Toxi Finals M4

• Target organ


  Most affected by a toxic agent
• Animal tests for toxicity have been conducted prior to and in parallel with human clinical investigations as part of the non-clinical laboratory tests of pharmaceuticals
• Toxicity Measurements and End points

  • Acute Toxicity
  • Subchronic Toxicity
  • Chronic Toxicity
  • Carcinogenicity
• Acute Toxicity


  Provide data on the relative toxicity likely to arise from a single or brief exposure, or sometimes multiple doses over a brief period of time
• Standardized tests have been developed for the following effects

  • Reproductive Toxicity
  • Developmental Toxicity
  • Dermal Toxicity
  • Ocular Toxicity
  • Neurotoxicity
  • Genetic Toxicity
• Reproductive Toxicity

  Intended to determine the effects of substances on gonadal function, conception, birth, and the growth and development of offspring. The oral route of administration is preferable
• Cancer


  A disease characterized by uncontrolled growth of altered cells and their ability to migrate from the original site and spread to different parts of the body

  
• Mutation


  A permanent change in the amount or structure of the genetic material in a cell
• The Cardiovascular System and the Blood

  • Blood and Cardiovascular/Cardiac Toxicity
  • Chronotropy
  • Inotropy
  • Vascular tone
• Chronotropy


  Effects of poisoning and overdose on the cardiovascular system - disturbances in the pattern of the pulse
• The pattern of the pulse, blood pressure, cardiac conduction and type of dysrhythmias may help identify the toxic agent. However, hypoxia, shock, hypothermia, and other superimposed complications may distort the typical pattern
• Target organ


  Most affected by a toxic agent
• Sympathetic response


  Increases the automaticity, conduction velocity, and contractility of the heart, and lengthens the refractory period and produces constriction of most vascular beds
• Animal tests for toxicity have been conducted prior to and in parallel with human clinical investigations as part of the non-clinical laboratory tests of pharmaceuticals
• Bradycardia


  May be produced by excess cholinergic activity, interference with release or depletion of the catecholamines, damage to the myocardium, or increased intracranial pressure
• Toxicity Measurements and End points

  • Acute Toxicity
  • Subchronic Toxicity
  • Chronic Toxicity
  • Carcinogenicity
• Dysrhythmias


  Caused by spontaneous depolarization (automaticity), abnormal impulse conduction (reentry), and "triggered" responses. They may be caused by: (a) direct or indirect sympathomimetic effects; (b) anticholinergic effects; (c) CNS-related regulation of peripheral autonomic activity; (d) direct effects on the myocardial membrane; (e) myocardial ischemia; or (f) secondary to hypotension, hypoxia, or disturbances in acid-base and electrolyte balance
• Acute Toxicity


  Provide data on the relative toxicity likely to arise from a single or brief exposure, or sometimes multiple doses over a brief period of time
• Correction of hypoxia and metabolic derangements (electrolyte imbalances, hypoglycemia, and acid-base disturbances) will spontaneously rectify many dysrhythmias
• Vascular tone


  Transient hypertension may be produced by substances acting indirectly to increase the release of NE from storage granules or by decreasing the re-uptake of norepinephrine. Substances also act directly to decrease the degradation of NE or to interact with the alpha receptors. The vascular tone may be reduced by agents that produce myocardial depression and a decrease in cardiac output or by dysrhythmias that interfere with cardiac filling. Vascular tone may be also influenced by agents affecting the ANS or peripheral effector sites. The cause may be hypoxia, volume depletion, and anaphylaxis
• Standardized tests have been developed for the following effects

  • Reproductive Toxicity
  • Developmental Toxicity
  • Dermal Toxicity
  • Ocular Toxicity
  • Neurotoxicity
  • Genetic Toxicity
• Cardiovascular effects


  • Hypertension with tachycardia
  • Hypertension with bradycardia
  • Hypertension initially associated with reflex bradycardia
• Hematotoxicology


  The study of adverse effects of drugs, non-therapeutic chemicals and other agents in our environment on blood and blood-forming tissues
• The consequences of direct or indirect damage to blood cells and their precursors are predictable and potentially life-threatening. They include hypoxia, hemorrhage, and infection. These effects may be subclinical and slowly progressive or acute and fulminant, with dramatic clinical presentations
• Reproductive Toxicity


  Intended to determine the effects of substances on gonadal function, conception, birth, and the growth and development of offspring. The oral route of administration is preferable
• Types of hematological disorders

  • Iron deficiency anemia
  • Sideroblastic anemia
  • Megaloblastic anemia
  • Aplastic anemia
  • Methemoglobinemia
  • Microangiopathic hemolytic anemia
• Cancer


  A disease characterized by uncontrolled growth of altered cells and their ability to migrate from the original site and spread to different parts of the body
• Mutation


  A permanent change in the amount or structure of the genetic material in a cell
• The Cardiovascular System and the Blood

  • Blood and Cardiovascular/Cardiac Toxicity
  • Chronotropy
  • Inotropy
  • Vascular tone
• Chronotropy


  Effects of poisoning and overdose on the cardiovascular system are disturbances in chronotropy
• The pattern of the pulse, blood pressure, cardiac conduction and type of dysrhythmias may help identify the toxic agent. However, hypoxia, shock, hypothermia, and other superimposed complications may distort the typical pattern
• Sympathetic response


  Increases the automaticity, conduction velocity, and contractility of the heart, and lengthens the refractory period and produces constriction of most vascular beds
• Bradycardia


  May be produced by excess cholinergic activity, interference with release or depletion of the catecholamines, damage to the myocardium, or increased intracranial pressure
• Dysrhythmias


  Caused by spontaneous depolarization (automaticity), abnormal impulse conduction (reentry), and "triggered" responses. They may be caused by direct or indirect sympathomimetic effects; anticholinergic effects; CNS-related regulation of peripheral autonomic activity; direct effects on the myocardial membrane; myocardial ischemia; or secondary to hypotension, hypoxia, or disturbances in acid-base and electrolyte balance
• Correction of hypoxia and metabolic derangements (electrolyte imbalances, hypoglycemia, and acid-base disturbances) will spontaneously rectify many dysrhythmias
• Vascular tone


  Transient hypertension may be produced by substances acting indirectly to increase the release of NE from storage granules or by decreasing the re-uptake of norepinephrine. Substances also act directly to decrease the degradation of NE or to interact with the alpha receptors. The vascular tone may be reduced by agents that produce myocardial depression and a decrease in cardiac output or by dysrhythmias that interfere with cardiac filling. Vascular tone may be also influenced by agents affecting the ANS or peripheral effector sites. The cause may be hypoxia, volume depletion, and anaphylaxis
• Cardiovascular effects


  • Hypertension with tachycardia
  • Hypertension with bradycardia
  • Hypertension initially associated with reflex bradycardia
• Hematotoxicology


  The study of adverse effects of drugs, non-therapeutic chemicals and other agents in our environment on blood and blood-forming tissues
• The consequences of direct or indirect damage to blood cells and their precursors are predictable and potentially life-threatening. They include hypoxia, hemorrhage, and infection. These effects may be subclinical and slowly progressive or acute and fulminant, with dramatic clinical presentations
• Types of hematotoxicity


  • Iron deficiency anemia
  • Sideroblastic anemia
  • Megaloblastic anemia
  • Aplastic anemia
  • Methemoglobinemia
  • Microangiopathic hemolytic anemia