8. Paediatric drug therapy.

Question 1

aspects of perinatal drug therapy should be focussed on what ?

Answer 1

access of the drug to the fetus

pharmacodynamics aspect of drug action during breast feeding

clinical pharmacology in pediatrics

Question 2

access of drug to the fetus depends on what ?

Answer 2

lipid solubility - lipid soluble drugs easily cross over the placenta

ionised drugs do not

molecular size

protein binding

placental and fetal metabolism

Question 3

placenta excludes drugs of what molecular weight ?

Answer 3

MM250-500 = readily cross the placenta
500-1000 = difficult to cross the placenta
more than a 1000 - excluded

the more the molecular weight the harder the drug to cross the placenta EXCEPT for maternal antibodies

Question 4

how does protein binding of a drug effect the drug given ?

Answer 4

if there is higher protein binding of the drug they will not readily diffuse through the placenta

plasma protein binding is also different in fetal blood there might be more free drugs in the fetal plasma than in the mother

such as sulfonimides , barbiturates , phenytoin

Question 5

in the placenta what type of metabolism takes place ?

Answer 5

placenta goes through aromatic oxidation reaction such as hydroxylation , n dealkylation , demythylation

phenobarbital is oxidied by the place

and 40-50 percent of umbilical venous blood enters the fetal liver

Question 6

what are the pharmacodynamic aspect of the drug action on the fetus ?

Answer 6

maternal drug action - mother may need to take drugs such as pregnancy induced diabetes or heart failure

therapeutic action on fetus - drugs given to stimulate the fetus and well being such as corticosteroids for lung development if preterm
phenobarbitural = induce fetal hepatic enzyme which glucorinide bilirubin

toxic action on fetus = opiates - cause withdraw syndrome
ACE INHIBITORS - renal toxicity

teratogenic action
acts predominantly in a defined stage of fetal life
dose dependancy

Question 7

what are the teratogenic antibiotics ?

Answer 7

ahminoglycosides
tetracylines ,
quinolones
sulfonamides

Question 8

what are the teratogenic effects of these antibiotics ?

Answer 8

ahminoglycosides :deafness , vestibular damage ,

tetracycline : anomalies of teeth and bone

sulphonamides - kernicterus

Question 9

why is anticholinergics teratogenic

Answer 9

cause meconium ileus

Question 10

why is anticoagulants such as warfarin teratogenic

Answer 10

skeletal and cns defects

Question 11

what are the anticonvulsant drugs which are teratogenic ?

Answer 11

carbamazepine - neural tube defects

phenytoin - growth retardation and CNS defects

valproic acid - neural tube defects

trimethadione - CNS and facial defects

Question 12

what are other teratogenic drugs ?

Answer 12

antidepressant - lithium - Epstein anomaly ( heart defect of the tricuspid valve)
hypotonia

ACE inhibitors - renal failure and decreased ossification

antithyroid - PTU - goiter , hypothyroidism

diuretics - furosemide - hyperbilirubinemia

thiazides - neonatal thrombocytopenia

Question 13

what are the things to consider of drugs on lactating mother ?

Answer 13

drug affects lactation

drug concentration in breast milk

pharmacodynamics of the drug ingested in breastmilk

Question 14

what dugs inhibit prolactin

Answer 14

bromocriptine , ergotamine , cabergoline , lisuride , metergoline

= estrogen anatgonises prolactin

Question 15

which drugs inhibit milk ejection and prolactin

Answer 15

clonidine

Question 16

which drugs suppress lactation ?

Answer 16

thiazides

Question 17

drug concentration in breast milk is directly proportional to what ?

Answer 17

maternal plasma concentration

milk concentration does not usually exceed the maternal plasma concentration

Question 18

what is the characteristic of drug which pass into the breast milk

Answer 18

through PASSIVE DIFFUSION - human milk is acidc , and drugs that pass into it are weak bases , water soluble , lipid soluble and poorly bound to proteins

Question 19

what servers as a ratio for drug excretion in milk ?

Answer 19

milk plasma ratio

Question 20

drug concentration in breast milk is difficult to predict and measured how ?

Answer 20

empirically -by observation or experience

rather than logistics

Question 21

drug affects on breast feeding mother is greater on whom the infant or the mother ?

Answer 21

the mother

Question 22

how can the amount of drug the baby ingest be reduced ?

Answer 22

feeding the infant just before or at the time of administration

this is because even if the M:P ratio was 1:0 the amount of drug ingested is not sufficient to attain therapeutic concentration

Question 23

even when M:P ratio is 1:0 why is not concerting

Answer 23

the amount of drug ingested is not sufficient to attain therapeutic concentration

Question 24

what concentration of drug in the childs system should be concerning

Answer 24

drugs in systemic circulation of over 10 percent

Question 25

what are some examples of breast milk drug ingested drugs adverse effects

Answer 25

tetracycline - permanent tooth staining in infants diazepam - sedation in infants cancer chemotherapy - immunosuprssion and neutropenia lithium - same conc of great milk as in plasma - tremor and involuntary movements amiodarone - thyroid disturbance because of high iodine content ASA - reye syndrome NSAID - premature closure of ductus arteriosusu chloramphenicol - grey baby syndrome = circulatory collapse sulphonamides - jaundice - competition of bilirubin binding to albumin quinines - cartilage development defect tinidazole - carcinogen and mutagen phenolphthalein contains laxatives - carcinogen cemtidine h2 antagonist - gastric acidity and inhibition of cp450

Question 26

what is the difference between pharmacokinetics and pharmacodynamics ?

Answer 26

``` kinetics drug dosage absorption distribution plasma conc metabolism excretion ``` dynamics sites of action clinical effects

Question 27

what are the things to consider in drug absorption in IM injection

Answer 27

blood supply and flow - exercise enhances absorption muscle mass - obese , malnourished muscle is more acidic than blood phenytoin is converted into acid in IM injection the sodium also precipitates at site of injection = flower absorption

Question 28

what are the things to consider with drug absorption from the GIT

Answer 28

gastric acidity slowly rises in premature infants gastric emptying is prolonged = increase absorption peristalsis is slower in neonates = increase absorption diarrhea = effects is exaggerated in neonates and drug action interference bacterial flora slowly rises

Question 29

what drugs with oral drug absorption in neonates is greater than that of a child

Answer 29

ampicillin | penicillin

Question 30

what are the drugs when oral drug absorption has lower in neonates that of a child

Answer 30

acetaminophen phenobarbitural phenytoin

Question 31

when is rectal administration of drugs used ? and which drugs does rectal Administration is most successful ?

Answer 31

in nausea , vomitting , status epileptics , induction of anaesthesia and for administration of drug that has large first pass metabolism ``` diazepam well absorbed rectally barbiturates midazolam lorazepam atropine - anticholinergic ```

Question 32

drugs given orally and nasogastrically may have altered absorption due to ?

Answer 32

altered PH edema of gastrointestinal mucosa alterations blood flow presence of ileum coadminisration of formulas

Question 33

what does drug distribution in children depend on ?

Answer 33

membrane permeability plasma protein binding bound drugs do not cross membrane malnourishes - decrease albumin and increased drug in plasma lipophilic profile lipophilic drugs readily cross the membrane nmore than unionised lipophilic drugs accumulate in adipose tissue volume distribution 24wks preterm infant - TBW = 86 percent (ecf= 60 percent , icf=35 percent) ``` term = 75 percent (ecf= 40 recent , icf = 35 percent) ``` neonates have larger plasma volume at around 3 months the switch comes 1 year = 60 percent (ecf=25 and icf 35) adult = 50-60 percent (icf=40, ecf= 20) ECF determines drug conc body fat has higher body weight percentage that extracellular fluid in 9months to 1 year old and stay equal till 10 years old until ECF takes over and body fat drops birth = 12 percent 6 months = 25 percent 1 year = 30 percent 5-6 years = 12 percent adult = 10 percent affecting distribution of lipid soluble drugs

Question 34

neonates undergo diuresis when

Answer 34

beginning 48 hours

Question 35

what affects protein binding in infants

Answer 35

conc of free ffatty acids and indirect bilirubin and albumin levels FFa and havs a high affinity for albumin result in competition and displacemnt of drugs = exp sufonamides and phenytoin change of affinity for albumin at different stages of maturation - acidic drugs high affinity to serum albumin over the frst few weeks of life

Question 36

where do drugs undergo metabolism

Answer 36

lungs blood liver

Question 37

why do the body undergo drug metabolism ?

Answer 37

to make the more water soluble so they can be excreted out however it can also transform drugs into an active compound a prodrug into an active drug

Question 38

drugs undergo two phases of metabolism what is part of PHASE1 ?

Answer 38

phase 1 - CYP450 located in the endoplasmic reticulum of hepatocytes goes through oxidation and reduction through hydrolysis demythlation methylation alcohol dehydrogenase

Question 39

drugs undergo two phases of metabolism what is part of PHASE 2 ?

Answer 39

a polar group conjugated to drug so increase in water solubility glycine (amminoacidi) , glucoroniditaion , acetylation , sulfation , acetyle group , glutathione

Question 40

slower drug metabolism in infants and neonates

Answer 40

yes

Question 41

when does Phase 1 reactionsreach maximal maturity?

Answer 41

6 months

Question 42

CP450 and conjugating enzymes are reduced in activity in neonates ?

Answer 42

yes

Question 43

Glucorunidation reach adult levels in?

Answer 43

3rd-4rth year of life

Question 44

Sulfation pathway-reach adult levels ?

Answer 44

days after birth

Question 45

Decreased ability of neonates to metabolize drugs result in

Answer 45

in prolonged elimination half lives leading to ADR or toxicity from overdose

Question 46

Infants more susceptible to drug toxicity vs adults when

Answer 46

drug must undergo hepatic elimination

Question 47

what are the different routes of elimination ?

Answer 47

pulmonary expired in air bile = excreted in feces be aware of enterohepatic circulation renal = be aware of GFR tubular reabsorption tubular secretion

Question 48

how does GFR increase after birth and when does it reach adult values ?

Answer 48

Week 1 GFR -30%-40% of adult values (even lower in prematures) Week 3 - 50-60% of adult values By 6-12 months -reaches adult values

Question 49

tubular secretion in neonates is how much lower compared to adults and when does it reach maturity ?

Answer 49

25-50% lower in newborn reaching adult levels at age 1- 3 years

Question 50

what is steady state ?

Answer 50

he amount of drug administered is equal to the amount of drug eliminated within one dosing interval resulting in a plateau or constant serum drug level

Question 51

which drugs reach steady state quicker ?

Answer 51

Drugs with short half-life drugs with long half-life take days to weeks to reach steady state

Question 52

when a CHILD has renal disease what can be done different to drug administration ?

Answer 52

hepatic metabolism unchanged same/ increased volume distribution prolonged elimination DOSING INTERVALS HAVE TO BE INCEASED

Question 53

when a CHILD has hepatic disease what can be done different to drug administration ?

Answer 53

elimination is constant same or increased volume distribution slow rate of enzyme metabolism DECREASE DOSE AND INCREASE THE DOSING INTERVALS

Question 54

when a child has cystic fibrosis what can be done to drug administration

Answer 54

increased metabolism and elimination larger volume distribution increase dosage decrease dosage intervals

Question 55

what entails pharmacodynamics ?

Answer 55

mechanism of drug action efficacy = degree drug can produce desired response potency = amount of drug needed to produce 50 percent of its maximal effect safety profile what does the drug do in a cellular level and general

Question 56

what does effective concentration mean

Answer 56

ED 50 = con of drug that induces a specific therapeutic response in 50 percent of the subjects

Question 57

what does lethal dose means ?

Answer 57

LD50 = conc of drug which bring death to 50 percent of subjects

Question 58

what is a therapeutic index ?

Answer 58

LD50/ED50 measure the safety of a drug

Question 59

what is margin of safety

Answer 59

margin between therapeutic and lethal effect doses of a drug

Question 60

what is pharmacogenetics ?

Answer 60

science of assessing genetical y determined variation in population and its effect on pharmacodynamics and pharmacokinetics

Question 61

in clinical practice how will you do a prescription

Answer 61

select drug select the dose select the formulation the route of administration the anticipated length of therapy

Question 62

what are other factors that needs to be looked at when prescribing drugs

Answer 62

drug to drug interaction - that can alter absorption , metabolism , protein binding competition and excretion drug food interactions - if given nasogastrially

Question 63

what are the special dosage form for infants and children ?

Answer 63

elixir = alcoholic solution where drug is dissolved no shaking is needed suspension - undissolved particles - MUST shake first dose will contain less drug than last dose chewable tablets

Question 64

when working with children and drugs what should we look out for

Answer 64

patient compliance

Question 65

how can we improve patient compliance ?

Answer 65

take time to explain the nature of the illness provide precise instruction for treatments give specific instructions about osage

Question 66

how can we calculate paediatric dosages ?

Answer 66

young's rule clarks rule - more precise BSA

Question 67

what is young's rule ?

Answer 67

adult dose x { (age in yrs)/ (age +12) } = child's dose

Question 68

what's clark's rule ?

Answer 68

child's dose = adult's dose x { weight kg / 70 }

Question 69

what is BSA ?

Answer 69

(neonate BSA / adult BSA ) x 100 = % adult dose needed

Question 70

labelling info of manufacturers do not contain dose information for people less than ?

Answer 70

12