Pharmacology L5

Question 1

How do drugs work

Answer 1

• drugs must exert some
  chemical influence on one or more constituents of cells
• there must be non-uniform distribution of drugs within the body
• they interact with specific binding sites to modify the physiological/ biochemical state of cells, tissues and organs

Question 2

Major targets of drug action are

Answer 2

-Hormones
-Ion channels
-Carriers
-Enzymes
- Membrane receptors
- Nuclear receptors
- DNA

Question 3

What are the levels of drug action

Answer 3

MOLECULAR
CELLULAR
TISSUE
SYSTEM

Question 4

Molecular level of drug action

Answer 4

Biomolecules as immediate targets of drugs

Question 5

Cellular level of drug action

Answer 5

Biochemical constituents in the process of transduction

Question 6

Tissue level of drug action

Answer 6

Alters organ function

Question 7

System level of drug action

Answer 7

Alters system function

Question 8

How do drug-receptor interactions occur

Answer 8

through reversible non-covalent bonds

Question 9

Drug-receptor interactions

Answer 9

• Highly stable ion-ion electrostatic attraction
• Partial charge dipole-ion electrostatic
• Partial charge dipole-dipole electrostatic
• Low strength van de Waals’ electrostatic attraction between apolar groups
• Hydrophobic interactions of apolar molecules in an aqueous environment

Question 10

How do most drugs exert their properties

Answer 10

by binding protein domains

Question 11

Protein targets for drug binding

Answer 11

• Receptors
• Ion channels
• Carrier
• Enzymes

Question 12

Specificity of drug action

Answer 12

reciprocal or dose-dependent

Question 13

Reciprocal drug action

Answer 13

Some drugs bind only to certain molecular and cellular targets. Certain molecular and cellular targets recognize only certain classes of drugs.

Question 14

Dose-dependent specificity of drug action

Answer 14

Increasing the dose of drug will affect molecular targets other than the principal pharmacological one, causing toxic side-effects.

Question 15

What is an Agonist

Answer 15

Drug that binds and activates its respective receptor.

Question 16

What is affinity

Answer 16

Tendency of a drug to bind to a receptor.
Receptor occupation by drug is governed by affinity.

Question 17

What is efficacy

Answer 17

Tendency of a drug, once bound, to activate the receptor. Receptor activation by bound drug is governed by efficacy

Question 18

What is an antagonist

Answer 18

Drug that binds to receptor without triggering activation, thus preventing binding of agonist/physiological ligand.

Question 19

What is a Maximal pharmacological response

Answer 19

The maximal response on a particular receptor differs between chemically
related agonists

Question 20

What is a maximal response

Answer 20

The largest response that a tissue can give
if triggered by a specific substance at high concentration.

Question 21

Why is the therapeutic dose of a drug sometimes lower then its maximal response dose

Answer 21

Due to toxic side effects

Question 22

What is a log-dose response used for

Answer 22

to quantify the relationship between biological responses and agonist concentration

Question 23

What is a full agonist

Answer 23

A drug that can produce a maximal response

Question 24

What is a partial agonist

Answer 24

A drug that can only trigger a sub-maximal response.

Question 25

What happens if a tissue contains a receptor reserve due to poor intrinsic efficacy

Answer 25

allows partial agonist to act as a full agonist.

Question 26

What is a receptor reserve

Answer 26

agonist only needs to activate a smaller number of receptors than the total number available to produce a maximal response

Question 27

what is intrinsic efficacy

Answer 27

the ability of a drug- receptor complex to produce a maximal response

Question 28

What is a competitive agonist

Answer 28

Substance that has no intrinsic efficacy and binds reversibly with receptor. It dilutes the receptor concentration. Importantly, an increase of agonist dose can return tissue response to normal. (uses up receptor that agonist can use, can be removed)

Question 29

What is an irreversible agonist

Answer 29

Causes blocking of a receptor that cannot be reversed by increasing the agonist concentration. high concentrations of agonist leads to depression of the maximum response.

Question 30

Function of agonistic versus antagonistic blocking action
in Nicotinic acetylcholine receptor (nAChR)

Answer 30

Skeletal muscles are relaxed during surgical procedures by using neuromuscular drugs (agonists/ antagonists) to cause clinical paralysis of voluntary muscles.

Question 31

What is the competitive antagonist that can function in nAChR

Answer 31

Tubocurarine

Question 32

How does Tubocurarine function as an antagonist

Answer 32

It competes with the native ligand neurotransmitter acetylcholine for the receptor. However, it does not cause a biological response

Question 33

What is the agonist that functions in nAChR

Answer 33

Suxamethonium

Question 34

How does Suxamethonium work

Answer 34

It depolarizes the neuromuscular junction but does not dissociate rapidly from the nAChR complex causing a neuromuscular block

Question 35

Molecular approaches used in the structural analysis of pharmacologically important protein receptors

Answer 35

¤ Protein purification and characterization
¤ Affinity purification and characterization
¤ Protein/peptide N-terminal sequence analysis
¤ Mass spectrometric analysis of protein subunits
¤ Cloning and sequencing of cDNA
¤ High-resolution x-ray crystallography
¤ High-resolution cryo-electron microscopy
¤ Differential co-immuno precipitation methodology
¤ Chemical cross-linking analysis
¤ Native two-dimensional gel electrophoresis
¤ Gel filtration analysis