Principles of Pharmacology 1 L1

Question 1

The receptor concept

Answer 1

• Drugs produce their effects by combining with specific receptor sites in cells
• response is a function of the number of occupied receptors

Question 2

Ways of regulating cell function

Answer 2

• altered membrane potential
• altered enzyme activity
• altered gene expression
• Some drugs may affect these directlye.g. tetrodotoxin (TTX) aspirin acridine dyes
• Most drugs affect these cell functions via (physiological) receptors

Question 3

The nature of drug receptors / targets

Answer 3

• Enzymes
  Cyclooxygenase; the aspirin ‘receptor’
• Ion channels
  Ca2+ channels blocked by nifedipine
• Transporters (pumps)
  Noradrenaline transporter blocked by cocaine
• “Physiological” receptors
  Receptors for hormones, neurotransmitters
  acetylcholine, histamine, insulin etc., etc.

Question 4

Receptor classification

Answer 4

• receptors are classified on the basis of the selective action of drugs
• named according to the transmitter or hormone with which they interact
  e.g. acetylcholine receptors
• most transmitters/hormones interact with more than one type of receptor
  -real differences in protein structure underlie differences between subtypes

Question 5

types of acetylcholine receptors

Answer 5

muscarinic and nicotinic

Question 6

Receptor superfamilies

Answer 6

• Integral (or ligand-gated) ion channelse.g. nicotinic receptor
• G protein coupled receptorse.g. muscarinic receptor
  adrenoreceptors

-Integral tyrosine kinasese.g. insulin receptor

-Steroid receptorse.g. oestrogen receptor

• Cytokine receptorse.g. prolactin receptor
  growth hormone receptor

Question 7

Affinity and Efficacy

Answer 7

Affinity - governs binding
Efficacy - governs activation

Question 8

The Law of Mass Action in pharmacology

Answer 8

Kd = [A][R] / [AR]
p = [A] / Kd + [A]
p = [AR] / [RT]
For a fixed number of receptors,
[RT] = [R] + [AR]
Fraction of receptors occupied by agonist is defined as Occupancy (p)

Question 9

shape of graph where occupancy / effect is on the y axis and log [ agonist ] is on the x axis

Answer 9

sigmoidal

Question 10

definition of affinity

Answer 10

• Affinity of a drug for its receptor is a measure of how well it binds to the receptor
• can be measured using a drug’s dissociation constant from its receptor, the Kd
• Kd equal to the concentration at which, at equilibrium, half the receptor population will be bound with drug

Question 11

EC50 definition

Answer 11

Effective concentration to produce 50% of the maximum response

Allows measure of potency

Defined as, the amount of a drug required to produce a particular level of effect/response

Question 12

Agonists definition

Answer 12

Agonists bind to a receptor/target and produce a response

Is response always proportional to occupancy?

No, efficacy is also important

Question 13

Efficacy

Answer 13

• Efficacy is a measure of the degree to which an agonist produces a response when binding a given proportion of receptors
• For a full agonist, the efficacy is 1
• For a partial agonist, the efficacy is less than 1
  (but greater than zero)
• low efficacy, partial agonists cannot produce the cell’s maximal response, even when bound to all available receptors
• some highly efficacious agonists can produce a maximal response without binding to all available receptors
  • this is evidence of ‘spare receptors’
• efficacy and potency are not the same

Question 14

Negative Efficacy

Answer 14

• it is possible to have a negative efficacy, i.e. less than zero
• drug is called an inverse agonist
• such drugs inhibit any intrinsic receptor activity that might exist in the absence of a ligand
• negative efficacy governs de- activation

Question 15

Antagonists

Answer 15

• Antagonists have zero efficacy
• block or reduce the response to an agonist
• can be of various different types
  Competitive , Irreversible ,
  Other