Basic Principles V

Question 1

pharmacokinetics

Answer 1

• Vd and clearance

- used to determine how often to dose, size of dose, length of effect, when to redose

Question 2

kinetic compartments

Answer 2

• the fluid space containing the drug
• useful for the mathematical calculations
• view the complete body as one or two compartments for simplicity
• CSF plasma interstitial fluid intracellular fluid

Question 3

movement of drug through the fluid compartments

Answer 3

-drug–>ka of absorption–> volume = Vd, concentration Ct—> Ke of elimination

Question 4

single dose therapy

Answer 4

• at top of curve absorption=elimination
• duration of drug is when reaches threshold to when it goes below
• intensity is from threshold to peak
• therapeutic range is from threshold to above peak
• onset is from admin to when it reaches threshold
• see picture

Question 5

absorption kinetics

Answer 5

-absorption rates are related to the transport processes involved, either zero order (carrier mediated with saturated carrier protein at Vmax- not sensitive to drug concentration) or at first order- sensitive to drug concentration

Question 6

zero order rate

Answer 6

• Ct= ka x t
• ct concentration of a drug in a volume of distribution of a single kinetic compartment after time t for zero order absorption
• amount per unit time
• IV infusion, transcutaneous patch
• when plotted quantity absorbed vs time- slope is ka and is a linear relationship

Question 7

first order rate

Answer 7

• Ct = (M/Vd) ^ (1-e^-kat)
• a proportion per unit time
• oral absorption of lipid soluble drug
• with time approaches a maximum amount absorbed that hopefully equals most of the dose
• the larger the dose, the faster the concentration rises in the compartment
• curves up

Question 8

elimination kinetics

Answer 8

• cl=clmet + cl renal
• a rate limiting step determines the rate of elimination
• independent of drug concentration occurs if rate limiting step is
  1. insensitive to drug concentration
  2. is saturated

Question 9

zero order elimination

Answer 9

• an amount per unit time
• enzyme systems are saturated at vmax
• ethanol-drops 0.02 per hour
• Ct = Co- ket
• slope is a negative linear relationship
• slope is negative ke
• phenytioin- small change in dose causes large increases in steady state concentrations, some patients are more sensitive
• hourglass

Question 10

first order elimination

Answer 10

• logCt= log Co- ket/2.303
• a proportion per unit time
• log paper line has negative linear relationship
• more capacity- isn’t saturated as colander

Question 11

experimental single dose administration

Answer 11

• half life can be determined
• half life only applies to first order processes
• take a concentration and cut it in half and find time it takes to get to new concentration

Question 12

rates of decrease

Answer 12

• when Ct &laquo_space;km, it is k X ct (can drop Km
• when Ct&raquo_space; Km, it is Vm- a constant in that system
• drugs can go from 1st order to zero order
• higher capacity to lower- half life becomes irrelevant

Question 13

half life

Answer 13

• different for different drugs
• can be the same type of drugs, just in different classes
• half life depends on what you are using drug for
• equal to 0.693/ke- physiologic parameter a person has
• therefore it is constant

Question 14

Vd, clearance, and half life

Answer 14

• c= dose/vd
• vd= dose/ co
• clearance = vd x ke
• half life = 0.693Vd/ Cl
• a decrease in clearance from renal or hepatic failure will increase half life