Frailty Flashcards
Persons aged 65 and older are prescribed the highest proportion of medications in relation to their percentage of the U.S. population
Now, 13% of total population buy ____of all prescription drugs
• By 2040, 25% of total population will buy ___ of all prescription drugs
33%
50%
• Nearly 1 in 3 acutely hospitalized older patients
Adverse drug reactions are the most common iatrogenic illness
Results are
functional losses and increased costs
Describe:
overused
underused
misused
overused: no indications: about 7-37% of drugs in this category
Unused: not prescribed when indicated; few indicated
Misused: inidation present, but wrong dose, duration or freqeuncy
Problems associated with medicatiosn and the elderly
inapp use causes hospital admits
hip fxr 2x more likely under influence of drug
1/1,000 elderly die of drug side effect
Mrs. J is an 89 year old woman with hypothyroidism. She is on replacement with Synthroid 0.20 mg qd. She recently had a hip fracture which was repaired. She has noted weight loss, jittery feelings, and malaise.
What might explain her symptoms?
What age related physiologic change might affect the pharmacokinetics of Synthroid?
Factors affecting drug dispotinon and response in the elderly:
body composition, reduced total body water, reduced lean body mass, body weight, increased body fat, protein binding, reduced serum albumin
What happens to body fat, plasma voluem and total body water as you age?
Body fat to total body wt will increase 35%
Plasma volume will decrease by 8%
Total body water will decrease by 17%
Functions of the kidney
Excretion of metabolic waste products and foreign chemicals
Regulation of water and electrolyte balances
Regulation of body fluid osmolality and electrolyte concentrations
Regulation of arterial pressure
Regulation of acid-base balance
Secretion, metabolism, and excretion of hormones Gluconeogenesis
Estimate the interstitial fluid volume of a healthy individual with a body mass of 60 kg.
9 Liters:
water is 2/3 of total body weight thus 40 L
of that 40 L, 1/3 is extracellular fluid about 13 L
of Extracellular fluid 2/3 is Interstital fluid thus
9L
By weight, the body is composed of 50-70% water. We’ll use the value of 60%. Lean subjects have _______than obese individuals.
greater water content
Intracellular Fluid (ICF) =
2/3 Total Body Water (40% of body weight)
Extracellular Fluid (ECF) =
1/3 Total Body Water (20% of body weight)
The average 70 kg man with ~42 liters of TBW would then have ~______in the ICF and ~______in the ECF.
28 liters (42 liters x 2/3)
14 liters (42 liters x 1/3)
The barrier between ICF and ECF is the
The barrier between the plasma and Interstitla fluid two compartments is
cell membrane.
the capillary wall
CALCULATE THE NORMAL BLOOD VOLUME
Plasma volume is ~3 liters and the hematocrit (packed red blood cell fraction of blood) averages 0.38-0.42.
So the average individual will have a blood volume of ~5 liters:
Plasma Volume / (1-Hct),
i.e., 3 liters / (1-0.4).
An individual of normal body composition (plasma osmolarity = 280 mOsm/l) ingests 1 liter of a solution containing 200 mmole/liter NaCl. After equilibration of body fluids, and before any renal excretion has occurred, which statement will be true?
His intracellular fluid osmolarity will be increased compared to initial conditions.
Capillary wall is highly permeable to _________, but not to ______
water, electrolytes, and other small molecules
proteins
Plasma ≈ ______, except for more proteins in plasma
Interstitial fluid
The cell membrane is highly permeable to___, but not to______
water
most electrolytes or proteins
Which compatment is High in Na+, Cl-, HCO3-
ECF:
Which compartment is High in K+, PO43- and organic anions, protein
ICF
What maintains the balance of Na+ and K between the ECF and ICF?
The Na/K ATPase pump
The______ is the barrier betwee the ECF and ICF and is goverend by the ______
cell membrane
osmotic forces
is a function of the total number of particles in solution, independent of mass, charge, or chemical composition.
Osmolarity
Dissolved particles in biological solutions are expressed in terms of milliosmoles (mOsm). Osmolarity is the concentration of
osmotically active particles in total solution and is expressed in terms of mOsm/liter of water.
How do you account for osmoles in a substance like glucose vs NaCl?
For substances that do not dissociate into smaller particles when dissolved (e.g., urea, glucose, inulin, etc.), 1 mole = 1 osmole and 1 mmole = 1 mOsm.
For substances that dissolve into two particles (NaCl) or three particles (CaCl2), the osmolarity will be double or triple the molarity (1 mmole NaCl = 2 mOsm).
the movement of water across a semi-permeable membrane due to differences in osmolarity (an osmotic pressure gradient). A 1 mOsm/l difference in osmolarity can exert an osmotic pressure equivalent to 19.3 mmHg.
Osmosis
What is the Influence of Adding Isotonic NaCl Solutions to the ECF on Total Body Water (TBW), Extracellular (ECFV) and Intracellular Fluid Volume (ICFV)?
TBW: Increase
ECV: Increase
ICFV: No change
Steady state osmolarity: Stays same
What is the Influence of Adding Hypertonic NaCl Solutions to the ECF on Total Body Water (TBW), Extracellular (ECFV) and Intracellular Fluid Volume (ICFV)?
TBW: Increase
ECFV: Increase
ICFV: Decrease
Steady State Osmolatiry: Increase
What is the Influence of Adding Hypotonic NaCl Solutions to the ECF on Total Body Water (TBW), Extracellular (ECFV) and Intracellular Fluid Volume (ICFV)?
TBW: Increase
ECFV: increase
ICFV: Increase
Steady State Osomolatiry: Decrease
What happens to serum albumin, kidney weight and hepatic blood flow in older adults?
All decrease
Q2: An individual of normal body composition (plasma osmolarity = 280 mOsm/l) ingests 1 liter of a solution containing 200 mmole/liter NaCl. After equilibration of body fluids, and before any renal excretion has occurred, which statement will be true?
The ingestion of a hypertonic NaCl solution will lead to an increase in TBW, an increase in ECFV, an increase in osmolarity in all fluid compartments, and a decrease in ICFV.
An 85 year old man presents to his primary care physician for a routine examination. At the completion of the exam, he is told that everything seems to be going well and that he should be seen again in one year unless any problems develop. As the physician is walking out of the exam room, the patient mentions that he has had difficulty sleeping. The patient states that he usually goes to bed by 9 PM. It takes him an hour to fall asleep and he wakes up at 4 AM. He generally takes a one hour nap each afternoon.
- Which of the following medications should be avoided as hypnotics in older patients?
a. diazepam b. flurazepam c. oxazepam d. lorazepam
Diazepam and Flurazepam should be avoided
Drugs that have decrease in hepatic clearance with age
Alprazolam Barbiturates Carbenoxolone Chlordiazepoxide Chlormethiazole Clobazam Desmethyldiazepam Diazepam Flurazepam Imipramine Meperidine Nortriptyline Phenylbutazone Propranolol Quinidine, quinine Theophylline Tolbutamide
Drugs that have no change to hepatic clearance with age
Ethanol Isoniazid Lidocaine Lorazepam Nitrazepam Oxazepam Prazosin Salicylate Warfarin
What happens to Phase II hepatic metabolism with age?
NO CHANGE:
mediated by cytoplasmi enZ and not often altered with age
Graph of 1/2 life changes in drugs as we age
see graph
Another graph with changes of 1/2 lifes to drugs as we age; not that important
see image
Mrs K has a serum creatinine of 1.0mg/dl. She weighs 72 kg. You feel she needs gentamicin. How do you go about dosing her? How would your approach differ is she were 40 years old? How would you follow her?
Generally, lean body mass (which is the source of creatinine) decreases with age. But renal function also declines, resulting in less creatinine clearance. Serum creatinine in the elderly will not increase until 50% of nephrons are no longer functional. Because of these age-related changes, any elevation of creatinine is significant, particularly when determining dosage for drugs primarily excreted by the kidney. Since serum creatinine is not a reliable indicator of renal function in the elderly, renal function is best assessed and monitored with a 24-hr urine test for creatinine clearance.
Equation for urinary excreation
Filtration - Reabsorption + Secreation
You obtain the following experimental data from a 70 kg male subject: urine flow rate = 1.0 ml/min, plasma concentration of inulin= 1.0 mg/ml, plasma concentration of PAH = 1.0 mg/ml, urine concentration of inulin= 60 mg/ml, urine concentration of PAH = 650 mg/ml, hematocrit = 50%. What is this individual’s GFR?
GFR = UV/P
Uinulin = 60mg/ml
V= 1.0ml/min
Pinluin=1.0mg/ml
60x1/1 = 60ml/min
Renal arterial input=
Urine Output + Renal Venous and Lymphatic Output
FOR THE NEPHRON
Filtered + Secreted = Reabsorbed + Excreted
OR In = Out
Since______ is freely filtered at the glomerulus but is not reabsorbed or secreted
Filtration of____ = Excretion of_____
Inulin
Equation for GRF using inulin
GFR X Pin = UF X Uin
rearranging gives:
GFR = (UF x Uin) / Pin OR UV/P
the volume of plasma from which a substance has been removed and excreted into the urine per unit of time (volume/time)
CLEARANCE : Cx = (UF . Ux) / Px
Clearance of ______– can be used to measure GFR with an endogenous compound
Creatinine (Ccreat)
A normal individual receives a drug that effectively halves his glomerular filtration rate. After a period of two weeks on this drug, this patient will have ________ plasma creatinine concentration, _________ creatinine clearance rate, and _________ creatinine excretion rate compared to values prior to taking the drug. Assume this patient has reached a steady-state after two weeks
increased, decreased, no change in
Clinical Estimates of GFR-1: Reciprocal of serum creatinine
If we assume we are in a steady state, then urinary excretion of creatinine can be considered a constant K =
(Ucreat . UF)
*Then: GFR = K / Pcreat
So: GFR ~ 1 / Pcreat
Since Pcreat normally equals 1 mg/dl, if we divide 100 / Pcreat we can determine the percentage of normal GFR–Serum Creatinine can therefore be used as a clinical index of a patient’s GFR
Effect of reducing glomerular filtration rate (GFR) by 50% on serum creatinine concentration and excretion rate
Creatinine clearance is a measure of GFR. The 50% reduction of GFR indicates that the clearance of creatinine will also be decreased 50%. In the initial hours and days after the reduction of GFR, creatinine production rate will exceed excretion rate until the individual reaches a new steady state. In the new steady state, creatinine clearance is reduced, plasma creatinine concentration is increased, and the creatinine excretion rate will be unchanged.
A subject has been followed by a nephrologist for the past five years due to a progressive elevation of plasma creatinine (from 2 mg/ml to 7 mg/ml) that is accompanied by increasing urine protein excretion. Which of the following would you predict to be best regulated (nearest normal levels) in this individual?
a) plasma creatinine
b) plasma urea
c) plasma sodium
d) plasma phosphate
e) plasma calcium
Sodium least affected
What are the effects of decreasing GFR on Creatine and urea in the plasma?
they increase a lot; they are freely filtered and excreation is done through the kidney
What minerals are least affected by decreased GFR?
Sodium, Potssium and Water
What happens to Bicarbonate, Calcium and Phosphate levels when GRF decreases?
afftected more then sodium and potassium but not as much as urea and creatine
Keys to avoiding adverse drug interactions in older patients
Start low, go slow
• Watch for key risk factors:
6 concurrent chronic diagnoses
12 doses of medications per day
9 medications
1 prior drug reaction
low body weight or body mass index
age 85 or older
estimated CrCl < 50 mL/minute
Frailty Syndrome “Scorable” items
Shrinking (wt loss: unintentional >10#/1 yr) or Sarcopenia
Weakness: grip strength: lowest 20% by gender and BMI
Poor Endurance: exhaustion or slowness
Low activity: Caloric expenditure at lowest 20%
0.5 to 1% loss of skeletal muscle mass, quality, and strength associated with aging and distinct from disease
Sarcopenia
Define Sarcopenia in relation to muscle mass and muscle function
– Low muscle mass: >2 SD below the mean measured in young adults aged 18-39y in 3rd NHANES.
– Low muscle function: defined by low gait speed – e.g. rate of <0.8m/s in the 4m walk test.
Proposed pathology for Sarcopenia
– Muscle atrophy with reduced tissue quality
– Altered metabolism
– Oxidative stress
– Neuromuscular junction degeneration
– Decreased satellite cell function
– Diminished GH and TTN anabolic signals
– Increased catabolic signaling
What is the clinical frailty scale?
Scale from 1 being very fit to 7 being severly frail: refer to image
What is the differnce between IADLs and ADLs?
IADLs are activities required to live in the community: meal prep, housework, managing finances and medications, phone use, shoppin
ADLs are non-instrumental activities of daily living related to personal care: eating, dressing, hygiene, bathing, transfer in/out bed, dressing
What is the Rockwood Frailty index?
of deficits individual accumulates/
Accumulation of comorbidities:
Total # of deficits considered index score
What is the purpose of the frailty index?
Frailty index identifies accumulation of deficits anddemonstrate remarkable consistency in how deficits accumulate with age, the limit to how many things can go wrong, and how deficit counts change over time.
What is the VES-13?
Vulnerable elders survey
takes into account: Age, self-reported health status, ADL and funcitonal abilities as well as IADLs
Frailty as a Chronic Progressive Disease
see image
What occurs in the Frailty projectory?
see image
Proposed pathophysiology of frailty
Balance between stressor reactions of senescence or apoptosis across the musculoskeletal, immunologic, and neuroendocrine systems.
What changes do we see in the Musckuloskeletal system in regards to Frailty
Decreased skeletal muscle mass
Decreased VO2 max
Decreased strength and exercise tolerance
Diminished thermoregulation
Decreased energy expenditure and resting metabolic rate
Diminished muscle innervation
Decreased glucose uptake
What immulogic markers decrease in the frailty process?
IgA, IgG, IL-2, mitogen response
What immunologic factors increase with fraility
IL-6, IL-10, CRP
What decreases as a result of Neuroendocrine frailty
Decrease GH, IGF1, Vit D and estrogen and Testosterone
What Neuroendocrine markers increase in frailty?
Insulin resistance
Cholecystokinin
Sympathetic tone
Steroid dysregulation
Aging is the progressive accumulation of
random damage to a complex system of redundant parts:
(aging) reduces this redundancy until the system becomes a series of elements connected in series–> this leads to vulnerability from exernal/interal stressors
Loss of adaptability reduces responses to stressors to the equilibrium, eventually pushing systems (organs) to failure thresholds with an increased risk of adverse outcomes; This concept is
Frailty
- Any symptom in a geriatric patient should prompt a :
- Electrolyte disorders are common in geriatric patients, can result in symptoms, are:
complete drug review, including over-the counter agents.
easily diagnosed and often correctable
