Pharmacology Flashcards
What is pharmacodynamics?
What a drug does to the body (biological effects and mechanism of action)
What is pharmacokinetics?
What the body does to a drug (absorption, distribution, metabolism and excretion of drugs and their metabolites).
What is a drug?
A SINGLE synthetic or natural substance of known structure - everyday substances, substances used for treatment and illicit substances.
What is a medicine?
A chemical preparation containing one or more drugs used with the intention of causing a therapeutic effect. Usually includes agents additional to the active drug.
Must act with a degree of selectivity
What is selectivity?
-the ability to distinguish between different molecular targets within the body and allows drugs to interact with select tissues to get the intended effect.
How do drugs act?
By binding to regulatory proteins to modify their function - enzymes, carrier molecules, ion channels, receptors
Or by binding to other targets - RNA and DNA
Very rarely there is no specific target
What are receptors?
Macromolecules in or within cells that mediate the biological actions of hormones, neurotransmitters and other endogenous substances
What is an agonist?
A drug that binds to a receptor to produce a cellular response. They bind reversibly to receptors to activate them temporarily by inducing a reversible confrontational change. Possess affinity (rate of agonist binding/rate of agonist unbinding) and efficacy (rate of receptor activation / rate of receptor deactivation)
What is an antagonist?
A drugs that reduces, or blocks the actions of an agonist by binding to the same receptor.
- bind but do not activate receptors
- posses affinity but not efficacy
Describe the relationship between affinity and dissociation in agonists.
Low affinity - ‘fast’ dissociation rate
High affinity - ‘slow’ dissociation rate
What is efficacy in agonists?
The ability of an agonist to evoke a cellular response.
Low efficacy = small response
High efficacy = big response
What happens when drug dose is too high?
Selectivity no longer works and negative effects can occur
What is the relationship between receptor occupancy and agonist concentration?
As agonist conc. increases the receptor occupancy increases correspondingly and the relationship of hyperbolic.
What is EC50 ?
The concentration of agonist that elicits a half maximal effect.
What is the relationship between concentration (dose) and effect?
The relationship is sigmoidal
Describe reversible competitive antagonism
Binding of antagonist and agonist (both reversible) occurs at the same (orthosteric) site and are competitive and mutually exclusive
It can be overcome by increasing concentration of agonists
Describe non-competitive antagonism
Agonist binds to orthosteric sure and antagonist binds to separate allosteric site and thus is not competitive.
Both may occupy the receptor reversibly and simultaneously but activation cannot occur when antagonist is bound
What do competitive antagonist do to the graph?
Cause a parallel rightward shift of the agonist concentration response curve but maximum response is unchanged
What do non competitive antagonists do to the graph?
Depress the slip and maximum of the concentration response curve but do not cause a rightward shift.
What are receptors and what are they targets of?
They are sending elements of chemical communication within the body and are the targets of ; -neurotransmitters, hormones, other mediators, therapeutic agents (agonists and antagonists, modulators)
What are autocrine, paracrine and endocrine signalling?
Autocrine - cell signals to itself
Paracrine - cell signals to its close neighbour
Endocrine - cell signals via molecules transported in the blood to target distant cells
Describe ligand gated ion channels
Located at the plasma membrane
Targeted by hydrophilic signalling molecules
Consists of separate glycoprotein subunits that form a central, ion conduction channel where ions flow down their electrochemical gradient.
Allows very rapid changes in permeability > Action in milliseconds
Eg. Nictonic acetylcholine
Describe G protein-coupled receptors
Located at the plasma membrane
Targeted by hydrophilic signalling molecules
Signal in seconds
Receptor - integral membrane protein, single polypeptide with extracellular NH2 and COOH terminus, contains seven transmembrane helical spans
Describe kinase linked receptors
Located at plasma membrane
Targeted by hydrophilic protein mediators (eg insulin)
Work on hours time scale