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NS 2 > Pharmacokinetics and Pharmacodynamics > Flashcards

Pharmacokinetics and Pharmacodynamics Flashcards

1
Q

—— and —— differ physiologically throughout development which influences the ——, —— and —— of medications

A

Children and adults differ physiologically throughout development which influences the pharmacodynamics, pharmacokinetics and ADME of medications

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2
Q 
Therapeutic Good Administration (TGA) Age Class:
Paediatric Subpopulation	Age Range
Preterm newborn	
Infant	
Child	
Adolescent
A 
Therapeutic Good Administration (TGA) Age Class:
Paediatric Subpopulation	Age Range
Preterm newborn	Birth - <28 days 
Infant	28 days - 23 months
Child	2-11 years
Adolescent 	12-17 years
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3
Q 
Age Classifications:
Class	Age
Neonate	
Infant	
Toddler	
Pre-school Child	
School age child 	
Adolescent
A 
Age Classifications:
Class	Age
Neonate	0 - 28 days
Infant	>28 days - 12 months
Toddler	>12 - 23 months 
Pre-school Child	2 - 5 years
School age child 	6 - 11 years
Adolescent 	12 - 18 years
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4
Q

What is Pharmacodynamics?

A

Drug action on target cells (mechanism of action) - drug impacting body

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5
Q

In paediatrics, the mechanism of drug actions (pharmacodynamics) can be affected by … (3)

A

Immature organ systems, body composition and genetic makeup

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6
Q

Changes in Metabolic Capacity (Developmental Changes in Physiologic Factors That Influence Drug Disposition in Infants, children, and Adolescents)

A

The activity of many cytochrome P-450 (CYP450) isoforms and a single glucuronosyltransferase (UGT) isoform is markedly diminished during the first two months of life

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7
Q

Developmental changes in distribution sites (Developmental Changes in Physiologic Factors That Influence Drug Disposition in Infants, children, and Adolescents)

A

Age-dependent changes in body composition influence the apparent volume of distribution for drugs. Infants, in the first six months of life, have markedly expanded total-body water and extracellular water, expressed as a percentage of total body weight, when compared with older infants and adults

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8
Q

Changes in gastrointestinal function (Developmental Changes in Physiologic Factors That Influence Drug Disposition in Infants, children, and Adolescents)

A

Age-dependent changes influence both the structure and function of the gastrointestinal tract. As with hepatic drug-metabolising enzymes the activity of CYP450 1A1 (CYP1A1) in the intestine is low during early life

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9
Q

Acquisition of Renal Function (Developmental Changes in Physiologic Factors That Influence Drug Disposition in Infants, children, and Adolescents)

A

The effect of post-natal development on the processes of active tubular secretion, represented by the clearance of para-aminohippuric acid and the glomerular filtration rate (GFR), approximate adult activity by six to 12 months of age

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10
Q

Integumentary Development (Developmental Changes in Physiologic Factors That Influence Drug Disposition in Infants, children, and Adolescents)

A

Age dependence influences the thickness, extent of perfusion, and extent of hydration of the skin and the relative size of the skin-surface area (reflected by the ratio of body-surface area to body weight). Although skin thickness is similar in infants and adults, the extent of perfusion and hydration diminishes from infancy to adulthood

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11
Q

What is pharmacokinetics?

A

The body’s action on the drug (ADME)

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12
Q

Absorption in paediatric patients (3)

A

• Oral Administrations:
○ Gastric emptying time can be prolonged and irregular (function occurs ~ 6-8 months)
○ Gastric acidity is very low 24 hours after birth and does not reach adult values until 2 years –> absorption of acid-labile drugs is increased
• Intramuscular Administrations:
○ Slow and erratic administration leads to delayed absorption due to low blood flow in first few days of life
○ Rapid absorption during early infancy (> neonates and adults)
• Transdermal Absorption:
○ Problems such as risk of toxicity can occur from topical drugs in infants as the stratum corneum is very thin and blood flow is greater than older patients. This means more rapid absorption

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13
Q

Which age range is intramuscular absorption most rapid ?

A

Early infancy

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14
Q

When does gastric acidity reach adult values ?

A

2 years (Gastric acidity is very low 24 hours after birth causing acid-labile drugs to be increased)

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15
Q

Gastric acidity is very low 24 hours after birth which allows increased absorption of which type of drugs

A

acid-labile drugs

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16
Q

What problems can occur in transdermal absorption in infants ?

A

Problems such as risk of toxicity can occur from topical drugs in infants as the stratum corneum is very thin and blood flow is greater than older patients. This means more rapid absorption

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17
Q

Distribution in paediatric patients (3)

A

• Protein Binding:
○ Drugs can be transported by binding to albumin and other plasma proteins - this is limited in infants (low albumin)
• BBB:
○ Effective means to stop chemicals from reaching the brain however not fully developed at birth and thus have easy access to the CNS
• Endogenous compounds compete with drugs for available binding sites:
○ Limited drug/protein sites in infants = lower dose needed (developed 10-12 months)

18
Q

Metabolism in paediatric patients

A

Hepatic Metabolism: Drug-metabolising capacity of newborns is low = especially sensitive to drugs primarily eliminated via hepatic metabolism (capacity increases after 1 month and liver maturations by 1 year of age)

19
Q

Excretion in paediatric patients (4)

A

(bowel, lungs, skin, renal)
• Renal: Kidney function reduced at birth = low renal blood flow, glomerular filtration and active tubular secretion = reduced dosage needed and/or longer intervals (Adult level of renal function achieved by 1 year of age)

20
Q

What should be considered in regards to dosage of medications for children? (3) Which is the most accurate indicator?

A

ADME should be considered when prescribing and administrating medications to children as adult doses can cause adverse effects
Body Weight
Body Surface Area - more accurate cf to weight

21
Q

Age related changes take place in adults aged ——. ADME of medications is decreased

A

19-64

22
Q

Physiologic changes with normal ageing include: (5)

A
  • Less body water
    • Muscle mass with more fat
    • Hepatic Metabolism slows
    • Decreased renal excretion
    • Decreased responsiveness and sensitivity of the baroreceptor reflex
23
Q

Physiologic Changes Associated with Disease States (specifically for older adults) - (4)

A

Increase in age also increases cardiac related problems, kidney disease, liver disease which affect ADME. Increase age also increases neurological conditions which may lead to decreased compliance

24
Q

Absorption in Older Adults (2)

A

Not significantly affected by normal ageing given the increase in gastrointestinal pH
Slowing of gastric motility/ emptying can lead to adverse effect drug levels

25
Q

Distribution in Older Adults (3)

A

Less volume = decrease the ability for distribution = high concentration of water-soluble drugs in the body
Decrease lean body mass and increase in body fat = increase volume distribution = prolonged action of fat-soluble drugs
Less circulating serum protein = increase concentration of unbound form of drug

26
Q

Metabolism in Older Adults (2)

A

Significantly slowed, particularly those associated with Phase I and CYP450 reactions like oxidation, reduction, dealkylation
Drug-drug interactions risk increases with number of drugs commonly associated with advanced age and deteriorating of bodily functions.

27
Q

Excretion in Older Adults

A

Decrease in bodily functions = decrease kidney mass, nephron size and number, and renal blood flow leads to decreased tubular secretions and GFR = drug metabolites may not be effectively eliminated and accumulate in the body = prolonged therapeutic action and adverse effects

28
Q

Polypharmacy

A

Simultaneous use of multiple drugs (5+) by a single patient for one or more conditions. In practice, polypharmacy is referred to as the use of more medication than is clinically indicated or warranted

29
Q

Why is polypharmacy an issue in older adults?

A

• The elderly typically use multiple drugs because illness is more common in this population.They may take more than one medication to treat conditions effective a number of body systems.
• Problems associated with polypharmacy in older adults include medication doses which are too high or that interact with or duplicate the actions of another medication
Some herbal supplements/remedies and some over-the-counter medications can interact with prescription medication

30
Q

In general, medication use during pregnancy and lactation should be —– due to the —– —– —– which can alter the pharmacokinetics of medications making drug effects —– and potentially ——

A

In general, medication use during pregnancy and lactation should be avoided due to the associated physiologic changes which can alter the pharmacokinetics of medications making drug effects unpredictable and potentially harmful

31
Q

Almost all medicines —— the placenta and reach the —– in measurable concentrations. However, medications do not necessarily need to —— the placenta to affect the —-.

A

Almost all medicines cross the placenta and reach the foetus in measurable concentrations. However, medications do not necessarily need to cross the placenta to affect the foetus.

32
Q

Maternal-placental-foetal circulation is completed in the —- week following conception

A

third

33
Q

When drugs cross into the foetal circulation via placenta, they remain pharmacologically —– and —— = devastating outcomes because of Medications due to (3):

A

When drugs cross into the foetal circulation via placenta, they remain pharmacologically active and unchanged = devastating outcomes because of Medications due to:
○ Metabolised slowly in the foetal liver
○ Distributed to the foetal brain easily
Excretion is slower in foetal kidneys

34
Q

Potential Adverse Effects causes by medications can be (6) - for bby and mum

A

Spontaneous abortions, Intrauterine growth retardation, Prematurity, Stillbirths, Obstetric complications and well as Neonatal and life long side effects

35
Q

Drug effects on the fetus are determined by (4):

A
  1. Type of drugs
    1. Amount of drugs
    2. Duration of exposure
      1. Level of Foetal growth and development when exposed to medications
36
Q

Timing of the exposure is important to the foetus as developmentof organs can be harmed by influx of these chemical compounds. Describe the developmental period of the fetus

A

§ Within the First Trimester (1-12 weeks) major organ systems being formed
§ In the Second Trimester (4-6 months) Cerebellum and urogenital system still forming and medications may effect the ongoing growth and functional development
§ Within the third Trimester (6-9 months) specific effects e.g. nonsteroidal anti-inflammatory drugs (NSAIDs) (pulmonary hypertension) beta-blockers (hypoglycaemia) can occur
In the near-term/During labour adverse effects on labour or on neonate after delivery can happen

37
Q

What is foetal therapeutics ?

A

Some medications are specifically administered to the mother to treat the foetus (e.g. Digoxin (heart failure), Levothyroxine (hypothyroidism), Penicillin (for exposure to maternal syphilis) and Corticosteroids (to decrease respiratory distress syndrome in preterm infants).

38
Q

What is teratogenicity ?

A

(birth defects): occurs during the first trimester of pregnancy with those in the second/third trimester drugs manifest adverse effects in the neonate or infant

39
Q

What is foetotoxicity

A

Toxic effects on a foetus of a substance

40
Q

Australian Categories for Prescribing Medicines in Pregnancy

A

Ref to notes.

NS 2 (16 decks)

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