challenge to stop bleeding and clotting at same time
Often give heparin – prevent clotting phase from being completed
Not usually good outcome – pt usually bleeds to death before it can be stopped

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Thrombolytic Agents Action

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Activate plasminogen to plasmin, which in turn breaks down fibrin threads in a clot to dissolve a formed clot

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Thrombolytic Agents Indications

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Acute MI, pulmonary emboli, and ischemic stroke

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Thrombolytic Agents Pharmacokinetics

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Drugs must be injected and are cleared from the body after liver metabolism

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Thrombolytic Agents Contraindications

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Allergy
Any condition that worsens through dissolution of clots
Pregnancy and lactation

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Thrombolytic Agents Adverse effects

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Bleeding
Cardiac arrhythmias
Hypotension
Hypersensitivity: rash, flushing, bronchospasm, and anaphylactic reaction

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Thrombolytic Agents Drug-to-drug interactions

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Anticoagulants
Antiplatelets

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Low-Molecular-Weight Heparins

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Inhibit thrombus and clot formation by blocking factors Xa and Iia
Do not greatly affect thrombin, clotting, or prothrombin times; therefore, they cause fewer systemic adverse effects
Block angiogenesis, the process that allows cancer cells to develop new blood vessels
Are indicated for specific uses in the prevention of clots and emboli formation after certain surgeries or bed rest

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Anticoagulant Adjunctive Therapy

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Lepirudin (Refludan)
IV drug
Treats rare allergic reaction to heparin
Protamine sulfate – antidote heparin – levels too high
Vitamin K – Coumadin levels too high

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Hemorrheologic Agent

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Pentoxifylline (Trental)
Induce hemorrhage
Decreases platelet aggregation and decreases fibrinogen
Decrease clots and increase blood through narrowed vessels
Treat intermittent claudication – painful vascular problem of legs
Associated with cardiovascular problems – monitor closely

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Activated Protein C

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Drotrecogin alfa (Xigris)
Anticoagulant effect – inhibits factors Va and VIIIa
Anti-inflammatory effect
Used in severe sepsis

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Bleeding Disorders Treated With Clotting Factors Hemophilia

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Genetic lack of clotting factors that leaves the patient vulnerable to excessive bleeding from any injury

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Bleeding Disorders Treated With Clotting Factors Liver disease

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Clotting factors and proteins needed for clotting are not produced

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Bleeding Disorders Treated With Clotting Factors Bone marrow disorders

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Platelets are not formed in sufficient quantity to be effective

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Antihemophilics Actions

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Replace clotting factors that are either genetically missing or low in a particular type of hemophilia

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Antihemophilics Indications

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Prevent blood loss from injury or surgery and to treat bleeding disorders

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Antihemophilics Pharmacokinetics

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Replace normal clotting factors; they are processed as such by the body

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Antihemophilics Contraindications

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Allergy
Factor IX in the presence of liver disease
Lactation

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Antihemophilics Caution

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Pregnancy

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Antihemophilics Adverse effects

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Risks associated with use of blood products
Headache, flushing, fever, chills, and lethargy
Nausea and vomiting
Stinging, itching, and burning at the site of injection

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Hemostatic Agents Action

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Stop the natural plasminogen clot-dissolving mechanism by blocking its activation or by directly inhibiting plasmin

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Hemostatic Agents Indication

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Prevent or treat excess bleeding in hyperfibrinolytic states

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Hemostatic Agents Pharmacokinetics

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Vary for each drug

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Hemostatic Agents Contraindications

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Allergy
Acute DIC

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Hemostatic Agents Caution

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Cardiac disease, renal or hepatic dysfunction, pregnancy, and lactation

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Hemostatic Agents Adverse effects

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Excessive clotting
CNS: hallucinations, drowsiness, dizziness, headache, and psychotic states
GI: nausea, cramps, and diarrhea
Weakness, fatigue, malaise, and muscle pain
Aprotinin: cardiac arrhythmias, MI, CHF, and hypotension

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Hemostatic Agents Drug-to-drug interactions

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Heparin
Oral contraceptives and estrogen