Weakness

Question 1

What are the 5 I’s of Geriatrics?

Answer 1

• Impaired homeostasis
• Incompetence
• Incontinence
• Impaired mobility, falls, weakness
• Iatrogenesis

Question 2

How common are iatrogenic illnesses in older patients?

What kind is the most common?

What is the result?

Answer 2

• 1/3 acutely hospitallized older patients
• Adverse drug reactions
• Functional losses & increased costs

Question 3

What are some factors that affect drug disposition & response in the elderly?

Answer 3

• Body composition
• Reduced TBW
• Reduced lean body mass/weight
• Increased body fat
• Protein binding
• Reduced serum albumin

Question 4

Elderly Patients

Drugs that distribute to body fat will have a (higher/lower) volume of distribution.

Drugs that distribute to TBW will have a (higher/lower) volume of distribution.

Answer 4

Drugs that distribute to body fat will have a higher volume of distribution.

Drugs that distribute to TBW will have a lower volume of distribution.

Question 5

What are the functions of the kidney?

Answer 5

• Excretion of metabolic waste products & foreign chemicals
• Regulation of water & electrolyte balances
• Regulation of body fluid osmolality & electrolyte concentrations
• Regulation of arterial pressure
• Regulation of acid-base balance
• Secretion, metabolism & excretion of hormones
• Gluconeogenesis

Question 6

Estimate the interstitial fluid volume of a healthy individual with a body mass of 60 kg.

• 36 liters
• 24 liters
• 12 liters
• 9 liters
• 3 liters

Answer 6

9 liters

• ICF = 40% body weight
• ECF = 20% body weight
• Interstitial fluid = 3/4 ECF
• Plasma volume = 1/4 ECF

Question 7

What is the equation for blood volume?

Answer 7

Plasma volume/(1-Hct)

Question 8

An individual of normal body composition (plasma osmolarity = 280 mOsm/l) ingests 1 liter of a solution containing 200 mmole/L NaCl. After equilibrium of body fluids, & before any renal excretion has occurred, which statement will be true?

• His TBW is reduced compared to initial conditions
• His interstitial fluid osmolarity will be reduced compared to initial conditions
• His plasma volume will be reduced compared to initial conditions
• His intracellular fluid osmolarity will be increased compared to initial conditions
• His intracellular fluid volume will be increased compared to initial conditions

Answer 8

His intracellular fluid osmolarity will be increased compared to initial conditions

• The ingestion of a hypertonic NaCl solution will lead to an increase in TBW, an increase in ECFV & an increase in osmolarity is all fluid compartments, & a decrease in ICFV

Question 9

What is the composition of the fluid in the different compartments?

Answer 9

water, electrolytes, non-electrolyte small molecules, protein

Question 10

What is the difference btwn plasma & interstitial fluid?

Answer 10

• Plasma ~ interstitial fluid, except for more proteins in plasma
• Capillary wall is highly permeable to water, electrolytes, and other small molecules, but not proteins

Question 11

What is the difference btwn ECF & ICF?

Answer 11

• ECF & ICF have substantial differences
• The cell membrane is highly permeable to water, but not to most electrolytes or proteins
• ECF: high in Na⁺, Cl^-, HCO₃^-
• ICF: high in K⁺, PO₄^3- & organic anions, protein

Question 12

What is responsible for the distribution of Na⁺ & K⁺ btwn ECF & ICF?

What is the barrier?

Answer 12

• Na⁺/K⁺ ATPase
  
  • 3 Na⁺ out, 2 K⁺ in
• Barrier: cell membrane
• Distribution governed by osmotic forces

Question 13

What is the definition of osmolarity?

Answer 13

• A function of the total number of particles in solution, independent of mass, charge or chemical composition
• The concentration of osmotically active particles in total solution
• Expressed in mOsm/L of water

Question 14

Osmolarity

For substances that do not dissociate into smaller particles when dissolved….

For substances that dissolve into 2 particles or 3 particles…..

Answer 14

• For substances that do not dissociate into smaller particles when dissolved
  
  • 1 mmole = 1 mOsm
• For substances that dissolve into 2 or 3 particles, the osmolarity will be double or triple the molarity
  
  • 1 mmole NaCl = 2 mOsm

Question 15

What is the definition of osmosis?

Answer 15

• The movement of water across a semi-permeable membrane due to differences in osmolarity (osmotic pressure gradient)
• A 1 mOsm/L difference in osmolarity can exert an osmotic pressure equivalent to 19.3 mmHg

Question 16

What is the influence of adding isotonic, hypotonic and hypertonic NaCl solutions to the ECF on TBW, ECFV & ICFV?

Answer 16

Question 17

What is a common pneumonic used when determining a differential diagnosis?

Answer 17

IPINGII

• Infection, infestation
• Physical/traumatic
• Immune
• Neoplastic
• Genetic/metabolic
• Iatrogenic
• Idiopathic

Question 18

What are some changes related to aging that affect pharmacokinetics of drugs?

Answer 18

• Decreased body water
• Decreased lean body mass
• Increased body fat
• Decreased serum albumin
• Decreased kidney weight
• Decreased hepatic blood flow

Question 19

Which of the following medications should be avoided as hyponotics in older patients?

• Diazepam
• Flurazepam
• Oxazepam
• Lorazepam

Answer 19

Diazepam, Flurazepam

• Phase I hepatic metabolism affected by aging
• Phase II hepatic metabolism NOT affected by aging (Oxazepam, Lorazepam)

Question 20

In which drugs is there an age-related decreased in hepatic clearance?

Answer 20

• Alprazolam
• Barbiturates
• Carbenoxolone
• Chlordiazepoxide
• Chlormethiazole
• Clobazam
• Desmethyldiazepam
• Diazepam
• Flurazepam
• Imipramine
• Meperidine
• Nortriptyline
• Phenylbutazone
• Propranolol
• Quinidine, quinine
• Theophylline
• Tolbutamide

Question 21

In which drugs is there no age-related difference found in hepatic clearance?

Answer 21

• Ethanol
• Isoniazid
• Lidocaine
• Lorazepam
• Nitrazepam
• Oxazepam
• Prazosin
• Salicylate
• Warfarin

Question 22

Describe Phase II hepatic metabolism

Answer 22

• Mediated by cytoplasmic enzymes
• Addition of water soluble moieties to drugs (acetylation, glucuronidation, sulfation, glycine conjugation)
• Not commonly altered with age

Question 23

How does creatinine clearance change with age?

Answer 23

• GFR decreases with age
• Creatinine clearance decreases with age
• Total body production decreases with age
• However, serum concentration doesn’t change very much because you don’t make as much, it no longer reflects renal function

Question 24

How is creatinine clearance calculated?

Answer 24

Cockgroft Gault Equation for Creatine Clearance​

• For women, multiply by 0.85

Question 25

What are the 4 kidney processes that determine the composition of urine?

Answer 25

* Filtration * Reabsorption * Secretion * Excretion

Question 26

You obtain the following experimental data from a 70 kg male subject: UFR = 1.0 ml/min, P_IN = 1.0 mg/ml, P_PAH = 1.0 mg/ml, U_IN = 60 mg/ml, U_PAH = 650 mg/ml, Hct = 50%. What is this individual's GFR? * 30 ml/min * 60 ml/min * 120 ml/min * 650 ml/min * 1300 ml/min

Answer 26

**60 ml/min** * **GFR = [UFR\*U_IN]/P_IN** * GFR = [(1 ml/min)(60 mg/ml)]/(1.0 mg/ml) * GFR = 60 ml/min

Question 27

What is the definition of mass balance for the kidney? For the nephron?

Answer 27

renal arterial input = urine output + renal venous & lymphatic output filtered + secretion = reabsorption + excretion

Question 28

How is inulin filtered through the kidney? How can this be used to estimate GFR?

Answer 28

* Inulin is freely filtered at the glomerulus but is not reabsorbed or secreted * Filtration of inulin = excretion of inulin * GFR x P_IN = UF x U_IN * **GFR = (UF x U_IN)/PIN**

Question 29

What is the definition of clearance? How is it calculated?

Answer 29

* The volume of plasma from which a substance has been removed & excreted into the urine per unit of time (volume/time) * **C_X = (UF\*U_X)/P_X** * Clearance of creatinine can be used to measure GFR with an endogenous compound

Question 30

A normal individual receives a drug that effectively halves his glomerular filtration rate. After a period of 2 wks on this drug, this patient will have ______ plasma creatinine concentration, _______ creatinine clearance rate, and _________ creatinine excretion rate compared