intro pharmodynamics, definitions and nomenclature

Question 1

Drug Classification

Answer 1

• Differs depending on drug class!
  1. Chemical structure
• eg: tricyclic antidepressant; benzodiazepine
  2. Mechanism of action
• eg: monoamine oxidase inhibitor; b adrenoceptor
  blocker
  3. Therapeutic use
• eg: second generation antipsychotic; mood
  stabiliser; general anaesthetic

Question 2

Drug Actions

Answer 2

• A drug must bind to one or more cell constituents to produce a pharmacological response

The ligand and the binding site must be
complementary:

• Charge attracts ligand to binding site, complementary positive negative charges [ionically]
  –> complementary binding forces
• Three dimensional structure of drug or target, ie: arrangement of functional groups, of both ligand and binding site [proteins/aa e.g.]

Question 3

Drug Nomenclature

Answer 3

• Chemical name (2RS,aRS)-2-[a-(2-ethoxyphenoxybenzyl] morpholine methanesulfonate
• CA registry number (Chemical Abstracts) 141425-90-3
• Code number eg:UK-92,480
• Generic name reboxetine
• Proprietary name Edronax ® = brand name, trade name / often a number of different trade names
• Drugs may have more than one generic name
• eg: paracetamol (Aust, UK) = acetominophen (USA) = analgesic
• Generic name is used by pharmacologists

Question 4

Pharmacodynamics

Answer 4

• Studies of the biochemical and physiological
  effects of drugs
  –> in cells
  –> in animals
  –> in people
• Emphasises the dose-response, or concentration-response, relationship - the relationship between drug concentration and drug effect

Question 5

Affinity

Answer 5

• Refers to the drugs ability to bind to the target
• (…a bit like the chemistry between two
  people…) = (…or strength of binding between the drug and the target…)
• Can measure drug affinity! = Quantified as concentration of drug required to occupy/bind to 50% of target proteins
• Drugs with higher affinity only need a very small concentration to bind to the target.

Question 6

Affinity vs Selectivity

Answer 6

• A drug can (and does) have affinity for more than one target – i.e. it is able to bind to more than just one type of protein.
• But it cannot bind to just any target! It can only bind to those targets for which it has affinity (based on complementary bonding with target, shape e.g. 3d structure and size of molecule)

Affinity is about how strongly a drug binds to its target.
Selectivity is about how specifically a drug binds to its intended target compared to other possible targets.

Question 7

Selectivity

Answer 7

Selectivity is concentration-dependent - as you increase the concentration, you reduce the selectivity

• no drug is totally specific to a target, hence we get side effects [off-target side effects]
• Selectivity = ability of a given drug concentration to produce one effect over another (eg: therapeutic effect over side effect)
• Since drugs are likely to have higher affinity (lower conc required) for some targets compared with others… we can choose a concentration of the drug that binds to one target but not others
• i.e. is selective for a particular target over other targets at the concentration chosen

Question 8

Intrinsic Efficacy

Answer 8

ability of a drug to elicit a response

Defined as the maximal effect a drug can produce on a specific tissue, expressed as a proportion of the maximal effect of a full agonist on that tissue
–> between 0-1 (antagonists, partial agonists and full agonists)

May account for factors such as:
* more than one activated state of a receptor
* binding to a small proportion of the total receptors
can give a maximum (100%) response

Question 9

Potency

Answer 9

concentration of a drug that causes a specified effect

high potency = high affinity
* A drug that causes a specified effect at smaller concentration is more potent
* Therapeutic drugs often have effects in the nM range
* High drug potency ensures that a pill is small enough to swallow!

Question 10

Receptors

Answer 10

• A receptor is a macromolecular complex which binds to a ligand with high selectivity, and with the consequence that a characteristic effect occurs

4 types:
* G protein-coupled receptors (metabotropic)
* Ligand-gated ion channels (ionotropic)
* Kinase-linked
* Nuclear

Question 11

Ligand-Receptor Interactions

Answer 11

• 3 stages of drug action:
  1. Binding
  2. Conformational change and transduction
  3. Response (biological effect)