Pharmacodynamics is often considered to be 'what the drugs do to the body' (in contrast to pharmacokinetics which is concerned with 'what the body does to the drugs'). It is obviously a vast topic, so the text below is an introduction to some key concepts.

Classically drugs exert their effect via interaction with a target, commonly (but not always) a protein. Targets may be intracellular or extracellular and can be a cellular receptor on the cell membrane, an intracellular receptor exerting an effect on the nucleus, an enzyme, transport proteins or even a specific nucleic acid sequence.

Within the cellular targets, there are 4 main types:

• Ion channels- These are the simplest form of receptor, once the drug binds to a receptor on this target the channel is either opened or closed dependent upon the action of the drug and whether it is an agonist or antagonist (see below). Examples of drugs working on ion channels include most local anaesthetics (e.g. lidocaine) that work on voltage-gated sodium channels.
• G-protein coupled receptors (GPCRs)- These are more complex than ion channels. When the drug binds to the target, it causes a sequence of events within the G-protein subunits which then leads to production of a secondary messenger such as cyclic AMP or a protein phosphorylation cascade. These second messengers are actually responsible for causing the effect. Adrenoreceptors are an example of G-protein coupled receptors.
• Tyrosine kinase receptors- these receptors are different in their mechanism to both ion channels and GPCRs. When a drug activates a tyrosine kinase receptor it leads to a series of steps within the cell, normally involving phosphorylation of targets, then causing effects which often include cell growth and differentiation. Insulin is a commonly used drug (as well as endogenous hormone!) that works via a tyrosine kinase receptor.
• Nuclear receptors- As the name suggests these receptors are located within the nucleus of the cell and activation or inhibition of these receptors typically causes increased or decreased gene transcription. Drugs interacting with these receptors must obviously be lipid-soluble in order to penetrate the cell membrane, after which it forms a complex with a receptor protein before exerting an effect. Commonly used drugs that work via this route are steroids such as prednisolone and other hormone replacements such as levothyroxine.

With all different receptor targets, it is also important to consider whether the drug has a 'positive' or 'negative' impact on the receptor.

• Agonists are drugs which activates the receptor.
• Antagonists are those which block a receptor preventing activation, it is important to note they do not deactivate a receptor.

Antagonists may be competitive or non-competitive. A competitive antagonist binds at the same site as an agonist, thereby occupying it and preventing an agonist occupying the site. A non-competitive antagonist occupies another site which often causes a conformational change in the binding site where an agonist would otherwise bind.

• 'Binding affinity' is a concept of how readily a drug will bind to the specific receptor, in most cases the more receptors that are occupied by a drug, the greater the effect produced.
• 'Efficacy' is the measure of how able an agonist is to produce a response once it has bound to the receptor.
• 'Potency' is related to the concentration at which a drug is effective.
• 'Therapeutic Index' is the ratio of the dose of a drug resulting in an undesired effect compared to that at which it produces the desired effect. Calculation of a therapeutic index is complex, however, it is sufficient to be aware of certain drugs with a 'narrow therapeutic index', such as the antibiotic gentamicin which whilst effective, requires close monitoring to avoid adverse effects.

Dose-response relationship

The relationship between the amount of drug given (dose) and the impact it has on the patient (response) is very rarely entirely linear. Often drugs that work by occupying a certain receptor may 'saturate' the available receptors and so further increased doses will not cause any more response. Many drugs do not start to have a significant impact below a certain dose and so are considered to be 'sub-therapeutic' below such a dose. The relationship between dose and response can be well illustrated on dose-response graphs with the dose on the x-axis and response on the y-axis; such graphs allow easy comparison of the characteristics of different drugs. It is, of course, important to remember that dose-response also varies between individuals.

Metabolism

loading dose takes volume of distribution into account while maintenance dose takes clearance into account. Because clearance is altered in renal and liver disease, maintenance dose must be decreased in these patients, but loading dose is unaffected.