What is the Difference Between Pharmakonetics and Pharmacodynamics?

Alongside the pharmacokinetic properties of a drug, pharmacodynamics is also important to consider.

Pharmacokinetics and Pharmacodynamics: Key Differences

Unlike pharmacokinetics, pharmacodynamics does not have a series of steps but is mainly based on the mechanism of action, the drug-targets and its molecular and physiological effects on the body including side effects such as inflammation and nausea. Another important aspect of pharmacodynamics is dose-response which looks at the toxic effects with increasing dose.

We will continue to use amoxicillin as an example as we explore its pharmacodynamics:

• Mechanism of action – amoxicillin inhibits the formation of the cross-links within the cell wall of bacterial pathogens leading to its destabilisation and bactericidal effects
• Targets of amoxicillin – amoxicillin targets a variety of infection-causing pathogens such as Helicobacter pylori, Streptococci, Enterococci, Haemophilus, Moraxella and Bacillus subtillis
• Molecular/physiological effects – there is limited information on the molecular effects of amoxicillin, however potential side effects include nausea and diarrhoea and the potential to cause a mild allergic reaction resulting in coughing, wheezing and itchy skin rash
• Toxicity – overdosing with amoxicillin can cause acute renal failure, haematuria, abdominal pain, vomiting, diarrhoea, rash, drowsiness and hyperactivity but due to its wide therapeutic range mild overdosing is not associated with significant toxicity.

The information obtained from the pharmacokinetic and pharmacodynamic (PK/PD) properties of a drug is invaluable. This information as well as the clinical picture of the patient and other factors helps healthcare professionals decide if the drug is appropriate to give to the patient considering all these aspects.

With the recent increase in the prevalence of multidrug-resistant bacteria in many parts of the world and the lack of new antibiotics in the foreseeable future, there has been increased interest in optimising the administration of existing antibiotics in order to improve patient outcomes (especially in critically ill patients), reduce toxicity and prevent, or at least, decrease the probability of selection and emergence of antimicrobial resistance.

Optimising PK/PD in patient care can have a great impact. Ensuring the correct antibiotic and dose is used against the right pathogen to improve the patient’s immune response to, and reduce the virulence of, the pathogen can lead to better patient outcomes, reduced toxicity and less resistance.

In order to optimise the PK/PD of antibiotics, good basic knowledge about PK/PD in different patient populations is necessary. It is important to keep in mind that PK/PD of a specific drug may differ among newborns, children, the elderly, the critically ill, the morbidly obese, patients on renal replacement therapy, different ethnicities, the two sexes, and patients with specific diseases such as cystic fibrosis, since the absorption, distribution, metabolism, and excretion of drugs may vary among these groups.

Unfortunately, detailed PK/PD data is lacking for numerous “old” antimicrobials since they were marketed at a time when such data were not required for authorisation by regulatory authorities and technical capabilities were limited (e.g. with regard to accurate measurement of drug levels and PK/PD simulations by computers). In addition PK/PD data may only exist for specific populations (e.g. healthy volunteers) and may thus be difficult to extrapolate to other populations.