Ch. 2-Drugs and their Targets Flashcards
chemical barrier
fluids, may affect solubility and ionization (charge) of the drug
anatomical barriers
membranes that prevent the drug from reaching its intended site of action
biochemical barriers
transport proteins, enzymes, and receptors resulting in movement of the drug, destruction of the drug, or production of target or unintended response
-ex) not enough transporters to move the drug, it won’t reach its target and is ineffective
drug actions depend on 3 properties
physiochemical properties, chemical properties, and stereochemistry
physiochemical properties of drugs
solubility, ionization, etc that influence how well the drug is absorbed and where it travels
chemical properties of drugs
resonance structure and inductive effects that play role in drug’s ability to bind
stereochemistry
shape and size of molecule that can influence how drug interacts with targets and if it can produce the right response
Can a drug create or confer a new biological function?
no, it can only increase or decrease the normal function
-ex) ibuprofen inhibits enzyme that synthesizes substances that cause inflammation
Proteins are needed for what in the body?
structure, function, and regulation of cells, tissues, and organs
What roles do proteins have?
regulating activation of genes, relaying signals between cells, driving metabolic processes, etc
4 Structures of protein
primary, secondary, tertiary, quaternary
primary structure of protein
sequence of amino acids that make up protein
-looks like string of beads
secondary structure of protein
determined by hydrogen bonding between amino acids to form alpha-helix or beta-sheets
tertiary structure of protein
highly organized, 3-D shape with distinct inside and outside; unfolded or folded
-has several binding sites where molecules can bind
quaternary structure of protein
2-6 polypeptide chains or subunits, often form a channel for entry into the cell
-acetylcholine receptor has 5 subunits that form a channel for sodium ions
4 Regulatory Protein Targets
- receptor proteins
- ion channel proteins
- enzymes
- transporters
receptor proteins
- receive and process signals from other cells
- ex)Zyrtec blocks H1 receptor (histamine receptor)
ion channel proteins
- control passage of solutes and ions in and out of cell
- ex) Novocain blocks sodium ion channel proteins to prevent pain signals
enzymes
- catalyze reactions
- ex) Celebrex inhibits COX2 enzyme to prevent synthesis of substances that cause inflammation
transporters
- bring materials in and out of cells
- ex) Prozac inhibits serotonin transporter (doesn’t move out of brain) resulting in elevated mood to relieve depression
agonist
initiates activity
antagonist
resists activity
blockers
block ion channels so certain ions cannot enter the cell
modulators
change the size of the opening in an ion channel
ligand
ion or molecule that binds to protein to form a complex (anything that binds to receptor)
- endogenous: already inside the body such as neurotransmitters
- exogenous: introduced into the body as a drug
pharmacophore
simplest structure that will bind to the target
-doesn’t take into account the different barriers or toxicity
3 groups of pharmacophore
vector groups, carrier groups, and vulnerable groups
vector groups
direct the drug to its site of action and can help minimize toxicity
-classified further as carrier groups and vulnerable groups
carrier groups
part of vector group
-control ionization and influence absorption, distribution, and excretion
vulnerable groups
part of vector group
-susceptible to enzyme action and responsible for determining drug’s metabolism
analog
compound with same or similar pharmacophore as the lead, with differences in other parts of the molecule
complementarity
physiochemical and steric
-determine strength of the type of interaction
physiochemical complementarity
several weaker noncovalent bonds attracting and keeping the two molecules together
- initial attraction between protein and ligand by long-range force such as ionic interaction between opposite charges
- short range forces (hydrogen bonds and van der Waals forces) hold them together as ligand gets closer
hydrophobic interaction
critical for protein-ligand interactions
-hydrophobic portion of ligand propels it from the water to the protein
electrostatic complimentarity
makes sure the ligand has the correct charged atoms for the interaction to occur so the wrong molecules don’t bind to active site
Region A of pharmacophore-The Amine Function
carries positive charge and can form ionic bond to negative site on receptor
Region A of pharmacophore-The R Group
size of R group increases, alpha receptor binding decreases and beta receptor binding increases
- hydrophobic binding also increases
- ex) R group changes from hydrogen to isopropyl group-drug only binds to beta receptors
what is most important for alpha receptor binding and activation?
ionic bonding
what is most important for beta receptor binding and activation?
hydrophobic binding
Region D-The Catechol Function
hydrophobic region of molecule, attracted to hydrophobic region of active site
-removing or replacing with less hydrophobic group reduces ability to bind to alpha and beta receptors
Region B-The alpha Carbon
inserting methyl group decreases alpha and beta receptor binding and activation
-physically interferes with ability of amine to bind to complementary active site
steric complementarity
determines shape and size that fit into shape of target on active site
stereoisomer
same molecular formula and sequence but different spatial arrangement
-can have dramatically different chemical, physical, and biological properties
chirality
geometric property, something can’t be superimposed on its mirror image
geometric isomers
restricted rotation around a bond
-cis and trans isomers
racemic mixtures
sample of compound that contains all its possible stereoisomers in equal propertions
isosterism
similarity in physicochemical properties bc of similarities in electron structures
bioisosterism
application of isosterism, allows the drug formula to be changed to improve the effect
-ex) Propanolol slows heart rate but is lipid soluble. modified to be Pindolol which is less lipid soluble
How does sulfonamide kill bacteria?
it is an isomer of PABA (para-aminobenzoic acid) which forms from folic acid and bacteria want to eat it. give the body sulfonamide and the bacteria eat it and can’t synthesize DNA to form new bacteria
How does ranitidine work?
it is an H2 blocker, and H2 is mainly present in the stomach. it causes excess stomach acid to be formed. ranitidine blocks the H2 receptors, inhibiting formation of stomach acid
For a drug to work, it has to be soluble in what?
balance between water soluble and lipid soluble
lipophilic
lipid-loving
they dissolve in lipids
cells and tissues contain lipids, and most drugs need to pass through those lipids
hydrophilic
water-loving
dissolves in water
most of the body is made of water, drug needs to dissolve in it so it can be transported throughout the body to its site of action
ionization
ability of a molecule to gain or lose electrons
Why is ionization important?
if a particle is charged, it won’t cross the cell membrane and it affects the structure, absorption, and distribution
efficacy
how effective something is
-how much of a drug you would need to produce the desired response
affinity
attraction, how compatible two molecules are and if they’ll stay together
