Pharmacology of disease

• Pharmacology

  The study of drugs and how they interact with other molecules in the body and how they affect the body

  
• Pharmacology


  • Diverse field including chemistry, molecular and cellular biology, pathology, clinical pharmacology and toxicology, regulatory affairs, quality control
• Drug


  Any substance that induces functional changes in an organism through its chemical action
• Diabetes Mellitus


  A metabolic disorder where the quantity of glucose in the blood is too elevated due to the body not producing enough insulin, producing no insulin, or having cells that do not respond properly to the insulin the pancreas produces (insulin resistance)

  
• Ebers Papyrus (16th Century BC) lists the extensive pharmacopia of that civilization: beer, turpentine, myrrh, juniper berries, poppy, lead, salt and crushed precious stones, animal product (lizard's blood, swine teeth, goose grease, ass hooves and various excreta)
• Hyperglycemia


  The quantity of glucose in the blood is too elevated

  
• Various Greek treatises (4th Century BC) and on 1st Century Dioscorides' five volume De Materia Medica (Latin translation)
• In 1809, François Magendie studied the effect of nux vomica (a strychnine-containing plant drug) on dogs, and demonstrated that the spinal cord was the site of its convulsant action
• Symptoms of Diabetes


  • Frequent urination
  • Increased thirst
  • Intense hunger
  • Unusual weight loss (usually with Type I)
  • Fatigue/ excess sleep
  • Blurred vision
  • Slow healing of cuts and bruises
• The 20th century witnessed a steady increase in the number of new drugs that would improve the human condition tremendously. It is hard to imagine our world without Ibuprofen, Penicillin or vaccines
• Types of Diabetes


  • Type I
  • Type II
  • Gestational Diabetes
• Chemical name


  Identifies the chemical and molecular composition of a drug, e.g. acetylsalicylic acid
• Generic (non-proprietary) name


  The name under which the drug is licensed by the manufacturer and internationally identified, with the initial in lower case, e.g. aspirin
• Type 1 Diabetes Mellitus (T1DM)


  • Most common cause of diabetes in children
  • Incidence peaks around 12–14 years of age
  • Autoimmune disease where the immune system destroys beta cells in the pancreas
• Trade name or brand name

  Indicates the medicine containing the drug, with the initial in large upper case, e.g. Aspirin, Aspro, Disprin
• Type 2 Diabetes Mellitus (T2DM)


  • Most common type of diabetes, accounting for >90% of cases
  • Multifactorial disease involving genetic and environmental factors
  • Characterized by beta-cell dysfunction, insulin resistance and chronic inflammation
• Prediabetes


  Higher than normal glycaemic levels, with an annual conversion rate of 3–11% per year to overt T2DM
• Cellular and molecular pharmacology


  • Branch that analyzes the general mechanisms underlying drug action in the body at molecular and cellular level
• Pharmacodynamics


  What the drug does to the body
• Parkinson's disease is a disorder of movement
• Pharmacokinetics


  What the body does to the drug
• Clinical Pharmacology


  Study of drug effectiveness and safety in humans
• Genetic susceptibility is a prerequisite for the development of Type 2 diabetes, though specific genes causing it are still unknown
• Parkinson's disease


  • Characterized by: Tremor at rest, Muscle rigidity, Suppression of voluntary movement
• Molecular and cellular basis of common diseases

  • Genetic disorders (e.g. Down's syndrome, cancer)
  • Ion channels disorders (e.g. Cystic Fibrosis)
  • Metabolic disorders (e.g. Diabetes Mellitus)
• Development of Type 2 Diabetes

  1. Insulin resistance

  2. Impaired glucose tolerance (IGT)

  3. Failure of insulin secretion from beta cells

  4. Overt Type 2 Diabetes

  
• Pharmacogenetics/Pharmacogenomics


  • Study of how genes affect individual responses to a drug
• Parkinson's disease affects the basal ganglia and is associated with loss of dopamine from substantia nigra and corpus striatum

  
• Toxicology


  • Study of harmful effects of drugs, contributing to drug profiling
• Impaired Glucose Tolerance (IGT)


  A venous plasma glucose level of 7.8-11.0 mmol/l two hours after a 75g oral glucose load, associated with a high risk for the development of Type 2 diabetes

  
• Pharmacovigilance


  • Discipline monitoring the occurrence of toxic effects after drug commercialization, e.g. Yellow card scheme (MHRA)

  
• Factors that influence the development and severity of insulin resistance are obesity/over nutrition and physical inactivity, while weight reduction, physical training and calorie restriction decrease insulin resistance
• Pharmacoeconomics


  • Study of drug cost/benefit from the economic point of view, including costs of production, sale price and economics of drug use, important in health policies
• The major factor determining conversion from IGT to overt Type 2 diabetes is a failure of insulin secretion from the beta cells

  
• Parkinson's disease is seen mainly in the elderly, but not exclusively
• ADME


  Absorption, distribution, metabolism and excretion
• The Ebers Papyrus described diabetes as a rare disease that causes the patient to lose weight rapidly and urinate frequently, thought to be the first reference to diabetes


  1550 BC
• Absorption


  The passage of the drug from its site of administration into the plasma, important for the drug to reach its receptor and elicit its function
• Ayurveda described several diseases of polyuric nature, including the equivalent of diabetes mellitus called "madhumeha" ("honey urine")


  5th-6th century BC
• Avicenna provided the first detailed account of Diabetes Mellitus, documenting the abnormal appetite, collapse of sexual functions, and sweet taste of diabetic urine


  980-1037