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
Mr. Paul Welford 