DRUG TARGETS

Question 1

to identify the target, study the ____ of the disease

Answer 1

pathophysiology

Question 2

The vast majority of drugs used in medicine are targeted to ____, such as receptors, enzymes, and transport proteins.

Answer 2

proteins

Question 3

it is important to understand ____ in order to understand drug action on proteins.

Answer 3

protein structure

Question 4

• Most abundant macromolecules
• Perform wide array of functions.

Answer 4

protein

Question 5

building blocks of proteins

Answer 5

amino acids

Question 6

For amino acids to polymerized they should form

Answer 6

peptide bonds

Question 7

PROTEINS

will be functional if they undergo ____

Answer 7

folding process

Question 8

PROTEIN STRUCTURES OR CONFORMATIONS

Polypeptide chain—proteins are not functional (nascent)

Answer 8

PRIMARY STRUCTURE

Question 9

PROTEIN STRUCTURES OR CONFORMATIONS

only structure left during denaturation because of peptide bonds

Answer 9

primary structure

Question 10

PROTEIN STRUCTURES OR CONFORMATIONS

• Folding of hydrogen bonds (interchain, intrachain)
• Alpha helices
• Beta pleated sheets

Answer 10

secondary structure

Question 11

banned in Paris on 1566

Answer 11

tartar emetic

Question 12

PROTEIN STRUCTURES OR CONFORMATIONS

• various bonds
• Functional (Native)
• Polypeptide (single subunit)
• Ex. Myoglobin

Answer 12

Tertiary structure

Question 13

PROTEIN STRUCTURES OR CONFORMATIONS

• More than 1 subunits
• Ex. Hemoglobin (4 subunits)

Answer 13

Quaternary structure

Question 15

Important component of collagen for strength

Answer 15

hydroxyproline

addition of hydroxyl

Question 16

Proline will undergo ____ (chemical reaction) to form hydroxyproline

Answer 16

hydroxylation

Question 17

Hydroxylation need ____ to produce many hydroxyproline

Answer 17

Vitamin C / Ascorbic acid

Question 18

• can be seen in the parietal cell of the stomach
• Exchange of potassium and proton
• proton will be released by parietal cell which higher of proton
• once proton secreted, it will react with chloride forming ultimately hydrochloric acid

Answer 18

proton pump

Question 19

↑H+ = ↑HCl =

Answer 19

hyperacidity

Question 20

blocks proton pump

Answer 20

proton pump inhibitor

Question 21

• Biological catalysts
• Lower activation energy

Answer 21

enzymes

Question 22

chemical reaction Without enzyme

Answer 22

slow

Question 23

chemical reaction With enzyme

Answer 23

faster

Question 24

enzyme that can convert oligosaccharides (complex carbohydrate) into monosaccharides (simple carbohydrate)

Answer 24

alpha-glucosidase (AG)

Question 25

↑ AG = ↑ glucose = ↑ blood glucose =

Answer 25

diabetes mellitus

Question 26

Alpha-glucosidase **inhibitors**

Answer 26

antidiabetic * Acarbose * Voglibose * Miglitol

Question 27

a **functional macromolecule** cell component with **specific stereochemical configuration** where a **ligand interacts** usually in a **lock-and-key** fashion

Answer 27

receptors

Question 28

# **RECEPTORS** only allows bindings of **specific compound**

Answer 28

specific

Question 29

# **RECEPTORS** **candidates for binding** ; it can be **natural compounds** (neurotransmitters, hormones, autacoids), **exogenous** (xenobiotics)

Answer 29

ligand

Question 30

# **TYPES OF RECEPTORS** * aka **Ionotropic** Receptor/ **Ligand-gated ion channels** (LGICs) * **membranous**, cell membrane * onset: **milliseconds** (**instant** effect, **fastest** onset) * Allow **movement** of ions

Answer 30

TYPE 1 RECEPTOR | **1onotropic, 1nstant**

Question 31

# **TYPES OF RECEPTORS** **Type 1** receptor is also known as

Answer 31

Ionotropic receptor Ligand-gated ion channels

Question 32

# **TYPES OF RECEPTORS | TYPE 1** more **cations** inside cell

Answer 32

**de**polarized **excited** / **active** cells

Question 33

# **TYPES OF RECEPTORS | TYPE 1** more **anions** inside cell

Answer 33

**hyper**polarized **depressed** or **relax**

Question 34

# **TYPES OF RECEPTORS** * **Most abundant** receptors in the body * aka **7**-transmembrane or **hepta**helical; **Serpentine** receptor (snake-like appearance) * **G-protein-coupled receptor**; **Metabotropic** receptor * cell membrane * onset: **seconds**

Answer 34

type 2

Question 35

# **TYPES OF RECEPTORS** **Type 2** receptor is also called

Answer 35

G-protein coupled receptor Metabotropic receptor Serpentine receptor

Question 36

# **TYPES OF RECEPTORS** **signaling protein** and has **3 subunits** (alpha, beta, gamma)

Answer 36

G protein

Question 37

**Alpha-1** receptors are

Answer 37

GPCRs

Question 38

responsible for **contraction** in **muscles**

Answer 38

calcium

Question 39

# **TYPES OF RECEPTORS** * **Kinase-linked receptor** (Tyrosine-kinase linked receptor) ➢ Transferase of Phosphate * Onset: **minutes** * Examples: ➢ Insulin receptor - ↓blood sugar ➢ Growth Factor receptor ❖ platelet-derived GF; epidermal GF

Answer 39

type 3

Question 40

act as **kinase**

Answer 40

tyrosine residues

Question 41

* **Lower** blood glucose levels

Answer 41

insulin receptor

Question 42

* **Gene-transcription-linked** receptor ➢ RNA * Nucleus: “Nuclear receptor” * Onset: **hours** * Steroidal **hormone** receptor * Thyroid **hormone** receptor * **Vitamin D** & Vitamin D derivatives

Answer 42

type 4

Question 43

receptors for **hypertension**

Answer 43

alpha 1

Question 44

The **interaction** of a drug with a macromolecular target involves a **process** known as

Answer 44

binding

Question 45

a **specific area** of the macromolecule **where binding takes place**

Answer 45

binding site

Question 46

**Most drugs** interact through **weaker forms of interaction** known as

Answer 46

intermolecular bonds

Question 47

**Drug** and **target** must have

Answer 47

complementary interactions

Question 48

include **electrostatic** or **ionic bonds**, **hydrogen bonds**, **van der Waals interactions**, **dipole–dipole inter- actions**, and **hydrophobic** interactions.

Answer 48

intermolecular bonds

Question 49

# **INTERMOLECULAR BONDS** ➢ **Opposite charges** (electrostatic forces) [+ & -] ➢ **Weaker** than covalent bond ➢ **Distance-dependent**

Answer 49

ionic bond

Question 50

# **INTERMOLECULAR BONDS** ➢ **H + electronegative atom** (F,O,N) ➢ **Weak** ➢ **Reversible**

Answer 50

H-bond

Question 51

# **INTERMOLECULAR BONDS** ➢ **Non-polar** (weak) ➢ **Reversible**

Answer 51

hydrophobic interactions Van der Waals London dispersion

Question 52

# **INTERMOLECULAR BONDS | H-bond** this compound leads to **phototoxicity**

Answer 52

Flourine

Question 53

# **INTERMOLECULAR BONDS** * not ideal * **strong bond** -- drugs will **not be released** -> will lead to **toxicity** * drugs with **heavy metal** * **Strongest** = **permanent** * **Irreversible** (↑ toxic) * Examples: ➢ **Phenoxybenzamine** – irreversible; non-selective α blocker ➢ **Organophosphates** – irreversible anticholinesterase

Answer 53

covalent bond

Question 54

# **CLASSIFICATION OF LIGANDS (DRUGS)** **activator** ; both have **affinity** and **intrinsic activity**

Answer 54

agonist

Question 55

# **CLASSIFICATION OF LIGANDS (DRUGS)** AGONIST: IA = 1

Answer 55

full

Question 56

# **CLASSIFICATION OF LIGANDS (DRUGS)** AGONIST; IA more than 0, less than 1

Answer 56

partial

Question 57

# **CLASSIFICATION OF LIGANDS (DRUGS)** AGONIST: IA less than 0

Answer 57

inverse

Question 58

# **CLASSIFICATION OF LIGANDS (DRUGS)** have **affinity** but **without intrinsic activity**

Answer 58

antagonist

Question 59

ability of drug to **bind to receptors**

Answer 59

affinity

Question 60

ability of drug to **activate the receptor**

Answer 60

intrinsic activity