Pharmacology

• Pharmacology: the science that looks at the composition, effect, and use of drugs

  This term derives from the Greek word 'pharmakon' meaning both 'remedy' and 'poison'
• Pharmacokinetics: the way in which drugs move through the body during absorption, distribution, metabolism, and elimination

  Pharmacodynamics: the effect drugs have on the body
• Pharmacokinetics:

  • this influences the decision about the route of administration for the drug

  This process occurs after drug administration and is broken down into 4 components...

  1. Absorption: how the drug will get in
  2. Distribution: where the drug will go
  3. Metabolism: how the drug will be broken down
  4. Excretion/Elimination: how the drug will leave
• What can affect drug absorption?

  • presence of food
  • the route of medication
  • whether the medication is coated
  • rate of gastric mobility
  • controlled release preparations
• Absorption:

  • oral, buccal, rectal - these are enteral routes
  • intravenous, intramuscular, subcutaneous, inhaled - these are parenteral routes

  Other routes:

  • intra-arterial, intrasternal, intrathecal, intra-articular, intraperitoneal, intraventricular, nasal, bronchial, vaginal, conjunctiva
• Distribution:

  Once a drug has been absorbed, they must distribute to the sight of action

  1. distribution into body fluids e.g., blood
  2. uptake into body systems or organs
  3. extent of plasma protein binding
  4. passage through barriers, placenta, or blood-brain barrier (BBB)
• Metabolism (Biotransformation):

  • biotransformation is the process of metabolising a drug
  • this occurs in the liver and goes into different compounds called metabolites
  • some drugs are referred to as pro-drugs - these are pharmacologically inert until metabolised by the liver and then become an active form

  E.g., Codeine metabolises into Morphine in the liver
• Metabolism: transformation of pharmaceutical substances in the body so they can be eliminated

  Metabolites: a product of metabolism
• Drug metabolism:

  • this is affected by dose size and drug frequency
  • drugs that metabolise quicker have a shorter duration of action and need to be administered more frequently
  • slower metabolising drugs have a longer duration and can be administered less frequently
  • metabolic processes convert drugs into water-soluble compounds like urine and bile
  • very few drugs can be eliminated without being metabolised
  • the therapeutic effect of a drug diminishes as it metabolises
• Therapeutic index:

  • a small number of drugs have narrow margins between safe and unsafe dosing, this is referred to as a Therapeutic Index
  • pharmacological monitoring is essential for safe and effective use
  • patients on these types of drugs require routine blood tests
• Factors affecting how the liver metabolises:

  • age - liver function and enzyme activity decline
  • liver disease e.g., hepatitis
  • grapefruit juice and St John's Wort inhibits the enzyme activity to metabolise statins
  • cranberry juice affects metabolic activity of enzyme Cytochrome P450 - this is essential for the metabolisation of Warfarin
  • cigarettes and brussel sprouts increase P450 activity
• Excretion:

  • this occurs in the kidneys
  • a few drug metabolites may have pharmacological effects, but they can also be harmful
  • if metabolites are not eliminated, they can accumulate in the bloodstream and cause toxic and unwanted effects
• Excretion by other routes:

  • small amounts of drugs excrete through sweat, saliva, and tears
  • some drugs may become concentrated within breast milk due to its natural acidity, therefore medication prescriptions need to be carefully considered with nursing mothers
  • excretion can occur in the hair and skin in very small quantities
• Pharmacodynamics: the study of the biochemical and physiological effects of drugs on the body
• Pharmacodynamics:

  There are 2 actions involves in this...

  1. drugs either change their environment of body cells e.g., antacids neutralise stomach acidity
  2. drugs bind receptors on cell membranes and alter cellular physiology e.g., Digoxin binds to receptors on myocardial cells and increases the myocardial force of heart muscle contraction
• How do drugs work?

  1. the plasma membrane surrounding each cell is studded with protein molecules which perform different functions, these are called receptors
  2. ion channels - these receptors work by blocking the drug channel (referred to as channel blocking receptors) OR allow the drug to enter the channel (referred to as channel modulating receptors)
  3. transport systems - these are referred to as carrier molecules, they facilitate transport of drugs across the plasma membrane into the cells
• Therapeutic effect: a desired effect of a drug e.g., Paracetamol facilitates pain relief

  Adverse effect: a harmful or abnormal result of a drug

  Side effect: undesired effects of a drug e.g., Codeine may cause constipation
• First pass metabolism:

  • some drugs undergo destruction by 'first pass metabolism' - this is through the liver
  • when drugs are absorbed through the stomach, the drug enters blood vessels which go directly to the liver, this is referred to as portal circulation
  • this means that any drug which is largely destroyed or broken down by liver enzymes will not enter the general systematic circulation - therefore, some drugs can not be given orally as they will not work
• Transdermal application:

  • delivery of a drug into the systematic circulation
  • some examples include nicotine patches and hormone replacement therapy (HRT)
  • these can last from 12 hours, to 24 hours, or longer
• Affinity:

  • affinity is referred to as preference
  • all drugs have an affinity for their receptors or chemical targets
  • drugs with a higher affinity bind first, in preference of other drug molecules e.g., Carbon Monoxide has a greater affinity on haemoglobin rather than Oxygen