Paediatrics Presentation 2024-2025 PDF

7PY023/7PY028 Paediatrics & Neonatology https://worldhelp.net/the-case-for-...

7PY023/7PY028 Paediatrics & Neonatology https://worldhelp.net/the-case-for- sponsoring-an-older-child/ http://www.parents.com/toddlers- preschoolers/development/growth/mil estones-12-17-months/ http://www.goodtoknow.co.uk/family/547880/top-baby-names-for-2017 Overview Drug treatment in children Administration of medicines to children Prescription writing of medicines Common conditions Licensed and unlicensed medication The Paediatric pharmacist Paediatrics Premature Infant (less than 36 weeks gestational age) Full-term infants (36-40 weeks gestational age) Neonates (first 4 post-natal weeks) Infants (week 5 to 52 post-natal) Children (1-12 years) Adolescents (12 to 16 years) Pharmacokinetics - Absorption Main factors affecting drug absorption are: pH-dependent passive diffusion Gastric emptying Both processes demonstrate age-related trend from birth into infancy and childhood. The neutral gastric pH (pH 6-8) at birth is related to the presence of amniotic fluid in the stomach. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566769/pdf/envhper00410-0109.pdf Clip Art Pharmacokinetics - Absorption Postnatally Gastric acid secretory capacity appears after the first 24 to 48 hours of life Gastric acidity decreases during the first weeks to months of life. Adult values are approached by 3 months of age. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566769/pdf/envhper00410-0109.pdf Pharmacokinetics - Absorption In premature infants, gastric pH may remain elevated due to immature acid secretion. Gestational age and postnatal age both affect gastric emptying rate with prolonged emptying times seen in premature infants. Additionally pancreatic enzyme function and bile acid secretion activities are diminished in the neonate. Pharmacokinetics - Absorption Immaturity of the gastrointestinal tract decrease the transit time, thus decreasing absorption in the gastrointestinal tract. Permeability is a significant factor in the absorption of medication in children. Increased permeability of the blood brain barrier can result in possible systemic toxicity. The central nervous system does not fully mature until approximately 8 months of age. Pharmacokinetics - Distribution Caution in sick and injured children as their water losses and fluid requirements are increased and often their fluid oral intake is decreased. Possible dehydration or circulatory compromise adds an increased risk of medication toxicity in children. The proportions of body weight consisting of fat increases with age, therefore fat soluble drugs undergo changing patterns of distribution from infancy through to adolescence. Pharmacokinetics - Distribution Total body water, expressed as a percentage of total body weight. Drugs with high affinity to body water content have higher volume of distribution in infants. Lipophilic drug such as diazepam would have a smaller volume of distribution in infants. Patient Total Body Water (TBW) Adult 55% Infant 70-75% Preterm infant 85% Pharmacokinetics - Distribution Drugs that bind to protein are generally bound to a lesser degree in children. Diminished protein binding may result in a portion of a drug remaining in an active, unbound state. This can produce or result in greater than expected activity. Clip Art Pharmacokinetics - Distribution The binding of drugs to plasma proteins is decreased in neonate and does not approach adult values until about 1 year of age, dependent on: Plasma albumin Total protein concentrations ά1-acid glycoprotein Clip Art Pharmacokinetics - Metabolism Pre-term and new born babies have immature liver enzyme systems. Beyond the new born period many drugs are more rapidly metabolised in the liver necessitating larger doses or more frequent administration. Other drugs may have decreased and incomplete metabolism and can impact on the renal clearance rate and extend therapeutic times. Clip Art Pharmacokinetics - Metabolism Hepatic enzyme activity and plasma/tissue esterase activity are both reduced during the neonatal period. Most enzymatic microsomal systems responsible for drug metabolism are present at birth and their activities increase with advancing gestational and postnatal age. Pharmacokinetics - Metabolism Hepatic phase 1 reactions (i.e., oxidation, reduction, hydroxylation) develop rapidly during infancy, with adult capacities attained by 6 months of life. Affects phenobarbital, phenytoin and diazepam Pharmacokinetics - Metabolism Phase II conjugation reactions are generally reduced at birth Enzymatic systems responsible for oxidation and methylation are active in premature neonates The development of enzymes for oxidative demethylation do not develop for several months of life Pharmacodynamics - Metabolism Speed of hepatic metabolism markedly elevated until the age of 2 years, then gradually declines Sharp reduction in the rate of metabolisation takes place at puberty, when adult values are reached When administering drugs that undergo hepatic metabolism may need to Increase dosage Reduce dosage interval Pharmacokinetics - Renal Excretion Neonates have altered drug clearance due to: Decreased glomerular filtration rates Immature liver function Relative deficiency in pancreatic enzymes Decreased total plasma protein and albumin levels Increased percentage of total body water Decreased gastrointestinal times Pharmacokinetics - Renal Excretion In neonates the kidney recei only a fraction of the total cardiac output. Glomeruli and renal tubule development is incomplete, and the loop of Henlé is shorter than in adults and this persists until 6 months of age As a result, neonates and infants have lower levels of renal function and concentration than older children and adults. Clip Art Pharmacokinetics - Renal Excretion At birth, glomerular filtration rate (GFR) is 2-4 ml/min in neonate and as low as 0.6-0.8 ml/min in premature Dramatic increases occur during the first 72hr of life where GFR may increase 4-fold Glomerular capability reaches adult levels by age 5 months and tubular secretion levels mature at approximately 1 year. In children, renal drug elimination depends on the level of maturation of the kidneys. Pharmacodynamics – Receptor Sensitivity Data available on receptor sensitivity during the neonatal period is limited. Neonates represent the most fragile group due to their physiological instabilities and their increased potential for toxic effects. Clip Art Blood-Brain Barrier The blood-brain barrier is not fully developed at birth Drugs and other chemicals have relatively easy access to the CNS Advantage in meningitis Infants especially sensitive to drugs that affect CNS function Also (unless preterm) relatively more body fat – tissue depot – prolonged effect Adverse Drug Reactions Unique ADRs relate to the immature state of organ systems and to ongoing growth and development. Growth suppression (glucocorticoids) Discolouration of developing teeth (tetracyclines) kernicterus (sulfonamides) Severe neurodevelopmental condition associated with hyperbilirubinaemia Calculations Medication doses are determined by: Age Weight Body surface area (BSA), Therefore, it is imperative that all children have an accurate weight and when indicated a height documented. Intranasal Medications Nasal mucosa produces plasma concentrations similar to the IV administration of some drugs. There is vast number of medications that can be given via the intranasal route and these include: Midazolam Fentanyl Morphine Clip Art Nasal Drops The child needs an age appropriate explanation and direction. Position the child, where possible with their head extended over a pillow or the edge of a bed. Hyperextension prevents the medication from trickling down the throat causing an unpleasant sensation. https://behzadisportsdoc.com/patient-education/spine/ Otic medications Instillation is not a painful procedure, but often otic medications are stored in the fridge and the cold liquid in the ear produces an unpleasant sensation for the child. Clip Art Ophthalmic medication Although eye drop instillation is usually not a painful procedure, it can cause an unpleasant sensation for children. Gaining the child’s co-operation can be difficult. One drop in the inner corner then press lightly on the nasolacrimal duct for 10-15 sec. Clip Art Topical Medications Children have a greater total body surface area to weight ratio compared to that of adults and this promotes greater absorption. Topically applied medication is more rapidly and completely absorbed in infants, therefore topically applied medication should be used sparingly in this population. Hypothalamic-pituitary-adrenal (HPA) axis suppression has been demonstrated with potent steroids Topical Medications Percutaneous absorption may be drastically increased in neonates owing to an immature epidermis and increased skin hydration, Drug absorption from an IM site may be unpredictable and decreased due to insufficient blood flow, poor muscle tone, and compromised muscle oxygenation. Intramuscular Medications Variable IM absorption has been demonstrated for digoxin, gentamicin, phenobarbital, and diazepam in neonates. Clip Art Rectal medications Should only be considered when the oral route is difficult or contraindicated. Rectal medication administration is an invasive and unpleasant procedure for a child that requires appropriate explanation to both the child and parent. Privacy and comfort for the child are important to consider in all ages. It is advisable to ensure at least 2 people are present when administering rectal medications and it is preferable that a parent is present at all times. Rectal medications Always use a water soluble lubricant to aid insertion. If the suppository is not Clip Art available in the prescribed dose it is not recommended that suppositories are cut as there is no guarantee that the drug is evenly distributed throughout the suppository. Nebulised and Inhaled medications Care must be taken when administering steroids via nebulisation and inhalation as they can cause side effects such as oral thrush, contact dermatitis and Clip Art cataracts. Many children requiring inhaled bronchodilators for mild / moderate asthma need to have these administered via a Metered Dose Inhaler (MDI) and spacer device. Nebulised and Inhaled medications It is important that parents and care givers are well educated and confident in the use and care of the MDI to ensure accurate medication administration. A useful tool to support parent education is the parent fact sheet is available at: https://www.asthma.org.uk/advice/child/medicines/ Parenteral medication Giving injections to children is an unpleasant procedure for all concerned. If there is another suitable route for the administration of the medication this is preferable. Clip Art How should IV antibiotics be given to Paediatrics? Remember that kids are smaller – need doses in smaller volumes Administered via Burettes See paediatric pharmacopoeia Remember normal sodium intake for kids is 3-5mmol/kg/day (this includes dietary sodium) http://www.globalsources.com/si/AS/JK- Medirise/6008847979070/pdtl/Measure- Volume-Burette-set-Micro-drip-Set- Mesure-V/1147191270.htm What to do when no paediatric dose form exists: Look at paediatric references Call specialist paediatric hospitals Do a trial dissolution of a tablet. Pharmaceutical Press Unlicensed drugs and off-label use of medicines Unlicensed/off-label medicines (1) Medications given to paediatric patients could be... Licensed medications Licensed medications used outside of the product licence Unlicensed medication Professional ethical standards state a licensed product should be prescribed and dispensed where a suitable product is available Unlicensed/off-label medicines (2) Medications often not licensed in children Due to lack of clinical trials due to complications and ethical difficulties Often manufacturers state their product is not intended for children, limited to certain age groups, indications or routes of administration. EU legislation now requires the pharmaceutical industry to conduct paediatric trials - cannot apply for marketing authorisation without them Unlicensed/off-label medicines (3) Some drugs which are unlicensed in children for valid reasons e.g. aspirin for management of fever Can cause Reyes syndrome (very serious condition leading to neurological impairment or death) Some due to lack of data Unlicensed/off-label medicines (4) Same safety, efficacy and quality standards are not guaranteed for unlicensed or off- label products Does not mean that unlicensed and off-label prescribing is inappropriate – sometimes the evidence to support such use is considerable Cannot deny a patient treatment because the drug/use is unlicensed = malpractice/negligence Unlicensed/off-label medicines (5) Responsibilities Licensed medications – pharmaceutical company are vicariously liable for harm to a patient was caused by a defect in a licensed medication they manufacture if its use is within the product licence Unlicensed/off-label medications Prescriber takes responsibility Pharmacist – responsible for the quality and constituents of any unlicensed medications provided to a patient – need to obtain certificates of conformity or analysis when purchasing unlicensed products Unlicensed/off-label medicines (6) Specials Unlicensed products purchased from specials manufacturers Made under controlled manufacturing conditions Quality assurance Lower risk than extemporaneous dispensing Certificate of analysis or conformity should be available Products more likely to be produced against formulae with evidence to support their physical, chemical and microbial stability However, different manufacturers may make to different formulation – therefore products obtained from different manufacturers may not be interchangeable or bioequivalent – patient may have to remain on a specific product from the same manufacturer Problems encountered with unlicensed medications Drugs often started in secondary or tertiary care – poor communication from the hospital regarding drug, indication, dosing and formulation can lead to poor continuity of care GPs often reluctant to prescribe due to cost and lack of familiarity Poor stock availability in community pharmacy – not items which are usually kept in on the shelf How does the community pharmacist clinically check the prescription/know the indication/dose is appropriate? The risk of errors can be high…. GP prescribed: Furosemide 50mg/5ml oral solution – 5ml BD Patient was 4 months old Assuming the patient is the average weight for a 4 month old and that furosemide is an appropriate choice for the patient and the prescription is legally valid… WOULD YOU DISPENSE THIS PRESCRIPTION? The risk of errors can be high…. The patient previously had a prescription for: Furosemide 50mg/5ml oral solution 0.5ml BD Your pharmacy technician noticed the large dose increase, phoned the GP surgery and an experienced receptionist told her that the dose was correct. The technician informs you of her conversation and documents on the computer system that the dose has been checked WOULD YOU STILL HAVE DISPENSED THIS PRESCRIPTION? The risk of errors can be high…. In pairs discuss: A root cause analysis – at what point was the error made and why do you think it happened? Was the pharmacist to blame? Should they have done anything differently? Information sources BNFC SPCs MI – local and regional centres Tertiary centres e.g. Alder Hey, Great Ormond Street, Birmingham Childrens’ Hospital Paediatric formulary (written by Guys and St Thomas) Neonatal formulary Martindale – good for unlicensed info Drug Tariff Park VIIIB – amount that will be reimbursed for supply of specials Information sources (2) Information leaflets on medicines/conditions http://www.medicinesforchildren.org.uk/ Information for parents from the NHS http://www.nhs.uk/conditions/pregnancy-and- baby/pages/pregnancy-and-baby-care.aspx Info on vaccinations https://www.gov.uk/government/collections/immunisation- against-infectious-disease-the-green-book Recommended reading General overview/info Walker and Whittlesea BNFC (in print or online) Access some of the information sources given in the earlier slide Recommended reading (2) http://www.nhs.uk/conditions/pregnancy-and- baby/pages/pregnancy-and-baby-care.aspx NHS information for parents From this link... Click on “Babies and toddlers” Look in the section “Baby health and care” Pay particular attention to.. Treating a high temperature Coughs, colds and ear infections Diarrhoea and vomiting Infectious illnesses Factors Affecting Paediatric Therapy - Cystic Fibrosis Most common inherited genetic disease Cystic fibrosis patient apparent volume of distribution of certain drugs may be altered higher doses of certain drugs Higher clearance of drugs such as: Gentamicin Tobramycin Amikacin Dicloxacillin Piperacillin Theophylline Factors Affecting Paediatric Therapy - Obesity 50% increased recurrence of acute lymphoblastic leukaemia in obese children older than 10 years of age compared with lean children with cancer. http://www.theyucatantimes.com/2017/01/obesity-rates-increase-as-more-latin-americans-eat-processed-junk-food/ Factors Affecting Paediatric Therapy - Obesity Limiting the dose in obese patients may lead to poorer outcomes and under-treatment. Higher proportion of body fat resulting in higher Vd for lipophilic drugs and lower Vd for hydrophilic medications compared with normal- weight children. Higher total body water, lower percent lean mass, increased organ mass, and greater cardiac output, GFR, and serum creatinine concentrations than normal-weight children. Factors Affecting Paediatric Therapy - Obesity Correction factors have been used to adjust drug dosing in obese children. A correction factor is multiplied by the actual body weight less the ideal body weight, and this figure is added to the ideal body weight. The drug dose is then determined based on this weight. Correction factors are 0.3 for β-lactams, 0.45 for ciprofloxacin, and 0.4 for aminoglycosides. When possible, plasma drug level monitoring should be used to adjust dosing Factors Affecting Paediatric Therapy - Obesity Many antibiotics are hydrophilic medications that distribute to extracellular water. Adipose tissue contains approximately 30% water, meaning that many antibiotics will not distribute adequately in obese patients. Factors Affecting Paediatric Therapy - Obesity Vancomycin distributes into total body water and other tissues and is eliminated primarily by glomerular filtration. Vancomycin is empirically dosed using actual body weight in overweight and obese children; the dose is not capped at the usual maximum adult dose. Every-8-hour dosing is used initially; the frequency can be increased to every-6-hour dosing for complicated infections using serum concentration monitoring to individualise the dose. Factors Affecting Paediatric Therapy - Obesity One study showed that obese children lose consciousness at a significantly lower propofol dose than patients with a healthy weight. Whereas an IV propofol dose of 2 mg/kg was effective in 95% of children with BMIs above the 95%, those with lower BMIs each required a higher dose of 3.2 mg/kg. Factors Affecting Paediatric Therapy - Other Conditions Paediatric patients with gastrointestinal disease (e.g., celiac disease, gastroenteritis, and severe malabsorption) may require dosage adjustments. Hypoxemia also has been shown to decrease the elimination of amikacin in low-birth-weight infants. Critically ill paediatric patients with severe head trauma require higher than normal doses of phenytoin in part because of increased intrinsic clearance. Pain Management Neonates and young infants may perceive pain more intensely and be more sensitive to pain than older children or adults. An inadequately treated initial painful procedure may decrease the effect of adequate analgesia in subsequent procedures as a result of altered pain response patterns. However children are also distract-able and diverting attention may help Alteration of Dosage Forms Many drugs used in paediatric patients are not available in suitable dosage forms. This necessitates dilution of high concentrations of drugs intended for adult patients. e.g. Atropine, carbamazepine, diazepam, digoxin, epinephrine, hydralazine, insulin, morphine, phenobarbital, and phenytoin. Alteration of Dosage Forms Volumes ranging from 0.01 to 0.1 mL must be measured to dispense these drugs for use in infants. Alteration of Dosage Forms Administration of oral drugs continues to challenge parents and nurses. Alteration of these drugs by crushing or mixing, refusal of patients to accept the medication, and loss of drug during administration are some factors that can affect paediatric therapy. A common practice is to mix medications in apple sauce, syrup, ice cream, or other vehicles just before administration to make the drugs palatable. (see above) Medication Adherence The issue of medication adherence is more complex in paediatric patients than in adults. Dose Requirements Antineoplastic agents, may be given based on BSA. In either case, the total amount of daily dose in a paediatric patient, especially an adolescent, should not exceed the amount of drug indicated in an adult patient. Generally, the highest drug dose recommended for a child is the maximum dose approved for adults. Drug Interactions Drug interaction studies in paediatric age groups generally are lacking. The data often are extrapolated from studies in adult populations. Special attention should be given to adolescents, who may concurrently use alcohol, recreational or illicit drugs, or Clip Art other prescription or non- prescription medications without the knowledge of the primary healthcare provider, who must attempt to determine their use to avoid drug interactions. Drug Efficacy and Toxicity The maintenance dose of digoxin is substantially higher in infants than in adults. This is explained by: a lower binding affinity of receptors in the myocardium for digoxin increased digoxin-binding sites on neonatal erythrocytes compared with adult erythrocytes. http://cvpharmacology.com/cardiostimulatory/digitalis Drug Efficacy and Toxicity Insulin requirements are highest during adolescence because of the individual’s rapid growth. Growth hormone therapy has allowed children with growth hormone deficiency to attain greater adult height. http://www.childhealth-explanation.com/normal-growth.html  Drug Efficacy and Toxicity Promethazine now is contraindicated for use in children younger than 2 years because of the risk of severe respiratory depression. Chloramphenicol toxicity is increased in newborns because of immature metabolism and enhanced bioavailability. https://mynotes4usmle.tumblr.com/post/64070033085/gray-baby-syndrome-chloramphenicol-toxicity#.WdfbnmhSyUk Drug Efficacy and Toxicity Ethanol is present in some oral drugs, including phenobarbital and ranitidine, and sorbitol is used in oral liquids, including diphenhydramine, ferrous sulfate, frusemide, ondansetron, and prednisolone. Safe and acceptable levels of intake of excipients have not been determined for infants and children. Often problematic in patients on multiple medications Drug Efficacy and Toxicity The common cold occurs frequently in infants and children and is often treated with antihistamines, decongestants, antitussives, and expectorants. “Cough and cold remedies containing the above ingredients should no longer be used in children under 6 years as the balance of benefits and risk has not been shown to be favourable. Products for children from 6 to 12 years will continue to be available in pharmacies where advice can be given. Medicines to treat cough and colds in older children (6 to 12 years) can be considered supplementary to basic principles of best care. Some combinations (such as cough suppressants and expectorants) are being phased out while all liquid products containing these ingredients will be in a child resistant container in future.” https://www.gov.uk/drug-safety-update/over-the-counter-cough-and-cold-medicines-for-children Drug Efficacy and Toxicity Tetracyclines are contraindicated for use in pregnant women, nursing mothers, and children younger than 8 years because these drugs can cause dental staining and defects in enamelization of deciduous and permanent teeth, as well as a decrease in bone growth. Drug Efficacy and Toxicity Some drugs may be less toxic in paediatric patients than in adults. Aminoglycosides appear to be less toxic in infants than in adults. In adults, aminoglycoside toxicity is related to both peripheral compartment accumulation and the individual patient’s inherent sensitivity to these tissue concentrations. Neonatal peripheral tissue compartments for gentamicin have been reported to closely resemble those of adults with similar renal function, gentamicin infrequently is nephrotoxic in infants. This dissimilarity in the incidence of nephrotoxicity implies that newborn infants have less inherent tissue sensitivity for toxicity than do adults. Communication Communication (1) Do you counsel the child or the parent/carer? Both where possible Involve the child in their own care Parent/carer responsible for child so will also need information How will the information/terminology differ when talking to the child and parent/carer? Communication (2) Can a child have an MUR? Yes, if they are competent (i.e. Able to give consent) and able to engage in discussion with a pharmacist Also could have NMS if meet criteria  Communication (3) General principles of good communication apply Helpful tips... Know your patients - if you make an effort to talk to them at every opportunity, this will help you get your point across if in the future you need to counsel them Make them feel important Familiar icons – cartoon characters on badges Try and crouch down to their level – it is intimidating if you are standing over them Do anything to make it fun – a sticker will usually get their attention Use plasters with a smiley face, or draw one on the plaster Nothing will work for every child – try different approaches and be adaptable Smile QUESTIONS?