Physicochemical Parameters in Drug Design Flashcards
Drug action requires
- absorption of the drug, distribution by body fluids thru membranes, escaping escessive distribution (or durg loss) and penetration at the active site
- the right orientation, shape and conformation in order to interact with receptors
- removal of the drug from the receptor and metabolism to an excretable form
drug action is dependent upon
- physicochemical properties of a drug
- host physiological and biochemical properties (biological action)
which parameters relatng to drug action can be changed
a) physicochemical properties of a drug
b) host physiology and biochem properties
physicochemical
hydrophilic molecules are
- polar, i.e. like water
- generally lipophobic i.e. not lipid soluble, don’t cross membranes
hydrophobic molecules
- non-polar; doesn’t like water
- lipophilic - lipid soluble, crosses membranes
the basis for drug design is
relationship between chemical structure and biological activity
pharmacological activity of drugs is either
- structurally specific
- structurally non-specific
Structurally specific pharmacological activity depends on
- the drugs chemical characteristics such as:
- the structure, shape, and conformation for binding of drug to receptor site
structurally non-specific pharmacological activity depends on
the interaction with cell membranes and is more dependent upon the drug’s physical characteristics than chemical characteristics
what is the receptor site theory
- ability of the drug to bind to the receptor
- lock and key - right configuration
what is the occupational theory of response
the intensity of drug effect is proportional to the number of receptors occupied by the drug
the ability of a drug to bind to the receptor relates to the
chemical structure of the drug
the chemical reactivity of the drug depends on
- bonding ability of drug to receptor
- precision of fit
- shape and conformation of the drug
a pharmacophore is
the functional group of a drug which is involved in binding to the receptor
Agonists have better drug receptor fit than antagonists which results in
increased drug response
True/False The stereochemistry of both receptor site surface and drug are important
True
differ in activity if interaction is at an asymmetrical carbon
enantiomorphs
contain groups that ar spatially and electronically equivalent
Bioisosteres
act as an antagonist to normal metabolites
isosteres
6 mechanisms of drug action
- induction of enzymes e.g. protein synthesis
- inhibition of DNA/RNA synthesis
- interference with protein synthesis
- inhibit enzyme catalyzed reactions
- formation of chelation complexes
- interference with cell membrane permeability
when drugs induce enzyme protein synthesis
- enzyme activity increases
- due to allosteric binding which triggers conformational changes in the enzyme allowing the substrate to bind more effectively
- coenzymes, vitamins & cofactors activate enzymes by complexation and stereochemical interaction
- e.g. barbituates, antihistamines
describe the MoA for drugs which interfere with DNA or RNA synthesis
- include antimetabolites, chelating agents, alkylating agents
- inhibit nucleic acid synthesis
- interefere with DNA replication or RNA protein transcription
the pharmacological effect of a drug depends on
- interactions between the drug molecule and receptor
- i.e. receptor binding
the ability of a drug to produce it effect depends on the complementatrity between
the drug and receptor