Pharmacology basics Flashcards
What experiments first introduced the idea of receptors? How?
Langley’s experiments with pilocarpine and atropine
Application of pilocarpine resulted in decreased heart rate and increased saliva production
Both were prevented by pre-application of atropine
Later on- nicotine application mimics effects of innervation but curare stopped this
stimulation of a nerve produced a substance the mimicked the effects of nicotine
What is the modern definition of affinity?
Tendency of a chemical/molecule to bind to a receptor
Ehrlich’s early experiments on blood cells
Proposed chemical interactions occurred between dyes and cells
There was a specificity which is governed by cell type and the chemical structure/solubility of the dye
What are chemical mediators?
Extracellular signal molecules that are detected by target cells by receptors
generate intracellular changes that alters the cells behavior
Why do cells express different kinds of receptors?
Integration of information
Coordination of responses
Amplification of signalling
What is the difference between endocrine and paracrine signalling?
Endocrine- over long distances to target organs through the bloodstream, distributed widely over the body (signalling molecules, mediators)
Paracrine- extracellular signals acting locally without diffusing too far, may be stored in vesicles or produced on demand
What does it mean when a cell is autocrine?
When a cell responds to paracrine signalling molecules that it produces itself
What are common examples of paracrine signalling?
Inflammation, controlling cell proliferation and wound healing
Smooth muscle relaxation and dilation by nitric oxide
Eciosanoids and endocannabinoids
What is contact dependent signalling?
Shortest range of all types of communication
When a cell surface bound molecule binds to a receptor on an adjacent cell
What are examples of contact dependent siganlling?
Used widely by the immune system
Immunotherapy to treat cancers
What is a bioassay?
Experimental assay in which the concentration or potency of a substance is determined by the biological response it produces
How is a mediator defined?
A chemical, peptide or protein that conveys information from one cell to another in response to a stimulus of some kind
What are the criteria for a mediator?
It is released from cells in sufficient amounts to produce a biological action on target cells within an appropriate time frame
Application of an authentic sample of the mediator reproduces the original biological effect
Interference with the synthesis, release or action ablates or modulates the original biological response
How is regulating the synthesis of small molecule mediators different to synthesis of peptide mediators?
Small molecule- regulated by specific enzymes
Peptide- regulated by transcription
What are the two types of chemical mediators?
Preformed mediators- stored in vesicles from which they are released by exocytosis allowing for rapid communication
Mediators produced on demand- released by diffusion or constitutive secretion which are slower and take minutes/hours to act
What are examples of preformed mediators and ones that are produced on demand?
Preformed- neurotransmitters, hormones, cytokines, growth mediators and neuromodulators
Produced on demand- nitric oxide, lipid mediators like prostanoids
How can drugs effect chemical communication?
Targeting transporters
Increasing release of neurotransmitters by displacing it from vesicles (sympathomimetic action)
Targeting ion channels involved in regulation of neurotransmission
What are the 4 classes or ‘super families’ of receptors targeted by synthetic drugs?
Ligand gated ion channels
G-protein coupled receptors
Kinase linked receptors
Nuclear receptors
What classes of receptors are found on the cell surface? What features do they have in common?
Ion channels, GPCRs and kinase linked
Transmembrane spanning segments composed of hydrophobic amino acids
Possess extracellular ligand binding domain
What type of receptor isn’t found on the surface of a cell membrane? What features do they possess?
Nuclear receptors as they are DNA linked
Regulate gene transcription#
Ligand must be able to cross plasma membrane
What are agonists? What are some examples?
Drugs or chemical mediators that bind to a receptor and produce a response
Pilocarpine, nicotine, acetylcholine, morphine