Practical pharmacology in paediatric emergencies

Published on 10/02/2015 by admin

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4 Practical pharmacology in paediatric emergencies

Do not skip this chapter! It is not mind-numbing pharmacology and should offer some useful tips on drug dosing in paediatric emergency management. (Please refer to Chapters 5 and 6 for drug dosing tables.)

Introduction

Pharmacologists acknowledge that it is important to strike a balance between science and practicality when it comes to the clinical determination of drug dosages in children. While we understand many of the changes in pharmacokinetics that are related to growing up and to differences in body composition (body water and fatness), it is extremely unclear how to translate these into meaningful information when standing in front of the patient. There is even less information about emergency drug dose determination in a patient whose physiology is deranged from critical illness or injury. Fortunately, many of these issues have less application to initial or stat doses than to repeat or subsequent doses and can, to some degree, be avoided in drugs that can be titrated to clinical effect. This chapter contains some useful information and guidelines on how to modify drug dosage based on age or body composition, to ensure that the desired efficacy is achieved and overdosage is avoided.

Overview

Pharmacology in children is difficult primarily because of the differences in pharmacokinetics (what the body does to the drug) of any given drug between neonates, infants, children and adults, whereas the pharmacodynamics (what the drug does to the body) of that same drug will remain much the same across all developmental stages. An approach to paediatric drug dosing ideally needs to be based on the physiological and body composition characteristics of the child and the pharmacokinetic and pharmacodynamic qualities of a particular drug. In the few drugs that have been tested in children, there can be a 3- to 6-fold increase in the variability of the pharmacokinetics of a single drug dose for paediatric patients when compared to adults. This difference between adults and children is likely to remain unclear because of the difficulty in performing dose escalation studies in the paediatric population. This necessitates the initial dose estimation in paediatrics to be obtained via extrapolation approaches. The validity of such an extrapolation hinges on the similarity of disease progression and concentration-responses between adults and children for any particular pathological process. All of this leads to the off-label use of many drugs in the paediatric population group. About 75% of drugs used in paediatrics have never been studied in children.

Pharmacokinetics in critical illness

Some general pharmacokinetic principles that are relevant to emergency drug administration in critically ill children:

• Hypoxaemia as well as poor perfusion leads to decreased or unpredictable drug absorption from the GIT. This, in addition to variable first pass metabolism, is one of the reasons that intravenous administration is favoured to ensure optimum bioavailability of the drug.

• Rectal absorption can vary because of hypoperfusion and depending on how high in the rectum the medication is administered – higher up means absorption into the portal system and a greater enterohepatic first pass metabolism with a resultant decreased bioavailability. Drugs administered low in the rectum are delivered systemically via the inferior and middle rectal veins, before passing through the liver.

• Hepatic and renal function may be impaired because of decreased cardiac output, leading to diminished clearance of drugs and prolonged duration of action.

• Significant oedema may change the volume of distribution of hydrophilic drugs.

Pharmacokinetics in the developing human

An insight into the changes in pharmacokinetics of the developing child will give you an appreciation of how drug dosing can be tailored to these developmental periods. Simplistically, the age-related changes are:

• Changes in volume of distribution – neonates have a relatively higher proportion of body water, which reaches adult levels before 1 year of age.

• Changes in plasma protein levels – these reach adult levels in early infancy.

• Changes in drug metabolizing enzyme systems – Phase I and Phase II liver enzymes reach adult levels of function by about 2 years of age (with much variation between individual enzymes).

• Changes in renal function – glomerular filtration rate and drug excretion reach adult levels at about 1 year of age.

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