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Pharmacology B > Lecture 12 - Pediatrics & Elderly > Flashcards

Lecture 12 - Pediatrics & Elderly Flashcards

1
Q

List some special populations

A
  • Infants and children
  • Elderly people
  • Pregnant & breastfeeding women
  • Obese/underfed
  • Patients with clinical issues:
    • Liver failure
    • Kidney failure and dialysis
    • Extracorporate membrane oxygenation (ECMO)
    • Therapeutic cooling
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2
Q

Why are these populations special?

A
  • Different PK/PD
  • Use different drugs
  • High potential of damaging self or other (pregnant/breastfeeding)
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3
Q

Why teach us about special populations?

A
  • Higher risks of adverse drug events
  • Higher risk of ineffective therapy
  • More complicated prescribing and dispensing
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4
Q

Describe the paradox of modern drug development

A

1) Clinical trials provide evidence of efficacy and safety at usual doses in NORMAL populations
2) Physicians treat individual patients who can vary widely in their response to drug therapy (no response, efficacious and safe, adverse drug reaction)

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5
Q

Drug prescriptions in pediatrics are often drugs used ____-______

A

off-label

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6
Q

Why is pediatric prescribing much more complicated than prescribing for adults?

A
  • the specific and general aspects of paediatric patients (size, immaturity)
  • the limitations of commercially available dosage formulations
  • the challenges of administering drugs
  • the dearth of information about drug use in children
  • the general inadequacy of clinical pharmacology training
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7
Q

For the reasons we just discussed about pediatric prescribing being more complicated than adult, how should practitioners handle pediatric prescribing?

A
  • prescribe judiciously
  • select carefully the safest dosage regimen available
  • educate their patients, caregivers and staff about their choices and expected positive and negative effects
  • have available and use written, electronic, as well as human sources of expert advice
  • document their therapeutic decisions and plans
  • carefully monitor their patients’ responses to therapy
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8
Q

Prescriptions may be off-label when given for a different: ??

A
  • age group
  • dosage
  • indication
  • dosage form
  • route of administration
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9
Q

___% of drugs prescribed in paediatrics are off-label

A

30-80

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10
Q

List some novel drug devices for drug administration to children

A
  • Modified teat/pacifier with drug-loaded reservoir
  • Dosing spoon filled with liquid medicine
  • Coated particles on dosage spoon (pulp-spoon)
  • Dropper tube
  • Dose-sipping technology (straw with medicine and beverage)
  • Solid dosing pen
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11
Q

List the divisions of childhood

A
  • Infancy
  • Toddler
  • Pre-School
  • School age
  • Adolescent
    • Early
    • Middle
    • Late
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12
Q

____ ______ may increase with weight, height, age, BSA and CLcr (creatinine clearance)

A

drug clearance

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13
Q

Ontogeny

A

the branch of biology that deals with the development of an individual organism or anatomical or behavioral feature from the earliest stage to maturity

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14
Q

What is involved in pharmacokinetics?

A

Absorption
Distribution
Metabolism
Excretion

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15
Q

Gastric pH is ____ in infants

A

lower

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16
Q

Infants have an _____ absorption of drugs degraded by acid (ex. penicillin)

A

increased

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17
Q

Biliary function is _____ in infants

A

reduced

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18
Q

Infants have a _______ absorption of some drugs such as Pleconaril

A

decreased

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19
Q

Infants have _____ gastric emptying which will cause an increased half-life of some drugs (ex. cisapride)

A

decreased

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20
Q

Infants have altered GI tract absorption of some drugs: ______ very poorly absorbed by infants

A

Phenytoin

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21
Q

Infants have ____ GI motility which can cause potentially greater absorption (ex. ahminoglycosides)

A

lower

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22
Q

Infants have a marked _______ in gut wall activity of Phase 1 and Phase 2 enzymes

A

reduction

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23
Q

Infants have ___ transporter function which can lead to reduced absorption

A

reduced

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24
Q

What factors influence extra oral drug absorption?

A
  • barrier thickness
  • regional blood flow
  • diffusional surface area
  • hydration
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25
Q

Distribution of drug through VoD effected by ??

A
  • Water-fat ratio
  • Plasma protein binding
  • Acid-base balance
  • Regional blood flow
  • Cardiac output
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26
Q

Do infants have more or less water than adults?

A

Infants have much more water (80%) than adults (60%)

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27
Q

Infants therefore have an ______ VD for water-soluble agents

A

increased

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28
Q

The BBB of infants is ___ functional

A

less

*this allows possibility for drug molecules that normally cannot access the brain to cross the BBB

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29
Q

Plasma protein binding is ____ efficient in infants

A

less

*this causes an increased clearance of highly bound drugs

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30
Q

Metabolic routes ____ at different rates

A

mature

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31
Q

____% of mothers initiate breastfeeding

A

80

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32
Q

___% of mothers take drugs

A

80

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33
Q

What is the MP ratio?

A

Milk-to-plasma ratio

34
Q

pH of milk?

A

7.0

35
Q

pH of maternal plasma?

A

7.4

36
Q

Most drugs are safe if:

??

A
  • They are commonly prescribed for infants
  • They are considered safe in pregnancy
  • They are not absorbed from the stomach or intestines
  • They are not excreted into the milk
37
Q

List some challenges of geriatric pharmacotherapy

A
  • New drugs available each year
  • HC approved and off-label indications are expanding
  • Changing managed-care formularies
  • Advanced understanding of drug-drug interactions
  • Increasing popularity of nutraceuticals
  • Multiple co-morbid states
  • Poly pharmacy
  • Medication compliance
  • Effects of aging physiology of drug therapy
  • Medication cost
38
Q

Elderly:

Rate of absorption may be ___

A

delayed

  • lower peak concentration
  • delayed time to peak concentration
39
Q

Elderly:

Overall amount absorbed (bioavailability) is _____

A

unchanged

40
Q

Elderly:
For drugs with extensive first-pass metabolism, bioavailability may _____ because less drug is extracted by the liver:
-Decreased liver mass
-Decreased liver blood flow

A

increase

41
Q

List some factors that affect absorption

A
  • Route of administration
  • What is taken with the drug
    • Divalent cations (Ca, Mg, Fe)
    • Food, enteral feedings
    • Drugs that influence gastric pH
    • Drugs that promote or delay GI motility
  • Comorbid conditions
  • Increased GI pH
  • Decreased gastric emptying
  • Dysphagia
42
Q

Elderly:

Have decreased body water which means decreased Vd for ______ drugs

A

hydrophilic

43
Q

Elderly:

Have decreased lead body mass so they have decreased Vd for drugs that bind to ____

A

muscle

44
Q

Elderly:

Increased fat stores which means _____ Vd for lipophilic drugs

A

increased

45
Q

Elderly:

Have _____ plasma protein (albumin) which means there is an increased percentage of unbound or free drug (active)

A

decreased

46
Q

Elderly:

Metabolic clearance of drugs by the liver may be reduced due to

A
  • decreased hepatic blood flow
  • decreased liver size and mass

Examples:

  • morphine
  • meperidine
  • metoprolol
  • propranolol
  • verapamil
  • amitryptyline
  • nortriptyline
47
Q

Phase 1 metabolism pathways

A

oxidation
hydroxylation
dealkylation
reduction

48
Q

Phase 2 metabolism pathways

A

glucuronidation
conjugation
acetylation

49
Q

Effect of phase 1 metabolic pathways

A

conversion to metabolites of lesser, equal or greater

50
Q

Effect of phase 2 metabolic pathways

A

conversion to inactive metabolites

51
Q

Medications undergoing Phase ___ hepatic metabolism are generally preferred in the elderly due to inactive metabolites (no accumulation)

A

2

52
Q

Other factors affecting drug metabolism?

A 
Gender
Comorbid conditions
Smoking
Diet
Drug interactions
Race
Frailty
53
Q

List some effects of aging on the kidney

A

-decreased kidney size
-decreased renal blood flow
-decreased number of functional nephrons
-decreased tubular secretion
Results in: decreased glomerular filtrate rate (GFR)

54
Q

Elderly:

Aged kidneys results in decreased drug clearance of which drugs?

A
  • atenolol
  • gabapentin
  • H2 blockers
  • digoxin
  • allopurinol
  • quinolones
55
Q

Elderly:

_____ ______ is used to estimate glomerular rate

A

creatinine clearance (CrCl)

56
Q

Elderly:

Serum creatinine alone not accurate in the elderly due to ???

A
  • lower lean body mass
  • lower creatinine production
  • lower glomerular filtration rate
57
Q

Elderly:

Serum creatinine stays in _____ range, masking change in creatinine clearance

A

normal

58
Q

Measuring Creatinine clearance is ??

A
  • time consuming

- requires 24 hr urine collect

59
Q

How do we estimate Creatinine clearance?

A

Cockroft Gault Equation:

(IBW in kg) x (140-age) / 72 x (Scr in mg/dL)

x 0.85 for females

60
Q

Pharmacodynamics

A

the time course and intensity of pharmacologic effect of a drug

61
Q

Age-related changes in pharmacodynamics:

Increased sensitivity to sedation and psychomotor impairment with ________

A

benzodiazepines

62
Q

Age-related changes in pharmacodynamics:

Increased level and duration of pain relief with _____ _____

A

narcotic agents

63
Q

Age-related changes in pharmacodynamics:

Increased drowsiness and lateral sway with _____

A

alcohol

64
Q

Age-related changes in pharmacodynamics:

Decreased HR response to ____ ______

A

beta blockers

65
Q

Age-related changes in pharmacodynamics:

Increased sensitivity to _______ _____

A

anticholinergic agents

66
Q

Age-related changes in pharmacodynamics:

Increased cardiac sensitivity to _______

A

digoxin

67
Q

PK and PD changes generally result in ______ clearance and ______ sensitive to medications in older adults

A

decreased clearance

increased sensitivity

68
Q

Elderly:

How do we decrease the risk of drug intolerance and toxicity?

A

use of lower doses, longer intervals, slower titration

careful monitoring is necessary to ensure successful outcomes

69
Q

What are some consequences of overprescribing?

A
  • Adverse drug events
  • Drug interactions
  • Duplication of drug therapy
  • Decreased quality of life
  • Unnecessary cost
  • Medication non-adherence
70
Q

List some most common medications associated with ADEs in the elderly

A
  • opioid analgesics
  • NSAIDs
  • anticholinergics
  • benzodiazepines
  • CV agents
  • CNS agents
  • musculoskeletal agents
71
Q

Patient risk factors for ADEs

A
  • polypharmacy
  • multiple co-morbid conditions
  • prior adverse drug event
  • low body weight or body mass index
  • age >85
  • estimated CrCl < 50 mL/min
72
Q

Most common DDIs?

A
  • CV drugs

- psychotropic drugs

73
Q

Most common drug interaction effects?

A
  • confusion
  • cognitive impairment
  • hypotension
  • acute renal failure
74
Q

Concepts in Drug-Drug Interactions?

A
  • Absorption may be increased or decreased
  • Drugs with similar effects can result additive effects
  • Drugs with opposite effects can antagonize each other
  • Drug metabolism may be inhibited or induced
75
Q

_____ alters Vd of lipophilic drugs

A

obesity

76
Q

______ alters Vd of hydrophilic drugs

A

ascites

77
Q

____ may increase sensitivity, induce paradoxical reactions to drugs with CNS or anticholinergic activity

A

dementia

78
Q

____ or _____ impairment may impair metabolism and excretions of drugs

A

renal or hepatic

79
Q

drugs may exacerbate a _____ ______

A

medical condition

80
Q

Principles of prescribing in the elderly

A
  • avoid prescribing prior to diagnosis
  • start with a low dose and titrate slowsly
  • avoid starting 2 agents at the same time
  • reach therapeutic dose before switching or adding agents
  • consider non-pharmacologic agents
81
Q

Elderly:

Factors in non-adherence?

A

Financial, cognitive or functional status

Beliefs and understanding about disease and medications

Pharmacology B (21 decks)

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