Lecture 1 - Introduction, General Terms, and Drug-Receptor Interactions

Question 1

Define

Site of Action

Answer 1

Location where the drug exerts its effect

Question 2

Define

Mechanism of Action

Answer 2

How a drug produces its therapeutic effect

through targetting receptors and regulating pysiological function

Question 3

Define

Receptor sites

Answer 3

Molecular level of where the drug exerts its effects

depends on cell type or subcellular location

Question 4

Define

Drug indication

Answer 4

a sign, symptom, or medical condition that leads to the recommendation of a drug

Question 5

Define

Contraindication

Answer 5

A situation when a particular drug should not be used

ex. with alcohol or other medications

Question 6

Define

Side effects

Answer 6

Causes slight discomfort but not harmful

Question 7

Define

Adverse effects

Answer 7

potentially harmful

ex. chemotherapy

Question 8

Define

Toxic effects

Answer 8

Extremely harmful

ex. fentanyl

Question 9

Define

Therapeutic Index (TI)

Answer 9

• Ratio of median lethal dose (LD50) to median effective dose (ED50)
• Gives an estimate of a drug’s relative safety

Question 10

What TI indicates a drug is safer?

Answer 10

> TI means the drug is safer

larger gap between effective dose and toxic dose

Question 11

Define

LD50

Answer 11

the lethal dose of a drug that kills 50% of the tested samples

Question 12

Define

ED50

Answer 12

specific dose of medication that produces a specific effect in 50% of the population that recieves that dose

measurements taken in vivo

Question 13

Where is Effective Concentration (EC) measured

Answer 13

in vitro

(outside the body)

Question 14

FDA Pregnancy Category A

Answer 14

Drug studies have not yet shown risk to fetus

Question 15

FDA Pregnancy Catergory B

Answer 15

Drug studies have not been preformed in pregnant women; no demonstrated risk to fetus in animal studies

Question 16

FDA Pregnancy Category C

Answer 16

No studies in human or animals; animal studies reveal teratogenic potential but risk to fetus is unknown

Question 17

FDA Pregnancy Category D

Answer 17

Adverse risk to fetus; benefit to risk ratio must be established

Question 18

FDA Pregnancy Category X

Answer 18

Teratogenic effects in women and animals; fetal risk outweighs benefits

Question 19

FDA Pregnancy Catergory NR

Answer 19

Not yet rated by FDA

Question 20

What is a teratogen?

Answer 20

An agent or factor which causes malformation of an embryo. May cause spontaneous abortion, growth retardation, or carcinogenesis

Question 21

Define

Controlled substance

Answer 21

A drug that has the potential for abuse and is regulated by the Drug Enforcement Agency (DEA)

Question 22

Schedule 1 Drugs

Answer 22

Drugs with high abuse potential and no accepted medical use

ex. heroin, hallucinogens

Question 23

Schedule 2 Drugs

Answer 23

Drugs with high abuse potential and accepted medical use

Ex. Narcotics (morphine), amphetamines

Question 23

Schedule 3 Drugs

Answer 23

Drugs with moderate abuse potential and accepted medical use

Ex. anabolic steroids, dronabinol

Question 24

Schedule 4 Drugs

Answer 24

Drugs with low abuse potential and accepted medical use | Ex. Zolpidem (Ambien), antianxiety drugs

Question 25

Schedule 5 Drugs

Answer 25

Drugs with limited abuse potential and accepted medical use | Ex. small doses of narcotics

Question 26

'Black Box' Warning

Answer 26

Issued by the FDA to label drugs with serious adverse reactions

Question 27

# Define Efficacy

Answer 27

Drugs ability to activate or inhibit the receptor | does NOT depend on dosage, expressed as a %

Question 28

# Define Potency

Answer 28

Amount if drug necessary to produce a desired effect | Dependent on affinity, expressed as IC50, ED50, etc

Question 29

# Define Affinity

Answer 29

How tightly the drug binds to the target receptor (Most common bond) Van der waals > hydrogen > ionic > covalent (least common bond) | Kd is the inverse of drug affinity to the binging site

Question 30

What are the fatcors that affect Kd (dissociation constant)

Answer 30

- Type of bonds - temperature - pH - receptor conformation - drug or receptor modification - competition with other ligands

Question 31

# Define Suicide inhibition/inactivation

Answer 31

When an enzyme binds a substrate analog and forms an irreversible coplex via covalent bond

Question 32

# Define Suicide substrate

Answer 32

Compounds that resemble the substrate of an enzyme and irreversibly binds to the enzyme to inactivate it

Question 33

How many human receptors are targeted by drugs? What are the drugs usually made of?

Answer 33

~1000 human receptors Most drugs are made form small molecules, a smaller amount is made from biologics

Question 34

# Define major type of drug/receptors interaction Ion channels

Answer 34

Ion channels span the plasma membrane. Binding causes an alteration in the channel's conductance

Question 35

# Define major type of drug/receptors interaction G protein-coupled receptors

Answer 35

Bound by drug at extracellular surface or transmembrane region of the receptor, affects downstream cell signal

Question 36

# Define major type of drug/receptors interaction Transmembrane receptors

Answer 36

Drug binds to extracellular end which causes change in signalling within the cell by activating/inhibiting an enzymatic intracellular domain

Question 37

# Define major type of drug/receptors interaction Cytoplasmic or Nuclear Receptors

Answer 37

drugs can diffuse through the membrane, often used by lipophilic drugs, ex. steroid hormone receptors

Question 38

What is the most common protein for drugs to target?

Answer 38

GCPRs

Question 39

# Describe Activation of Adenylyl Cyclase (AC) by G Proteins

Answer 39

Agonist binds to GPCR --> GTP activates AC to convert ATP to cAMP --> To PKA pathway for protein phosphorylation

Question 40

# Describe Activation of Phospholipase C (PLC) by G Proteins

Answer 40

Agonist binds to GPCR --> GTP activates PLC to convert PIP2 into DAG and IP3 --> DAG activates PKC, IP3 causes release of Ca2+ from ER --> activated PKC and Ca2+ leads to protein phosphorylation

Question 41

# Action of G-protein Subtypes Gs (stimulatory)

Answer 41

- Activates Ca2+ channels - Activates Adenylyl Cyclase

Question 42

# Action of G-protein Subtypes Gi (inhibitory)

Answer 42

- Activates K+ channels - Inhibits adenylyl cyclase

Question 43

# Action of G-protein Subtypes G0

Answer 43

Inhibits Ca2+ channels

Question 44

# Action of G-protein Subtypes Gq

Answer 44

Activated PLC

Question 45

# Action of G-protein Subtypes G12, G13

Answer 45

Diverse ion transporter interactions

Question 46

# Regulation of Receptor Response Tachyphylaxis

Answer 46

Repeated administration of the same dose of a drug results in a reduced effect of the drug overtime

Question 47

# Regulation of Receptor Response Desensitization

Answer 47

Decreased ability of a receptor to respond to stimulation by a drug or ligand - homologous: gecreased response at a single type of receptor - heterologous: decreased response at two or more types of receptors

Question 48

# Regulation of Receptor Response Inactivation (Ion channels)

Answer 48

Loss of ability of a receptor to respond to stimulation by a drug or ligand

Question 49

# Regulation of Receptor Response Refractory

Answer 49

After a receptor is stimulated, a period of time is required before the next drug-receptor interaction can produce an effect

Question 50

# Regulation of Receptor Response Down-regulation

Answer 50

Repeated or persistent drug-receptor interaction results in removal of the receptor from sites where subsequent interactions could take place

Question 51

Inactivation vs. desensitization

Answer 51

Inactivation --> for ion channels (remain in refractory period) or enzymes Desensitization --> for receptors