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Geri PK Flashcards

1
Q

What makes geriatrics a special population? (5)

A
  1. Health
  2. Changing demographics
  3. Epidemiology of drug use in the older adult
  4. Drug effects
  5. Available PK/PD information
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2
Q

What makes geriatrics a special patient population in terms of health? (4)

A
  1. Heterogenous population
  2. The aging process is unpredictable
  3. Multiple simultaneous disease states
  4. Chronic illness
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3
Q

What changing demographics make geriatrics special? (2)

A
  1. Population composition
  2. Institutionalization
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4
Q

How does epidemiology of drug use in the older adult make them special? (2)

A
  1. Polypharmacy
  2. Underuse of potentially beneficial therapy
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5
Q

How are drug effects special in geriatrics? (2)

A
  1. Drug related problems and adverse drug effects
    - 3 to 10-fold greater ADRs in older adults vs. younger
  2. Drug-drug and drug-disease interactions
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6
Q

What is special about geriatric ‘available PK/PD information’? (3)

A
  1. Evidence base for prescribing in older adults is limited
  2. Clinical studies not representative of older adult population
  3. Exclusion criteria (explicit and implicit)
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7
Q

Physiological changes with aging influences PK and PD. How so? (4)

A
  1. Age-related changes in organ function will alter drug PK and PD resulting in alterations in pharmacological response
  2. Physiological aging does not necessarily correspond to
    chronological aging.
  3. Age-related changes in-of-themselves are often not sufficient to compromise normal function. However, with underlying pathological conditions (e.g. HF, decreased renal function), such age-related changes may have significant consequences on PK/PD.
  4. Environment, genetics, and physiological and pathological factors additionally influence apparent age-related differences in ADME.
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8
Q

How do the following change with aging?
1. Total body water
2. Intracellular fluid volume
3. Lean body mass
4. Body fat

A
  1. Decrease
  2. Decrease
  3. Decrease
  4. Increase
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9
Q

How do the following change with aging?
1. Serum albumin
2. Serum alpha1-acid glycoprotein (AAG)

A
  1. No change or decrease (and possibly decreased affinity for binding)
  2. No change or increase (maybe 2° to underlying inflammatory disease)
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10
Q

How do the following change with aging?
1. Myocardial sensitivity to beta-adrenergic stimulation
2. Baroreceptor activity

A
  1. Decrease
  2. Decrease
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11
Q

How do the following change with aging?
1. Cardiac output
2. Resting heart rate
3. Systemic vascular resistance
4. Systolic blood pressure

A
  1. Decrease
  2. Decrease
  3. Increase
  4. Increase
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12
Q

How does the following change with aging?
1. Weight and volume of brain
2. Cerebral blood flow
3. Permeability of BBB

A
  1. Decrease
  2. Decrease
  3. Increase
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13
Q

How do the following change with aging?
1. Thyroid gland
2. Testosterone
3. Diabetes, thyroid disease

A
  1. Atrophy (menopause)
  2. Decrease
  3. Increased incidence
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14
Q

How do electrolyte abnormalities change with aging?

A

They increase

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15
Q

How do the following change with aging?
1. Gastric pH
2. Gastric emptying

A
  1. No change or sometimes increase
  2. Delayed
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16
Q

How do the following change with aging?
1. Splanchnic blood flow
2. Intestinal transit rate
3. Absorptive surface
4. Passive intestinal permeability
5. Active nutrient transport

A
  1. Decrease
  2. Decrease
  3. Decrease (mucosal atrophy)
  4. No change
  5. Decrease
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17
Q

With age, incidence of urinary incontinence _________

A

increases

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18
Q

How does cell-mediated immunity change with aging?

A

Decreases

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19
Q

How do the following change with aging?
1. Liver size and # of hepatocytes
2. Liver blood flow
3. Oxidative and conjugative metabolism

A
  1. Decrease
  2. Decrease
  3. Unknown
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20
Q

How do the following change with aging?
1. Cartilage
2. Bone porosity
3. Bone density and mass
4. Muscle size and mass
5. Peripheral motor neurons

A
  1. Increase breakdown in joints
  2. Increase
  3. Decrease
  4. Decrease
  5. Decrease
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21
Q

How does nutrition change with aging? (2)

A
  1. Possible protein energy malnutrition (hospitalized patients)
  2. Increased anorexia and micronutrient deficiencies
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22
Q

How do the following change with aging?
1. Respiratory muscle strength
2. Chest wall compliance
3. Total alveolar surface
4. Vital capacity

A
  1. Decrease
  2. Decrease
  3. Decrease
  4. Decrease
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23
Q

How do the following change with aging?
1. GFR
2. Renal blood flow
3. Tubules (2 parter)

A
  1. Decrease
  2. Decrease
  3. Increase in tubular atrophy, and decrease in tubular secretory function (decreased urine concentrative ability)
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24
Q

How do the following change with aging?
1. Compensatory acid-base and electrolyte balance
2. Renal mass
3. Fibrosis
4. Arteriosclerosis

A
  1. Decrease
  2. Decrease (decreased functional nephrons)
  3. Increase
  4. Increase
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25
Q

How vision change with aging? (2)

A
  1. Decreased accommodation of the lens of the eye
  2. Decreased visual and auditory acuity
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26
Q

How do the following change with aging?
1. Dryness, wrinkling
2. Number of hair follicles and melanocytes
3. Epithelial and dermal thickness

A
  1. Increase
  2. Decrease
  3. Increase epithelial thinning and loss of dermal thickness
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27
Q

How do the following change with aging?
1. Wound healing
2. Thermoregulation
3. Vitamin D function
4. Photosensitivity

A
  1. Decrease
  2. Decrease
  3. Decrease
  4. Increase
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28
Q

Any factor that _______ systemic clearance (Cls) will cause an increase in Css, and may increase risk of ________

A

reduces; toxicity

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29
Q

What are 2 factors that influence half-life (think of the equation for t1/2)

A
  1. Vd
  2. Cls
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30
Q

How can toxicity in geriatrics be avoided?

A

Toxicity may be avoided by accounting for PK changes in the older adult and making the appropriate dosage adjustments (i.e. size of dose, dosage interval) when initiating therapy

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31
Q

How does GI absorption change with age? (2)

A
  1. Age-related changes may lead to impaired/delayed drug absorption as rate and/or extent of absorption is altered, but usually clinically irrelevant.
  2. GIT is a common site of distress in older adults, possibly due to changes in eating habits and elimination, alterations in nutrition, etc
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32
Q

In terms of GI absorption changes with aging, what happens with passive diffusion and bioavailability (F) related to that?

A

No change in either

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33
Q

In terms of GI absorption changes with aging, what happens with active transport and bioavailability (F) related to that?

A

May see decreased active transport (uptake) –> decreased F for some drugs

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34
Q

In terms of GI absorption changes with aging, what happens with first-pass effect and bioavailability (F) related to that?

A

May see decreased first-pass effect –> increased F for high extraction ratio drugs

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35
Q

In terms of GI absorption changes with aging, what happens with intestinal first pass?

A

Unknown intestinal first-pass, but polypharmacy and diet changes will alter food-drug and drug-drug interaction potential

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36
Q

In terms of GI absorption changes with aging, what happens with rate and extent of absorption?

A

Decreased or no change in rate of absorption and usually no change in extent of absorption

37
Q

Volume of distribution is influenced by age-related changes in: (3)

A
  1. Body composition (lean body mass, fat mass, total body water (TBW))
  2. Blood flow rates (cardiac output (CO), hepatic and renal blood flow)
  3. Binding to biologic material (i.e. plasma proteins and tissue binding)
38
Q

How does Vd and Cp change for some water-soluble drugs (in aging ofc)?

A
  1. Decrease Vd
  2. Increase Cp
39
Q

How does Vd and half-life change for some fat-soluble drugs (in aging)

A
  1. Increased Vd
  2. Increased half-life
40
Q

How fu(b) change for the following in aging:
1. Highly plasma protein bound drugs, that is:
- Albumin bound
- AAG bound

A
  1. Increase or decrease or no change fu(b) of highly plasma protein bound drugs
    - Increase fu(b) for drugs bound to albumin
    - Decrease fu(b) for drugs binding to AAG
41
Q

If Vd increases then t1/2 _________ and, hence, should ________ dosing interval

A

increases; increase

42
Q

How is AUCunbound or Css,unbound influenced by changes in plasma protein binding? (oral and IV)

A

Not significantly influenced by changes in plasma protein binding following oral administration
- Only changes for high EH drugs that are highly plasma protein bound following intravenous administration

43
Q

For extensively bound drugs, lower albumin levels increase unbound fraction in the blood (fu(b)) with the following consequences: (2)

A
  1. Increase in Vd (depending on magnitude of Vd)
  2. No increase in intensity of effect when administered orally as there is no change in Css,unbound. (Only high EH, IV administered drugs show a change in Css,unbound with changes in fu(b))
44
Q

Phase I or II metabolism more affected in aging?

A

In general, phase I more affected and usually there are limited alterations in phase II metabolism (in vivo)

45
Q

How does hepatic metabolism change with aging? (2) (Cls, t1/2, enzymes)

A
  1. Decreased Cls and increased t1/2 for some oxidatively metabolized low EH drugs due to decreased Clint
  2. Increased, decreased, or no change in enzyme induction or inhibition potential
46
Q

How does hepatic blood flow change in aging (QH, ClH) for a high EH drug?

A

Decreased QH and ClH

47
Q

How does renal blood flow, tubular secretion, and GFR change with age?

A

They all gradually decline with age

48
Q

What is the most important renal function parameter?

A

GFR - this is usually assessed by evaluation of creatinine clearance

49
Q

Decreases in GFR may be matched by what?

A

By decreases in muscle mass and urinary excretion of creatinine; hence, the mean serum creatinine concentrations may remain the same

50
Q

How does renal excretion change in aging? (ClS and t1/2)

A

Decreased ClS and increased t1/2 of renally eliminated drugs

51
Q

t1/2 and time to reach steady state both increase with aging. How does Vd and ClS affect that? (3 combos)

A
  1. Increased Vd and neutral Cls results in increased t1/2
  2. Decreased ClS and neutral Vd results in increased t1/2
  3. Decreased ClS and increased Vd results in increased t1/2
52
Q

Low extraction ratio drugs and drugs eliminated by renal GFR (IV or oral). How does Css,free and Css,total change with increase or decrease in fu(b)

A
  1. Increase or decrease fu(b) has no effect on Css,free
  2. Increase or decrease fu(b) results in decrease or increase Css,total, respectively, because ClS changes
53
Q

With high extraction ratio IV drugs how does Css,free and Css,total change with increase or decrease in fu(b)?

A
  1. Increase or decrease fu(b) has no effect on Css,total
  2. Increase or decrease fu(b) results in increase or decrease Css,free, respectively
54
Q

With high extraction ratio oral drugs how does Css,free and Css,total change with increase or decrease in fu(b)?

A
  1. Increase or decrease in fu(b) has no effect on Css,free
  2. Increase or decrease in fu(b) results in increase or decrease Css,total, respectively
55
Q

How do loading doses change with aging?

A

Change in Vd may require a change in LD, but usually unlikely to be clinically important

56
Q

How does maintenance dose change with aging?

A

Changes in ClS require changes in MD to maintain Css

57
Q

How does dosing interval change with aging? (2 - think Vd and ClS)

A
  1. Vd influences t1/2 which influences time to reach steady state. This is an important consideration in dosage interval
  2. ClS influences t1/2 which influences time to reach steady state. This is an important consideration in dosage interval
58
Q

What physiologic change is associated with body weight and vital organ function in aging?

A

Generally reduced

59
Q

What physiological consequences are associated with body weight; vital organ function in aging? (2)

A
  1. Decreased heart, kidney, muscle, and liver
  2. Decreased tissue fluid
60
Q

What pharmacokinetic consequences are associated with body weight; vital organ function in aging?

A

Young adult dose leads to higher Cp in older adult

61
Q

What therapeutic consequences are associated with body weight; vital organ function? (3)

A
  1. Overdosing
  2. Increased side effects
  3. Increased toxic effects
62
Q

What physiological changes are associated with GIT secretion and motility in aging? (3)

A
  1. Decreased acid/enzyme secretion
  2. Decreased motility
  3. Decreased cell number
63
Q

What physiological consequences are associated with GIT secretion and motility in aging? (3)

A
  1. Increased gastric pH
  2. Decreased gastric emptying
  3. Decreased mixing of GIT contents
64
Q

What are the pharmacokinetic consequences of GIT secretion and motility in aging? (4)

A
  1. Altered dissolution rate
  2. Altered drug ionization and solubility
  3. Decreased absorption rate (increased tmax)
  4. Variable effect on ka, tmax, Cmax, and F
65
Q

What are the therapeutic consequences of GIT secretion and motility in aging? (3)

A
  1. Increased time to onset of effect
  2. Decreased intensity of effect
  3. Increased duration of effect
66
Q

What are the physiologic changes seen in body composition in aging? (3)

A
  1. Decreased TBW
  2. Decreased lean body mass
  3. Increased fat/lean ratio
67
Q

What are the physyiological consequences with body composition in aging? (1)

A

Organ function changed

68
Q

What are the pharmacokinetic consequences with body composition in aging? (2)

A
  1. Decreased Vd of water-soluble drug
  2. Increased Vd of lipid-soluble drug
69
Q

What are the therapeutic consequences with body composition in aging? (4)

A
  1. Overdosing
  2. Increased side effects
  3. Increased onset of effect
  4. Increased accumulation
70
Q

What are the physiologic changes seen with kidney in aging? (3)

A
  1. Decreased renal blood flow
  2. Decreased GFR
  3. Decreased tubular secretion
71
Q

What are the physiological consequences seen with kidney in aging? (2)

A
  1. Decreased creatinine clearance
  2. Decreased renal function
72
Q

What are the pharmacokinetic consequences seen with kidney in aging?

A

Increased elimination t1/2 of drugs eliminated via the kidney

73
Q

What are the therapeutic consequences seen with kidney in aging? (4)

A
  1. Overdosing
  2. Increased duration of effect
  3. Increased side effect
  4. Increased toxic effects
74
Q

What are the physiologic changes seen in liver with aging? (3)

A
  1. Decreased blood flow
  2. Decreased oxidative metabolism (?)
  3. Decreased hepatic mass
75
Q

What are the physiological consequences seen in liver with aging?

A

Decreased hepatic function

76
Q

What are the pharmacokinetic consequences seen in liver with aging? (3)

A
  1. Decreased ClS and increased t1/2 for some Phase I drugs
  2. Decreased ClS and increased t1/2 of drugs with high extraction
  3. Decreased first-pass effects
77
Q

What are the therapeutic consequences seen in liver with aging? (4)

A
  1. Overdosing
  2. Increased duration of effect
  3. Increased side effects
  4. Increased toxic effects
78
Q

What are the physiologic change seen in plasma proteins in aging?

A

Decreased albumin

79
Q

What are the physiological consequences seen with plasma proteins in aging?

A

Hypoalbuminemia

80
Q

What are the pharmacokinetic consequences in plasma proteins in aging?

A

Saturation of protein binding and increased Cunbound

81
Q

What are the therapeutic consequences in plasma proteins in aging? (3)

A
  1. Overdosing
  2. Increased intensity of effect
  3. Increased side/toxic effects
82
Q

What is the physiologic change in homeostasis in aging?

A

Abnormal lability

83
Q

What are the physiological consequences in homeostasis in aging? (2)

A
  1. Decreased range regulatory functions
  2. Decreased functional reserve
84
Q

What are the therapeutic consequences in homeostasis in aging?

A

Paradoxic drug reactions

85
Q

What to know about drug-drug interactions in older adults?

A

Older adult patients more likely to be treated with multiple medications; this increases the risk for a drug-drug interaction

86
Q

What to know about drug-nutrition interaction in older adults? (2)

A
  1. Older adult pts may have decreased nutritional status
  2. Dietary composition may be an important environmental determinant of drug metabolism and drug toxicity (i.e., inhibition, induction)
87
Q

What to know about drug-disease interaction in older adults? (2)

A
  1. Certain diseases alter the PK/PD of a drug and older adults often have more than one disease
  2. The interaction between aging and disease may or may not be predictable
88
Q

What are the general guidelines for PK and drug response in older adults? (3)

A
  1. Age-related physiological changes may act singly or in combination to influence many PK processes.
    - E.g. age-related decreases in CO and regional blood flow may influence ADME processes
  2. Older adults may have multiple diseases, take multiple medications, have an increased potential for altered drug response and for the occurrence of adverse drug events.
    - Older adult populations exhibit more variability in drug response; impaired homeostatic mechanisms may increase risk and severity of drug-induced toxicity.
  3. Bottom line: geriatric dosing regimens must be designed with full consideration of the potential effects aging has on drug PK and PD and the potential for adverse effects.

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