Basic Principles VII

Question 1

steady state

Answer 1

drug enters a compartment at a constant rate and is eliminated in a manner proportional to the concentration in the Vd. eventually the elimination increases to equal the rate of entry and steady state is achieved.

Question 2

repeated administration

Answer 2

repeated administration of a fixed dose of a drug at a fixed time interval. first order absorption and first order elimination. plasma concentration reaches steady state level.

Question 3

achieving steady state with repeat individual doses

Answer 3

when dose interval is approximately equal to half life or less, a steady state can be achieved

Question 4

loading doses

Answer 4

rapid attainment of therapeutic plasma level. used to change the steady state concentration

Question 5

iatrogenic toxicity

Answer 5

may be predictable, may be dose dependent

Question 6

spontaneous toxicity

Answer 6

not predictable, not dose dependent.

Question 7

allergy

Answer 7

immunologically mediated, reproducible in the same patient

Question 8

idiosyncratic

Answer 8

not immunologic, not necessarily reproducible

Question 9

tolerance

Answer 9

decreased response to continued administration. receptors and metabolism

Question 10

resistance

Answer 10

refractoriness to the drug effect. can happen in receptors as well as bacteria

Question 11

side effects

Answer 11

may be toxic, innocuous, or beneficial. secondary receptors or actions

Question 12

cumulation

Answer 12

drug administered faster than it can be eliminated. increase in plasma levels, toxicity possible.

Question 13

drug dependence/addiction

Answer 13

1. tolerance 2. homeostasis 3. physical withdrawal syndromes

Question 14

ED50, TD50, LD50

Answer 14

effective dose in 50% of the population, toxic dose in 50% of the population, and Lethal dose in 50% of the population

Question 15

margin of safety

Answer 15

TD50 - ED50

Question 16

therapeutic index

Answer 16

TI = Toxic Dose / Therapeutic Dose = TD50/ED50 - comparisons

Question 17

ideal clinic

Answer 17

TD1 / ED99

Question 18

drug interactions

Answer 18

direct molecular: antibiotics and calcium
change absorption
protein binding and displaceemnt
receptor effects (inhibition)
change metabolism
change excretion
change pH or other electrolytes

Question 19

unique features of newborn physiology

Answer 19

increased extracellular fluid. immature enzyme systems. decreased renal function. constant alteration of fluid composition with age. redistribution of circulation with shunting.

Question 20

factors influencing oral drug absorption in the newborn

Answer 20

gestational age, solubility of the drug, gastric emptying time (shortening increases absorption), gastric acidity, intestinal motility, presence of food in the stomach, splanchnic circulation

Question 21

causes of low drug binding in the newborn

Answer 21

low albumen, competitive binding. results in increased AVd

Question 22

drug biotransformation in the newborn

Answer 22

introduction of polar groups as well as conjugation

Question 23

rate of biotransformation slower in newborns

Answer 23

oxidation reactions slow. glucuronidation deficient at birth. acetylation somewhat deficient, hydroxylation depressed, sulfation active. rate varies with gestational maturity. postnatal maturation for individual drugs variable. vulnerability to pathologic states, alternative pathway activation

Question 24

factors influencing renal excretion of drugs in the newborn

Answer 24

low renal blood flow, low glomerular filtration rate, low tubular function, glomerular predominance, nephron heterogeneity.

Question 25

plasma half life in the newborn

Answer 25

much longer than in adults. very large individual variability

Question 26

therapeutic considerations in the newborn

Answer 26

elimination prolonged compared with distribution. apparent volume of distribution increased. loading dose higher per Kg. maintenance dose lower