1. MISTAKE IN PEDIATRIC PHARMACOTHERAPY Jarosław Woroń PharmD, PhD Chair Of Pharmacology, Dept. Of Clinical Pharmacology Jagiellonian University College of Medicine Krakow

2. ADVERSE DRUG REACTIONS  Are one of the first ten causes of death  20% of funds spent on health protection is used for ADR  10-15% of hospitalization is connected with ADR  5-9% of hospitalization costs are costs of ADR  30-60% of cases of ADR can be prevented

3. TYPES OF ADR A Connected with mode of action of drugs and the used dose. B They don’t correlate with the dose - atopic - idiosyncratic C Connected with the dose and the time of administration D Delayed E Connected with stopping administration of the drug F Unexpected failure of treatment

4. FACTORS INCREASING THE RISK OF MAKING A MISTAKE IN PHARMACOTHERAPY 1.polypharmacy 2.Patients treatment by a few doctors who don’t consult the given pharmacotherapy w 3.Lack of accepted standards in pharmacotherapy 4.Lack of pharmacotherapy control- the posibility of repeating mistakes 5.Self- medication

5. SOURCES OF MEDICAL MISTAKES IN PHARMACOTHERAPY - attractive pharmacotherapy- for the patients is the one which brings fast results and can put the patients in danger of side effects - the rule of three- wrong drug in the wrong dose for the wrong patient - the pharmacotherapy without considering the limits and contraindications, before starting the treatment carelessly intervied patient - treating the child as a miniature of an adult- a lot of ADR depend on the age of the patient

6. DIFFERENCES IN PHARMACOKINETIC PARAMETERS IN PEDIATRICS - small area of gastrointestinal tract - lower production of acid, pepsynogen and slower emptying of the stomach, irregular peristalsis, lower production on pancreas enzymes and bile - immaturity of intestinal enzymes- CYP3A4 and P-glycoprotein - it’ s best to give to children drugs in the form of syrupes and solutions

7. DISTRIBUTION - in distribution we observe increased volume of distribution in the water phase- it’s better to calculate the doses depending on the area of the body, weaker connection of drugs with albumins, increased permeability of blood/brain barrier- increased risk of ADR

8. METABOLISM Unsatisfactory ability of cytochrome P450 isoenzymes, which take partin drug metabolism, weaker connection with glucuronic acid

9. ELIMINATION - kidney activity in newborn babies constitutes 30-40% of activity in comparison with adult

10. OFF-LABEL DRUG USE - every disease has its own characteristics - lack of possibility of observationof drug safety profile - lack of information about ADR - lack of possibility of determiningthe ratio between the benefit and the risk

11. CONTRAINDICATION OF DRUG USE DEPENDENT ON AGE Can be used above -Thiocodin -12 years of age - Sulfarinol -12 years of age - Dextrometorphan- 6 years of age - Detreomycin maść- 11 years of age - Acetylosalicylic acid- 12 years of age - Actifed, Actitrin- 6 years of age

12. USE OF PROMETAZINE IN CHILDREN- DOUBTED BENEFIT AND HIGH RISK  Absolutly contraindicated undre 2 years of age- can cause breath depresion and it can result in sudden newborn death syndrome  drowsiness  dizziness  Weakening of the muscles  Poor slightniewyraźne widzenie  Combined with metamizole increases the risk of hypothermia

13. DRUG INTERACTIONS - pharmacokinetic - pharmacodynamic - common profile of side effects

14. HOW TO PREVENT ADR IN CHILDREN - use of the drugs according to registration - avoidance of unwanted drug interactions - monitoring of ADR - it must be remembered a child is not a miniature of an adult