Drug Binding Flashcards
In what media does drug binding occur?
Aqueous solution
What increases drug binding - lipophilicity of hyrdophilicity?
Lipophilicity.
When a drug binds it moves from a very hydrophilic to a hydrophobic environment.
What 3 factors affect the ability of a drug molecule to permeate a membrane?
Size
Charge
Lipophilicity
Which types of molecules are likely to be lipophilic?
Those with structures containing only carbon and hydrogen
Which types of molecules are likely to be hydrophilic?
Structures containing polar functional groups with heteroatoms (amines, alcohols, carboxylic acids)
Eukaryotic cells
Have a nucleus which contains DNA - aka human cells.
Cytoplasm
Fluid content of a cell
Organelles
Functional structures within a cell
Mitochondria
Responsible for energy production
Ribosomes
Responsible for protein synthesis, located on rough endoplasmic reticulum.
Smooth endoplasmic reticulum
Where lipid and carbohydrates metabolism takes place
Cell membrane
Is selectively permeable, controlling movement of molecules into and out of the cell. Maintains electrolyte balance (cell potential).
What proteins can be found on the cell membrane?
Signalling (receptors)
Transport (Ion channels)
Recognition (Glycoproteins)
Catalysis (Enzymes)
Phospholipid bilayer
Makes up the cell membrane
Has polar heads and non-polar tails that face each other, creates an inwards hydrophobic environment (VDWs)
Passive transport
Diffusion through the cell membrane, can be facilitated. Doesn’t require ATP.
Active transport
Diffusion through the membrane that requires ATP.
Rate of diffusion across a membrane
From quickest to slowest:
Hydrophobic molecules (O2, CO2, N2)
Small uncharged polar molecules (H2O, indole, glycerol)
Large uncharged polar polar molecules (glucose, sucrose)
Ions (Cl-, K+, Na+)
Basic steps of drug action
Recognition based on intermolecular interaction (non-covalent)
Interaction producing pharmacological response (reversible or irreversible)
Induced fit binding accompanied by conformational change in protein and/or drug.
Induced fit
When Ligands and/or drugs bind to a proteins binding site and they both change conformation to increase intermolecular interactions
Electrostatic interactions
Ionic bonds resulting from attraction of molecules bearing opposite charges.
Salt bridges
A type of ionic bond that involves the CO2- and NH3+ residues of proteins present on binding site at pH 7.4 interacting with opposite charge on drug.
Hydrogen bonding
Formed between an electron deficient hydrogen and an electron rich heteroatom (O or N)
Van deer waals
Weak interactions caused by temporary dipoles caused by areas of high and low electron density
Aromatic stacking
Aromatic rings in drugs can bind with aromatic rings at binding site (histidine, phenylalanine) to from either sand which or T-shaped modes.
