Special Populations Flashcards

1
Q

Who is considered special populations?

A

Children, elderly, pregnant and breastfeeding, obese, dialysis, ECMO, cooling

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2
Q

What does scaling adult doses to infants based on body weight or surface area not account for?

A

Developmental changes that affect drug disposition and tissue/organ sensitivity
By basing only or weight or surface area can result in ineffective treatment or toxicity

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3
Q

What makes drug research in children so difficult?

A

Different ethics, population, parents, formulations, groups and outcome measures
Smaller blood volume, fewer draws

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4
Q

Why are most drugs prescribed to pediatrics off-label?

A

There is a lack of appropriate safety and efficacy date and shortage of child-friendly formulations (oral solid multiparticulate formulations in development)

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5
Q

What may drug clearance increase with?

A

Weight, height, age, body surface area and creatinine clearance

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6
Q

How does gastric pH change throughout life?

A

At birth, gastric pH is 6-8 but it rapidly falls within 3-5 hours to adult values (pH 1-5)

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7
Q

How do gastric secretions change with age?

A

HCl production increases with age.
Gastrin production decreases with age.
Volume increases
Approach adult values by age 2

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8
Q

How does gastric emptying time change with age?

A

In the neonatal period, gastric emptying rate is variable and unpredictable, partially dependent on type of formula.
Approaches adult values within 6 to 8 months

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9
Q

How does splanchnic blood flow change with age?

A

Changes in the first 2-3 weeks of life may influence absorption rates by altering the concentration gradient across the intestinal mucosa

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10
Q

How does biliary function change with age?

A

The rate of synthesis, pool size and intestinal transport of bile acids are reduced in neonates
Lipase activity is present by 34-36 weeks of gestation and increases rapidly up to 9 months old.

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11
Q

What is involved in intestinal drug metabolism?

A

Efflux transporter P-glycoprotein (multidrug resistance protein-1)

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12
Q

How does barrier thickness affect drug absorption?

A

Skin layer is thinner in newborns, so topical application can be quicker

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13
Q

How does skin hydration change throughout life?

A

Hydration will lead to better absorption. Better in newborns.

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14
Q

How does diffusional surface area differ in newborns?

A

Surface area to weight is much higher, giving quicker absorption

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15
Q

How does regional blood flow differ in newborns?

A

The muscle mass to body mass ratio is lower with reduced skeletal muscle blood flow and inefficient muscular contractions reduce drug dispersion and absorption
May be offset by high density of skeletal muscle capillaries

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16
Q

How does metabolism change with age?

A

Metabolic routes mature at different rates

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17
Q

How do DME vary with age?

A

CYP 2C9 is very very low as a neonate then increase at birth.
SULT 1E1 decreases at birth and with age.

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18
Q

How does degree of protein binding differ in newborns?

A

A reduction in total quantity of plasma proteins, increasing free drug and drug availability
Higher concentrations of free fatty acids and unconjugated bilirubin compete for binding to the protein, leaving more free drug.

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19
Q

What happens when drugs compete with and displace bilirubin from albumin?

A

Ampicillin, Diazepam, Phenytoin, Sulfonamides can increase a neonate’s risk for developing kernicterus

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20
Q

How can hyperbilirubinemia affect drug protein binding?

A

Can reduce the protein binding of ampicillin, penicillin and phenobarbital

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21
Q

How does body composition differ in newborns?

A

The amount of water in the body is higher than in adults, thus hydrophilic drugs have a higher volume of distribution and lipophilic have a lower
Skin and brain, mostly everything else are a much higher percentage of body weight

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22
Q

How does the permeability of cell membranes differ in newborns?

A

The blood brain barrier is much less efficient, leading to more CNS side effects but also to better permeability

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23
Q

How does receptor ontogeny work?

A

Expression tends to follow a general maturation pattern from birth to adult levels but the time course varies widely
Abundance does not often equate directly to pharmacological response

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24
Q

How does transporter ontogeny work?

A

Expression pattern follows a general maturation pattern

Alterations in expression are more readily translated into clearance

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25
Q

What are some drugs that are excreted into breast milk?

A

Ranitidine, Nadolol, Sotalol, Atenolol, Metoprolol, Morphine

26
Q

How should drugs in breastfeeding be treated?

A

Understand the mechanisms of drug absorption, just because there aren’t studies doesn’t mean it isn’t safe. Don’t want to miss necessary treatments, always check the latest literature

27
Q

Where can information about drugs in pregnancy and lactation be found?

A

Briggs textbook, Teratology service, SickKids Motherisk service, Medical Genetics

28
Q

Which drugs are usually safe in breastfeeding?

A

The drugs are commonly prescribed for infants (amount through milk is much less than normally), considered safe in pregnancy, not absorbed from stomach or intestines or are not excreted into the milk

29
Q

How does aging affect absorption?

A

The rate of absorption may be delayed with a lower peak concentration and delayed time to peak concentration
Overall bioavailability absorbed is unchanged

30
Q

How does aging affects first pass metabolism?

A

The bioavailability of drugs with extensive first-pass metabolism may increase because less drug is extracted by the liver due to decreased liver mass and blood flow

31
Q

What factors affect absorption?

A

Route of administration, what is taken with the drug, comorbid conditions, increased GI pH, decreased gastric emptying, dysphagia

32
Q

What things taken with a drug can affect its aborption?

A

Divalent cations (Ca, Mg, Fe), food, enteral feedings, drugs that influence gastric pH and drugs that promote or delay gastric motility

33
Q

How is body water changed with aging? What is it’s effect on volume of distribution?

A

Decreased body water. Decreased volume of distribution for hydrophilic drugs
Ethanol, lithium

34
Q

How is lean body mass changed with aging? What is it’s effect on volume of distribution?

A

Decreased lean body mass.
Decreased volume of distribution for drugs that bind to muscle
DIgoxin

35
Q

How are fat stores changed with aging? What is it’s effect on volume of distribution?

A

Increased fat stores.
Increased volume of distribution for lipophilic drugs
Diazepam, trazodone

36
Q

How is albumin changed with aging? What is it’s effect on volume of distribution?

A

Decreased albumin
Increased fraction of unbound or free drug that is active
Dizaepam, valproic acid, phenytoin, warfarin

37
Q

How is alpha-1 acid glycoprotein changed with aging? What is it’s effect on volume of distribution?

A

Increased alpha-1 acid glycoprotein
Decreased fraction of unbound drug
Quinidine, propranolol, erythromycin, amitriptyline

38
Q

How does aging affect hepatic metabolism?

A

Metabolic clearance of drugs by the liver may be reduced due to decreased hepatic blood flow, decreased liver size and mass

39
Q

What are some examples of drugs metabolized by the liver?

A

Morphine, meperidine, metopolol, propranolol, verapamil, amitryptyline, nortriptyline

40
Q

What are some examples of phase I metabolism?

A

Oxidation, hydroxylation, dealkylation, reduction

Diazepam, quinidine, piroxicam, theophylline

41
Q

What is the effect of phase I metabolism?

A

Conversion to metabolites of lesser, equal or greater activity

42
Q

What are some examples of phase II metabolism?

A

Glucuronidation, conjugation, acetylation

Lorazepam, oxazepam, temazepam

43
Q

What is the effect of phase II metabolism?

A

Conversion to inactive metabolites

Generally preferred in elderly to avoid accumulation

44
Q

What are some other factors affecting drug metabolism?

A

Gender, comorbid conditions, smoking, diet, drug interaction, race and frailty

45
Q

What are the effects of aging on the kidney?

A

Decreased kidney size, renal blood flow, number of functional nephrons, tubular secretion
Resulting in decreased glomerular filtration rate (GFR)

46
Q

Which drugs have decreased renal clearance in the elderly?

A

Atenolol, gabapentin, H2 blockers, digoxin, allopurinol, quinolones

47
Q

How is GFR estimated usually?

A

Creatinine clearance (CrCl) is usually used

48
Q

How is GFR estimated in the elderly?

A

Serum creatinine clearance alone is not accurate in the elderly due to decreased lean body mass (less creatinine production) and decreased GFR
Need to have 24 hour urine collection or estimate with cockroft gault equation

49
Q

What are some age related changes in pharmacodynamics?

A

Increased sensitivity to sedation and psychomotor impairment with benzodiazepines
Increased level and duration of pain relief with narcotic agents
Increased drowsiness and lateral sway with alcohol
Decreased heart rate response to beta-blockers
Increased sensitivity to anti-cholinergic agents
Increased cardiac sensitivity to digoxin

50
Q

How can we change drug dosing in the elderly?

A

Use lower doses, longer intervals and slower titration

Careful monitoring

51
Q

What are the consequences of overprescribing?

A

Adverse drug events (falls), drug interactions, duplication of drug therapy, decreased quality of life, unnecessary cost, medication nonadherence

52
Q

What are the most common medication associated with adverse drug events (ADEs) in the elderly?

A

Opioids, NSAIDs, Anticholinergics, Benzodiazepines, cardiovascular agents, CNS agents, musculoskeletal agents

53
Q

What is the Beers Criteria?

A

A listing of drugs that are categorized by their potential for adverse drug effects

54
Q

What are some patient risk factors for adverse drug events?

A

Polypharmacy, multiple comorbid conditions, prior adverse drug event, low body weight or BMI, >85 years old, estimated CrCl

55
Q

What is the prescribing cascade?

A

Drugs keep getting prescribed to counteract the adverse effects of another drug

56
Q

Which drugs are the most common to have drug interactions?

A

Cardiovascular drugs, psychotropic drugs

57
Q

What are the most common effects of drug interactions?

A

Confusion, cognitive impairment, hypotension, acute renal failure

58
Q

What are the concepts of drug-drug interactions?

A

Absorption may be increased or decreased
Drugs with similar effects can have additive effects
Drugs with opposite effects can antagonize
Metabolism can be inhibited or induced

59
Q

What are some principles for prescribing for the elderly?

A

Avoid prescribing prior to diagnosis, start low go slow, avoid starting 2 agents at the same, reach therapeutic dose before switching or adding agents, consider non-pharms

60
Q

How can we prevent polypharmacy?

A

Review medications regularly and each time a new medication is started or dose is changed
Maintain full and accurate medication records
Brown bag: Make drug taking as simple as possible (adherence)

61
Q

What are some factors in non-adherence?

A

Financial, cognitive or functional status

Beliefs and understanding about disease and medications