Introduction to pharmacology

Introduction to Pharmacology 

Pharmacology is the study of drugs on living systems

Why Pharmacology?

  • Diagnostic skills useless without properly prescribed medication
  • Fractured lower limb > 10 drugs used during process
  • Most errors are due to prescribing errors
  • Patients are better informed – doctors need to be too
  • Drugs are chemicals producing a biological effect
  • Drugs can be endogenous substances, given artificially

Fundamentals of pharmacology:

  • Pharmacodynamics – what drug does to body
  • Pharmacokinetics: what body does to drug: route into body, metabolised where
  • Mechanism
  • Indications: hence Clinical uses
  • Adverse effects
  • Contraindications
  • Eg. Aspirin – NSAID. Anti platelet aggregation properties.
  • The process is the most important thing – the mechanism
  • Aspirin inhibits COX enzymes, which catalyzes the breakdown of arachdonic acid to prostaglandins (PGs)
  • By knowing action of PGs, possible to learn pharmacology and physiology
  • By blocking PGs, GI healing is impaired. Can cause Reye’s syndrome in children and bronchial constriction in asthmatics
  • Long term use: adverse effects influence treatment

Properties of Drugs

  • Tissue selective
  • Chemical selectivity
  • Amplification of action – small dose producing profound effects
  • Drugs act at RECEPTIVE sites – expressed in selective tissues
  • Most drugs act at specific receptors including 4 main types: receptors, enzymes, carrier molecules, ions channels
  • eg B adrenoceptor in heart. The drugs changes action of protein channel, amplifying effect.
  • There are hundreds of thousands of receptors – new receptor = new drug
  • Receptor – target site, which produces cellular response/biological effect
  • Agonist – produces biological effect
  • Antagonist – blocks receptor
  • Occupancy =Affinity – ability to bind (therefore antagonist has affinity, not efficacy)
  • Efficacy – response from drug

Binding – different types:

  • Mostly reversible, weak (hydrogen bonds, van der vaals)
  • Or permanent (aspirin) by covalent bonding
  • Affinity- Reversible binding governed by law of mass action
  • Drug dose based on equilibrium constant (50% of receptors are free, 50% bound to agonist). Level of drug required to reach equilibrium constant describes affinity
  • Each drug has KA (affinity value)
  • Higher affinity means lower dose can be used
  • Affinity give sigmoid curve, as there is finite number of receptors available
  • EC50 – effective concentration giving 50% biological response. (Depends on affinity and efficacy). EC50 is used to compare drug potency
  • Pharmacokinetic properties (how well absorbed) will also affect drug potency
  • This is a basic explanation; because pharmacogenetics will also have an effect (receptor density varies)
  • Remember: receptors amplify signals. You don’t need full occupancy to provide an EC50.

Partial and Inverse Agonist

  • Full agonist – full efficacy
  • Partial agonist used in opioid addict
  • Antagonist – no efficacy
  • Inverse angonist – reduces basal receptor activity (has an action so is not an antagonist). Effect could be to reduce heart rate, for example. Could prevent action of another route

Competitive antagonism

  • Eg. Beta blocker
  • Agonist and Antagonist compete for binding site. Both bind reversibility.
  • Surmountable antagonism – To overcome antagonist, increase concentration of agonist
  • Sigmoid curve shifts to right
  • Non-surmountable antagonism consists of:
  • Non-competitive antagonism – agonist binds to different site to antagonist
  • Irreversible antagonism
  • Competitive antagonism is surmountable

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