Geriatric Patients

how old do you have to be to be considered a geriatric patient?

How much of our population is considered elderly?

What is that number expected to rise to by the end of 2030?

older than 65 years old

15-20%

greater than 20%

why is recocognizing changes in pharmacokinetics and pharmacodymnamic changes in geriatric patients important?

1. they make up a large portion of our population (15-20%)

2. consume a large portion of healthcare dollars (30-35%)

3. more than 25% of Adverse Drug Events are from this population

in 1950 ages were visualized as pyramids but are now cylindrical as of 2010. What does that mean, why is this important as pharmacists?

there is alot more elderly people alive than before.

in the pyramid scheme, the older you got, the less people there were in the population, but now there are alot more 90 year olds alive than before

this is important for pharmacists as they make up a large percentage of our patients, more than ever before

why are there so many adverse drug events from geriatric patients?

1. polypharmacy (they are taking a lot of drugs at once)

2. multiple concurrent disease states

what is the difference between chronological age and biological age?

chronical age- actual age

biological - functional/ physiologic age

what are the three principles of drug action?

1. pharmaceutical phase

2. pharmacokinetics phase

3. pharmacodynamics phase

physical and chemical processes determining the fraction of the dose available for ABSORPTION

pharmaceutical phase

biological processes determining the fraction of a dose available for action

relationship between _____ vs ________

pharmacokinetic phase

drug concentration vs time

all biological processes involved in a drug’s effect

• relationship between_________ and _________

pharmacodynamics

• drug concentration and pharmacologic effect

does the majority of data come from PK or PD?

PK

What is the pharmacokinetic-based theory of altered drug activity?

drug disposition and metabolism declines as you age

What is the pharmacodynamic-based theory of altered drug activity?

altered quantity and/or quality of drug RECEPTOR SITES

which theory pharmacokinetic or pharmacodynamic has more studies to evaluate it?

pharmacokinetic

what are the age comparisons that complicate the design and interpretation of age related studies ?

continuum over years vs. arbitrary definition (at this age you are considered elderly vs gradually experiencing elderly symptoms)

what are the age changes that complicate the design and interpretation of age related studies ?

longitudinal (age changes)

cross sectional (age differences)

Which factors complicate the design and interpretation of age-related studies?

1. age definition (biological vs chronological)

2. age comparisons (arbitrary vs continuum)

3. age changes (longitudinal vs cross sectional)

4. health status (institutionalized vs home)

5. drug therapy

6. nutritional status

7. environmental exposure

does aging lead to achlorhydria (lack of HCl secretion)?

NO

although aging may decrease HCl secretion there is little evidence to prove that it completely eliminates HCl secretion

what happens to gastric pH as you age?

increase in pH due to decreased HCl secretion

true/false: the dissolution rate decreases for majority of drugs as an individual ages

NO

it MAY be effected if dissolution is depended on pH

what is an example of a drug that is unstable in acid?

what would happen to the absorption of this drug in an older patient?

Penicillin G and erythromycin

Absorption increases because they are unstable in acid, but because of decreased HCl secretion in the elderly, they are stable and able to be absorbed in a more basic condition

would the activity of prodrugs increase or decrease in geriatric patients?

DECREASE bc/ many prodrugs require acid to cleave them into their activated form

due to decreased HCl secretion, there would no longer be an acidic environment to cleave prodrug into their active counterparts

what is an example of a prodrug that would have decreased absorption in elderly patients?

clorazepate

explain why there would be less absorption of calcium carbonate and more absorption of calcium citrate in elderly patients?

calcium carbonate requires an acidic environment to be absorbed

calcium citrate may be absorbed in a basic environment

stomach HCl is reduced in geriatric patients which is why calcium carbonate absorption is decreased and calcium citrate absorption is increased in basic environment

what happens to gastric/splanchnic blood flow with age?

decreases

how does decreased splanchnic blood flow impact drugs that are typically effected by first-pass metabolism?

splanchinic blood flow includes hepatic blood flow and if there is less blood going to the liver than there is less of the drug being metabolized by the liver so there is higher absorption of drugs that are typically effected by first pass metabolism

is gastric emptying delayed or sped up in the elderly? why may this lead to increased GI irritation?

delayed

drugs that cause irritation to the stomach (such as NSAIDS) stay longer in the stomach causing urther irritation

Slower GI motility in geriatric patients may be further compounded by medications which slow GI motility such as ________ and _________

opiates and anticholinergics

is the surface area of absorption increased or decreased in geriatric patients?

decreased due to villa atrophy and increased mucosal connective tissue

how much of the surface area is decreased in geriatric patients?

20%

Are active, passive, or both modes of transport disrupted in geriatric patients?

ACTIVE trasnportation is decreased but passive remains the same

there is less area for the transporters but the drug will still move from where there is more to where there is less

what are examples of nutrients absorbed through active transporters that are DECREASED in geriatric patients?

1. folic acid

2. thiamine

3. calcium

4. iron

5. sugars

6. amino acids

GERIATRIC ABSORPTION SUMMARY:

what happens to the following and why:

• rate

• extent

• onset

• Cmax

rate is decreased because gastric emptying into the intestine is delayed so the rate in which the drug gets to the blood and then the rest of the body is decreased

extent is unchanged bc/ most drugs undergo PASSIVE diffusion (more drug to less drug) which is unchanged despite decreased absorptive surface area

onset is delayed because of delayed gastric emptying, takes time for drug to reach blood

Cmax is increased because splanchnic blood flow is decreased and less drug makes it into the liver and less is metabolized

concentration in blood =

dose (amount in body) / Vd

does total body water increase or decrease in geriatric patients?

decrease

do water soluble polar drugs have a higher or lower Vd in geriatric patients ?

low Vd

there is less water for the drug to dissolve in so the majority will stay in the blood (denominator so Vd lower)

why would you want to administer lower doses of

• aminoglycosides

• ethanol

• lithium

in geriatric patients

since they have lower total body water alot of the water soluble drug will stay in the blood so if you increase the dose it may lead to toxic levels of drug in the blood

what happens to lean body mass and adipose tissue in geriatric patients?

lean body mass decreases

adipose tissue increases

is the volume of distribution increased or decreased for lipophilic drugs in geriatric patients?

would this delay the effect of the drug, why or why not?

Vd in increased bc/ less drug will be in the blood and more drug will be dissolved within fat since there is excess

yes because there is less reaching the blood to be distributed to other organs

Why are lipophilic drugs at risk of accumulating and having prolonged action?

since overall fat is increased in geriatric patients, the drug will absorb into large portions of the body and accumulate

what are examples of drugs that may accumulate and have prolonged action in geriatric patients?

tricyclic antidepressants and benzodiazepines

lipid soluble

would lipophilic or hydrophilic drugs have increased half-life in geriatric patients? why?

lipophilic

the drug will absorb into excess fat and action will be prolonged

would lipophilic or hydrophilic drugs have increased concentration in the blood?

hydrophillic

there is less water for the drug to absorb into so much of it will stay in the blood increasing the concentration but decreasing the Vd

what are examples of hydrophilic drugs that have increased concentration in the blood of geriatric patients ?

• procainamide (pro— pro in the blood)

• aminoglycosides (gentamicin)

• quinidine

• theophylline

• warfarin

paq the way (tw) into the blood ayee

what are examples of lipophilic drugs that have increased halflife in geriatric patients?

Benzodiazapines

Barbitruates

Steroids

Phenothiazines

BB is SPecial (but depressed)

is albumin increased or decreased in geriatric patients?

why is this the case?

albumin is DECREASED bc/ nutrients such as amino acids which are absorbed through active transport are decreased due to decreased surface area and are unable to create proteins such as albumin

are there higher unbound concentrations of unbound drug in elderly patients?

how does polypharmacy tie into this?

yes bc/ albumin is limited due to nutritional malabsorption

polypharmacy can lead to toxic levels of drugs as they are competing or albumin which is already sparse leading to their being more unbound active drug

are alpha-1 acid glycoprotein levels increased or decreased in geriatric patients?

they are variable so they can be increased, decreased, or unchanged

Since alpha 1-acid glycoprotein is an acute phase reactant, it may be increased/decreased in the elderly with multiple disease states, leading to higher/lower levels of unbound basic drugs

what is an example?

increased lower

ex. lidocaine

would you need increased or decreased dose of lidocaine in elderly patients and why?

increased dose because lidocaine is bound to alpha-1 acid which is increased and less is in the blood

How is resting cardiac output vs. cardiac output under stress changed in elderly individuals?

cadiac output under stress DECREASED

resting cardiac output UNCHANGED

how does decreased cardiac output under stress effect the Vd and clearance of elderly patients?

Vd and clearance is decreased and there is less flow to take the drug to other organs and tissues

what three aspects of DISITRIBUTION are impacted in the elderly population?

1. lipophilicity/ hydrophilicity of drugs more fat and less water so lipophillic drugs have higher Vd and hydrophilic has lower Vd

2. Perfusion (Cardiac Output)

   there is less blood flow to organs leading to a lower Vd and clearance

3. Protein Binding

   Albumin decreased due to malabsorption of nutrition and alpha 1- acid glycoprotein can be increased or decreased. Give lower doses of competitive albumin binding drugs or else you will reach toxic levels

Changes in liver composition (what happens to):

• hepatic blood flow

• hepatic mass

• number of functional hepatocytes

• flow decrease

• mass decrease

• functional hepatocyte decrease

due to decreased hepatic blood flow, decreased functional hepatocytes and mass, do both phase I metabolism and phase 2 metabolism decrease?

NO only phase 1 is effected

out of these metabolism reactions which would you expect to decrease with age?

• oxidation

• conjugation

• reduction

• hydrolysis

• glucuronidation

phase I: oxidation, reduction, hydrolysis

which drug typically has a half-life of 15-20 hours in non-elderly patients that increases to 80+ hours in the elderly

why is this the case?

diazepam

mostly metabolized by phase I reactions, which are diminished in the elderly

what would expect to happen to the half life of oxazepam as a patient ages?

remain the same at 7 hours because the drug is metabolized by phase II reactions which are unchanged in elderly

the ability to _____ and ______ metabolic enzymes may be blunted (data can be conflicting)

induce and inhibit

is the metabolism of the LOT drugs effected in elderly patients?

NO

• lorazepam

• oxazepam

• temazepam

metabolized by phase II reactions so they are unaffected

true/false: clinical predictors of hepatic function in terms of drug selection and dosing are generally reliable

FALSE

unreliable

drug metabolism is not only impacted by the loss of mass, hepatocytes, and blood flow but also by

• genetic polymorphisms

• smoking

• diet

• gender

• other drugs

• disease states

what decreases in terms of the kidney in geriatric patients?

• size

• number of nephrons

• renal blood flow

• glomerular filtration rate

• tubular function

what percentage of the elderly are able to mainitain normal renal function?

20%

true/false: Serum creatinine concnetrations alone can be a reliable predictor of renal function in the elderly

why or why not?

FALSE

the patient may have higher or lower levels of creatinine due to changes in muscle wasting so just seeing that the patient has high levels of creatinine doesn’t necessarily mean there is an issue with clearance, it could just mean that their body is producing more

what is the Cockcroft/Gault equation for creatinine clearance?

(140-age) (body weight x 0.85 if female) / 72 x SCr

serum creatinine is APART of the equation not good enough to use on its own so its factored in with age, weight, and gender

would the creatinine clearance be the same, greater, or less for a 30 year old vs a 70 year old who have the same body weight ?

greater for 30 year old because 140-30 is greater than 140-70 in creatinine clearance equation:

(140-age) (BW) (0.85 if female) /

(72 x serum creatinine)

What are examples of drugs that are renally eliminated that need to undergo dose adjustments in geriatric patients who have decreased renal excretion?

1. Antimicrobials

2. Cardiovascular

3. H-2 receptor blockers

4. Lithium

5. Metformin

6. Meperidine

7. Procainamide

ACH LMMP

they ache and they limp cause they usually renally excreted but not they extra

all of the following are

• acyclovir

• aminoglycosides

• cephalosporins

• imipenem

• penicillin

• vancomycin

why should we give our elderly patients dose adjustments of these medications?

antimicrobials

these drugs are renally excreted and renal function is decreased in the elderly

all of the following are

• atenolol

• captopril

• digoxin

why should we give our elderly patients dose adjustments of these medications?

cardiovascular

these drugs are renally excreted and renal function is decreased in the elderly

all of the following are

• cimetidine

• nizatidine

• famotidine

why should we give our elderly patients dose adjustments of these medications?

H2 receptor blocker

these drugs are renally excreted and renal function is decreased in the elderly

Which antimicrobials, when taken in high doses by the elderly, can lead to the risk of seizure ?

why is there a risk?

Acyclovir

Cephalosporins

Imipenem

Penicillin

these antimicrobials are renally excreted

renal excretion is decreased in elderly

drug stays in body longer

Which antimicrobials, when taken in high doses by the elderly, can lead to the risk of nephrotoxicity and ototoxicity?

why is there a risk?

aminoglycosides and vancomycin

these antimicrobials are renally excreted

renal excretion is decreased in elderly

drug stays in body longer

which of the cardivascular medications can lead to cardiac toxicity?

digoxin (sounds toxic)

which of the cardivascular medications can lead to are titrated to effect?

atenolol and captopril

what are the atypical adverse drug reactions that take place in elderly patients on H2 receptor blockers (cimetidine, nizatidine, famotidine)?

• mental status changes

• confusion

what is a rare but severe side effect experienced by elderly patients taking metformin

why is this the case?

lactic acidosis

metformin is typically renally excreted but the renal excretion of elderly is limited

What are two drugs whose metabolites are typically renally excreted and are toxic if they accumulate?

meperidine and procainamide

What effect do toxic levels of procainamide have on the elderly?

decreased seizure threshold

it takes a lot less to get to a seizure

NAPA is the toxic metabolite of ________, leading to _________

procainamide

pro-arrhythmic effects

drugs eliminated by ________ _______ or ________ ________ generally have a decreased elimination and should be avoided or used with caution.

Many require dose adjustment BASED ON (estimated or measured) ________ _________

glomerular filtration or tubular secretion

creatinine clearance

how can aging impact the pharmacodynamics of drugs?

• changes in multiple organs

• changes in drug receptors

• changes in cells

nearly all organs are affected by aging in some way

which three are focused on in class?

cardiovascular

hepatic

renal

Mechanisms of homeostasis may be altered in elderly patients:

ex. decreased baroreceptor response may increase risk of ________ _________

orthostatic baroreceptors

which drugs will have increased sensitivity to their receptors as the patient ages? (want to give lower doses)

hypotensives

opiates

phenothiazines

benzodiazepines

NSAIDS

warfarin

Central effects of Anticholinergics

HOP in my BNW Car for increased sensitivity

which drugs will have decreased sensitivity to their receptors as the patient ages? (want to give higher doses)

• Beta adrenergic modulators (agonists AND antagonists)

• Calcium channel blockers (-pine)

decreased sensitivity in ancient BC times

what can be a consequence of the decreased sensitivity of beta adrenergic agonists and antagonists?

• decreased signaling of hypoglycemia (patients may not get natural signals provided by beta agonists that their blood sugar is low)

• orthostatic hypotension (the body is not responding to the adrenergic signal to constrict blood vessels and increase contractility leading to hypotension)

a decreased sensitivity to calcium channel blockers as seen in the elderly may lead to

• increased/decreased sensitivity to AV node blockade

• increased/decreased sensitivity to hypotensive effects

decreased

increased

Cellular Pharmacodynamic Changes:

• Increased sensitivity to the central effects of anticholinergic agents such as _________ __________ which may result in ________, ________, and ________________

• increased/decreased sensitivity to the effects of diuresis

  • what happens to potassium levels?

  • what happens to sodium levels?

• incerased/decreased sensitivity to anticoagulation effects of warfarin

tricyclic antidepressents

fatigue, confusion, lethargy

• increased (more water and sodium out while potassium stays in)

• hyperkalemia (increased potassium due to increased sensitivity to diuresis)

• hypOnaturemia (excess water decreased sodium)

• increased sensitivity

true/false: “equal” concentrations of warfarin will result in equivalent International Normalized Ratios (INR) in the elderly vs nonelderly adults

does INR remain unchanged?

NO they may have different INR (monitoring) based on their age

do elderly patients experience increased or decreased cellular response to the CNS depressant effects of benzodiazepines?

increased response

Dopamine-receptor blocking agents such as _________ and _________ may induce parkinson’s 's-like symptoms

metoclopramide and antipsychotics

why must you be careful when administering metoclopramide and antipsychotics to elderly patients?

metoclopramide and antipsychotics may INDUCE parkison’’s like effects since they block dopamine

elderly patients experience an increased susceptibility to the GI adverse effects of ___________

Avoid administering __________ because of the increased risk of CNS toxicity, which may lead to confusion and lethargy AS WELL AS OTHER ATYPICAL ADVERSE DRUG REACTIONS

NSAIDS

indomethacin

in general for geriatric patients you want to

• start _________

• go ______but ____

• don’t ______ too soon

start low

go slow BUT GO

don’t STOP too soon

what is most likely the change in half life of drugs and time to reach steady state?

increased bc/ many drugs are unable to be eliminated increasing half life

Css = 4 x halflife

changes in _______/_______ may be a marker of toxicity!

CNS / mental status