Physiologic changes related with aging

  • Ocular (vision):  decreased accommodation of the lens of the eye leads to the elderly being more farsighted
    • Other vision problems:  glaucoma (especially in blacks), age-related macular degeneration, yellowing of the lens, cataracts (lens opacity)
    • Treatment of vision problems is generally surgery
    • Glaucoma (optic nerve damage) is the leading cause of blindness in the US
      • Angle closure glaucoma is a medical emergency
      • Primary open-angle glaucoma is treated with pharmacotherapy (adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors, latanoprost, pilocarpine)
  • Auditory:  impaired sensitivity to sound, delayed processing of auditory changes & a decrease in high frequency hearing
  • CNS:  cerebral blood flow decreases, BBB becomes more permeable, decline in short term memory, brain atrophy is common
  • Renal:  decreased GRF, renal mass & blood flow
  • CV:  decreased myocardial sensitivity to beta-adrenergic stimulation, baroreceptor activity & overall cardiac output
    • Increased total peripheral resistance
  • Pulmonary:  decreased gas exchange
    • Increased chest wall rigidity
  • Body composition:  increased fat but decreased lean tissue & decreased TBW
  • GI:  decreased saliva production, esophageal motility, HCl secretion & gastric emptying rate
    • Increased gastric emptying time
  • Skin/hair:  skin dryness, wrinkling, changes in pigmentation, epithelial thinning, loss of dermal thickness, decrease in the number of hair follicles & the number of melanocytes in hair bulbs
  • Genitourinary:  atrophy of vag due to decreased estrogen production, BPH due to androgenic hormonal changes, age-related changes may also lead to incontinence
  • Generally speaking:  there is a decrease in functional reserve capacity & thus there’s a decreased ability to preserve homeostasis which results in a decreased ability to respond to stress & therefore even little stressors can result in major morbidity & mortality

Pharmacokinetic and pharmacodynamic changes associated with aging

  • Absorption
    • GI:  decrease in active transport (problem with vit B12, Ca, Fe, gabapentin), decreased first pass extraction & thus increased bioavailability for some drugs, decreased GI blood flow, delayed gastric emptying
      • Increased gastric pH
      • All of these together don’t significantly change the quantity of drug absorbed but they may affect the time to onset or peak concentrations
      • Drug absorption may also be affected by the elderly having swallowing difficulties, poor nutritional status, erratic meal patterns, interactions w/ other drugs or other comorbities
    • Transdermal, SQ, IM
      • Atrophy of the epidermis & dermis in addition to decreased tissue blood perfusion may result in a decreased rate of transdermal drug absorption, decreased/variable rate of IM/SQ drug absorption
  • Distribution
    • Decreased TBW & lean body mass in combo with Increased body fat
    • Decreased Vd & increased concentration of water-soluble drugs (EtOH, digoxin, Li, theophylline)
    • Increased Vd & increased half life for fat soluble drugs (valium, amiodarone, verapamil)
    • Protein binding
      • May have the same or decreased serum albumin which binds to acidic drugs (phenytoin & warfarin)
        • The lower the serum albumin, the higher the concentration of free drug
      • Increased alpha-1-acid glycoprotein (AAG) which is a marker of inflammation & binds to basic drugs
      • Overall:  may either have an increased or decreased free fraction of highly plasma protein bound drugs
  • Metabolism:  decrease in liver size & blood flow resulting in a decreased metabolism of high extraction ratio drugs
    • All of this results in a decrease in phase 1 (Redox reactions) metabolism (decreased drug clearance, increased half life)
    • Generally only phase 1 reactions are affected (phase 2, CYP, enzymes are generally unaffected)
  • Elimination:  decreased GFR, renal mass & blood flow
    • Results in decreased clearance & increased half-life of renally eliminated drugs & active metabolites
    • SCr isn’t a reliable measure of renal decline in the elderly b/c they can have significantly decreased renal function but yet have normal SCr
      • CrCl:  30-60 requires a minor dosage adjustment for renally eliminated drugs,   15-30 requires a moderate dose adjustment & < 15 mL/min requires a major dose adjustment
        • Watch out for renally eliminated drugs that also have active metabolites (ex. Meperidine, morphine & carbamazepine)
      • GFR is a more accurate measure of renal function in the elderly
        • GFR decreases by 25-50% in the elderly

Drug therapy needs to be modified based on the pharmacokinetic and pharmacodynamic changes observed in elderly patients

  • There is also evidence of altered sensitivity to drugs in older adults
    • Possible mechanisms for altered drug response:  change in the # of receptors, receptor affinity, post-receptor alterations, or age-related impairment of homeostatic mechanisms
  • CV:  decreased homeostatic mechanisms.  Increased susceptibility to orthostatic hypotension when taking CV drugs (especially with CCBs)
    • Decreased beta-adrenergic receptor function (less sensitive to both agonists & antagonists)
    • Increased risk of QT prolongation & torsades
    • Start low & go slow
  • CNS:  BBB is more permeable, decrease # of cholinergic neurons, increased Ach-esterase, increased # of dopamine type 2 receptors, decreased # of dopamine & dopaminergic neurons in substantia nigra
    • Alcohol increases drowsiness, increased CNS response to benzos, increased analgesic response to opioids, more susceptible to delirium & EPS
    • Selective decline in cholinergic neurons (avoid anticholinergic meds)
      • Anticholinergic meds can cause increased mental confusion, memory impairment, delirium, constipation, BPH, incontinence, glaucoma
      • Need to look at the anticholinergic load (how many anticholinergic meds is the patient taking)
        • Med scale:  0 = none     1 = moderate    2 = strong   3 = very strong      (higher the score, the more adverse effects)
          • Highest scores:  antispasmodics (ex. Hyoscyamine), antiparkinsons drugs (ex. Benztropine), muscle relaxants, antihistamines, hypnotics (ex. Hydroxyzine), antidepressants (ex. amitriptyline), antipsych (ex. Thiodiazine)
            • Antiarrhythmics (ex. Quinidine) & herbs (ex. Nightshade) are also noted but aren’t ranked
        • Want to reduce the # of meds w/ similar SE profiles
  • Fluids & electrolytes:  Elderly are at an increased risk of dehydration, hyponatremia, hyperkalemia & prerenal azotemia especially when on a diuretic
  • Decreased glucose tolerance with age
  • Increased effects of warfarin  (greater inhibition of vitamin K dependent clotting factors)
  • Drug therapy modifications should especially be considered for high-risk elderly patients {i.e. patients who are taking many drugs & those on high risk drugs (ex. Warfarin, digoxin, insulin, etc)}

Laboratory values that may be affected with aging

  • Lab values may or may not change with age
  • There aren’t really reliable reference ranges for lab values in the elderly so generally use the same range as used for younger adults
    • More difficult b/c of multiple disease states, polypharmacy, atypical disease presentation, med therapy that alters lab test results
      • Misinterpretations are common
  • Serum albumin decreases slightly (usually due to malnutrition, disease or being hospitalized)
  • Fasting glucose is usually higher in the non-diabetic elderly  (decreased glucose tolerance)
  • Uric acid rises minimally with age (may be due to decreased renal function)
  • Total cholesterol increases by 30-40 mg/dL by age 55 in women & age 60 in men
  • Triglycerides increase by 30% in men & 50% in women between ages 30-80
  • Serum B12 concentrations slightly decrease
  • Alkaline phosphatase increases by ~20% in ppl between age 30-80  (probably due to changes outside the liver)
  • CrCl decreases by ~ 10 mL/min/decade
    • SCr may be normal even though CrCl is decreased
  • Hypernatremia = dehydration
  • Hyponatremia = probably caused by a drug
  • Serum Mg decreases over time
  • Erythrocyte Sedimentation Rate (ESR–sign of inflammation) increases with age
    • Normal ESR in men = age/2
    • Normal ESR in women = (age + 10) / 2
  • Hypothyroidism is more common in the elderly
  • PSA levels usually increase with age
  • Anemia:   Hgb < 13 g  in men         Hgb < 12 g in women

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