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pediatrics > 8. Paediatric drug therapy. > Flashcards

8. Paediatric drug therapy. Flashcards

1
Q

aspects of perinatal drug therapy should be focussed on what ?

A

access of the drug to the fetus

pharmacodynamics aspect of drug action during breast feeding

clinical pharmacology in pediatrics

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2
Q

access of drug to the fetus depends on what ?

A

lipid solubility - lipid soluble drugs easily cross over the placenta

ionised drugs do not

molecular size

protein binding

placental and fetal metabolism

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3
Q

placenta excludes drugs of what molecular weight ?

A

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

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4
Q

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

A

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

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5
Q

in the placenta what type of metabolism takes place ?

A

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

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6
Q

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

A

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

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7
Q

what are the teratogenic antibiotics ?

A

ahminoglycosides
tetracylines ,
quinolones
sulfonamides

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8
Q

what are the teratogenic effects of these antibiotics ?

A

ahminoglycosides :deafness , vestibular damage ,

tetracycline : anomalies of teeth and bone

sulphonamides - kernicterus

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9
Q

why is anticholinergics teratogenic

A

cause meconium ileus

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10
Q

why is anticoagulants such as warfarin teratogenic

A

skeletal and cns defects

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11
Q

what are the anticonvulsant drugs which are teratogenic ?

A

carbamazepine - neural tube defects

phenytoin - growth retardation and CNS defects

valproic acid - neural tube defects

trimethadione - CNS and facial defects

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12
Q

what are other teratogenic drugs ?

A

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

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13
Q

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

A

drug affects lactation

drug concentration in breast milk

pharmacodynamics of the drug ingested in breastmilk

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14
Q

what dugs inhibit prolactin

A

bromocriptine , ergotamine , cabergoline , lisuride , metergoline

= estrogen anatgonises prolactin

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15
Q

which drugs inhibit milk ejection and prolactin

A

clonidine

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16
Q

which drugs suppress lactation ?

A

thiazides

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17
Q

drug concentration in breast milk is directly proportional to what ?

A

maternal plasma concentration

milk concentration does not usually exceed the maternal plasma concentration

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18
Q

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

A

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

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19
Q

what servers as a ratio for drug excretion in milk ?

A

milk plasma ratio

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20
Q

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

A

empirically -by observation or experience

rather than logistics

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21
Q

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

A

the mother

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22
Q

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

A

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

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23
Q

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

A

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

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24
Q

what concentration of drug in the childs system should be concerning

A

drugs in systemic circulation of over 10 percent

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25
Q

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

A

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

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26
Q

what is the difference between pharmacokinetics and pharmacodynamics ?

A 
kinetics 
drug dosage 
absorption 
distribution 
plasma conc 
metabolism 
excretion

dynamics
sites of action
clinical effects

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27
Q

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

A

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

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28
Q

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

A

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

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29
Q

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

A

ampicillin

penicillin

30
Q

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

A

acetaminophen
phenobarbitural
phenytoin

31
Q

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

A

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
32
Q

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

A

altered PH

edema of gastrointestinal mucosa

alterations blood flow

presence of ileum

coadminisration of formulas

33
Q

what does drug distribution in children depend on ?

A

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

34
Q

neonates undergo diuresis when

A

beginning 48 hours

35
Q

what affects protein binding in infants

A

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

36
Q

where do drugs undergo metabolism

A

lungs
blood
liver

37
Q

why do the body undergo drug metabolism ?

A

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

38
Q

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

A

phase 1 - CYP450
located in the endoplasmic reticulum of hepatocytes

goes through oxidation and reduction

through hydrolysis
demythlation
methylation
alcohol dehydrogenase

39
Q

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

A

a polar group conjugated to drug so increase in water solubility

glycine (amminoacidi) , glucoroniditaion , acetylation , sulfation , acetyle group , glutathione

40
Q

slower drug metabolism in infants and neonates

A

yes

41
Q

when does Phase 1 reactionsreach maximal maturity?

A

6 months

42
Q

CP450 and conjugating enzymes are reduced in activity in neonates ?

A

yes

43
Q

Glucorunidation reach adult levels in?

A

3rd-4rth year of life

44
Q

Sulfation pathway-reach adult levels ?

A

days after birth

45
Q

Decreased ability of neonates to metabolize drugs result in

A

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

46
Q

Infants more susceptible to drug toxicity vs adults when

A

drug must undergo hepatic elimination

47
Q

what are the different routes of elimination ?

A

pulmonary expired in air

bile = excreted in feces be aware of enterohepatic circulation

renal =
be aware of GFR
tubular reabsorption
tubular secretion

48
Q

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

A

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

49
Q

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

A

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

50
Q

what is steady state ?

A

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

51
Q

which drugs reach steady state quicker ?

A

Drugs with short half-life

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

52
Q

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

A

hepatic metabolism unchanged

same/ increased volume distribution

prolonged elimination

DOSING INTERVALS HAVE TO BE INCEASED

53
Q

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

A

elimination is constant

same or increased volume distribution

slow rate of enzyme metabolism

DECREASE DOSE AND INCREASE THE DOSING INTERVALS

54
Q

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

A

increased metabolism and elimination

larger volume distribution

increase dosage decrease dosage intervals

55
Q

what entails pharmacodynamics ?

A

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

56
Q

what does effective concentration mean

A

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

57
Q

what does lethal dose means ?

A

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

58
Q

what is a therapeutic index ?

A

LD50/ED50

measure the safety of a drug

59
Q

what is margin of safety

A

margin between therapeutic and lethal effect doses of a drug

60
Q

what is pharmacogenetics ?

A

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

61
Q

in clinical practice how will you do a prescription

A

select drug

select the dose

select the formulation

the route of administration

the anticipated length of therapy

62
Q

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

A

drug to drug interaction - that can alter absorption , metabolism , protein binding competition and excretion

drug food interactions - if given nasogastrially

63
Q

what are the special dosage form for infants and children ?

A

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

64
Q

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

A

patient compliance

65
Q

how can we improve patient compliance ?

A

take time to explain the nature of the illness

provide precise instruction for treatments

give specific instructions about osage

66
Q

how can we calculate paediatric dosages ?

A

young’s rule

clarks rule - more precise

BSA

67
Q

what is young’s rule ?

A

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

68
Q

what’s clark’s rule ?

A

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

69
Q

what is BSA ?

A

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

70
Q

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

A

12

pediatrics (19 decks)

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