Receptor-Mediated Cell Signaling

Question 1

Antagonist

Answer 1

Block receptors and have no inherent ability to elicit a response

Question 2

Competitive antagonist

Answer 2

molecule that competes for the same binding site as an agonist; low concentrations can be overcome by the agonist; effects depend upon its concentration which is influenced by the rate of metabolic clearance or excretion

Question 3

Non-competitive antagonist

Answer 3

• have depressive effects on maximal agonist response but do not compete for same binding site as the agonist
• blockade is fixed and cannot be overcome by the agonist
• usually have prolonged effects and receptor blockade reversal is slow
• duration of action depends upon rate of receptor turnover
• Ex: ketamine blocks channel functioning of NDMA receptor channel for glutamate

Question 4

Chemical antagonist

Answer 4

a drug that binds directly to an agonist and deactivates the agonist (form an inactive compound) e.g. tannins

Question 5

Physiological antagonist

Answer 5

any drug or chemical that has an opposite effect, but through different physiological pathways e.g. histamine and epinephrine (contract vs. dilate sm mm of airway)

Question 6

Pharmacologic antagonist

Answer 6

any drug that binds to a receptor and prevents the activation of the receptor

Question 7

Drug-Receptor Interactions

Answer 7

• most drugs bind in reversible manner - unbinding and binding occurs very fast
• drug binding chemical interaction is determined by structure of drug relative to receptor binding site

Question 8

Properties of drug-receptor interactions:

Answer 8

1. Saturable (maximal) response (finite # of receptors)
2. Reversibility
3. Good potency (many drugs act @ very low concentrations)
4. Chemical sensitivity
5. Competitive blockade by antagonists
6. Amplified responses

Question 9

Dissociation constant (Kd)

Answer 9

• the concentration at which 50% of the binding sites (receptors) are occupied by the drug; can be determined for an agonist or antagonist
• expressed as a concentration
• provides info about affinity of the drug for a receptor
• High affinity - low Kd; Low affinity - high Kd

Question 10

Affinity

Answer 10

how well a drug binds a receptor; helps define the drug’s potency

Question 11

Potency

Answer 11

amount of drug required to produce a desired effect; used as means to compare drugs, (higher potency, less drug required)

Question 12

EC50

Answer 12

drug concentration producing 50% of a maximal effect; typically used for in vitro studies

Question 13

Efficacy

Answer 13

the maximum effect a drug can produce

for drugs w/ similar maximal efficacy, increasing drug potency decreases EC50

Question 14

ED50 or effective dose

Answer 14

dose that causes a desired effect in 50% of the population receiving it; effect must be all or none (quantal effect)

Question 15

Specificity

Answer 15

measure of a drug’s ability to produce a desirable effect relative to its ability to produce an undesirable effect

Specificity = ED50 (desirable)/ ED50 (undesirable)

If ED50 (un) >>>ED50 (des) = high (good) specificity

If ED50 (un) = ED50 (des) = low (bad) specificity

Question 16

Therapeutic Index (TI)

Answer 16

a quantal response; ratio of LD50 (lethal dose in 50%) and ED50; the larger the TI, the safer the drug is

TI = LD50/ED50

Question 17

Margin of Safety

Answer 17

ratio of drug that is just within the lethal range (1%) to the dose that is 99% effective; more stringent index of safety

MOS = LD1/ED99