Dosificació antibiòticaSantiago Grau Cerrato

Servei de Farmàcia

Hospital del Mar

Barcelona

Physiologic and pharmacokinetic changes in elderly patients

Physiologic change Potential pharmacokinetic effect

Absorption

Increased gastric pH

Decreased small bowell surface area

Decreased blood flow to small bowell

Decreased gastric emptying and gastrointestinal motility

Decreased absorption pf pH-dependent antimicrobials andincreased absorption of acid-labile antimicrobials

Decreased absorption

Decreased absorption

Decreased or delayed absorption

Physiologic and pharmacokinetic changes in elderly patients

Physiologic change Potential pharmacokinetic effect

Distribution

Increased ratio of adipose tissue to Lean tissue

Decreased total body water

Decreased plasma albumin level

Increased plasma alfa1-acid glycoprotein level

Increased half-life of lipid-soluble antimicrobials

Increased concentration of water-soluble antimicrobials

Increased free concentration of acidic antimicrobials(penicillins, ceftriaxone...)

Decreased free concentration of basic antimicrobials(macrolides)

Physiologic and pharmacokinetic changes in elderly patients

Physiologic change Potential pharmacokinetic effect

Metabolism

Decreased phase 1 enzyme (CYP 450) activity

Decreased hepatic blood

Increased half-life of antimicrobials metabolized byphase 1 enzimes

Decreased first-pass metabolism

Physiologic and pharmacokinetic changes in elderly patients

Physiologic change Potential pharmacokinetic effect

Elimination

Decreased renal blood flow and glomerular filtration rate

Increased half-life of renally eliminated antimicrobials

Physiologic and pharmacokinetic changes in elderly patients

Increasedproportion of adipose tissue

Increasedaccumulation of lipophilic drugs

Volume of distribution

Prolonged drughalf-life

Standard dose isinadequate

RifampinFluroroquinolones

MacrolidesOxazolidinones

TetracyclinesAmphotericin B

Imidazole antifungals

Physiologic and pharmacokinetic changes in elderly patients

Decreased in total body water

and lean mass

Decreaseddistribution of water soluble

drugs

Volume of distribution

Increased plasma concentrations

Standard dose isinadequate

AminoglycosidesGlycopeptidesBeta-lactams

Physiologic and pharmacokinetic changes in elderly patients

Increasedproteinuria or

decreased albuminproduction due to

chronic disease

Decreased plasma albumin

Volume of distribution

Decrease in protein-bound drug fraction

(inactive) and increase in free drug

in plasma (active)

Standard dose isinadequate

Physiologic and pharmacokinetic changes in elderly patients

Physiologicalaging

Liver disease

Decreasedhepatic blood

flow or decreasedfunction

Drug metabolismIncreased half-life

of hepaticallycleared drugs

Standard dose isinadequate

MacrolidesTetracyclines

Fluoroquinolonesantifungals

Physiologic and pharmacokinetic changes in elderly patients

Polypharmacy(concomitant

disease)

Competitionfor CYP-450metabolism

Drugmetabolism

Inhibition of metabolism of

competingdrug-

accumulationof

unmetabolizedform

Enhacedmetabolism

of competingdrug-

increaseddrug activity

Competitionfor albumin

binding sites-accumulation

of drug notpreferentially

bound to albumin

Standard dose isinadequate

Physiologic and pharmacokinetic changes in elderly patients

Reduced renal function

Decreased blood flowDecreased glomerular

filtration rateDecreased drug removal

Renal drug elimination

Increased drug-half-life, inability to remove drug

from the plasma, accumulation of drug in

plasma

Dose adjustment forsome drugs based on

type of therapy

Objective

To examine whether living in a nursing home with high antibiotic use associated with an increased risk of antibiotic-related adverse outcomes for individual residents.

110.656 older adults 607 nursing homes

50.953.000 resident-days

55 antibiotic-days/1.000 resident-

days

20,4/1.000 resident-days

192,9/1.000 resident-days

Antibiotic treatmentprovided2.783.000

P<0,001

Fluoroquinolones• Cardiac toxicity (QT) (dose-dependent?)

• Hypoglycemia

• CNS: headache, confusion, tremor, dizziness, anxiety, insomnia, hallucinations(especially >80 years old; dose not renally adjusted)

Beta-Lactam agents

• Well tolerated

• Most renally excreted

• Cephalosporins (e.g. ceftazidime, cefepime): concern for non convulsive status epilepticus, esp without dose adjustment

Nitrofurantoin

• Decreased activity with decreased renal function

• Cutoff: CrCl </= 60 ml/min vs 40 ml/min ??

• Concern of serious liver, lung toxicity with longer term treatment (e.g., prophylaxis)

• Peripheral neuropathy

• Dose-dependent?

Aminoglycosides

• Increased risk of toxicity vs other agents

• Nephrotoxicity, ototoxicity: increased risk in elderly, dehydration, pre-existing renal

• Needs monitoring!! CLcr (2-3 x / week), levels

• Renally eliminated; need dosing adjusted; lower doses

Compliance

• Polypharmacy

• Fear of interactions

• Inability to follow directions

• Poor comprehension/memory

• Adverse effects

Conclusions

• Numerous challenges associated with antibiotic use exist in the elderly

• Antibiotics can be life saving drugs, but also carry significant potentialharms

• Risks of adverse effects and antibiotic resistance can be minimized in theelderly by:

• Appropriate dosing in patients with decreased renal/liver function

• Attention to drug interactions, especially in patients on multiple medications