Pediatrics pharmacology 2

Dr.Azad Abduljabar Haleem Al Mezori

azad82d@gmail.com

Pediatrics prescribing

• Legal responsibility lies with the doctor who signs the prescriptions??

PAEDIATRIC DOSING

• Pharmacokinetic and pharmacodynamic data are seldom available for the paediatric population,

• this is because most medications are only licensed for adult use and have not undergone specific pre-marketing clinical studies in children.

• Data on therapeutic dosing for children are often anecdotal and based on case reports or very small population studies.

• The surface area and the weight are the only common methods currently available to predict paediatric therapeutic doses from those used for adults.

Surface area

• The surface-area or percentage method for estimating doses is calculated as follows:

• (Surface area of child (m2)/1.76m2)*100• where 1.76 m2 is the average adult surface area.• Children are often said to tolerate or require larger doses of

drugs than adults based on a weight basis, and the percentage method helps to explain this phenomenon.

• Body water (total and extracellular) is known to equate better with surface area than body weight.

• It thus seems appropriate to prescribe drugs by surface area if they are distributed through the extracellular fluid volume in particular.

Weight

• Adult dose (mg)/70kg=mg/kg dose• where 70 kg is the average adult weight.• This method will give lower doses than the

surface-area method. • It is far less accurate in clinical terms and is

usually inappropriate for accurate therapeutic dosing.

• However, as it gives lower and thus safer estimates of what the toxic dose may be, it is a more practical and reasonably cautious method for extrapolating toxic doses.

• Most paediatric doses given in textbooks are described in small age or weight groups on a mg/kg basis.

• However, these will often have been originally obtained from surface-area data and thus are larger than the adult dose divided by 70.

• There are, however, many medications which can be used in children and accuracy of prescribing is essential because of the vast physical size differences in children (i.e. from 0.5 kg to 120 kg) let alone their changes in kinetics.

• Children should be regularly weighed so that up-to-date weights can be used for prescribing.

• However, remember the practicalities of what is to be given to the child.

• If a child is 6.5 kg and requires 2 mg/kg of ranitidine, it would seem wiser to prescribe 15 mg, which is 1 ml of the oral liquid, rather than 13 mg, which equates to 0.867 ml.

• Some knowledge of the therapeutic range of the drug is required to know when and by how much it is suitable to round doses, however, and sometimes awkward quantities are required.

DRUG MONITORING

• Most drugs have wide therapeutic windows and thus toxicity is unlikely at 'normal doses'.

• It is usually easy to see a medication effect, e.g. analgesics take away pain.

• There are, however, certain circumstances when it is important to measure drug levels to ensure that there are adequate levels for effect and/or that the levels are unlikely to cause toxicity.

• A drug with a narrow therapeutic window has a narrow range between the drug concentration exhibiting maximum efficacy and that producing minimum toxicity.

• Medications that have narrow therapeutic windows are often monitored, as it is hard to predict whether a dose for an individual patient will be clinically effective or will cause toxicity.

• Common drugs for therapeutic monitoring:

• Phenytoin

• Phenobarbital

• Warfarin

• Carbamazepine

• Gentamicin

• Vancomycin

• Digoxin

• Theophylline

Indications for monitoring:

• • To confirm levels are not toxic and are at a level that is normally effective (usually checked once steady-state has been reached), e.g. gentamicin, vancomycin

• • If toxicity is expected• • If external factors may have changed a level

(change in renal/hepatic function)• • To check compliance It is important to know

that a drug was at a steady state when a level was measured and whether trough levels or peak levels are important.

INTERACTIONS

• Many situations arise where interactions between different medications are important.

• Drugs may either inhibit or induce the liver enzyme systems as follows:

Drugs and the liver

• Liver induction

• • Will lead to treatment failure of:

• • Warfarin, phenytoin, theophylline.

• • Caused by:

• • Phenytoin, carbamazepine, barbiturates, rifampicin.

• liver inhibition

• • Will lead to potentiation of:

• • Warfarin, phenytoin, carbamazepine, theophylline, cyclosporin

• • Caused by:

• • Omeprazole, erythromycin, valproate, isoniazid, cimetidine.

Compatibility

• When medications are administered, always be aware of their interactions before they enter the body.

• This is particularly important with parenteralmedication.

• Many medications interact to produce non-effective products, toxic products or precipitates.

• Examples of incompatible injections:

• Gentamicin: is partly inactivated by penicillin, so lines must be flushed between administrations.

Drugs in breast milk

• There is now a great deal of evidence establishing the benefits of breast-feeding for both the mother and the baby.

• The ability of a drug to pass into the breast milk will depend on its partition coefficient, pKa, its plasma and milk protein binding and selective transport mechanisms.

• Unfortunately, lack of knowledge about drug safety in breast-feeding often causes women to:

• stop breast-feeding or never start in the first place because of their own anxiety or that of the health-care professionals involved in their care.

• It must always be remembered that even if drugs do enter the breast milk they must still go through the infant's gut to be absorbed and this offers another barrier to many drugs such as omeprazole.

• The infant's short gastric emptying time also reduces exposure to some drugs.

• The frequency and volume of the feeding must also be considered as there will be less exposure to the drug if the infant is receiving supplementary feeds and/or other liquids.

• Further reassurance can be given to a parent if the medication that is being given has a long term history of safety in children at therapeutic levels.

• Taking all this into consideration there are very few drugs that are contraindicated in breastfeeding women.

• The benefits of breast-feeding usually outweigh the small theoretical risk of harm to the neonate.

• This said we should never become complacent and should look for the evidence and approach newer drugs with more caution.

Drugs which are contraindicated in breast feeding

• Cancer chemotherapy• Radiopharmaceuticals• Antithyroid drugs, Iodine, Iodides• Amiodarone• Androgens • Indomethacin• Nalidixic acid• Nitofurantoin & Sulphonamide (in G6PD-deficient infants)• Chloramphenicol• Tetracyclines• Vitamins A and D (high dose)

Thanks