Ch. 2-Drugs and their Targets

Question 0

chemical barrier

Answer 0

fluids, may affect solubility and ionization (charge) of the drug

Question 1

anatomical barriers

Answer 1

membranes that prevent the drug from reaching its intended site of action

Question 2

biochemical barriers

Answer 2

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

Question 3

drug actions depend on 3 properties

Answer 3

physiochemical properties, chemical properties, and stereochemistry

Question 4

physiochemical properties of drugs

Answer 4

solubility, ionization, etc that influence how well the drug is absorbed and where it travels

Question 5

chemical properties of drugs

Answer 5

resonance structure and inductive effects that play role in drug’s ability to bind

Question 6

stereochemistry

Answer 6

shape and size of molecule that can influence how drug interacts with targets and if it can produce the right response

Question 7

Can a drug create or confer a new biological function?

Answer 7

no, it can only increase or decrease the normal function

-ex) ibuprofen inhibits enzyme that synthesizes substances that cause inflammation

Question 8

Proteins are needed for what in the body?

Answer 8

structure, function, and regulation of cells, tissues, and organs

Question 9

What roles do proteins have?

Answer 9

regulating activation of genes, relaying signals between cells, driving metabolic processes, etc

Question 10

4 Structures of protein

Answer 10

primary, secondary, tertiary, quaternary

Question 11

primary structure of protein

Answer 11

sequence of amino acids that make up protein

-looks like string of beads

Question 12

secondary structure of protein

Answer 12

determined by hydrogen bonding between amino acids to form alpha-helix or beta-sheets

Question 13

tertiary structure of protein

Answer 13

highly organized, 3-D shape with distinct inside and outside; unfolded or folded
-has several binding sites where molecules can bind

Question 14

quaternary structure of protein

Answer 14

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

Question 15

4 Regulatory Protein Targets

Answer 15

1. receptor proteins
2. ion channel proteins
3. enzymes
4. transporters

Question 16

receptor proteins

Answer 16

• receive and process signals from other cells

- ex)Zyrtec blocks H1 receptor (histamine receptor)

Question 17

ion channel proteins

Answer 17

• control passage of solutes and ions in and out of cell

- ex) Novocain blocks sodium ion channel proteins to prevent pain signals

Question 18

enzymes

Answer 18

• catalyze reactions

- ex) Celebrex inhibits COX2 enzyme to prevent synthesis of substances that cause inflammation

Question 19

transporters

Answer 19

• 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

Question 20

agonist

Answer 20

initiates activity

Question 21

antagonist

Answer 21

resists activity

Question 22

blockers

Answer 22

block ion channels so certain ions cannot enter the cell

Question 23

modulators

Answer 23

change the size of the opening in an ion channel

Question 24

ligand

Answer 24

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

Question 25

pharmacophore

Answer 25

simplest structure that will bind to the target | -doesn't take into account the different barriers or toxicity

Question 26

3 groups of pharmacophore

Answer 26

vector groups, carrier groups, and vulnerable groups

Question 27

vector groups

Answer 27

direct the drug to its site of action and can help minimize toxicity -classified further as carrier groups and vulnerable groups

Question 28

carrier groups

Answer 28

part of vector group | -control ionization and influence absorption, distribution, and excretion

Question 29

vulnerable groups

Answer 29

part of vector group | -susceptible to enzyme action and responsible for determining drug's metabolism

Question 30

analog

Answer 30

compound with same or similar pharmacophore as the lead, with differences in other parts of the molecule

Question 31

complementarity

Answer 31

physiochemical and steric | -determine strength of the type of interaction

Question 32

physiochemical complementarity

Answer 32

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

Question 33

hydrophobic interaction

Answer 33

critical for protein-ligand interactions | -hydrophobic portion of ligand propels it from the water to the protein

Question 34

electrostatic complimentarity

Answer 34

makes sure the ligand has the correct charged atoms for the interaction to occur so the wrong molecules don't bind to active site

Question 35

Region A of pharmacophore-The Amine Function

Answer 35

carries positive charge and can form ionic bond to negative site on receptor

Question 36

Region A of pharmacophore-The R Group

Answer 36

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

Question 37

what is most important for alpha receptor binding and activation?

Answer 37

ionic bonding

Question 38

what is most important for beta receptor binding and activation?

Answer 38

hydrophobic binding

Question 39

Region D-The Catechol Function

Answer 39

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

Question 40

Region B-The alpha Carbon

Answer 40

inserting methyl group decreases alpha and beta receptor binding and activation -physically interferes with ability of amine to bind to complementary active site

Question 41

steric complementarity

Answer 41

determines shape and size that fit into shape of target on active site

Question 42

stereoisomer

Answer 42

same molecular formula and sequence but different spatial arrangement -can have dramatically different chemical, physical, and biological properties

Question 43

chirality

Answer 43

geometric property, something can't be superimposed on its mirror image

Question 44

geometric isomers

Answer 44

restricted rotation around a bond | -cis and trans isomers

Question 45

racemic mixtures

Answer 45

sample of compound that contains all its possible stereoisomers in equal propertions

Question 46

isosterism

Answer 46

similarity in physicochemical properties bc of similarities in electron structures

Question 47

bioisosterism

Answer 47

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

Question 48

How does sulfonamide kill bacteria?

Answer 48

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

Question 49

How does ranitidine work?

Answer 49

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

Question 50

For a drug to work, it has to be soluble in what?

Answer 50

balance between water soluble and lipid soluble

Question 51

lipophilic

Answer 51

lipid-loving they dissolve in lipids cells and tissues contain lipids, and most drugs need to pass through those lipids

Question 52

hydrophilic

Answer 52

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

Question 53

ionization

Answer 53

ability of a molecule to gain or lose electrons

Question 54

Why is ionization important?

Answer 54

if a particle is charged, it won't cross the cell membrane and it affects the structure, absorption, and distribution

Question 55

efficacy

Answer 55

how effective something is | -how much of a drug you would need to produce the desired response

Question 56

affinity

Answer 56

attraction, how compatible two molecules are and if they'll stay together