Preventing prescribing cascade:
- avoid prescribing until results confirm suspected diagnosis
- start with low dose and titrate slowly
- when possible, avoid starting multiple meds simultaneously
- reach therapeutic dose before swithing or adding agents
Pysiological change with aging - Body composition:
- dec total body water
- dec lean body mass
- inc body fat
- same or dec serum albumin
- inc alpha1 acid glycoprotein
Pysiological change with aging- cardiovascular
- dec myocardial sensitivity to beta-adrenergic stimulation
- dec baroreceptor activity
- dec cardiac output
- inc total preiph resistance
Pysiological change with aging - liver
- dec hepatic size
- dec hepatic blood flow
- dec activity of Phase 1 enzymes (p450s)
- PHase 2 is NORMAL
- clearance of a drug is decreased
Pysiological change with aging - renal
- dec GFR
- dec RBF
- dec filtration fraction
- dec tubular secretory function
- dec renal mass
What parameter of pharmacokinetics is least effected by aging?
absorption/bioavailability
What are drugs that have decreased absorption bc of dec stomach acidity?
- digitalis
- ampicillin
Highly lipophilic drugs - what happens to volume of distribution?
-huge dec INC? in volume of distribution - most drug wll bind to lipid
Higher concentration drug in the plasma - relationship to distribution in the blood?
lower Vdistribution bc its not in the tissues
Plasma binding factor
- effect on Vd
- age related changes?
- hgihly protein bound = cant distribute to tissues = smaller Vd
- dec ablumin=binds acidic drugs
- inc alpha1 glycoprotein binds to basic drugs
Tissue binding properties
- effect on Vd
- age related changes?
- tightly bind tissues = higher Vd
- dec lean body mass
- inc adiposity
- Digoxin and Vd in elderly?
- how to fix dosing?
- Digoxin likes to bind muscle –> so less muscle in elderly = inc active fraction in circulation
- need to give lower dose
Lipid to water coefficient
- effect on Vd
- age related changes?
- lipid soluble drugs like to pass through lipid membranes so they like to enter tisses more = larger Vd
- water soluble have lower Vd
- inc in body fat–>Inc Vd for lipid soluble
- dec body water–>dec Vd for water soluble
How to give loading dose of water soluble drugs in elderly
-must decrease loading dose to avoid toxicity from high initial concentration
Clearance of a drug and flow rate limited phase 1 eliminated drugs?
Dosing?
- clearance will be decreased
- dosing will need to be decreased
Clearance of a drug and liver enzyme function (capacity limited) drugs?
-Dosing changes for phase 1 and 2 eliminated?
- No change in clearance or dosnig if phase 2 metabolized drug
- dec clearance and dosing if metabolized by phase 1 drugs
How to dose drugs with a narrow therapeutic index (warfarin and gentamycin) in elderly with dec kidney function
must use the cockcroft gault (measure of creatiniine clearance) equation bc there is individual variability.
What is a more accurate measure of creatinine clearange?
-use direct creatinine clearance measurement - need 24 hr urine collection and not cockcroft gault equation
CALCULATE halflife of a drug?
t.5=.693XVd/CL
two factors that have greatest effect on the halflife of a drug?
decreased hepatic and renal function
GI issue with aging+drug?
- decreased acid = dec absoption of some drugs
- dec first pass extraction and inc bioavailability for some drugs
- no change in most drugs
Distribution issue with aging +drug?
- dec Vd and inc plasma concentration for water sol drgs
- inc Vd and inc terminal deposition halflife for fat soluble drugs
- inc or dec free fraction of highly plasma protein bound drugs
Hepatic metabolism issue with aging+drug?
- dec clearance and inc t.5 for some oxidatively metabolized drugs (Phase 1 metabolism)
- dec clearance and inc t.5 for drugs that are flow limited
Renal excretion issue with aging + drug?
-dec clearance and inc t.5 for renally eliminated drugs and active metabolites
