Pharmacology

• Pharmacology definition

  The study of the effect of drugs on the function of living systems
• Pharmacodynamics

  The effects of the drug on the body e.g., paracetamol mechanism of action dependent of the inhibition of prostaglandin synthesis
• Pharmacokinetics

  The effects of the body on the drug (A.D.M.E)
• ADME


  absorption, distribution, metabolism, excretion
• What is a drug?


  A biologically active compound of a known structure (other than a nutrient or essential dietary ingredient) taken with the intent to produce a beneficial change in the body.
• What is medicine?

  A chemical preparation which usually contains one or more drugs administered with the purpose of producing a therapeutic effect. Usually contains other substances to make them more convenient to use e.g. a coating
• What are the 3 drug classes?

  -Class

  -Therapeutic action

  -Chemical property
• What is a drug target?

  -A molecular recognition site where a drug will bind e.g., Lovastatin binds to substrate to break down cholesterol.

  73% of drug targets are human proteins, 16% are microbial or viral, 11% miscellaneous.
• What are the 4 principles of pharmacology? (A.S.T.E)

  Active ingredient

  Selectively bind to molecular targets to exert an effect on cells or system

  Therapeutic effect: Concentration dependent find "sweet spot"

  Efficacy: Usefulness of drug/medicine is supported by clinical trials using agreed outcome measures
• What is a receptor?

  Specific macromolecules at which a ligand birds and alters biochemical activity
• Paul Ehrlich

  -Interested in staining cellular components.

  -Looked for a treatment for syphilis, took 3 years

  and 300 synthesis attempts to produce salvarsan.

  -Set the basis for receptor concept.
• What is the Magic bullet theory?

  "Therapy without toxicity"

  -Drug should have selective toxicity ideally with little action of host cells even at high dose.

  DISPROVED: drugs work by binding to receptors
• What did Langley prove?

  Discovered receptors as major targets for drugs by applying nicotine to muscle fibres causing them to contract
• Why is it difficult to class drugs?

  -Due to the different needs of chemists, pharmacologists, and doctors.

  -Nomenclature- it is not always practical to present each drug under a single name as formulations vary widely

  -Any drug can be put into 3 different classes.
• What is classical drug discovery?

  Drugs identified by exploring disease mechanisms.
• What is post genomic drug discovery?

  Drugs identified by analysing genetic basis or susceptibility to disease
• How many drugs are approved each year?

  ~25

  In 2021 50 new drugs approved

  2020- 53
• Conventional routes of drug target identification :

  -Analysis of pathophysiology (understand how drug works)

  -Analysis of mechanism of action of existing therapeutic drugs (repurposing)
• Novel routes of drug target identification:

  -"Trawling genome" to find disease modifying genes whose altered gene expression may be involved in disease development or

  -Genes that encode for functional proteins whose activity is altered in disease state
• Genome trawling success and failure

  Success: imatinib a highly specific tyrosine kinase inhibitor that treats chronic myeloid leukaemia. Frustrations: cystic fibrosis, Alzheimer's.
• Transgenic models:


  -Mouse models that have had their genomes altered for the purpose of studying gene functions

  -Gene of interest is engineered to lack or overexpress
• Accidental discovery example:

  Amphetamine trialled as headache remedy -> seen to decrease agitation in children -> Ritalin for ADHD
• Human genome and druggable targets:

  -30,000 genes in the human genome

  -3000 (10% of the genome) are disease modifying genes.

  -600-1500 drug targets which are "druggable".
• What are biological assays?

  A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions.
• What is Homeopathy?


  Based on 2 principles:

  1."Like cures like" (virus can cure viral disease)

  2. The grater the dilution the more potent the medicine. 30C dilution "most effective" Homeopathy is a placebo treatment and does not necessarily work. Should not be endorsed by the NHS.
• Acupuncture:

  -No direct evidence with over 3000 trials.

  -Acupuncture works better than a placebo. Doesn't cure anything.
• How long does it take to develop a new medicine and what is the cost?

  12-15 years

  1.3 billion