Pharmacology Thrombolytic Anticoagula

Thrombotic stroke is the result of thrombosis or narrowing of the blood vessels, is the most common cause of strokes (Sanford & Lallion, 2010, p. 1603) Thrombolytic medications are approved for the immediate treatment of Thrombotic Stroke, and Heart attack. (MI). The two main drugs are tissue plasminogen activator (t-PA) and anisoylated plasminogen streptokinase activator complex (APSAC) (Lilley, Harrington, & Synder, 2011, p. 538). Mechanism of action and drug effect Thrombolytic convert plasminogen to plasma, which breaks down, or lyses the thrombus. Plasmin is a proteolytic enzyme, meaning it breaks down protein.

Plasmin is relatively nonspecific serine protease that is capable of degrading such protein as fibrin, fibrinogen, and other procoagulant proteins. In other words, the substance that forms clots, are destroyed by plasmin. Thrombolytic drugs work by mimicking the body’s own process of clot destruction (Lilley et al. , 2011, p. 539). Streptokinase (SK), the original thrombolytic enzyme, binds with plasminogen to form SK- plasminogen complex, which then acts on other plasminogen molecules to form plasmin. The plasmin formed then lyses the clots.

Sk is not clot specific, however SK activates fibrinolysis throughout the body; it breaks not only the thrombus in the coronary artery but also any clots in the body (Lilley et al. , 2011, p. 539). Indications The purpose of all thrombolytic drugs is to activate the conversion of plasminogen to plasmin, the enzyme that breaks down a thrombus. The indication of thrombolytic therapy includes acute MI, arterial thrombosis, DVT, occlusion of shunts or catheters, pulmonary embolus and acute ischemic stroke. Contraindications Known drug allergy to the specific product and to any preservatives and concurrent use with other drugs that alter clotting.

Adverse effects The most undesirable effect of thrombolytic therapy is: ? internal, ?intracranial, and ?superficial bleeding. PHARMACOLOGY 3 ?Other problems include hypersensitivity, anaphylactic reactions, nausea, vomiting, and hypotension. Also can induce cardiac dysrhythmias. Interactions Increased bleeding tendency resulting from the concurrent use of anticoagulant, antiplatelet, or other drugs that affect platelet function. One laboratory test interaction that can occur with thrombolytic drugs is a reduction in the plasminogen and fibrinogen levels.

Nurse’s considerations oIv should be administrated per manufacture guidelines and per protocol. oIv infusion should be monitoring frequently for bleeding, redness and pain. oIntramuscular injections of other drugs are contraindicated to prevent tissue damage and bleeding. oAny bleeding from the gums or mucous membrane and increase pulse greater that 100 beats /minute should be reported to the physician. oMonitoring for hypotension, restlessness, and a decrease of hemoglobin should be reported. Nursing interventions following thrombolysis treatment ?

Once thrombolysis infusion has finished, the stroke nurse accompanies the patient to the hyperacute stroke unit. ?The neurologist or stroke team reviews the patient two hours following thrombolysis. ?There should be a one-to-one patient-to-nurse ratio for the first 24 hours. ?The patient should be in an electric bed, with cot sides up, head at a 30° angle with continuous monitoring of oxygen saturation and electrocardiogram. ?Oxygen (to maintain oxygen saturation over 95%) and suction should be available at the bedside. ?

Observations should be taken every 15 minutes during the first two hours, every 30 minutes during the next six hours and hourly for the next 15 hours. PHARMACOLOGY 4?

Neurological observations should be recorded hourly for a minimum of 24 hours. ?The patient should be on strict bed rest for 24 hours. The patient should be supervised in using a commode to minimize risk of falling. ?A routine computed tomography scan should be scheduled for 24 hour following thrombolysis. ?The nurse should assess the patient’s mouth for presence of angioedema at least every hour. (Paterson, 2012, p. 4) 2) What is included in thrombolytic therapy? How would be administrated this care to Pierre? Only patients who suffer an ischemic or embolic stroke are potential candidates for thrombolytic therapy.

Those who have had a brain hemorrhage don’t need a drug that is going to increase their risk of bleeding. The diagnosis for Pierre DuPont was Ischemic stroke and thrombolytic therapy it is the most effected medications to dissolve the clot quickly. However, the treatment needs to be administrated within 4. 5 hours of symptoms onset. Is very important that healthcare providers are train properly to give this medication. The thrombolytic drug ( enzyme ) is given as IV: oLoading dose of 250,000 units over 30 minutes following by maintenance infusion of 100,000 units/hr for 24-72 hr.

oNo anticoagulant or antiplatelet drugs are giving for 24 hours after tPA treatment. Here is a Summary of a Thrombolysis Pathway 1) Triage by paramedics 2) Emergency department team (either the nurse or doctor) bleep stroke team on arrival of a patient with suspected stroke 3) Assessment of the patient by team from the hyper acute stroke unit 4) Computed tomography scan in imaging unit 5) Stroke team make a decision regarding thrombolysis 6) Thrombolysis administration by the stroke team 7) Patient monitored by the stroke nurse in the hyper acute stroke unit (Paterson, 2012, p.35).

Anticoagulants PHARMACOLOGY 5 The use of anticoagulants in he emergency phase following an ischemic stroke is not indicated. However the use of anticoagulant as an adjunct to tPA is under investigation. Iv heparin is used on occasion in acute stroke management. Iv Heparin is administrated via continuous infusion and partial thromboplastin time (PTT) is closely monitored (Sanford & Lallion, 2010, p. 1610) Coumadin is the most common anticoagulant used. Mechanism of Action and Drug Effects Anticoagulants also called antithrombotic drugs, because all work to prevent the formation of clots or thrombus (Lilley et al. , 2011, p. 529). ?

Heparin works by binding to a substance called antithrombin III, which shuts the three main activator factors: activated II (Thromin), activated X, and activated IX. ?The overall effects of Heparin is that it turns off the coagulation pathway and prevents clots from forming. ?Warfarin sodium (COUMADIN) also acts by inhibiting vitamin K synthesis by bacteria u=in the gastrointestinal tract. This, in turn, inhibits production of clotting II, VII, IX, and X. these four factors are normally synthesized in the liver and are known as vitamin K-dependent clotting factors.

Indications The ability of anticoagulants is to prevent clot formation and they are used in different situations: for example: Myocardial infarction, unstable angina, atrial fibrillation, indwelling devices such as mechanical heart valve, and conditions which blood flow maybe slow. ?The ultimate consequence of a clot can be a stroke or heart attack, a DVT, or a pulmonary embolism. ?Warfarin can prevent the any of these events, but both unfractionated heparins, and LMWS (low-molecular-weight heparin) are use for prevention and treatment.


PHARMACOLOGY 6 ?Drug allergy to specific product ?Warfarin it should be avoided in any disease state where is already a high risk of bleeding, like hemorrhagic stroke, and within 72 hours of a mayor surgery. ( ?Leukemia, pregnancy, surgery ?Warfarin is strongly contraindicated in pregnancy; at the first semester is teratogen. Adverse effects One particular common adverse effect of heparin is heparin-induced thrombocytopenia (HIT) also called heparin-associated thrombocytopenia (HAT). Thombocytopenia is in independent marker of risk of death and life-threatening events.

It is an allergic reaction mediated by the production of immunoglobulin (Ig)G antibodies (Lilley et al. , 2011, p. 529). Other adverse effects: Bleeding, dizziness, chest discomfort, hematoma, rash, gastrointestinal distress, UTI, anemia. The main adverse effect of warfarin is hemorrhage. The main sites for hemorrhage are the nose, gums, gastrointestinal tract, urinary tract, and the brain. The main at risk group is the elderly, and it is important to ensure that this group understands clearly the dose regimes and the need to be vigilant over taking any over the counter painkillers such as non-steroidal anti-inflammatory drugs (Panchmatia, 2012, p.134)

Interactions The importance of drug interactions with warfarin is due to the narrow therapeutic index of warfarin. This means that the small change in the amount of warfarin in the body could cause an adverse reaction (for example bleeding) or treatment failure. The most common adverse consequence of warfarin drug interactions is bleeding due to the potentiation of warfarin activity by other drug. Warfarin liver enzymes inactivate it by the addition of a hydroxyl group to form 7- hydroxywarfarin.

Hence any drugs that may interfere with the activity of liver microsomal PHARMACOLOGY 7 enzymes will affect the activity of warfarin (Panchmatia, 2012, p. 135). Nursing considerations and Patient teaching ? Is important to know the antidote of anticoagulants. The antidote to hemorrhage or uncontrolled bleeding resulting from heparin or LMWH therapy is protamine sulfate. ?

Patient should be though that these drugs are given for specific purpose( e. g. , preventing of serious complications related to clotting, such as with strokes, heart attacks, heart valve replacement, mini-strokes, TIAS, or transient ischemic attacks) is important to understand that health life style is an important part of therapy.

?Patient should take the medication as prescribed ?Frequent blood test is important ?Patient should inform all health providers including dentists, about their medication. Her is some food and supplements affecting with Warfarin ¦¦Glucosamine (potentiation) ¦¦St Johns Wort (antagonism) ¦¦.

Alcohol: chronic heavy intake can induce metabolism of warfarin ¦¦Alcohol: acute heavy ingestion can inhibit warfarin metabolism and therefore increase INR ¦¦Cranberry and grapefruit juice (potentiation) ¦¦Foods containing large amounts of vitamin K (such as broccoli, Brussels sprouts, green leafy vegetables, liver) can affect INR if the patient changes their consumption levels of these foods. (Panchmatia, 2012, p. 136).

Antiplatelet Antiplatelet drugs are used to prevent the formation of blood clot in the arteries (atherothombus) and to reduce the risk of cardiovascular and cerebrovascular events (Panchmatia, 2011, p. 293). Mechanism of action The mechanism of action of the antiplatelet drugs vary depending on the drug. Aspirin, PHARMACOLOGY 8 clopidogrel, dipyridamole, pentoxifylline, anagrelide, abciximab, tirofiban, and eptibatide are some antiplatelet drugs.

But I will have the information of the most common so, that will be Aspirin,and clopidogrel (Plavix) and combination dipyrimole and aspirin (Aggrenox) (Sanford & Lallion, 2010, p. 1607) Aspirin exerts its antiplatelet action by reducing the formation of TXA2 . It irreversibly inhibits the cyclooxygenase- 1 (COX-1) enzyme, which is found in platelets. As platelets cannot synthesize more COX-1, the effect of the inhibition will last for 7–10 days, i. e. the entire life of the platelet. As the selectivity of aspirin for COX-1 is 200 times greater than that for COX-2, only low doses (75 mg) of aspirin are necessary to inhibit platelet aggregation.

As can be expected, aspirin will prolong bleeding times, by stopping platelets from forming a platelet plug. However, aspirin will also increase the risk of damage to the gastric mucosa, because it inhibits the formation of gastro-protective prostaglandins by inhibiting the production of the COX-2 enzyme (Panchmatia, 2011, p. 293). In addition , aspirin may also affect vitamin K dependent clotting factors VII, IX, and x, by interfering with the action of vitamin K, in a manner similar to the warfarin (Lilley et al., 2011, p. 535).

Indications Aspirin has multiple therapeutic effects, although many of the effects vary depending on the dose. Aspirin is recommended for stroke prevention in daily doses of 50 to 325mg (accordantly with the pharmacology book. Medical-surgical book says that more commonly dose of aspirin is 81 to 325mg/d) . Antiplatelet drugs used in the treatment of Stroke Type Drugs Transient ischaemic attack Aspirin + dipyridamole MR, or Dipyridamole MR only PHARMACOLOGY 9 (if aspirin is not tolerated)

Ischaemic stroke Aspirin 300 mg daily for 14 days Initial management after thrombolysis, or Clopidogrel 75 mg daily if aspirin not tolerated (unlicensed) Ischaemic stroke Clopidogrel 75 mg daily, or Long-term management Aspirin + dipyridamole MR if clopidogrel is not tolerated, or Dipyridamole MR monotherapy if aspirin/clopidogrel not appropriate MR=modified-release From: NICE (2010); Joint Formulary Committee (2011) Table Contraindications The use of antiplatelet drugs include known drug allergy to a specific product, thrombocytopenia, active bleeding, leukemia, traumatic injury, gastrointestinal ulcer, vitamin k deficiency, and recent stroke (Lilley et al. , 2011, p. 535).

Adverse effects T Drug Major adverse Major drug Major drug reactions interactions contraindications Aspirin Bronchospasm; gastro- SSRIs, coumarins, Bleeding disorders. intestinal (GI) irritation; heparins, methotrexate, active peptic ulceration hemorrhage NSAIDs, phenindione, venlafaxine Clopidogrel Dyspepsia, abdominal pain, Some antibiotics, some Patients at risk of diarrhea; bleeding anti-epileptics, PPIs, bleeding (e. g. surgery) disorders (including GI cimetidine, coumarins and intracranial) Prasugrel Hemorrhage No major interactions Bleeding risk, stroke, listed in the BNF TIAs.

Dipyridamole MR GI symptoms, hypotension Adenosine, coumarins, Caution in patients with phenindione severe coronary artery PHARMACOLOGY 10 disease Abciximab Haemorrhage, nausea, No major interactions Patients at risk of vomiting listed in the BNF bleeding (e. g. surgery) SSRIs=selective serotonin reuptake inhibitors; NSAIDs=non-steroidal anti-inflammatory drugs; PPI=proton pump inhibitorntipl Patient Teaching Patients should be taking aspirin or aspirin like products with a least 240ml of water and with food to help avoid stomach upset. PHARMACOLOGY 11 Antiplatelet drugs: mechanism of action and main indications.

Table 1. Antiplatelet drugs: mechanisReferences Buckley, L. , & Schub, T. (2013). Stroke, Ischemic: Treatment with Thrombolysis. Retrieved from http://web. ebscohost. com. ezproxy. agpc. talonline. ca/ehost/pdfviewer/pdfviewer? sid=25952af4-0d26-49d4-a83a-175968a222af%40sessionmgr4003&vid=27&hid=4107 Lilley, L. L. , Harrington, S. , & Synder, J. S. (2011). Pharmacology for Canadian health care practice (2nd ed. ). Toronto, ON: Elseiver Canada. Panchmatia, S. (2011). The pharmacology and prescribing of antiplatelet drugs. Nursing Prescribing, 9, 293-298. Retrieved from http://web. ebscohost. com. ezproxy.

agpc. talonline. ca/ehost/pdfviewer/pdfviewer? sid=ab207ce1-a0a0-4b37-8aa9-9d1eea7c231c%40sessionmgr4001&vid=6&hid=4112 Panchmatia, S. (2012). Aspect of the pharmacology and prescribing of oral anticoagulants. Nursing Prescribing, 3, 132. Retrieved from http://web. ebscohost. com. ezproxy. agpc. talonline. ca/ehost/pdfviewer/pdfviewer? sid=b8a59cde-6a7f-4ad1-aae3-a0ae26b034c0%40sessionmgr4001&vid=7&hid=4214 Paterson, J. G. (2012). A thrombolysis pathway for patients following acute ischaemic stroke. Retrieved from http://web. ebscohost. com. ezproxy. agpc. talonline. ca/ehost/pdfviewer/pdfviewer?

sid=25952af4-0d26-49d4-a83a-175968a222af%40sessionmgr4003&vid=27&hid=4107 Paterson, J. G. (2012, april 4 ). A thrombolysis pathway for patients following acute ischeaemic stroke. Art and Science, 26, 35-42. Retrieved from http://web. ebscohost. com. ezproxy. agpc. talonline. ca/ehost/pdfviewer/pdfviewer? sid=ab207ce1-a0a0-4b37-8aa9-9d1eea7c231c%40sessionmgr4001&vid=13&hid=4112 PHARMACOLOGY 12 Sanford, J. T. , & Lallion, L. V. (2010). Nursing Managment: Stroke. In S. L. Lewis, M. M. Heitkemper, S. R. Dirksen, & P. G. O’Brien (Eds. ), Medical-Surgical Nursing in Canada (2nd ed. , pp. 1599-1624). Toronto, On, Canada M6K 3G9: Elseiver Canada.

Heparin, otherwise known as Hep-Lock, Hep-Lock U/P, or Monoject Prefill, is an anticoagulant and an antithrombotic drug. According to Linda Skidmore-Roth’s book entitled Mosby’s Drug Guide for Nursing Students (2013), heparin is used to prevent deep vein thrombosis (DVT) and …

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Pharmacology Nurse Jovanna Rios 11/25/13 Pharmacology is the study of the physical, biological and chemical actions of drugs (Bryant & Knights, 2011). In the practice of medicine, drugs are used to diagnose, treat or prevent disease so for the registered …

1. Protamine sulfate: antidote for heparin (use is when patient’s aPTT is very high) Vitamin K: antidote for coumadin (uses PT/INR); both work slowly. 2. Why are Coumadin and Heparin given together? If you have DVT treatment, it can keep …

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