Clinical Chemistry 2 - Midterms

• Pharmacology


  Science which deals with the study of drug action and drug conversion on the body
• Drug


  A chemical substance that is used in the cure, treatment, or prevention of diseases in man and animals
• Standard Dosage


  Statistically derived from observations in a healthy population
• Factors influencing standard dosage

  • Patient age
  • Gender
  • Genetics
  • Recent food consumption
  • Prescription drugs
  • Self-administered over-the-counter drugs
  • Naturopathic agents
• Therapeutic Range


  Level of concentration in the bloodstream which provides the optimum amount of medication for treatment of the clinical disorders
• Therapeutic Index


  The ratio of the threshold of toxicity to minimal therapeutic level
• Bioavailability


  The extent to which a drug can be successfully absorbed from the gastrointestinal tract and be therapeutically active
• Steady-state


  The rate of administration is equal to the rates of metabolism and excretion
• Half-life


  The time required for the concentration of the drug to decrease by 50%
• Therapeutic Drug Monitoring (TDM)


  • Involves coordinated effort of several healthcare professionals to measure and monitor circulating drug levels
  • An individualized system of treatment and management of drug therapy and deals with the measurement of drug concentrations during therapy with pharmaceutical agents
• Goal of TDM


  Keep the trough level from dropping down a concentration of therapeutic benefit and to keep the peak concentration from rising to the toxic level
• Prime Candidates for TDM

  • Patients who are at the extremes of age
  • Patients with other mitigating medical conditions
  • Patients undergoing multiple drug therapy
• Applications of TDM


  • Used for narrow therapeutic index
  • Serum concentration should be determined after initiation of therapy or when the dosage regimen or drug formulation has been changed
  • Procedure is usually done after the drug has reached a steady-state concentration
• Common Indications for TDM

  • Identifying non-compliance in patients
  • Preventing the consequences of overdosing and underdosing
  • Maximizing therapeutic effect
  • Optimizing a dosing regimen based on drug-drug interactions or a change in a patient's physiologic state
• Purpose of TDM


  • Identify when the drug is above or below a therapeutic range which may lead to either inefficacy or toxicity
  • Ensure that a given drug dosage is within a range that produces maximal therapeutic benefit
• Advantages of the TDM Program

  • Noncompliance can be recognized
  • Patients in whom drug disposition characteristics are unusual can be recognized
  • Therapeutic drug regimens can be adjusted during periods of continuous physiological change
  • Baseline concentrations associated with an optimal therapeutic regimen can be identified
  • The most appropriate drug dosing regimens can be initiated and monitored for a particular patient
• In neonates and infants, more frequent monitoring is necessary because renal and hepatic functions change rapidly during development
• Drug levels should be monitored during illness, especially when the illness involves impairment of renal, hepatic, gastrointestinal, or cardiovascular function, because significant changes in serum concentration may occur
• Monitoring is indicated whenever the medication is unexpectedly ineffective or toxic
• Dosage adjustment may be required when a new drug is added to the patient's regimen because of possible interactions
• Routes of Drug Administration

  • Enteral: Oral, Sublingual, Rectal
  • Parenteral: Intravascular/Intravenous (IV), Intramuscular (IM), Subcutaneous (SC)
  • Others: Inhalation, Intranasal, Intrathecal (injection in spinal canal), Intraventricular, Topical, Transdermal, Suppository
• Discontinuous drug administration


  Commonly seen in oral drugs
• Continuous drug administration


  Commonly seen in IV drugs
• Factors influencing drug activity in the body

  • Absorption
  • Distribution
  • Metabolism
  • Excretion
• Important physiological factors affecting blood drug level

  • Absorption of the drug into the blood
  • Distribution or equilibration of the drug with body tissues
  • Metabolism of the circulating drug, primarily by the liver
  • Elimination, usually by the kidney
• Absorption


  The transfer of a drug from its site of administration into the BLOODSTREAM
• Factors influencing drug absorption

  • Drug's dissociating form from its dosing form
  • Dissolving in gastrointestinal fluid
  • Diffusing across biological membranes into bloodstream
• Absorption of weak acids vs weak bases

  Weak acids: efficiently absorbed in the stomach due to gastric acidity

  Weak bases: preferentially absorbed in the intestine where the pH is more alkaline
• Transport of drug from GIT

  • Passive Diffusion
  • Active Transport
• Physical factors influencing absorption

  • Blood flow to the absorption site
  • Total surface available for absorption
  • Contact time at the absorption surface
  • Intestinal motility
  • pH
  • Inflammation
  • Presence of food or other drugs
  • Coadministered drugs
  • Morphine
• Distribution


  The process by which a drug reversibly leaves the bloodstream and enters the INTERSTITIUM (extracellular fluid) and/or the CELLS OF THE TISSUES
• Drug distribution based on properties

  • Hydrophobic drugs can easily traverse cellular membranes and partition into lipid compartments

  Polar but not ionized drugs can cross cell membranes but do not sequester into lipid compartments

  Ionized drugs diffuse out of the vasculature at a slow rate
• Free vs Bound Drugs

  • Most drugs in circulation are subject to binding with serum constituents, most are drug-protein complexes

  Acidic drugs primarily bind to albumin

  Basic drugs primarily bind to alpha1-acid glycoprotein (AAG)

  Only free drugs can interact with target sites and produce a response

  Most TDM assays quantify total drug concentration rather than free drug
• Metabolism


  The conversion of the parent drug to its metabolites
• First pass effect


  Absorbed substances from intestine to liver
• Cytochrome P450


  One of the most prominent gene families that affect drug metabolism
• Elimination


  The process where drugs are cleared from the body
• Routes of drug elimination

  • Kidney into the urine

  Bile

  Intestine

  Lungs

  Milk in nursing mother
• The drug elimination follows first-order pharmacokinetics in which the clearance of a drug is linearly related to dose of drug
• All drugs are eventually excreted, either unchanged in the urine, or as metabolites of the parent drug