Ch 48 - Drugs Affecting Blood Coagulation Flashcards
What is coagulation?
When you receive an injury the vascular system must maintain an intricate balance between the tendency to clot or form a solid state, the need to “unclothe” or reverse coagulation to keep the vessels open and the blood flowing.
What is the clotting process 4 steps?
- Vasoconstriction - the first reaction to a blood vessel injury is local vasoconstriction.
- Platelet aggregation - injury exposes blood to the collagen and other substances under the endothelial lining of the vessel this causes platelets to stick or adhere to the site of injury. Once they stick they release ADP, serotonin, and other chemicals that’s attract other platelets, ADP is a precursor of the prostaglandins form which thromboxane A2 is formed this causes lack vasoconstriction and further platelet aggregation and adhesion. This events forms a platelet plug
- Intrinsic pathway - as blood comes in contact with exposed collagen a clotting factor Hageman factor (factor XII) a chemical substance that is found in circulating blood is activated. This starts a number of reactions in the area: The clot formation process is activated, the clot-dissolving process is activated and the inflammatory response is started. The Hageman factor activates a cascading series of coagulant substances (intrinsic pathway) that ends with the conversion of prothrombin to thrombin. Calcium is the catalyst. Activated thrombin breaks down fibrinogen to form insoluble fibrin threads.
- Extrinsic pathway - while the coagulation process is going on inside the blood vessel via intrinsic pathway the blood that has leaked out of the vascular system into the surrounding tissues is caused to clot by the extrinsic pathway, injured cells release tissue thromboplastin which activates clotting factors in the blood and starts the clotting cascade to form a clot on the outside of the blood vessel
What is clot resolution and anticlotting process?
Plasma also contains anticlotting substances that inhibit clotting reactions that a might lead to an obstruction of blood vessels by blood clots, Antithrombin III prevents the formation of thrombin, thus stopping the breakdown of the fibrin threads. Another substance is plasmin or fibrinolysin dissolves clots to ensure free movement of blood through the system. Plasmin is a protein-dissolving substance that breaks down the fibrin framework of blood clots and opens up vessels
What disorders affect blood coagulation?
- Thromboembolic disorders - involve the formation of thrombi result in dec blood flow through or total occlusion of a blood vessel. Signs and symptoms are hypoxia, anoxia, or even necrosis in areas affected by the dec blood flow. In some pieces of the thrombus called an emboli can break off and travel through the CV system. Conditions can predispose a person CAD (coronary artery disease) involves a narrowing of the coronary arteries, thrombi tend to form along the damaged endothelial lining.
- hemorrhagic disorders - in which excess bleeding occurs, include hemophilia, liver disease and bone marrow disorders.
What are antiplatelet agents? Abciximab, aspirin, ticagrelor
Drugs that affect clot formation antiplatelet drugs alter platelet aggregation and the formation of the platelet plug. Dec the formation of the platelet plug by dec the responsiveness of the platelets to stimuli that would cause them to stick and aggregate on a vessel wall
Abciximab
Indications: Prevention of acute cardiac events during transluminal coronary angioplasty when used in conjunction with heparin and aspirin; early treatment of unstable angina and non-Q wave MI.
Pharmacokinetics: Route. IV
Aspirin
Indications: Reduction of risk of recurrent TIAs or strokes in men with a history of TIA due to fibrin or platelet emboli; reduction of death or non fatal MI in pt with a history of infarction or unstable angina; MI prophylaxis; also used for its anti-inflammatory, analgesic, and antipyretic effects.
Pharmacokinetics: Route PO, Onset 5-30 mins Peak .25-2 h Duration 3-6h.
T 1/2: 15 mins to 12 h; metabolized in the liver and excreted in the urine.
Adverse effects: Acute aspirin toxicity with hyperpnea, possibly leading to fever, coma, and CV collapse; nausea, dyspepsia, heartburn, epigastric discomfort, GI bleeding, occult blood loss, dizziness, tinnitus, difficulty hearing, anaphylactic reaction.
Ticagrelor
Indications: To reduce the rate of thrombotic coronary collateral vessel events in pt with acute coronary syndrome. Route: PO.
Drug-drug: risk of excessive bleeding inc if any of these drugs is combined with another drug that affects blood clotting
What are anticoagulants? Heparin, rivaroxaban, warfarin.
Which interfere with the clotting cascade and thrombin formation; are drugs that a interfere with the normal coagulation process by interfering with the clotting cascade and thrombin formation.
Heparin
Indications: Prevention and treatment of venous thrombosis and PE; treatment of AF with embolization; diagnosis and treatment of DIC; prevention of clotting in blood samples and heparin lock sets.
Actions: Inhibits thrombus and clot production by blocking the conversion of prothrombin to thrombin and fibrinogen to fibrin.
Pharmacokinetics; IV immediate, minutes 2-6 hr. SC 20-60 mins 2-4 hrs 8-12 hr.
T 1/2: 30 - 180 mins; metabolized in the cells and excreted in the urine.
Adverse effects: Loss of hair, bruising, chills, fever, osteoporosis, suppression of renal function
Rivaroxaban (xaralto) 10 mg/d Po within 6-10 of surgery for knee replacement continuing for 35 d for hip 12 d for knee. Prevention of DVTs that may lead to PE.
Warfarin (Coumadin) 10-15 mg/d Po, then 2-10 mg/d Po based on PT ratio or INR. Treatment of AF, artificial heart valves, or valvular damage the makes pt susceptible to thrombus and embolus formation, prevention and treatment of venous thrombosis.
What are thrombolytic agents? Urokinase, altplase.
Break down the thrombus that has been formed by stimulating the plasma system.
Urokinase
Indications: Lysis of Pe or PE with unstable hemodynamics in adults.
Actions: Converts endogenous plasminogen to plasmin, which breaks down fibrin, clots, fibrinogen, and other plasma proteins, loses thrombi and emboli.
Route IV 4400 - 10000 units/min for up to 2h based on clinical response. Onset immediate, Peak end of injection Duration unknown
T 1/2: Unknown, metabolized in the plasma. Excretion method unknown.
Adverse Effects: Headache, angioneurotic edema, hypotension, skin rash, bleeding, breathing difficulties, bronchospasm, pain, fever, anaphylactic shock.
Alteplase 100 mg IV over 2 h, Treatment of MI, acute PE, and acute is he mic stroke, restoration of function in occluded central venous access devices.
What is low molecular weight heparin? Dalteparin, enoxaparin, tinzaparin.
These drugs inhibit thrombus and clot formation by blocking factors Xa and 11a. Because of the size and nature of the molecules, these drugs do not greatly affect thrombin, clotting, or the PT, therefore, they cause fewer systemic adverse effects. Have also been used to block angiogenesis, the process that allows cancer cells to develop new blood vessels.
Dalteparin (fragmin) DVT 2500-500- u/d SC starting 1/2 h before surgery and then for 5-10 d. Angina 120 is/kg sc q 12 h with aspirin therapy for 5-8d. Prevention of DVT that may lead to PE after abdominal surgery or hip replacement, treatment of unstable angina and non - Q wave MI.
Enoxaparin (lovenox) Hip surgery 30 mg SC q 12h for 7-10d Abd surgery 40 mg/d sc for 7-10 d DVT or PE 1 mg/kg sc q 12h angina 1 mg/kg sc q 12h, Prevention of DVT inn high-risk pt. 40 mg/d sc for 6-14 d. Prevention of DVT that may lead to PE after hip replacement or abdominal surgery, with warfarin to treat acute DVT or PE, prevention of ischemic complications of unstable angina or non-Qwave MI, prevention of DVT in pt with severely restricted mobility due to illness.
What are antihemophilic agents? Antihemophilic factor
The drugs used to treat hemophilia are replacement factors for the specific clotting factors that are genetically missing in that particular type of hemophilia.
Antihemophilic factor
Indications: Treatment of classic hemophilia to provide temporary replacement of clotting factors to correct or prevent bleeding episodes or to allow necessary surgery.
Actions: Normal plasma protein that is needed for the transformation of prothrombin to thrombin, the final step in the clotting pathway.
Pharmacokinetics: Route IV, Onset immediate, Peak unknown
T 1/2: 12 hrs, cleared from the body by normal protein metabolism.
Adverse effects: Allergic reaction, stinging at injection site, headache, rash, chills, nausea, hepatitis, AIDS
What is hemostatic agents? Aminocaproic acid
Some situations result in a fibrinolyticc state with excessive plasminogen activity and risk of bleeding from clot dissolution. They are used to stop bleeding.
Aminocaproic Acid
Indications: Treatment of excessive bleeding resulting from hyperfibrinolysis; also used to prevent the recurrence of subarachnoid hemorrhage, for management of megakaryocytic thrombocytopenia, to dec the need for platelet administration, and to abort and treat attacks of hereditary angioneurotic edema.
Actions: Inhibits plasminogen activator substances and has anti plasmin activity that inhibits fibrinolysis and prevents the breakdown of clots
Pharmacokinetics: Route PO Onset rapid peak 2 h durataion unknown. Route IV onset immediate, peak minutes, duration 2-3h.
T 1/2: 2 hours, excreted unchanged in the urine.
Adverse effects: Dizziness, tinnitus, headache, weakness, hypotension, nausea, cramps, diarrhea, fertility problems, malaise, elevated serum creatine phosphokinase
