Lecture 3

Question 1

Describe a graded dose-response and its normal curve shape

Answer 1

• change in biological effect is measured against increasing concentrations/dose of a drug. This measure is continuous e.g. smooth muscle contraction; (blood vessels easy -have many target receptors)
• plotted as Concentration-effect curve (EC50) or Dose-effect curve (ED50) - can be linear or logarithmic
• Commonly plotted as log dose versus effect
• Effective doses estimates frequencies that each dose elicits in
• the population
• Rectangular hyperbola

Question 2

Define Emax and ED50 values

Answer 2

Emax = maximum effect drug has on system (i.e. max point on curve)

EC50 = concentration of drug that will elicit 50% of maximal effect
(also called ED50) (i.e. Find Emax determine biological effect 1/2 that and determine dose by going across and down

Question 3

Define Therapeutic Index (TI) and how you would calculate it from a Quantal Dose-Response curve

Answer 3

Is a measure of drug safety

TI = LD50/ED50

Question 4

Define Efficacy and Potency

Answer 4

Efficacy : This describes the ability or “strength” of a single drug-receptor complex in evoking a response in tissue. This applies only to those compounds that elicit a response namely agonists. For antagonists, efficacy is zero.

Potency : The dose of drug required to produce a given effect.

In a graded dose-response curve say drug A and B have the same sigmoid curve on a log scale and get the same biological effect at ED50 but drug B is further to the right thus requiring a higher dose (ED50). Drug A is therefore more potent than B but they have the same efficacy. Then imagine drug C has an Emax = to 50% the biological effect of Drug A & B. Drug C thus has the least potency and efficacy of all

Question 5

Define biological specificity and give examples of drugs with high and low biological specificity

Answer 5

Biological specificity: compound must bind to, and act on, only certain cells and tissues

HIGH BIOLOGICAL SPECIFICITY

Histamine (potency=10-8 M) Selected sites (bronchial & vasc. smooth muscle)

LOW BIOLOGICAL SPECIFICITY

Ethanol (potency=10-2 M) Similar effects on most cells & tissues

Question 6

Define chemical specificity and give examples of drugs with high and low chemical specificity

Answer 6

Chemical specificity: is the ability of a protein’s binding site to bind specific ligands. The fewer ligands a protein can bind, the greater its specificity.

Effect of changes in the chemical structure of a drug on pharmacological activity

HIGH CHEMICAL SPECIFICITY

Histamineimidazole (pot=10-5M) to pyrrazole (potency=10-8 M)

LOW CHEMICAL SPECIFICITY

Ethanol (potency=10-2 M) Similar actions to other simple molecules (diethylether, chloroform)

Question 7

Where can Drugs originate from and what effect can they have on biological processes?

Answer 7

Drugs can be biological in origin

• Noradrenaline (norepinephrine), adrenaline - non-selective agonists
• Made by the body but used theraputically

Drugs can be non-biological in origin

• Clenbutarol (beta agonist), atenolol (beta blocker)

Drugs can block biological processes (slow the system down)

• Propranolol (beta blocker), practolol (beta blocker)

Drugs can enhance biological processes

• Salbutamol (beta agonist)

Question 8

Define a Receptor

Answer 8

1. Broadly, any target molecule with which a drug molecule has to combine in order to elicit an effect.
2. Usually, a site through which some molecule (drug, hormone, neurotransmitter) acts to initiate a biochemical or physiological chain of events.

Question 9

Define Ligand

Answer 9

Any molecule that binds to another biological entity. Agonists, antagonists, drugs, etc can be described as ligands.

Question 10

Define agonist

Answer 10

Substance which acts at a receptor to initiate a Response

Question 11

Define Antagonist

Answer 11

Substance that binds to the receptor without causing activation.

Question 12

How can you compare different drugs

Answer 12

1. measuring the response of a drug on an appropriate biological system
2. calculating the actual amount of drug that binds to specific receptor sites.

Question 13

Describe a Quantal Dose-Response curve and its normal curve

Answer 13

• all or nothing pharmocological effect
• relates dose to frequency of effect (population study)
• Sigmoid curve

Proportion of individuals responding varies according to dose

Gives a population (or normal) distribution

• conscious vs unconscious
• seizure vs no seizure
• live vs dead

Question 14

Define LD50

Answer 14

LD50 = Lethal dose - dose that kills 50% of the population