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

Introduction to Imaging

Introduction to Imaging

  • X-Ray – first image of bones of hand. Silhouette of anatomy.
  • Silhouette sign – bony material silhouetted against air. Lost on chest X-ray with pathology
  • Age of patient important in radiology. Multiple lesions on chest X-ray – most likely secondary.
  • Only 25% of world has access to X-ray
  • First scanner developed in Wimbledon by Godfrey Hansfield – a SGUL graduate. First scan in 1976
  • CT chest = 400 chest X-rays. Particularly important to consider in children. And brain/eyes are particularly radiosensitive. Repetitive exposure give cumulative risk. Risk of cancer with CT chest 1 in 1000 (smoking doubles your risk).
  • Childrens’ doses kept low with ultrasound where possible.
  • CT scanning has evolved due to computer progress.
  • EMI record label funded 1st CT, so The Beatles indirectly helped fund CT scanning
  • Functional CT due to labelled glucose – tumours can be imaged due to glucose uptake
  • PET (functional) and CT (anatomy) scans fused together allows tumour to be staged -PETCT
  • All imaging carries risk, due to energy being imputed to patient (ultrasound and MRI heat, X-ray ionising).
  • 1/3 of admissions are for chest pain. Half don’t have heart. Computed coronary angiography is 99% effective for screening. Very high negative predictive value.
  • In fluoroscopy, user gets dose (cardiologists, interventional radiologists and some surgeons are high risk users)
  • Ultrasound – Ian Donald. Uses sonar (WWII technology) used first in 1950s, published in Lancet. High frequency bell which rings
  • Risk is tissue cavitation
  • Black on image is fluid (transmits), white (reflects), grey (partially reflects).
  • Seeing the anatomy can sometimes give you the diagnosis.
  • Doppler effect can assess patency of blood vessels
  • Moore’s law. Every 10 years, size halves. Ultrasound is now ‘point of care’, can be size of smartphone.
  • Ultrasound can image stomach – eg. Pyloric stenosis in child
  • Ultrasound – high negative predictive value, good for excluding pathology inc fractures in remote locations, due to portability
  • Ultrasound prices £40-£120,000
  • MRI – invented by Peter Mansfield in Nottingham
  • 20% of patients cannot tolerate
  • Protons align due to magnetic field, water has most protons,
  • Magnetic field strength is icreasingtarted with 1tesla, now 3tesla which improves signal to noise ratio
  • Radio frequency added (this causes the noise during the scan), which knocks protons off axis. During time they are knocked off, they emit signal, which can be measured
  • Exquisite resolution. Can see bone bruises, MS plaques, tumour inc blood vessels
  • Cannot perform with pacemaker, metal artefacts, certain heart valves
  • Can image mother in first trimester
  • Shall we image early? – eg locked knee before pt sees surgeon
  • Cost of MRI is coming down, more private providers, hence availability is going up