School of Pharmacy, University of Otago PHCY 473: QUALITY USE OF MEDICINES C Module 4: Special Populations Workshop 7: Therapeutics Paediatric

Disorders
Case 1 Jessica, a 9 month old, is admitted to the Childrens ward you cover as clinical pharmacist with a three day history of diarrhoea (needing 10 nappy changes a day) and vomiting. Her mother has been trying to get Jessica to drink oral rehydration solution (obtained from her local Pharmacy yesterday) but Jessica has tolerated less than 100 mL in the last 12 hours. The pharmacist had advised Jessicas mother to seek medical advice if Jessica continued to suffer from diarrhoea for another 24 hours. Jessica is exhibiting signs of dehydration. Jessica receives IV fluids for 48 hours before the paediatric consultant decides that she has recovered sufficiently for her mother to restart her normal feeds as she has only had 3 episodes of diarrhoea in the last 12 hours and has stopped vomiting. During the next 24 hours her diarrhoea and vomiting worsen and she is restarted on IV fluids. Discuss this case using the headings Problems, Options, Plans. Problems

Diarrhoea and vomiting for 3 days o Severe, 3 nappy changes every day o Refusing oral rehydration solution, has become dehydrated o Check for: Clinginess Changes in behaviour Looking unwell Abdominal pain Bloody stools Dehydration o Check by: Skin test, see if skin rebounds properly Dry mucous membranes Sunken eyes Reduced urine output Pale and cold peripheries Drowsiness and irritability o Signs and syumptoms :mild Thirsty, restless Alteration of normal behaviour

 Pulse normal (strong) Respiration is normal BP is normal Skin turgor is normal (pinched tummy skin springs back quickly) Tears can be seen Eyes normal Mucous membranes are still moist Urine output is normal o Moderate: Thirsty and irritable and lethargic and drowsy Fast pulse and weak Respiration is deeper (rate normal?) BP is normal to low Skin turgour, slow retraction Sunken eyes Tears absent Mucous membranes are dry Urine output is reduced and dark o Severe: Very drowsy, sweaty and limp and floppy (can be comatose) Rapid and feeble pulse Rapid and deep respiration BP is low to very low Skin very slow to retract Eyes very sunken No tears Mucous membranes are very dry No urine passed for several hours, bladders empty o Required IV fluids for 48 hours (nasogastric tube can be used if not vomiting, because vomiting can cause the water to be expelled before absorption) IV in this case due to vomiting AND couldnt tolerate it before o Showed some improvement, but required again after relapsing Feeds restarded, and then symptoms have returned Maybe a cows milk allergy or lactose intolerance or the formula is non-tolerant If rechallenged again, and shows signs of rejecting formula, then they are allergic against cows milk (whey proteins) o Soy mlik is the way to go, there can be cross interaction with goats milk o Pepti-junior is hydrolysed whey protein, can be used second line if soy doesnt work o Neocate can be used (pretty much just amino acids only) really cant be allergic, so it can be given third line o Both are available on special authority But it could be temporary if she has had the formula normally before, remember gastro causes temporary intolerance Skin test to see if shes truly intolerant to something

Options Oral fluids 5-10ml every 5-10ml Require 100ml/kg/day (maintanence) Diarrhoea and vomiting 50-100ml each event Any juices or soft drinks should be avoided or at least watered down (avoid sugar) Preferentialy water or ORS Continue to offer feeds as often as possible (i.e. breast feed) DO NOT WITHHOLD

Choose oral fluids to suit their taste, just try a couple of flavours Plans

Case 2 James, a 3 year old, is brought to your pharmacy by his babysitter, Jackie, for advice about a rash. Jackie says that James mother was reluctant to go to work in the morning as James was off his food and had a slight temperature, but she had to go as she had an important meeting. When Jackie arrived she noticed that James was not his usual boisterous self and has become even quieter and very clingy during the course of the morning. He usually takes great pride in the fact that he can go to the toilet on his own, but he wanted Jackie to help him today. When they went to the toilet an hour ago Jackie noticed that James felt very hot and was holding his head at a funny angle, when she pulled down his pants she noticed a rash on his leg. Jackie has tried to get hold of James mother but she is unavailable, so Jackie decided to bring James to see you for advice, as she was afraid that James has meningitis (Jackie cannot drive and your pharmacy is only 4 doors down from James house). You agree with Jackie that James probably does have meningitis and you call an ambulance. 1. Outline the signs and symptoms that James is displaying that are highly suggestive of meningitis. Then: Tachycardia and high respiratory rate Cyanosisand hypoxia Changes in mood or behaviour Poor urine output (showing the kidney function is failing Cold extremities (periphery circulation shut down in septacemia) Adominal pain Photophobia Diarrhoea Increased capillary refill (press on finger if its elevated. The colour should return to the finger in less than 4 seconds, checks for perfusion, which is reduced in sepsis as circulation to the ) Hypotension is late state Italics = early sign of shock 2. Describe the investigations that you would expect James to undergo on admission to hospital. Still early stage of meningococcal So: Fever o Fast to devlop Non-blanching Rash (press glass against rash, wont go away) o Indicates meningococcal infection Stiff neck o Cant kiss their knee Cant pull down pants (join pain- septisemia) Refusing to eat Becoming clingy (non-general symptom) really shows they are feeling very unwell (but if they can run around, then its fine)

Lumbar puncture o CSF apparence (cloudy or bloody, should be clear) o Culture of bacteria present (also see sensitivity) Nesseria Strep pneumonia HiB Then modify therapy depending on what o Glucose (reduced in bacterial, not in viral) But start antibiotics empirically without waiting Idealy, lumbar puncture before antibiotics, but given the fast progression of the disease, need to give antibiotics fast Can have a false negative if taken 2 hours after antibiotics (so take puncture quickly as well Fluctuating levels of consciousness should be checked o Raised bulging fontanelles if less than 3 o This is due to raised intracranial pressure o CT scan if really felt like it o Hypertension and brady cardia associated well o Can shine light into eyes, pupul response different o Odema and seizures o WITHOLD lumbar puncture if seen rd 3 generation cephasporin can enter brain o Cetriaxone dosed based on weight (80-100mg/kg) BP and HR and respiratory rate (tachycardia) Oxygen sat (cyanosed) CRP Temperature Urine and electrolytes, can go into metabolic alkalosis or acidosis with sepsis

James cerebrospinal fluid is cloudy and contains white cells and protein. 3. Discuss the antibiotic treatment that James should receive (he weighs 15 kg). As above (ceftriaxone) Cefotaxine can also be used as well Dexamethasone to reduce inflammation and intracranial pressure as well o Only for 2 days, want to stop it, because a little bit of inflammation allows drugs to permeate better anyway o Reduces chances of neurological damage Deafness Epilepsy Paralysed Neonates a bit different: o Emperical is amoxicillin and gent (cover against listeria) o 5-7 days if confirmed infection o Changed to cefotaxine and gent if confirmed

In addition to your recommended antibiotic treatment James is started on 2.25 mg dexamethasone iv every six hours. 4. Explain the rationale for treatment with dexamethasone. As above James is found to have Neiserria meningtidis and is transferred by helicopter to an Intensive Care Unit 24 hours after admission as his rash was spreading and he had become hypotensive, extremely drowsy, and showed signs of respiratory distress. He was thought to have developed meningococcal septicaemia. 5. What treatment would you expect James to receive? Full on Septic shock (especially with hypotension) Support therapies to help: Ionotrophs can be used to increase cardiac output Dopamine: o Increase heart rate o Can be used together with below as infusion Dobutamine: o Increase perfusion to kidneys and liver to be protected o Causes vasoconstriction to increase BP as well IF kidneys failing: o Dialysis may be required to remove wastes Pulomary odema due to SOB Peripherial fluids given can exacerbate it In shock, the proteins leak out and water can now leak into the lungs Supportive oxygen required Sometimes, albumin infusion can be given if much too low Increased drowsiness due to incracranial pressure Furusemide Muscle relaxant to keep them still in ICU and in the chopper Benzodiazepines (lorazepam IV) Thrombocytopenia- give infusion of platelets Blood transfusion if other bloods drop Consider amputations if perfusion to peripheries has been shut down too long Gut can get ischemic as well, if amputation is required, they can get short gut syndrome, they will require TPN (but they will still eat some stuff and absorb it, but needs to be supplemented with PN, so its not technically TPN), so use the gut if you can 6. James has a 6 month old brother (7 kg) and a 10 year old sister (30 kg), recommend suitable prophylactic antibiotics for them. Yes, consider it because it was serious Rifampicin bd for 2 days OR

 Interactions via CYP as well Ciproflocaxin once (theoretical damage to cartilage, only in animal models, so use second line) Be wary of interactions, strong CYP interaction Adults: Same as above (at adult doses obviously) Also required for doctors and other healthcare workers dealing with them 7. Who else should receive prophylaxis and what should they receive? As above James makes a full recovery and is discharged after 1 month in hospital.

Case 3 Claire is an 8 year old asthmatic who is well known to you. She has suffered from asthma since she was a baby and has required numerous hospital admissions for acute asthma attacks. The most recent one was 3 months ago and she spent 3 days in intensive care. When her mother comes to collect Claires regular prescription for budesonide turbuhaler 200 g bd and terbutaline turbuhaler 1 puff when required, she mentions that Claire has been needing to use her reliever at least twice a day. Claires mother is concerned that Claire is going to develop some of the steroid side effects as Claire cannot reduce her dose of inhaled steroids without having an asthma attack. She asks if there are any other treatments available for asthma that can be used in children like Claire. 1. Outline the treatment options for Claires asthma. Include consideration of availability of the treatment in NZ and subsidy arrangements in NZ. Long acting beta 2 agonists can be considered if it isnt controlled (using reliever bd regularly), because shes using highish doses of budesonide Eformeterol or salmeterol o But its only available funded as a LABA + steroid combination product o E.g. salmeterol + fluticasone o Monodose available, but only partially funded only Regular bd Reduces need for steroids and controls night time symptoms Funded for her (see schedule now) o Under 12, not controlled on 200ug budesonide The SABA (terbutyline) Can change to inhaler (e.g. salbutamol) with a spacer, hard to coordinate to use the turbuhaler properly, their breath activation isnt strong enough Check her inhaler techniques (especially for the steroids) to see if can Check to see if they are empty o Shake MDIs, they should have stuff inside them o Especially for turbuhaler, because theres a small window Dont see anticholinergics here, its mainly for COPD as it acts slow and longer Oral steroid short term exacerbations only Theophyliles (use as a bronchodilator) are not advised, use SABAs instead as its got CYP interactions (1A2 and 3A4) along with a narrow therapeutic range Smokers have induced CYP, so they require more (watch out if they are trying to quit, will require dose adjustments) Nausea and vomiting High protein diets increase CYP Leutotrine reaceptor antagonists are the last line Reduce inflammation Good for exercise induced asthma Can be added to therapy if corticosteroids arent working

Hypersensitivity possible Dry mouth Nightmares Not subsidised

Review her meds, poorly controlled because asthma attacks if trying to drop down So add on a LABA and review in a month to 3 months to step down the steroid Give her or check the asthma action plan Turbuhaler vs spacer, because they can prefer one or the other Test to see if she has enough strength to use the turbuhaler Smart regimen (not covered in our course) 2. Briefly describe the side effects associated with steroid inhalers. Oral thrush Hoarseness of the voice Rinse mouth or brush teeth Osteoporosis eventually Alendronate later in life if remaining on oral steroids Adrenal suppression Shorter (growth stunted)- review to drop steroid use if possible Cushing syndrome Keep in dry area, do not keep in moist bathroom (its a powder after all)

Case 4 GR is a 6-month old girl who was diagnosed with gastro-oesophageal reflux causing failure to thrive. She weighs 5.5 kg. Her medical team decides to start her on a course of daily omeprazole. The junior doctor contacts you to help with dose calculation. Later, GRs mother asks you for a suitable dose of paracetamol for GR given her low weight. Failture to thrive occurs if they really cant take their feeds properly, needs intervention Capping dose is 10mg if under 20kg, overwise 1-2mg/kg

1. Recommend a suitable dose and formulation of omeprazole for GR.

Try 5mg daily initial, increase if required Take capsules and mix it into bicarbonate to form a suspension OR since it tastes horrible, just 5mg amount of capsules (uncrushed) mixed into applesauce has been shown to be good 82.5mg for paracetamol, thats 1.65ml of 250/5 suspension

2. What advice are you going to give to GRs mother in regard to the dose and formulation
of paracetamol?

Two years later, GR is diagnosed with epilepsy. She has been suffering from generalised tonicclonic seizures and her medical team decides to start her on carbamazepine. GR now weighs 12 kg.

3. Devise a suitable treatment plan for GR including a suitable dose and formulation.
Suspensions again See NZF for doses Autoinduction means TDM needs to be taken later Unfortunately, GR developed a maculopapular rash two weeks later which was attributed to carbamazepine. The drug had to be discontinued.

4. Devise a suitable alternative treatment plan for GR including a suitable dose and
formulation.

Change to: Valproate (in practice) Levetiracetam can be considered Phenytoin (proper answer, because wanted to try it first because she has no systemic symptoms, also warning: differences between free phenytoin and sodium salt, and also its non-linear, wait till steady state for TDM 7 days) and lamotrigine are in the same class as CBZ, avoid if autoimmune reactions are being seen (fever, liver symptoms etc.)