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1. Discuss briefly the relevant pathophysiology of this condition
2. Discuss the pharmacological management (e.g. prescribed and OTC medications) and current pharmacological research into this condition. This can include laboratory, clinical, prehospital or emergency department studies.
Include in your discussion the mechanism of action of the particular drug classes. This section should form an important part of your review and analysis of the articles is important ?
3. Critically examine the (or any) potential relevance of your findings to your practice as a paramedic (this also should form an important component of your review).I will discuss this point further in the lectures
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Pathophysiology
Acute coronary syndrome (ACS) is the new medical terminology being used for myocardial infarction. ACS refers to acute myocardial infarction also including STEMI (ST segment elevation myocardial infarction) and unstable angina. Different forms of MI has been defined with various symptoms and diagnostic methods. For example, MI type 1 (rupturing of atherosclerosis plaque) & type 2 (myocardial injury). Any change in cardiac biomarker is considered as diagnostic criteria for myocardial infarction (Thygesen, 2012). Evidences for this particular disorders needs to find out symptoms of ischemia heart disease, evidence of loss of myocardium, changes in electrocardiogram (EEG), changes related with Q waves in EEG etc. Recent evidence shows a significant reduction in STEMI incidences over the years and less burden on healthcare system
Acute coronary syndrome has become one of the most cause death worldwide. The chances of occurrence is highest for male in comparison with female. The incidence rate is high among age group of 30-70 years. Disease severity increases with age due to life style changes. Certain factors are responsible for this particular heart disease – age, family history, early menopause etc. Other modifiable factors are smoking, obesity, reduced physical activities, obesity, hypertension, and diabetes (Gabriel et al, 2012).
Thrombosis is responsible for all types of acute myocardial infarctions exceptions include arteritis, coronary emboli & spasm etc. Thrombosis also plays a major role for unstable angina. It is evident from research studies that approximately 50-80% of death deaths occur due to thrombosis. Events of acute coronary syndrome happens as the status changes from no thrombus to thrombus.
Early stages of disorder show evidence of damage to endothelium though not become visible until plaque formation progresses through stage 4. Most of the structural changes are seen in advanced stage providing signals of onset of the disease symptoms. In comparison with normal arteries, endothelium shows enhanced growth between plaques that implies abnormal physiologic activity of endothelial cells. Over the plaque, a process called endothelial denudation occurs which expose underlying tissues and results into adherence of platelets at the site. Formation of minute thrombi begins which are invisible for angiography but release platelet-derived growth factor for the plaque formation (Gabriel et al, 2012).
Endothelial erosion occurs which happens because of the proximity of macrophage cells. These cells are responsible for endothelial cells apoptosis by producing proteases that help to loose endothelial cells from their adherence to the wall. Thrombus formation starts due to the result of plaque disruption. Virtually it begins within the plaque but expands into arterial lumen later on. Plaque disruption reflects highly active inflammatory activities happening with the plaque. Such activities inhibits functions of smooth muscle cells which in turn reduces formation of collagen. Macrophage also produces degrades collagen and tissues by releasing metalloproteinases. The production of metalloproteinases becomes unregulated during plaque disruption which is associated with enhanced inflammatory reaction.
Degree of erosion and disruption vary among different patient groups. Endothelial erosion is an important factor among approximately 50% of women while disruption is the major cause for males.
Pharmacological management
Management depends upon patient health condition as defined in terms of stages, criticality etc. It can be started in two steps – pre hospital and after admission. Delay in call for an ambulance could be life threatening for the patients as it could lead to death. There are two types of patient; one who has already experienced the same situation and the new patient who never came across. So if a patient is not responsive to glyceryl trinitrate (GTN) must be taken to the hospital immediately. The following assessment must be started once a patient got admitted in the hospital –
Patient must be monitored continuously for oxygen, heart rate, pulse, blood pressure. ECG is also performed to measure any feature of T wave inversion, ST segment depression.
Initial management therapy has one of its main objective to normalize the patient condition by relieving pain. It is generally done by administrating anti-thrombotic and anti-ischemic drugs. Nitrates are given for initial pain relief along with beta blockers for symptomatic relief.
Assessment of STEMI is a complicated task and requires trained healthcare professionals (McManus, 2011).An organized approach is needed for treatment of STEMI (ST segment elevation MI) and reperfusion protocol needs to be followed during an emergency situation (Mehta et al,2008). The first task is to evaluate the patient condition along with risk stratification. Immediately ECG report is obtained along with detailed history of the patient. The evaluation is done for pain, chest discomfort, previous cardiovascular history, and other contributing risk factors (Smith et al, 2015). As a part of reperfusion protocol, fibrinolytic is given within thirty minutes of patient arrival if found with STEMI. Any delay in decision making may worsen the patient condition further hence physician has to take quick decisions regarding treatment (Saczynski et al, 2008).
Cardiac biomarkers are also used as an important diagnostic tools but it is time taking process. If a patient is having persistent pain more than 6-8 hours then only cardiac biomarker would be helpful for treatment. Reperfusion therapy cannot be delayed for cases of STEMI as they need quick treatment to survive (Rathore et al, 2009). Patient with complete blockage of epicardial coronary artery is considered for STEMI treatment. Physician attending patient in an emergency must identifies symptoms for STEMI and also plan out a strategy for reperfusion protocol. Patient with unstable stigma and NSTEMI (Non ST segment elevation MI) are difficult to assess but they also need to be identified immediately for early treatment to start O'Gara,Kushner & Ascheim,2013).
Initial therapy line
Glyceryl Trinitrate (GT)
Glyceryl Trinitrate has beneficial effects in terms of dilation of coronary artery. It is an important therapy line for ACS treatment. Up to 3 doses of GT are administered at 5 minute interval to relive chest pain. Patient with extreme bradycardia, hypnotension are not administered GT (Diercks et al, 2005).
Anti-thrombotic therapy
Anti-thrombotic therapy includes various drugs depending upon situation- Aspirin, Prasugrel, Ticagrelor, Clopidogrel, abciximab, tirofiban.
Mechanism of action
Mechanism of action of anti-thrombotic drugs begins by inhibiting functions of platelets. These drugs directly act upon platelets and inhibits their activation which results into disruption of formation of fibrin. Risk associated with cardiovascular problems is reduced by approximately 30% through administration of these anti-thrombotic drugs. It has been found that dual treatment therapy functions effectively for acute coronary syndrome for example, a combination of clopidogrel along with aspirin works efficiently rather than single drug. Aspirin is the preferred choice for stroke prevention purpose because of its high efficacy rate for such cases. Patients are administered aspirin along with dipyridamole for prevention of chances of secondary stroke. These drugs have side effects of bleeding but balance between risks and benefits defines their role for cardio vascular disease (Antithrombotic Trialists, 2009).
Aspirin differs in its mechanism of action from other anti-thrombotic drugs. It acetylates COX 1 (cyclooxygenase 1), and inhibits thromboxane A2 synthesis which is completely dependent on COX 1. thromboxane A2 is triggers aggregation of platelets and act as vasoconstrictor. Proper dose of aspirin is required to generate enough anti-inflammatory response. Aspirin has been found effective at low dose if an individual has high level of CRP (C reactive protein).
Mechanism of action of dipyridamole is different from aspirin. It inhibits phosphodiesterase and reduces the concentration of ADP (Adenosine diphosphate). This results in lower platelet exposure for ADP.
Remaining drugs interfere between ADP and platelets and blocks the function of P2Y12 receptor. This mechanism is involved in platelet aggregation induced by ADP and also responsible for secretion of pro thrombotic factors that works in coordination with Aspirin and stabilization of platelet derived aggregates. Few of these drugs have slower onset of action for example, Ticlopidine. Newer drugs are available replacing Ticlopidine by Prasugrel which has showed faster onset of action with better efficacy rate.
Anticoagulant agents
Anticoagulants have their own importance for treatment of cardiovascular diseases. Their basic function is to inhibit formation of fibrin along with inhibition of thrombin. Also disrupts platelet activation process. Heparin has indirect effect on antithrombin, coagulation inhibitor which inhibits thrombin, and other factors (XIa, IXa, Xa). Another agent, Warfarin reduces synthesis of various factors (X, IX, VII, II). These agents play an important role for ACS treatment and management particularly thrombo-embolism. The role of heparin (low molecular weight) is well established in this regard. Associated risk of bleeding with heparin is outweighed by its benefits for acute stroke. Stroke risk can be reduced among high risk patient through these anticoagulant. Efficacy rate of Heparin varies individual to individual for example, age, genes, and weight. It is an essential to monitor during Heparin treatment as it is responsible for bleeding.
Another factor for treatment of ACS has been introduced recently, Fondaparinux. Ongoing clinical research studies have discovered newer agent having direct coagulation effect, Dabigatran and Rivaroxaban. One of the benefits of these agents is they do not require continuous monitoring (Connolly, Ezekowitz & Yusuf, 2009). Trials are in place to assess the role of these new agents for atrial fibrillation.
Potential relevance of the findings
Prompt treatment plays an important role for treatment of cardiovascular disorders particularly the first hour is very crucial after having symptoms related to particular condition. Focused treatment can effectively reduce the disease severity and improve the overall outcome. Early evaluation and treatment is required for better recovery for STEMI patient. There are few important points which need to be dealt with great care – pre hospital management, early diagnosis, correct assessment, preparation for reperfusion therapy for STEMI etc. (Gabriel et al, 2012). Quick response and care is needed at three check points- delay in transport to hospital, delay in diagnosis, and delay in emergency ward. Any delay at these points can be life threatening for the patient. Delay in recognition of condition and delay in decision-taking process for constitute longer time period of delay in management and treatment. On the other hand, identification of ACS symptoms is an important aspect of care. It is all done through various diagnostic tests, identification of risk factors, persistent pain, chest discomfort, biomarkers etc. It is important to stratify the risk factor for associated condition. Beginning with the initial treatment, health care service providers should be trained for onset of ACS and related disease symptoms. During initial assessment, patient must be given oxygen along with aspirin. Then a dose of nitroglycerin is generally administer at regular intervals of 5 minutes. Patients unresponsive for nitroglycerin are given morphine for control of symptoms. Drug administration requires attention as these drugs can cause adverse reactions. Generally 12 lead ECG is performed for the assessment purpose. This technique is highly recommended for assessment of ACS. Confirmed STEMI cases are administered fibrinolytic and it is recommended to initiate the treatment within 30 minutes of contact (Widimsky et al, 2010)
Focused treatment of suspected or conformed cases starts after risk stratification based on ECG result. Another diagnostic assessment tool is cardiac biomarkers but it takes time for the measurement. Hence STEMI cases are not kept pending for a longer time period. Patients with STEMI have a blockage in epicardial coronary artery. Initial therapeutic management of ACS includes administration of oxygen and aspirin. Nonsteroidal anti-inflammatory drugs are also given along with aspirin. Early administration of these drugs is associated with lower mortality rate among patients with STEMI. Other antithrombotic drugs are Clopidogrel, Prasugrel, Ticagrel, Abciximab, Eptifibatide, Tirofiban. Additional measures are considered depending upon condition for example, coronary intervention is the preferred choice for STEMI cases (Gabriel et al, 2012). Percutaneous coronary intervention is considered as superior to fibrinolysis method of ACS treatment. It has gained popularity over the years because of treatment outcome. Clinical guidelines strongly recommends practice of using concomitant anti-thrombotic line of therapy for ACS patients. Aspirin can be given in combination with clopidogrel for better results. Dual line of therapy reduces the risk of death associated with vascular diseases (Cheng,2013).
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