L2 Pharmacodynamics and Bio Site

Question 1

what type of bond is ideal for for drugs binding to receptor

Answer 1

Electrostatic
-Van der waals and Hydrogen

• You DON’T WANT covalent bond

Question 2

how do drugs cause adverse (side) effects

Answer 2

act not only at site intended but also at other sites (side effects)

Question 3

Describe the Philadelphia Chromosome

Answer 3

translocation between chromosome 9 and 22

Question 4

What is the treatment for Philadelphia Chromosome

Answer 4

• Imatinib- when it binds via hydrogen/ van der waals bonds, it prevent the conversion of kinase enzyme

Imatinib causes less side effects because of the specificity for that receptor and enzyme indicated for chronic myeloid leukemia

MOA: highly selective inhibitor of BCR- ABl tyrosine kinase that is encoded by Philadelphia Chromosome

Over next month the cells containing the Philadelphia Chromosome disappear

Question 5

What are the 4 types of drug receptors

Answer 5

-Transmembrane Ion Channel
-Transmembrane Linked to Intracellular G- Proteins (GDP)
-Transmembrane with Enzymatic Cytosolic Domain withIntracellular or Extracellular Enzyme adhesion
-Diffusion (steroid molecules)

Question 6

What is the main ligand for the nicotonic receptor

Answer 6

Acetylcholine

Question 7

Ligand-Gated Nicotinic Acetylcholine Receptor is what type of receptor

Answer 7

Transmembrane Ion channel
-sodium is associated with receptor

Question 8

Describe the Ligand-Gated Nicotinic Acetylcholine Receptor

Answer 8

-Has a total of 5 subunit
2 alpha, 1 Beta, 1 Gamma, and 1 Delta

-Acetylcholine binds to the alpha subunit, causes channel to open
-sodium transverse through the channel when the channel opens

-A drugs whose mechanism of action is to block sodium are local anathetics, therefore sodium does not go through the channel. Ex: benzodiazepine

Question 9

Describe Receptor-Mediated Activation of a G Protein and the Resultant Effector Interaction

Answer 9

-It is heptahelical structure spanning the membrane
-GTP to GDP
-Ex; Beta 1,2,3 receptor, Dopamine receptor, Seratonin receptor, opoid receptor

Question 10

What is an example of a molecule for Transmembrane Receptors with Enzymatic Cytosolic Domains

Answer 10

Insulin

Question 11

B adrenergic receptor

Answer 11

-Agonist is norepineherine (increase HR)
-Antagonist is propranolol (net effect is decrease HR)

Question 12

Magnitude of response is dependent on…

Answer 12

the concentration of the agonist at the receptor site [L] - Measurable

Question 13

Magnitude of response is…

Answer 13

proportional to number of drug-receptor complexes
[LR]- Measurable

Question 14

difference between Graded Dose-Response Curve and Quantal Dose-Response Curve

Answer 14

◼Graded Dose-Response Curve Response vs. Dose in a single individual (R vs [L])
◼Quantal Dose-Response Curve %Patients Responding vs. Dose in a group of individuals; Response is QUANTIZED

Question 15

Reduced responsivity:

Answer 15

Chronic use of an agonist can result in the receptor- effector system becoming less responsive

– eg. alpha-adrenoceptor agents used as nasal decongestants

Myasthenia gravis: decrease in number of functional acetylcholine nicotinic receptors at the neuromuscular junction.

Question 16

Competitive inhibitor

Answer 16

Compete for the
binding site. Response is
shifted to the right.

Question 17

Non-competitive Inhibitor

Answer 17

Prevent agonist binding or prevent agonist from
activating the receptor

Question 18

Partial agonist

Answer 18

Produces smaller effect than a full agonist and antagonizes a full agonist

Question 19

Efficacy

Answer 19

is the maximal response produced by a drug

-depends on number of drug- receptor complexes and the efficiency

Question 20

Potency

Answer 20

◼ Also called effective dose (ED) concentration
◼ Potency is a measure of how much drug is required to elicit a given level of response
◼ Potency is expressed as the dose that
gives 50% of E (called ED 50)

Question 21

Therapeutic Index

Answer 21

Toxic Dose/Effective Dose

• Measure of the drug’s safety
• Large value indicates a wide margin between doses that are effective and doses that are toxic.

-Examples
: Warfarin has narrow index
(~2). Penicillin has large therapeutic window (10x)

Question 22

Tachyphylaxsis

Answer 22

Rapidly emerging tolerance
* Will not work with 1-2 hours
* Ie Bretylium`