Receptors

Question 1

What is the difference between Pharmacodynamics and Pharmacokinetics?

Answer 1

Pharmacodynamics: Biochemical and physiologic effects of drugs

Pharmacokinetics: Refers to the movement of drug into, through and out of body

Question 2

Define Receptor

Answer 2

The component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drug’s observed effects

Question 3

What are Four Major Types of Receptors?

Answer 3

1. Ion Channels (fast neurotransmitters e.g. ACh)
2. G-Protein Coupled Receptor (slow neurotransmitters e.g. NA)
3. Tyrosine Kinase Coupled Receptors (e.g. insulin)
4. Intracellular Receptors (e.g. steroids)

Question 4

Define Ligand

Answer 4

A substance that forms a complex with a biomolecule to serve a biological purpose

Question 5

Define Agonist

Answer 5

A chemical that binds to a receptor and activates it to produce a biological response

Question 6

Define Antagonist

Answer 6

A type of receptor, ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor, rather than activating it

Question 7

What are Four Major Drug Targets?

Answer 7

1. Receptors
2. Ion Channels
3. Enzymes
4. Membrane Transporters

Question 8

What are the types of forces that cause binding of drugs to their receptors?

Answer 8

1. Van der Waals Forces (weakest non-covalent bonds)
2. Hydrophobic (more of a characteristic of a compound)
3. Hydrogen bonds
4. Ionic bonds (strongest non-covalent bonds)
5. Covalent bonds

Question 9

What is the Law Mass of Action?

Answer 9

The rate of any reaction is proportional to the concentrations of the reacting substances

Question 10

Are covalent bonds described as reversible or irreversible interactions?

Answer 10

Covalent bonds are described as irreversible under biological conditions because once the covalent bond is formed, the resulting structure is typically extremely stable

Question 11

Define B

Answer 11

Drug Bound (fraction or percent of maximum)

Question 12

Define Bmax

Answer 12

Maximal drug binding (100%)

Question 13

Define Kd

Answer 13

Dissociation constant (concentration of drug required to saturate 50% of the receptors)

Question 14

What are the Six Major Characteristics of Receptors?

Answer 14

1. Recognition
   
   • must exist in conformational state allowing for recognition and binding of a specific compound
2. Saturability
   
   • exist in finite numbers
3. Reversibility
   
   • binding must occur non-covalently
4. Stereoselectivity
   
   • should recognise only one naturally occurring optical isomers
5. Agonist Specificity
   
   • structurally related drugs should bind well, dissimilar compounds bind poorly
6. Tissue Specificity
   
   • binding should occur in tissues known to be sensitive to the endogenous ligand
   • binding should occur at physiologically relevant concentrations

Question 15

Why isn’t the ‘Lock and Key’ model not entirely correct?

Answer 15

Because it cannot explain the fact that some drugs bind to the receptor very efficiently but are still not able to activate it

Question 16

Conformational Selection Model of Drug-Receptor Interaction Conditions

Answer 16

1. Receptor is spontaneously changing between numerous conformations
2. Each drug selects and stabilises one particular conformation
3. If the drug selects and stabilises proper (active) conformation, such binding will result in biological activity [agonist of receptor]
4. Stabilising active conformation initiates intracellular signalling events mediating drug biological activity
5. If the drug binds and stabilises inactive conformation, it is an antagonist
6. If the drug does not bind to receptor at all, it is inactive

Question 17

Why is the amount of drug bound at any time determined by number of receptors?

Answer 17

• There are finite number of receptors
• When a sufficient number of receptors are bound on or in a cell, the cumulative effector of receptor may become apparent in that cell

Question 18

Why is the amount of drug bound at any time determined by concentration of ligand?

Answer 18

• When ligand concentration increases, the concentration of bound receptors increases
• An increase in the effect of a drug can result from an increase in the concentration of either the ligand or receptor

Question 19

Why is the amount of drug bound at any time determined by affinity of drug for its receptor?

Answer 19

• Measure of the tightness with which a drug binds to the receptor
• If Drug A has a low affinity for a receptor but drug B has a much higher affinity, Drug B will displace Drug A and bind to the receptor

Question 20

What is the definition of Therapeutic Index?

Answer 20

A comparison of the average dose of a drug that causes the therapeutic effect to the average dose that causes toxicity

TI = TD50/ED50

TI = Max dose/Min dose

Question 21

What is the difference between competitive antagonists and non-competitive antagonists?

Answer 21

Competitive Antagonists: Bind to receptors at the same active site as the endogenous ligand or agonist, but without activating the receptor

Non-Competitive Antagonists: Binds to a non-agonist site on the receptor to prevent activation of the receptor