FARMACOLOGIA Clase 21 de mayo

Fibrinolytics Overview and Clinical Application

Introduction to Fibrinolytics

• The discussion begins with a review of fibrinolytic drugs, which have been in use since the late 1980s.

• These medications significantly improve both anatomical and functional prognosis for patients experiencing ischemic strokes, acute myocardial infarctions, and acute pulmonary embolisms.

Mechanism of Action

• Fibrinolytics stimulate the coagulation cascade by activating thrombin, plasminogen, and plasmin to induce fibrinolysis.

• The therapeutic window for administering these drugs is critical; if administered too late (beyond 7 hours), they can increase the risk of hemorrhage rather than improve patient outcomes.

Enzymatic System and Drug Classification

• The fibrinolytic system balances the formation and elimination of fibrin. Key components include thrombin (essential for clot formation) and plasmin (the main enzyme in fibrinolysis).

• Fibrinolytics are categorized into three groups based on their action: those that activate plasminogen directly, inhibitors of fibrinolysis activated by thrombin, and direct plasmin inhibitors.

Clinical Use of Specific Fibrinolytics

Historical Context and Current Usage

• Urokinase and streptokinase were commonly used in the past but are now less favored due to anaphylactic reactions; currently, tenecteplase is preferred for acute myocardial infarction.

Administration Techniques

• Tenecteplase can be given as a single bolus dose without requiring central venous catheters, contrary to previous practices aimed at reducing peripheral vascular injury.

Dosage Considerations

• Alteplase is primarily used for ischemic strokes with a dosage calculated based on patient weight; it requires careful administration over one hour after an initial bolus.

Adverse Effects and Contraindications

Risks Associated with Fibrinolytic Therapy

• Hemorrhagic complications are significant risks associated with fibrinolytic therapy; intracranial hemorrhage is particularly concerning.

Management Strategies for Complications

• In cases of severe bleeding post-fibrinolysis, treatment may involve discontinuing the drug or administering fresh frozen plasma or prothrombin complex concentrates.

Patient Selection Criteria

Absolute Contraindications

• Patients with recent cranial surgery or trauma should not receive fibrinolytics due to high bleeding risk. Other contraindications include active internal bleeding or uncontrolled hypertension.

Relative Contraindications

• Recent surgeries or biopsies may allow for consideration depending on platelet counts. Careful evaluation is necessary before proceeding with treatment in such cases.

This structured overview provides a comprehensive understanding of key concepts related to fibrinolytic therapy while ensuring easy navigation through timestamps linked directly to specific discussions within the transcript.

Clinical Case Discussion on Neurological Deterioration

Overview of the Patient's Condition

• The patient is a 70-year-old presenting with neurological deterioration and a time window exceeding 14 hours since symptom onset.

• A simple cranial CT scan reveals a large hypodense area, indicating an older infarct rather than a recent one. This suggests that at least 12 to 24 hours have passed since the event occurred.

Imaging Insights and Treatment Recommendations

• Before administering fibrinolytics, it is crucial to perform a CT scan to assess the extent of the infarct; this patient is not a candidate for thrombolysis but requires craniectomy due to increased intracranial pressure risk.

• The presence of acute ischemic signs, such as the "Arterial Sign," indicates that if observed within five to six hours post-event, thrombolysis may still be viable. Conversely, significant density changes between hemispheres suggest an ongoing infarction.

Differential Diagnosis Considerations

• Hypoglycemia must be ruled out in cases of neurological deterioration; failure to do so could lead to inappropriate thrombolytic treatment if blood glucose levels are critically low (e.g., below 40). This scenario poses legal risks for practitioners.

Thrombolytic Therapy Protocol

• Alteplase can be administered at a dosage of 0.9 mg/kg, with specific infusion protocols outlined for optimal effectiveness within designated time frames post-symptom onset. Monitoring clinical improvement is essential during treatment. Signs include gradual recovery in neurological status and reduced pain levels in myocardial infarction contexts.

Monitoring and Managing Complications Post-Thrombolysis

Clinical Monitoring Requirements

• Continuous monitoring of neurological status post-thrombolysis is critical; any decline necessitates immediate cessation of therapy and further imaging studies to rule out complications like hemorrhage or worsening ischemia. Fresh frozen plasma transfusion may be required if bleeding occurs.

Case Study: Acute Ischemic Stroke Presentation

• A new case involves a 65-year-old male who experienced sudden right-sided weakness and speech difficulties after breakfast, with hypertension noted upon examination (190/105 mmHg). This situation highlights the importance of rapid response in stroke management despite elevated blood pressure not being an absolute contraindication for thrombolysis when managed appropriately with antihypertensives like beta-blockers or calcium channel blockers prior to treatment initiation.

Understanding Anemia Management in Clinical Practice

Iron Metabolism Essentials

• Iron absorption primarily occurs in the duodenum; understanding its metabolism is vital for managing conditions like anemia effectively, especially considering dietary intake variations among populations (e.g., menstruating women losing iron). The average daily absorption rate ranges from 3 to 4 mg under normal circumstances but can vary significantly based on individual health factors and dietary habits.

Implications of Iron Deficiency

• Chronic iron deficiency leads to various forms of anemia; recognizing symptoms such as fatigue or pallor can guide timely interventions including supplementation or transfusions where necessary—especially critical in patients undergoing renal dialysis who often present normocytic anemia due to erythropoietin deficiencies resulting from kidney dysfunction. Understanding these nuances aids clinicians in tailoring effective treatment plans while avoiding potential complications associated with over-supplementation leading to hemachromatosis or other adverse effects related to excess iron accumulation within tissues over time.

Absorption and Transport of Iron

Mechanisms of Iron Absorption

• The absorption of iron occurs primarily in the duodenum, specifically in the proximal portion, where specialized proteins facilitate its uptake.

• Active transport mechanisms are involved, with DMT1 (Divalent Metal Transporter 1) playing a crucial role in transporting ferrous iron across intestinal cell membranes.

Iron Transport and Storage

• Once absorbed, iron is transported into the bloodstream via ferroportin after being oxidized by specific groups. Excess iron is stored as ferritin within intestinal cells.

• In plasma, iron binds to transferrin for transport to developing erythroid cells; transferrin receptors mediate this process through endocytosis.

Regulation and Elimination of Iron

• Transferrin-receptor complexes recycle back to the plasma membrane post-internalization. There is no active mechanism for iron excretion; minimal amounts are lost through cellular exfoliation and bodily fluids like bile and urine.

Conditions Affecting Iron Absorption

Factors Influencing Absorption

• Effective absorption requires healthy intestinal epithelial cells; poor conditions can lead to malabsorption syndromes or diarrhea that hinder iron uptake.

• Ferrous iron is transported into the bloodstream via cotransporters, combining with apoferritin for storage as ferritin before distribution to macrophages and hepatocytes.

Parenteral Iron Administration

Clinical Use of Parenteral Iron

• Parenteral forms of iron are primarily used in hematology for patients with severe hemolytic anemias. These medications have a short half-life but can cause adverse reactions such as anaphylaxis or fever.

Dosage Recommendations

• Initial doses should be small to monitor patient tolerance; maximum doses should not exceed 100 mg three times weekly due to risks associated with hemocromatosis.

Considerations for Renal Patients

Adjustments Based on Patient Context

• Total accumulated dosage must reflect each patient's total deficit based on hemoglobin levels and body weight, especially in renal patients who may require higher dosages due to chronic anemia.

Megaloblastic Anemia Overview

Causes and Nutritional Deficiencies

• Megaloblastic anemias often stem from deficiencies in folic acid or vitamin B12, particularly prevalent among post-surgical patients experiencing malabsorption issues.

Role of Folic Acid in Metabolism

Biochemical Functions

• Folic acid plays a critical role in amino acid metabolism and nucleotide synthesis essential for DNA formation. It’s recommended that women prepare their bodies pre-pregnancy by taking folic acid supplements.

Vitamin B12: Importance and Forms

Active Forms of Vitamin B12

• Vitamin B12 exists mainly as cobalamin derivatives (e.g., cyanocobalamin), which serve vital roles as coenzymes necessary for various metabolic processes including red blood cell formation.

Conclusion & Next Steps

Upcoming Topics

• Future discussions will cover cardiac arrhythmias treatment strategies along with vascular events related to fibrinolytics. Students are encouraged to study diligently ahead of exams.