Receptor Theory, Signal Transduction, And Dose-Response

Question 1

Drugs

Answer 1

. Small organic molecules that have specific 3D shape and electronic charge configuration
. Interact w/ macromolecules that have complementary configurations (receptors)

Question 2

Examples of drug receptors

Answer 2

. NT and hormone receptors 
. Enzymes 
. Transport proteins 
. Ion channels 
. Ion receptors 
. Cell recognition and adhesion molecules
. Nuclei acids

Question 3

For most drugs, the duration of action is directly related to ______

Answer 3

. Time in which drug is bound to receptor

. When drug is cleared from bloodstream it dissociates from receptor and it’s action ends

Question 4

Examples of drugs that do not act at specific receptors

Answer 4

. Antacids

. Cheating agents

Question 5

Forces involved in drug-receptor interactions

Answer 5

. Electrostatic interactions (btw functional groups w/ opposite charges
. Hydrophobic ( non polar regions of drug and receptor interact)
. Van der waals
. Covalent bonding (drugs bind irreversibly w. Receptor through covalent binding)

Question 6

Types of Electrostatic interactions

Answer 6

. Ionic: fully charged
. Dipolar: partially charged
. H bonding

Question 7

Drug-receptor interactions have a high degree of ____ specificity

Answer 7

. Structural

. Slight changes in structure of drug causes large changes in activity

Question 8

Agonism

Answer 8

. Drugs interact w/ receptors that activate receptor-effector mechanism (signal transduction pathways) and alter function of target cell

Question 9

Competitive antagonism

Answer 9

. Drug occupies receptor and prevents agonist from binding to receptor
. Need more conc. Of agonist in order to reach same intensity of response

Question 10

Affinity

Answer 10

. Propensity of drug to bind to given receptor

Question 11

Intrinsic activity

Answer 11

. Ability of drug to initiate a response by producing conformational changes needed to activate receptor-effector mechanism

Question 12

. Agonist has both ___ and _____ drug-receptor interactions

Answer 12

. it has affinity and intrinsic activity

Question 13

Does a competitive antagonist have affinity or intrinsic activity?

Answer 13

. It has affinity

. Has no intrinsic activity

Question 14

Other types of actions besides competitive antagonism

Answer 14

. Partial agonists
. Mixed agonist/antagonists
. Inverse agonists

Question 15

Inverse agonists

Answer 15

. Drugs that can bind to receptor and stabilize the receptor in an inactive state
. Results in effects on the signaling pathway that are opposite those of an agonist
. Drug decreases basal activity of signaling response mechanism

Question 16

Non-competitive antagonism

Answer 16

. Antagonist on the same molecule but at different binding site than antagonist
. Never get to same intensity of response as agonist alone

Question 17

Chemical antagonism

Answer 17

. Antagonist interacts directly with agonist drug an inactivates it

Question 18

Functional antagonism

Answer 18

. Antagonist acts through a completely different mechanism to counteract the effects of the agonist

Question 19

Concentration-effect relationships

Answer 19

. Intensity of drug effect is dependent on drug conc. At site of action

Question 20

General process and assumptions of concentration-effect relationships

Answer 20

. Relationship is reversible, equilibrium process
. One drug molecule combines w. One receptor
. Response is directly related to number of receptors occupies
. Amount of drug actually bound is negligible compared to the amount free

Question 21

Equation to determine concentration of drug to get certain intensity of drug’s effect

Answer 21

. Effect = Max effect [D]/(Kd + [D])
. [D] is free drug conc.
. KD is dissociation constant and represents drug conc. At which effect is 1/2 of the max

Question 22

Drug-receptor interactions follow principles described for ___ interactions

Answer 22

. Enzyme-substrate

Question 23

Michealis Menten equation

Answer 23

V = Vmax[S]/(Km+[S])

Question 24

Drug potency

Answer 24

. Amount of drug needed to produce given effect

Question 25

Efficacy

Answer 25

. Ability of drug to product an effect w/o regard to concentration

Question 26

Graded dose response relationship

Answer 26

. Shows intensity of a drug effect in a subject is a function of the drug dose . Has biological variation . Potently is the position of the curve on X axis determined by pharmacokinetics and inherent ability fo drug to bind to receptor and product effect

Question 27

. Threshold dose

Answer 27

. Any dose below that amount no effect would be seen

Question 28

Maximal effect (efficacy)

Answer 28

. Determined by pharmacokinetics of drug and inherent ability to produce an egg etc

Question 29

Quantal dose-response relationship

Answer 29

. Shows the percent of subjects in a population that exhibit a response of given intensity as a function of a drug dose . Curves can be used to compare effect of different drugs in population os test subjects . Useful to compare dose of single drug that produces different effects in a population of subsections

Question 30

Therapeutic index

Answer 30

LD50/ED50 . LD50: lethal dose. Where 50% of subjects died . ED50: 50% of subjects reached efficacy in response of drug

Question 31

Toxicity index

Answer 31

. TI = TD50/ED50 . TD50: dose amount where 50% of subjects felt toxic effect . TD50: dose amount where 50% of subject felt efficacy response

Question 32

Tolerance

Answer 32

. Dec. sensitivty to drug | . Seen after chronic treatment

Question 33

Pharmacokinetic tolerance

Answer 33

. Due to induction of enzymes that metabolize drug

Question 34

Pharmacodynamic tolerance

Answer 34

. Due to changes in sensitivity of drug receptors | . Usually involves compensatory changes in number of receptors or sensitivity of receptors (effector mechanisms)

Question 35

Tachyphylaxis

Answer 35

. Rapidly developing pharmacodynamic tolerance

Question 36

Physical drug dependence

Answer 36

. Tolerance . Withdrawal syndrome ( physiologic symptoms that appear when drug is abruptly stopped, effects opposite of effect drug produces)

Question 37

Pharmacodynamic basis of tolerance and dependence

Answer 37

. Related to compensatory changes in receptors and effector mechanism

Question 38

Idiosyncratic effect

Answer 38

Unusual drug effect in certain individuals

Question 39

Drug allergy

Answer 39

. Drug acts as allergen to activate immune response

Question 40

Additive effects

Answer 40

. Combined drug effect is equal to sum of effects of each drug

Question 41

Synergistic effect

Answer 41

. Combined drug effect of 2 drugs is greater than sum of the effects of each drug alone

Question 42

Potentiation

Answer 42

. 1 drug enhances the toxic actions of another