PK/PD in Elderly Flashcards
1
Q
Why is geriatric PK important?
A
- People 65 y.o. and older are prescribed the highest percentage of mediations
- Currently, 13% of population buy 33% of Rx
- By 2040, 25% of the population will buy 50% of Rx
2
Q
Adverse Drug Events
A
- ADE - 5-28% of acute geriatric hospital admissions
- ADE occur in 35% of community-dwelling elderly
- ADE incidence: 26/1000 hospital beds
- In nursing homes, they spend $1.33 on ADE for every $1 they spend on medications
3
Q
Risk of ADE in Elderly
A
- Multiple medications: >20% of elderly use 3+ medications (increases frequency of drug-drug interactions, and decreases likelihood of adherence)
- Multiple comorbidities
- Age-related changes in PK
- Age-related changes in PD
* *All increase risk of ADE**
4
Q
ADE General Risk Factors
A
- 6+ concurrent chronic conditions
- 12+ doses of drugs per day
- 9+ medications
- Decreased body weight/BMI
- Age: 85+ y.o.
- Estimated CrCl < 50 mL/min
5
Q
Prescribing Basics for Elderly
A
- Start with low dose
- Titrate up slowly as tolerated by the patient
- Avoid starting 2 drugs simultaneously
- Consider deprescribing
6
Q
ADE Cascade
A
- Prescribed one drug, have ADE
- Prescribed second drug for last drug’s ADE, experience new ADE
- Prescribed third drug…… and so on
7
Q
Questions to Ask Before Starting New Medication
A
- Is this medication necessary?
- What are the therapeutic endpoints?
- Do the benefits outweigh the risks?
- Is it used to treat effects of another drug?
- Could one drug be used to treat 2 conditions?
- Could it interact with disease states or other drugs?
- Does patient know what it’s for, how to take it , what ADEs to look for?
8
Q
Aging + Absorption
A
- Clinical significance is not well characterizes
- Most drugs are passively absorbed through proximal small bowel
- Exception: Levodopa, 3x increase in bioavailability due to decreased dopa-decarboxylase activity in stomach wall
9
Q
GI Absorption Alterations
A
- Alterations in GI from decreases parietal cell function - decrease in HCl secretion (increases pH) which can effect drug absorption of drugs like iron and ketoconazole
- Decrease in gastric emptying - antichol. Fe, anticonvulsants
- DDI - Divalent cations (iron, magnesium) + Fluoroquinolones (ciprofloxacin)
10
Q
Topical Absorption Alterations
A
- Patches, creams, ointments, etc.
- Thinning and reduction of absorptive surgaces
- Skin atrophy and reduction in fat
- Reduction in vascular network and increased risk of contact dermatitis
11
Q
Aging + Vd
A
-Depends on physiochemical properties of individual medications mainly
t1/2 = 0.693 * Vd / Cl
12
Q
Physiologic Changes + Vd
A
- Decreased in body water (10-15%) - decreased in Vd for hydrophilic drugs like warfarin, digoxin, lithium, APAP
- Decrease in lean body mass - decrease in Vd for muscle binding drugs
- Increase in fat store - increase in Vd for lipophilic drugs like diazepam, lidocaine, TCA, propranolol
13
Q
Distribution
A
- Decreases Serum Albumin
2. Increases in alpha-1-acid-glycoprotein
14
Q
Decreases in Serum Albumin
A
- 10-20% in hospitalized/poorly nourished
- Increase in fraction unbound of highly protein bound, acidic drugs
- Monitor drug levels - warfarin, phenytoin, naproxen (levels of free phenytoin with decreased albumin)
15
Q
Increased Alpha-1-acid-glycoprotien
A
- Decrease in unbound fraction of highly protein bound basic drugs
- Includes lidocaine, propranolol, imipramine
16
Q
Aging + Metabolism Changes
A
- Decrease in hepatic blood flow
- Decrease in liver size
* *Liver is most common site of metabolism**
17
Q
Decrease in Hepatic Blood Flow
A
- 40-45% with aging (connected to cardiac function)
- Increase in bioavailability
- Decrease in first pass metabolism - more parent drug which means you can lower initial dose and titrate up
18
Q
Decrease in Liver Size
A
- 25-50% decline in absolute weight up to age 80%
- Decrease in total amount of metabolizing enzymes
- Decrease in Cl and increase in half life
- Start with lower dosages
- CAUTION WITH TOXIC METABOLITES (Ex: Meperidine)
19
Q
Elimination
A
- Most exit via kidney
- Decrease elimination leading to drug accumulation and toxicity
- Aging and common disorders can impair kidney function
20
Q
Aging + Kidneys
A
- Decrease in kidney size
- Decrease in renal tubular secretion
- Decrease in renal blood flow (~1%/year after age 50)
- Decrease in number of functioning nephrons
RESULT: Decreased GFR, ~35% in healthy individuals ages 20-90; leads to drug accumulation and increased toxicity risk. EX: Lithium, NSAIDs, captopril
21
Q
SCr Doesn’t Equate to CrCl
A
- Decrease in lean body mass leads to decreased SCr production
- Therefore leads to decreased GFR
- Result: elderly can have normal SCr levels that masks changes in CrCl
22
Q
CrCl Measurement Methods
A
- Time-consuming in order to be accurate
- 24-h urine collection
- 8-h collection may be accurate, not widely accepted
