[SIM] Mechanism of Drug Action

Question 1

What is the receptor for Norepinephrine?

Answer 1

Beta-2

Question 2

What is responsible for phosphorylation of Myosin?

Answer 2

Myosin Light Chain Kinase

Question 3

What state does Myosin have to be to have a greater affinity for Actin in muscle contraction?

Answer 3

Phosphorylated

Question 4

Function: Salbutamol

Answer 4

Binds to B2 Adrenergic Receptors, mimicking Norepinephrine causing relaxation of airways

Question 5

Differentiate Salbutamol at Low Doses and High Doses

Answer 5

Low Dose: Specific to B2 Adrenergic Receptors

High Dose: Decreased specificity to B2 Adrenergic Receptors; may cause tremors and tachycardia

Question 6

What are the receptors of Acetylcholine?

Answer 6

Nicotinic

Muscarinic

Question 7

[Type of Receptor]

Nicotinic

Answer 7

Ionotropic

Question 8

[Type of Receptor]

Muscarinic

Answer 8

G Protein Coupled Receptor

Phospholipase C/IP3 Pathway

Question 9

Function: M2 Receptors

Answer 9

Bringing the heart back to normal after actions of the sympathetic nervous system

Question 10

Components: Atropine

What is the component responsible for most of its physiologic effects?

Answer 10

D-Hyoscyamine
L-Hyoscyamine

L-Hyoscyamine

Question 11

This is a competitive inhibitor of Acetylcholine

Answer 11

Atropine

Question 12

[Type of Receptor]

Insulin

Answer 12

Ligand-gated Tyrosine Protein Kinase

Question 13

Components of Insulin Receptors

Answer 13

2 Alpha Subunits
2 Beta Subunits

Linked by disulfide bonds

Question 14

Where is the insulin-binding domain located?

Answer 14

Extracellular Alpha Sub-units

Question 15

Which component of the insulin receptor has the cytoplasmic kinase activity?

Answer 15

Beta Sub-unit

Question 16

Effect of Tyrosine Kinase Receptor Activation (Insulin Receptors)

Answer 16

Releases Phosphatidyl Inositol-3-Phosphate (PI3P) and increases the number of GLUT4 on the outer membrane, allowing entry of Glucose into the cell

Question 17

What causes Type II Diabetes?

Answer 17

Insulin insensitivity or decrease in Insulin Receptor Signaling

Question 18

Differentiate Tyrosine Kinase receptors from GPCRs in terms of Gene Expression

Answer 18

Tyrosine Kinases affect downstream events in gene expression

Question 19

What is the most prevalent form of Estradiol and Estrone?

Answer 19

Estrogen

Question 20

Where is Estrogen produced?

Answer 20

Ovaries

Question 21

2 Main Targets of Estrogen

Answer 21

Breast

Uterus

Question 22

Estrogen receptors are stabilized by?

Answer 22

Heat Shock Proteins

HSP90

Question 23

Differentiate the 2 Kinds of Estrogen Receptors

Answer 23

1. ER-Alpha
   - Made up of 500 AAs
   - Mostly in Endometrium and Breast Cancer
2. ER-Beta
   - Made up of 600 AAs
   - Present in Granulose Cells and Osteoblasts

Question 24

What activates transcription in the ER-Alpha Receptor?

Answer 24

ER-Alpha:Estradiol Complex

Question 25

What do Breast Tumor Cells need for growth and proliferation?

Answer 25

Estrogen

Question 26

Drug for Breast Cancer Patients How does it work?

Answer 26

Tamoxifen Competitive, partial agonist inhibitor of Estrogen

Question 27

Tamoxifen requires processing in the liver to become this activate metabolite that has a higher affinity to Estrogen Receptors

Answer 27

4-Hydroxytamoxifen (Endoxifen)

Question 28

Limitations of Tamoxifen Therapy

Answer 28

1. Only efffective in women who have ER+ BRCA | 2. More than 1/3rd of these do not respond to Tamoxifen though

Question 29

Lack of this liver enzyme may interfere with Tamoxifen metabolite production

Answer 29

Cytochrome P450 2D6 | CYP2D6 and CYA3P4

Question 30

2 Mechanisms of Sensitization

Answer 30

Homologous | Heterologous

Question 31

Differentiate Homologous and Heterologous Sensitization

Answer 31

Homo: Loss of responsiveness of the specific receptor that has been exposed repeatedly Hetero: Desensitization of one receptor also results in desensitization of another receptor not directly activated by agonist in question

Question 32

Function: Chelating Agent

Answer 32

Prevent/Reverse heavy metal toxicity on enzymes or cellular targets by binding to them

Question 33

Used for serious lead poisoning and lead encephalopathy

Answer 33

Ethylene Diamine Tetraacetate CaNaEDTA

Question 34

[Treatment] Dimercaprol

Answer 34

Arsenic, Mercury, Gold, Lead, Antimony, and other Toxic Metal Poisoning

Question 35

[Treatment] Succimer

Answer 35

Lead Poisoning

Question 36

[Treatment] Penicillamine

Answer 36

Copper Poisoning

Question 37

[Treatment] Antacids

Answer 37

Patients with dyspepsia and acid-peptic diseases

Question 38

[Treatment] Mannitol

Answer 38

 Use to treat oliguric phase of ARF  Promotes the excretion of toxic substances  Use to reduce intracranial pressure  Used in the treatment of cerebral edema

Question 39

[Treatment] Ammonium Chloride

Answer 39

Lowers blood pH after being metabolized to Urea and Hydrochloric Acid

Question 40

[Treatment] Ascorbic Acid

Answer 40

Acidifies urine, providing hydrogen ions and lowering urine pH

Question 41

[Treatment] Acetazolamide

Answer 41

Increases excretion of Bicarbonate Ions, lowering blood pH

Question 42

Who experimented on chicks (the animal) with Curare and Nicotine?

Answer 42

Langley (1905)

Question 43

Any cellular macromolecule that a drug binds to initiate its effects; a component of the organism with which a drug acts in some specific manner to cause an action which results to observable effects

Answer 43

Receptor

Question 44

Agents that bind to receptors (include drugs, hormones, autacoids, growth factors, neurotransmitters, etc.)

Answer 44

Ligands

Question 45

An agent that elicits a biological effect by binding to a receptor.

Answer 45

Agonist

Question 46

Drugs binding to receptors but do not initiate change in cellular function. Blocks the binding of agonists. An agent that by itself is devoid of biological activity but binds to the receptor and prevents the biological effect of an endogenous agonist.

Answer 46

Antagonist

Question 47

Endogenous substances (generated by the agent-receptor complex which) which serve as signaling mechanisms that enable drugs/endogenous substance to exert their biologic effects.

Answer 47

Second Messengers

Question 48

The measure of tightness with which a drug binds to a receptor.

Answer 48

Affinity

Question 49

Measure of the ability of a drug, once bound to the receptor, to produce measurable physiologic effects

Answer 49

Intrinsic Activity

Question 50

Receptors are present in finite numbers.

Answer 50

Saturability

Question 51

Binding is a noncovalent interaction due to weak intermolecular forces.

Answer 51

Reversibility

Question 52

Many natural occurring agonists exist as optical isomers (+ or -, l or d, S or R); preference for naturally- occurring stereoisomers (e.g. 1- vs d-norepinephrine)

Answer 52

Stereoselectivity

Question 53

Preference for specific or closely related, agonist and should not recognize chemically dissimilar endogenous agents

Answer 53

Agonist Specificity

Question 54

Binding should be present in tissues known to be biologically sensitive to the hormone/drug and should take place at concentrations consistent with the physiological concentrations of the endogenous agents

Answer 54

Tissue Specificity

Question 55

Neurotransmitter used by all motor neurons

Answer 55

Acetylcholine

Question 56

Components of Acetylcholine Receptors

Answer 56

5 Subunits: 2 Alpha Sub-units 1 Beta Sub-unit 1 Gamma Sub-unit 1 Delta Sub-unit

Question 57

How many units of Acetylcholine is needed to activate the Nicotinic Acetylcholine Receptor?

Answer 57

2

Question 58

[Treatment] Turbocurarine

Answer 58

Neuromuscular blocking drug | Skeletal muscle relaxant

Question 59

[Mechanism of Action] Turbocurarine

Answer 59

Competitive antagonist of ACH that acts predominantly on Nicotinic Receptor Sites

Question 60

Where are the Nicotinic Receptor Sites found on the ACH Receptors?

Answer 60

Alpha Sub-units

Question 61

Differentiate Tachyphylaxis and Tolerance

Answer 61

Tachyphylaxis: Rapid desensitization as a result of acute effects Tolerance: Long term effect