Pharmacodynamics II

Question 1

Give examples of intracellular receptors

Answer 1

Corticosteroids
Mineralocorticoids
Sex  steroids
Vitamin D
Thyroid Hormone

Question 2

How do intracellular receptors work?

Answer 2

Binding specific DNA sequences near the gene whose expression is to be regulated. This causes changes in protein transcription.

Question 3

Course of action for steroid drugs?

Answer 3

Characteristic Lag Period

Effects persist after the concentration has been reduced to zero due to slow turnover of most enzymes and proteins

Question 4

Examples of protein tyrosine kinases.

Answer 4

Insulin
EGF
PDGF

Question 5

Protein tyrosine kinases span the lipid bilayer ____ times

Answer 5

one

Question 6

What is the mechanism for protein tyrosine kinase activity

Answer 6

Hormone binds EC domain and change conformation
Receptor molecules bind, brining together kinase domains
Kinase phosphorylates itself
Tyrosine residues in both cytoplasmic domains become phosphorylated
Enzymatic Activity is activated

Question 7

How are protein tyrosine kinases turned off?

Answer 7

Receptor Down Regulation and endocytosis of receptors

Question 8

Examples of ligand-gated channel drugs

Answer 8

Acetylcholine
GABA
Glycine, Aspartate, Glutamate

Question 9

Acetylcholine causes the opening of the _____ channel

Answer 9

nicotinic acetylcholine receptor

Question 10

Time delay between agonist binding an ligand gated channel opening?

Answer 10

milliseconds

Going very fast is important for things like nerve signalling

Question 11

Three common second messengers of GPCRs

Answer 11

cAMP
Calcium Ion
Phosphoinositides

Question 12

Describe the process of GPCR activity

Answer 12

G-GDP inactivity, G-GTP can activate

Phosphorylation inactivates

Question 13

What is EPAC?

Answer 13

Exchange Protein Activated by cAMP

A cAMP stimulated kinase recently discovered that may influence many effects of GPCRs

Question 14

Phospholipase C results in the release of _____ and _______

Answer 14

Phosphoinositides and Diacylglycerol

Question 15

Downstream effect of photphoinositides

Answer 15

Release of Calcium

Question 16

Downstream effect of diacylglycerol

Answer 16

Protein Kinase C activation

Question 17

Quantal log-dose response relationships are…

Answer 17

Quantal log-dose response relationship

ex. sleep and death

Question 18

What is a drug threshold?

Answer 18

The minimum effective dose of the drug which evokes an all-or-none pharmacological response

Question 19

How are the doses required to produce a quantal effect typically distributed?

Answer 19

log-normally

The resulting cumulative frequency constitutes a quantal dose-response curve

Question 20

What is Median Effective Dose (ED50)

Answer 20

Dose required to produce the stated effect in 50% of the population

Question 21

What is the median lethal dose?

Answer 21

The dose required to produce death in 50% of the population

Question 22

What is the Therapeutic Index/Ratio?

Answer 22

LD50/ED50 OR TD50/ED50

Question 23

What does one look for in a therapeutic index in a potential drug

Answer 23

A larger ratio indicate a larger gap between effective and toxic doses that will imply a decreased likelihood of accidental patient harm when pursuing a maximal efficacy

Question 24

What is seen in graded log-dose response relationships

Answer 24

The responding system is capable of showing progressively increasing effects with increasing concentrations of the drug

Question 25

What is drug tolerance?

Answer 25

A condition of decreased responsiveness to a drug acquired after prior or repeated exposure to a given or related drug

Question 26

Two ways for development of drug tolerance

Answer 26

- Decrease in effective concentration of the agonist at the site of action - Decrease in the normal reactivity of the receptor

Question 27

What drugs most commonly cause downregulation of receptors or changes in receptor affinity?

Answer 27

CNS drugs such as narcotics, depressants, and stimulants

Question 28

What is cross tolerance?

Answer 28

Tolerance developed to one drug that is also seen with drugs belonging to the same class Ex. Morphine use leads to tolerance of all narcotics

Question 29

Important molecular steps in receptor downregulation

Answer 29

GPCR kinase is triggered. It phosphorylates beta arrestin, which binds to the receptor and internalizes it for degradation or recycling.

Question 30

What is tachyphylaxis?

Answer 30

Acute development of tolerance following a rapid, repeated administration of a drug. Ex. ephedrine

Question 31

What is a drug allergy?

Answer 31

An adverse response to a foreign chemical resulting from previous exposure to the substance.

Question 32

What happens at inital exposure when developing a drug allergy.

Answer 32

Drug or metabolite acts as a hapten and combines with a protein to generate an antigen. The antigen induces latent synthesis of antibodies. Subsequent exposure to drug results in an antigen-antibody response.

Question 33

Describe the drug allergy dose response.

Answer 33

There isn't an apparent one. A minute amount of drug results in response.

Question 34

How could you test for a drug allergy?

Answer 34

Skin Test

Question 35

Unique characteristic of Type I allergic response?

Answer 35

First exposure IgE to be produced Becomes fixed to mast cells and basophils Subsequent exposure causes drug to bind to Fab of IgE Histamine, PGs released

Question 36

Unique characteristic of Type II allergic response?

Answer 36

Ab dependent cytolytic response IgG and IgM mediated Abs activate the complement system, resulting in cell lysis Blood Cells are primary targets

Question 37

Unique characteristic of Type III allergic response?

Answer 37

Immune complex fomation Drug reacts with soluble Ab (IgG) Deposits in vasculat endothelium, Cell mediated inflamm. Serum sickness, hemolysis, and allergic nephritis

Question 38

Unique characteristic of Type IV allergic response?

Answer 38

Hours or Day after exposure before reaction Mediated with antigen contact with sensitized T lymphocytes and macrophages Release of cytokines --> Neutrophils and macrophages

Question 39

Example of a Type IV drug reaction

Answer 39

Contact dermatitis with a topical cream

Question 40

Idiosyncratic reactions to drugs are often caused by...

Answer 40

differences in drug metabolizing enzymes