Pk 2-2

Front 1

pharmacokinetic-based theory on altered drug activity

Back 1

age-related decline of drug disposition & metabolism

Front 2

pharmacodynamic-based theory on altered drug activity

Back 2

altered quantity and/or quality of drug receptor sites

Front 3

general geriatric absorption changes (4)

Back 3

1. ↑ pH ( ↓ gastric acid secretion)
2. ↓ gastric (splanchnic) blood flow
3. ↓ gastric emptying rate
4. ↓ absorptive surface area (villa atrophy & ↑ mucosal connective tissue)

Front 4

↑ pH affect on drugs (2)

Back 4

1. dissolution rate of drugs
2. drug stability

Front 5

↑ pH affects which drugs and how? (5)

Back 5

1. penicillin (stabilized)
2. erythromycin (stabilized)
3. clorazepate (needs acid-cleaving, thus ↓ absorption)
4. dapsone (↓ absorption)
5. itraconazole (↓ absorption)

Front 6

↓ gastric (splanchnic) blood flow affect on which drugs and how?

Back 6

may ↑ availability of drugs w/ significant first-pass metabolism

Front 7

↓ absorptive surface area implications (2)

Back 7

1. ↓ active transport mechanisms (calcium, iron, thiamine, folic acid, sugars, amino acids)
2. no change in passive absorption

Front 8

extent of absorption

Back 8

unchanged in geriatrics

Front 9

Cmax in geriatrics & implication

Back 9

possible ↑ due to ↓ elimination

clinically manifest as delayed onset of action

Front 10

geriatric changes in distribution (3)

Back 10

1. alterations in body composition
2. alterations in serum proteins
3. perfusion

Front 11

alterations in body composition (2)

Back 11

1. ↓ TBW
2. ↓ lean muscle mass & ↑ body fat

Front 12

↓ TBW implications & drugs affected (7)

Back 12

↓ TBW, ↑ concentration of water soluble drugs

1. aminoglycosides
2. ethanol
3. lithium
4. procainamide
5. quinidine
6. theophylline
7. warfarin

Front 13

↓ lean muscle mass & ↑ body fat implications & drugs affected (5)

Back 13

↓ lean muscle mass & ↑ body fat , ↑ distribution of lipid soluble drugs thus delayed effect, drug accumulation, ↑ HL & prolonged action

1. TCA
2. benzodiazepines
3. barbiturates
4. steroids
5. phenothiazines

Front 14

alterations in serum proteins (2)

Back 14

1. ↓ albumin
2. ↑ alpha-1 acid glycoprotein

Front 15

↓ albumin implications & drugs affected

Back 15

↑ unbound fraction for highly bound acidic drugs

phenytoin

Front 16

↑ alpha-1 acid glycoprotein

Back 16

acute phase reactant that may be ↑ in elderly w/ multiple disease states, thus ↑ binding of highly basic drugs & ↓ in unbound drug fraction

lidocaine

Front 17

perfusion & implications (2)

Back 17

1. ↓ CO
2. ↓ Vd

Front 18

metabolic changes in the elderly (3)

Back 18

1. changes in liver composition
2. biotransformation
3. induction/inhibition of drug metabolism

Front 19

changes in liver composition (3)

Back 19

1. ↓ hepatic blood flow
2. ↓ hepatic mass
3. ↓ functional hepatocytes

Front 20

biotransformation (2)

Back 20

1. Phase I (p450, mixed function oxidase reactions) ↓ w/ age
2. Phase II (conjugation, glucuronidation, etc.) not changed w/ age

Front 21

Phase I drugs affected

Back 21

benzodiazepines

Front 22

changes in kidneys (3)

Back 22

1. ↓ renal blood flow
2. ↓ renal tubular function
3. ↓ GFR

Front 23

renally dose-adjusted antimicrobials (6)

Back 23

1. acyclovir
2. aminoglycosides
3. cephalosporins (most)
4. imipenem
5. penicillins (most)
6. vancomycin

Front 24

renally dose-adjusted cardiovasculars (3)

Back 24

1. atenolol
2. captopril
3. digoxin

Front 25

renally dose-adjusted H2 blockers (3)

Back 25

1. cimetidine
2. ranitidine
3. famotidine

Front 26

misc. renal dose-adjusted drugs (4)

Back 26

1. lithium
2. metformin
3. meperidine
4. procainamide

Front 27

drugs w/ ↑ receptor sensitivity (7)

Back 27

1. benzodiazepines
2. warfarin
3. hypotensives
4. central effects of anticholinergics
5. NSAIDs
6. phenothiazines
7. opiates

Front 28

drugs w/ ↓ receptor sensitivity (2)

Back 28

1. possibly CCBs
2. β-adrenergic blockers & agonists

Front 29

implications of ↓ beta receptor sensitivity

Back 29

Beta-adrenergic mediated signs of hypoglycemia may be attenuated in the elderly and delay its detection

Front 30

implications of ↓ adrenergic receptor sensitivity

Back 30

Diminished myocardial response to adrenergic stimuli may contribute to orthostatic hypotension

Front 31

↑ central effects of anticholinergics implications

Back 31

confusion, lethargy, drowsiness

Front 32

diuresis

Back 32

↑ sensitivity to diuresis

Front 33

electrolyte changes

Back 33

↑ effects of hyperkalemia & hyponatremia

Front 34

dopamine-receptor blocking agents (2) & implications

Back 34

ex. metoclopramide & antipsychotics may induce Parkinson’s like syndromes

Front 35

NSAIDS (2)

Back 35

1. ↑ susceptibility to the GI AEs of NSAIDS
2. avoid indomethacin because of ↑ risk of CNS toxicity (confusion, lethargy)