Toxicology

• Drug misuse


  What constitutes drug misuse
• At risk of drug misuse

  Who is at risk of drug misuse
• Prescription vs over the counter medicine

  What distinguishes between a prescription and an over the counter medicine
• Drugs of Abuse UK Classification


  • All are controlled drugs under the Misuse of Drugs Act 1971
  • The Misuse of Drugs Act states that it is an offence to: possess a controlled substance unlawfully, possess a controlled substance with intent to supply it, supply or offer to supply a controlled drug (even if it is given away for free), allow a house, flat or office to be used by people taking drugs
  • Drug trafficking attracts serious punishment, including life imprisonment for Class A offences
• Underdose of medical concern


  Too low a dose taken
• Conditions where underdose is of medical concern

  • Blood pressure
  • Asthma
  • Cancer
  • Mental Health
  • Psychosis
  • Infection – antibiotic resistance
• Kinetics, The Steady State and therapeutic window


  This example typical for antibiotics, but the concepts can be applied to determining blood levels for a prescription drug
• Plasma drug concentration


  Time
• Overdose of clinical concern


  Too high a dose taken
• Effects of overdose


  • Heart, lung, brain effects - behavioural
  • Kidney & Liver organs attempt to eliminate the high drug load
  • If metabolites are toxic, can result in liver or kidney damage
  • Unless the drug is removed, the healthy organs are destroyed
• Causes of overdose


  • Accidental – Clinical settings (children eating tablets, elderly cannot remember correct dose)
  • Intentional – Forensic settings (e.g. call for help, suicide, Poisoning)
• Poison


  "any substance which, taken into or formed in the body, destroys life or impairs health"
• Xenobiotic


  Foreign body (drug, pesticide, dietary supplements)
• Dose determines toxicity, as almost all substances, if given in high enough dose can be toxic
• How drugs are eliminated from the body

  • Absorption (Ability to cross membranes, Fat solubility – BB barrier, Protein-binding, Affected by route of admin)
  • Metabolism (GI, Hydrolysis, Prodrug or reactive metabolite?)
  • Excretion (Lungs, Kidneys, Faeces)
• ADME and toxicity of MDMA


  Species differences
• Pharmacokinetics profiles


  Differ for different drugs and poisons
• t1/2


  Peak plasma concentration
• How drugs induce pathological change

  • Acute toxicity
  • Chronic toxicity
• Organs most at risk: Heart, kidney and liver
• Cardiotoxicity


  Dr Patel's lectures
• Kidney Function


  • Most drugs are lipid soluble, aiding them to cross membranes
  • The kidneys excrete only water soluble drugs
  • Metabolism converts fat-soluble drugs into water soluble drugs
• Biomarkers of kidney damage

  • Glomerulus
  • Proximal tubules
  • Loop of Henle
  • Distal tubules
  • Collecting duct
• Drugs that elicit site-specific injury in the kidneys

  • Proximal tubules: cancer drugs, antibiotics
  • Loop of Henle: analgesics
• Glomerular Filtration Rate (GFR)


  The test estimates the volume of blood that is filtered by your kidneys over a given period of time
• Creatinine


  Muscle breakdown product that is cleared from the blood by healthy kidneys
• Revision from 1st year physiology and anatomy
• Serum liver aminotransferases


  Typical serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values for various diseases. These are often normal in patients with cirrhosis. In patients with uncomplicated alcoholic hepatitis, the AST value is rarely greater than 500 U per L and is usually no more than 200 to 300 U per L. The highest peak aminotransferase values are found in patients with acute ischemic or toxic liver injury.
• Revise use of logs