Pharmacokinetics and Pharmacodynamics - Intro

Terminology

Pharmacology

The scientific study of chemicals (drugs) and their effects on living organisms

Pharmacokinetics

How the body acts on a drug when administered and how it moves through the body (absorption, distribution, metabolism, excretion) 

Pharmacodynamics 

How a drug acts on the body after administration to exert its effects 

Prefix ‘pharma’

Relating to pharmaceuticals or pharmacology

Suffix ‘kinetics’

Motion or movement

Suffix ‘dynamic’ 

Continuous and productive activity or change 

Therapeutic

Having a positive effect relating to the treatment of disease

Therapeutic range

The range of plasma concentrations in which most veterinary patient have the desired drug effect with minimal toxicity 

Therapeutic Index

A quantitative measure of the relationship between drug safety and efficacy

The therapeutic Index uses a ratio that compares …

The drug concentration that elicits toxicity in 50% of the population (TD50) to the concentration that elicits a therapeutic in 50% of the population (ED50) 

Wide/large therapeutic index

Difference between the two concentrations in large = safter/less chance of toxicity

Narrow/small therapeutic index

Difference between the two concentrations in small = may be harmful if dosing is not accurate due to higher chance of toxicity

Half-life

• The amount of time is takes for the concentration of a medicine administered to be reduced by half

• Will be different in different species due to how they metabolise and excrete the drug 

• Individual patient factors may also influence the half life in that patient 

An animal with reduced liver or kidney function may clear a drug more slowly, leading to a ..

Prolonged half-life compared to that stated n the product literature

Steady State concentration is dependant on ..

The elimination half-life of the drug

The steady state concentration

An equilibrium in which drug concentrations consistently stay within the therapeutic limits

Steady state concentration occurs when ..

The amount of a drug is being absorbed by the body

Repeated dosing 

Dosing at separate intervals e.g. giving a tablet three times a day/every 8 hours as prescribed by a veterinary surgeon

Continuous dosing

An intravenous infusion/constant dosing e.g. adding glucose to a patient’s intravenous fluid bag

Steady state concentration - The leaky bucket analogy

The same amount of a drug is being absorbed by the body is the same amount they is being cleared from the body → concentration remains stable or consistent when the drug is administered repeatedly or continuously

The rate at which a drug reaches SSC depends on its half-life (time taken for the body to eliminate half of the drug) typically stated as 5 half-lives (t1/2). During this time, the drug concentration .. 

Gradually increases until it reaches a plateau where the administration and elimination rates become equal 

Half-life often defines the redosing interval. For drugs with a half-life between 8-24 hours this leads to dosing between 1 and 3 times daily. Shorter intervals than this are often not practical. Medicines with a half-life shorter than 8 hours will often be given in bigger doses to allow for extended intervals. This is only possible if the medicine has .. 

A wide therapeutic index 

If a drug has a half-life of 8 hours, how long will it take to reach SSC?

Half-life = 8 hours, steady state typically takes 5 half-lives. Therefore, time to SSC 5×8 = 40hours 

If a drug has a half-life of 24 hours, how often should it be administered?

Half-life = 24 hours, dosing likely to be once per day