Pharmacodynamics

Question 1

What are the five main molecular targets for drug action?

Answer 1

Enzymes

Carrier Molecules

Ion Channels

Nucleic Acids

Receptors

Question 2

What are receptors and how can they be utilised as molecular targets for a drug’s action?

Answer 2

A receptor is a specific macromolecule, usually a protein, situated either within the cell or within the cell membrane, to which a specific group of ligands (molecules that bind to a receptor - can be exogenous substances such as drugs or naturally occurring substances such as hormones or neurotransmitters) can bind and produce pharmacological effects.

There are three types of ligands:

Agonists - a substance that stimulates or activates a receptor to produce and effect (e.g salbutamol activates B2 receptors to induce bronchodilation). Drugs that act as agonists mimic the effect of endogenous messengers

Antagonists - a substance that prevents the action of an agonist/ endogenous messenger but does not have any effect itself (e.g Iosartan binds to an angiotensin II receptor, preventing it from activating the recpetor)

Partial Agonists - stimulates receptors to a limited extent, preventing any further stimulation from naturally occurring agonists (e.g buprenorphine partially activates opioid receptors)

Question 3

How can enzymes be used as molecular drug targets?

Answer 3

Enzymes, like receptors, are protein macromolecules with which substrates interact to produce activation or inhibition. Drugs in common clinical use which exert their effect through enzyme action generally do by via inhibition, for example…

Aspirin inhibits platelet cyclo-oxygenase (COX), an enzyme that produces prostoglandins and thromboxame from arachidonic acid

Ramipril inhibits the action of angiotensin-converting enzyme

Question 4

How can ion channels be utilised as molecular targets for drug actions?

Answer 4

The conduction of impulses in nerve tissues and electromechanical coupling in muscle depend on the movement of ions, particularly sodium, calcium and potassium, through membrane channels. Several groups of drugs interfere with these processes, for example…

Nifedipine inhibits the transport of calcium through the slow channels of active cell membranes

Furosemide inhibits potassium, calcium and sodium co-transport in the ascending limb of the loop of Henle (the ‘U’ shaped part of the nephron, whose main function is to re absorb water and sodium chloride from the filtrate)

Question 5

What are transport proteins and how can they be utilised as molecular targets for drug action?

Answer 5

Transport proteins are molecules that are involved in the transport of biological compounds across cell membranes such as proteins, DNA, RNA, electrons or protons.

An example of a transport protein is the sodium-potassium ATPase pumps which are responsible for active ion transport across the membranes of cardiac muscle cells to enable their contraction

The drug Digoxin (used to treat atrial fibrillation, abnormal cardiac rhythms etc) inhibits the action sodium-potassium ATPase pumps, increasing intracellular sodium levels, driving an influx of calcium into the heart enhancing contractility

Question 6

What two drug properties govern a drug’s interaction with receptors?

Answer 6

Affinity - The drug’s ability to bind to receptors

Efficacy - The drug’s ability to activate receptors after binding

Question 7

How to affinity and efficacy affect agonists and antagonists?

Answer 7

Agonists have affinity and efficacy

Antagonists have affinity but have zero efficacy