Fundamentals of Pharmacology

Question 1

What are the sites of drug action in the body?

Answer 1

The sites of drug action within the body , or chemically sensitive sites are usually on proteins

Question 2

What is affinity?

Answer 2

• Affinity of a drug for its receptors is a measure of how well it binds a chemically active site, or receptor
• Drugs bind to a receptor site ata rate proportional to the drug concentration
• They unbind at a rate that depends only on the chemical properties of the drug receptor complex

Question 3

For the interaction of a drug (D) with its receptor (R) we have the chemical formula:

D+R-DR

Answer 3

• Law of mass action implies that the forward rate is k+[D][R], where the square brackets are conc and k+ is the forward rate constant

Question 4

This formula lets us know the relationship between drug concentration and binding

Answer 4

• When plotted on a log linear (semilog) graph, the formula gives a sigmoidal shape
• Increasing competitve

Question 5

Agonists and antagonists?

Answer 5

• Competitive
• Non competitive
• Most are competitive
• Gives a right shift in relationship between agonist concentration and binding

Question 6

Affinity and Efficacy?

Answer 6

• Affinity - tendency of a molecule to bind to a receptor
• Efficacy - how well an agonist achieves a response

Question 7

Efficacy and potency: G protein coupled receptors?

Answer 7

• G protein receptors: targets for many commonly used drugs
• Signal to other proteins using small molecules called G proteins
• Potency of a drug described by the conc (dose) that is able to elicit 50% of maximal response (EC50/ED50)
• Drug that has a higher potency achieves that size of response at a lower concentration

Question 8

Partial Agonists

Answer 8

• Partial agonist is a drug that has a lower maximal response resulting from lower efficacy

Question 9

Allosteric Modulators?

Answer 9

• Allosteric modulators bind to proteins at sites other than that of the binding site for the principle agonist. They:
  
  • alter affinity of binding sitefor its agonists
  • change the efficacy of the response when the agonist binds
• To complicate matters their actions can be:
  
  • positive (increase potency of agonist)
  • negative (decrease potency of agonist)

Question 10

A 38 year old man, with a 15 pack year history attempts to stop smoking for three weeks without any replacement therapy. However cravings remain strong, so he obtains nicotine patches. As his desire is still strong, he decides to use 3x the recommended dose. Over the next two hours he feels nauseated and his heart is racing. After this, symptoms subside and he feels better able to avoid smoking.

Answer 10

Peripheral desensitization to the effect of drugs dose does not require that the activity of the receptors change: True!

• There are many ways that the response can desinsitize, such as adaptation of intracellular second messenger pathways, or even changes outside
• For example, loss of a sense of nausea maybe a central nervous system adaptation - if nicotine causes a GI response that is regularly associated with central reward, then
• what was an aversive peripheral signalmay now be interpreted positevely and hence will no longer be associated with the sensation of nausea

Question 11

What is tolerance?

Answer 11

• Associated with long term use of opiod drugs
• is a biochemical response that involves increased production of mediators in the pathway affected by the drug

Question 12

Tachyphylaxis?

Answer 12

• A general term that describes a decline in response to repeated doses of an agonist
• doesn’t imply a particular mechanism

Question 13

Absorption and distribution of a drug within the body can differ even for drugs that have the same molecular target. For example differences in lipid solubility of statins can markedly affect drug concentrations in different body compartments.

Answer 13

• Simvastatin - Lipophillic (fat loving)
• Pravastatin - Hydrophillic (water loving)