Geriatrics Flashcards
In the absence of specific information, it is generally prudent to do what when administering drugs to aged patients?
“Start low and go slow”
Aging has been described as a progress I’ve loss of…
Physiologic processes necessary to maintain homeostasis
Death being the ultimate failure of these mechanisms
In the elderly passive gastric absorption is
Not markedly altered
Drugs that inhibit intestinal motility have greater effect than
Age
Due to erratic absorption and a tendency to develop sterile infiltrates, IM and SQ injections are generally recommended or not in the elder patients?
Not!
Total Body water is decreased by what % in elderly?
10-15%
Due to decreased thirst, elder patient may be
Dehydrated
A decrease in TBW, in combination w/changes in the distribution of CO, results in a
Decreased central compartment volume
Initial plasma concentrations following rapid IV admin may be increased b/c of the decreased size of the central compartment, yet the steady state distribution vol is?…. and why?
May be larger d/t increased body fat
Body fat increases and muscle mass decreases in the elderly by what%?
How does this impact lipophillic drugs?
20-40%
So lipophillic drugs will have a large vol of distribution
Even in healthy and exercising elderly, what is lost?
Muscle mass
Failure to adjust for weight raises concern for this?
Over medication
Are plasma protein levels a major concern in geriatric pharmacology?
No - not been identified
Hepatic blood flow declines how much?
Liver mass reduces?
20-53% while liver mass is reduced 11-36%
Tell me about hepatic function of the elderly in regards to:
Endoplasmic reticulum
Hepatic extracellular space
Bile flow
Endoplasmic reticulum is diminished
Hepatic extracellular space increased
Bile flow decreased
What phase of liver metabolism is effected in the elderly? Why?
Phase I - which is catalyzed mainly by microsomal CYP450 enzymes may be decreased.
Enzyme activity is relatively preserved.
Are phase II reactions affected in old age?
Appears to be unaltered
Generally, age reduces clearance of flow-limited drugs by what ___%? Similar to the decrease in hepatic BF, but there’s is no alteration for _______ drugs.
30-40%
Capacity limited
How much does GFR decrease per yr?
1ml/yr
What’s the overall consensus generally about renal function and aging?
In the absence of disease
Although there is a small decrease in GFR, it probably decreases less than once thought.
Aging doesn’t appear to diminish renal drug excretion significantly
In the elderly what happens to CO?
With coexisting disease, what happens to circulation time?
CO is maintained.
With coexisting dx - circulation times appear to increase
Due to increased circulation times and the delay of initial drug effects, what is a prudent action to reduce overdose and adverse CV impact?
Slower bonus injections
Opioid elimination occurs mainly by
Hepatic metabolism with renal excretion of metabolites and some parent drugs
What factors influence opioid metabolism?
Genetics Gender Age Environmental Factors Current medications Diet Disease
Name three opioids with active metabolites:
Codeine, Morphine, Meperidine
The metabolites of some opioids that are active account many side effects as well as
Persistent analgesia
The primary risks of opioids with the elderly
Respiratory depression
The incidence is increased with age
Respiratory depression was more problematic with _____ vs meperidine.
What is seen in pts receiving fentanyl?
Morphine
And no resp depression in pts receiving fentanyl
Fentanyl is a highly selective:
Mu receptor agonist
Fentanyl is metabolized by
CYP3A4 to inactive and nontoxic metabolites
Early studies suggested what regarding fentanyl?
What was the conclusion?
Early - elimination 1/2 life was prolonged in the elderly as no change in vol of distribution was found.
Concluded that clearance was decreased and that fentanyl last longer in the elderly
Later studies found aging had minimal influence on fentanyl pharmacokinetics with what exception?
A transient concentration increase following the start of drug infusion
Attributed tod decreased rapid intercompartmental clearance
Aging effects pharmacodynamics or pharmacokinetics greater?
Pharmaco-Dynamics
“DEF”
“Dynamics effect fentanyl”
Elderly pts are more sensitive to fentanyl and should receive reduced doses. What should be similar to that of young pts?
The offset of drug effect (despite smaller doses)
With oral transmucosal fentanyl, what impact did aging have on the pharmacokinetics?
None.
However study in healthy older pts; so add co-morbidities and that could change
Fentanyl plasma concentrations depend on the rates of release and
Penetration through the skin layers
The mean half time (time for plasma concentrations to double after patch application) in younger (24-38yrs) and elderly (64-82) where?
Young: 4.2 and elderly 11.1 hours
In the elderly, integumentary system factors increased absorption of fentanyl overa. Longer period of time.
Despite this absorption delay, what is significant about the subcutaneous fat in elderly?
It acts as a secondary reservoir — prolonging release even after removal of patch
Morphine is metabolized by what?
It’s metabolites are?
Glucuronidation to morphine-3-glucoronide and to Morphine-6-glucuronide (M6G)
Tell me about M6G
Can it pass BBB?
Is it effective as an analgesic?
Eliminated by?
BBB crosses extremely slowly
It is an effective analgesic
Eliminated by the kidney
What is seen in pts with elevated creatinine concentrations with morphine administration?
Peak?
Accumulation of both morphine glucuronides
Peak effect approx. 90min after a bolus dose
Meperidine is a relatively weak mu-agonist. It has approx ___% effectiveness of morphine
10%
Half life of meperidine is
~3hrs
Meperidine is metabolized in the liver to normeperidine.
It’s half life is?
What can it cause in high concnetrations?
15-30hours
Causes agitation and seizures at high conc.
Meperidine has complex pharmacology… explain some of it
Local anesthetic activity
negative inotropic effects
Intrinsic anticholinergic props — may increase HR
When combined with MAOI’s, meperidine is associated with
Severe serotonergic reactions
Normeperidine likely accumulates in elderly due to reduced renal excretion with ..
Repeated doses
Aside from tax for post op shivering, meperidine is not a good drug in the elderly.
It’s associated with this post op complication
Post op delirium
Why do we want to stop shivering?
Increased myocardial o2 demand
Remifentanil undergoes rapid hydrolysis by
Nonspecific tissue and plasma esterase
Due to its rapid hydrolysis, after a 4 hour infusion, context sensitive half life of remifentanil remains at
4 mins
Is remifentanil good in elderly populations?
Yes.
Onset and offset are slower in elders but blood concentrations are similar to younger pts
After bolus injection; Peak drug effect of remifentanil
Young vs old
90s vs 2-3 mins in elder
It’s recommended that elder subjects need about half the bolus dose of remifentanil than younger pts. How does this impact the effect of the drug?
Same drug effect
Remifentanil has an increased pharmacokinetic or pharmacodynamic impact?
Pharmacodynamic
Remi gtts need to be reduced about what of younger pts?
1/3 of younger pts
Remi infusion rates are about one-third that of younger patients because of:
Combined impact of
INCREASED sensitivity and
DECREASED clearance
Primarily b/c the elderly are more sensitive, opioid doses should be
Reduced by 50%
Propofol pharamacodynamics are significantly altered with aging.
Loss of consciousness EC 50 values for 25, 50, and 75 yrs were?
25: 2.35 mcg mL-1
50: 1.8
75: 1.25
Nearly a 50% decrease
Age related changes were found in both induction and infusion doses of propofol.
Pts older than 70 reached deeper EEG stages than younger pts.
They needed more time to reach the deepest EEG stage and….
Needed more time until a lighter EEG stage was regained
In general - elderly need less propofol. Current literature suggests what % of reduction for induction bolus?
20%
Tell me the dose range for propofol that may be appropriate for elderly?
0.8-1.2 mg/kg
Propofol infusion rates to achieve a persistent level of moderate sedation are ______ in the elderly
Lower
Recent data indicates that propofol clearance is altered more by what in females than in males.
Age
This factor has not effect on BIS rate with increasing propofol concentration
Age
Goal BIS monitoring number
50 (40-60);
Less than 40 = stage 4
With increasing age what is known to decrease to a greater degree than BIS - but more slowly?
Systolic blood pressure
Midazolam has been found to have significantly different _____ in elderly
Kinetic
Midazolam Clearance is reduced in the elderly by what % from that of young adults.
As much as 30%
Midazolam clearance reduction in the elderly is due to what two reasons:
- Loss of functional hepatic tissue
2. Decrease in hepatic perfusion
Midazolam undergoes significant metabolism, primarily to:
Hydroxymidazolam
Hydroxymidazolam is the primary metabolite of?
Is it active or inactive?
Midazolam
Active
Hydroxymidazolam (pharmacologically active) is excreted:
May accumulate in patients with?
Renally excreted
Accumulate in patients with diminished renal function
Why are elderly patients significantly more sensitive to Midazolam than younger patients?
Primarily b/c of a pharmacodynamic difference
The recommended Midazolam dose reduction from the 20 yr old to the 90 yr old?
75%
Paradoxical reactions are
When pts become agitated rather than sedated
How do you tx paradoxical reaction to midazolam ?
Flumazenil may reverse the episode
NMBD’s inhibit transmission at the NMJ and exert their effect
Postsynaptically
In the elderly, the average muscle mass decrease is
25-35%
Beyond the avg muscle loss, some elderly pts have significant muscle loss and weakness. This resulting state is defined as
Frail
Aging is associated with structural changes at the NMJ. What is one of the intriguing alterations in elderly muscle?
The presence of extrajunctional acetylcholine receptors
…. have no known impact on NM function
Young vs old patient; ED95 for NMBD?
Essentially the same
With age, The pharmacokinetics of muscle relaxants are
Significantly altered
Onset of NMBD’s is dependent on a number of factors including
Muscle mass
CO
— that may be altered in elderly
Hepatically metabolized drugs
Vec and Roc
Vec & Roc (hepatic metabolized) manifest
Prolonged recovery
With Vec, in elderly vs younger pts; what is seen in regards to E 1/2t, clearance and recovery time?
Spontaneous recovery time was longer
- E1/2 t was prolonged
- plasma clearance was reduced
Are their differences b/w young and old with the pharmacokinetics of atracurium and cisatracurium?
Minor
Clearance of anticholinestearse in the elderly
May be prolonged.
…. may be beneficial given clinical applications
Geriatric pts appear more susceptible to what SE associated w/the reversal of NMBlockade?
Cardiac arrhythmias
NMBD doses in elderly?
Are not altered. But the clinician must wait longer for the full effect (pump is slower)
Is the dose of anicholinesterase reversal drugs altered by aging?
No
The principal physiologic mechanisms involved in the uptake and distribution of volatile anesthetics are
Minute ventilation and CO
MV, CO and the blood/gas partition coefficient of the drug determine the rate of equilibration b/w
- The alveolar partial pressure and
2. The inspired anesthetic partial pressure
Senescence is associated with majors changes to what functions?
However in healthy elderly pts, their baseline CO is maintained
both CV and pulmonary
MV is typically controlled during anesthesia. So what is the cause for the decreased volatile dose concentration in elderly?
Pharmacodynamic
In volatiles; this is a majore modifier of anesthetic action
Age
Two analyses found a MAC reduction of
6% per decade of life (after 1 yr age)
Also seen in MAC-awake
Is the MAC reduction found with aging consistent in all, some, or none of the gases?
Name them?
Consistent across all.
Halothane, enflurane, isoflurane, sevo, des and N2O
On avg. volatile anesthetic MAC decreases what % per decade?
6.7% per decade
MAC for Nitrous decreases what % (and over what time period?)
7.7% per YEAR
MAC awake decreases with age
Proportionate to MAC
Monk et al study reported that what two factors were significant independent predictors of increased mortality:
- Cumulative deep hypnotic time
2. Intraoperative hypotension
Should we avoid volatiles in elderly patients?
There is no compelling evidence
Increase in body fat and decrease in muscle mass means for lipophillic drugs:
They’ll have a large vol of distribution
A decrease in total body water, in combo w/changes in the distribution of CO =
A decreased central compartment volume
Does aging diminish renal drug excretion?
Not significantly
Opioid doses in elderly should be reduced by
About 50%
Pharmacokinetic changes are important only when
Long term infusions are contemplated (opioids?)
Do you adjust the dose of Narcan with the elderly? If so, how
No alteration
The primary risk with increased incidence in the elderly of opioids is:
Respiratory depression
Sedative hypnotics should be SIGNIFICANTLY decreased in elderly.
To minimize hemodynamics consequences, Induction doses should be
Infused more slowly
What’s one anesthetic that appears to have both pharmacokinetic and pharmacodynamic differences b/w young and old recipients?
Propofol
Elderly patients may be most sensitive to what drug?
What kind of reactions may occur?
Midazolam
-may have paradoxical reactions
Biggest take aways regarding NMBDs with the elderly?
Doses don’t need to be altered
But the clinician must wait longer for full effect
MAC of volatiles in the elderly
Significantly reduced
