Lec 4- IV bolus dose

Question 1

Terminology

Answer 1

• T_1/2-
• C₀-
• K_el -
• Cl -
• V_d-
• IV bolus does- direct injection into venous circulation F=100%

Question 2

IV bolus dose- calculations

First order kinetics

Answer 2

• The rate of change of drug depends on the amount of drug present
• Need rate of reaction changes
• Need to transform into a linear graph
  
  • C_p=(C_p)₀e^-Kt => InY= lnY₀ - Kt

Question 3

Calculation (graphical analysis)- zero and first order

Answer 3

• Pharmacokinetics of most drugs is typically classified by the way it eliminates from the body, and nearly all of PK deals with 1st order reactions
• C_P= (C_P)₀e^-Kt
• lnY (concentration) = lnY₀ (intercept) - Kt (gradient x time)
  
  • Need log transformation to anlayse information- must be straight line

Question 4

Calculation (graphical analysis)

Answer 4

• Conc =(ln)=> ln(conc)- can be -ve sometimes
  *

Question 5

Why is this important

Answer 5

• Once you calculate the gradient and intercept (basic maths) then you are then able to calculate other important pharmacokinetic terms
• T_1/2
• C₀
• Kel
• Cl
• V_d

Question 6

Calculations- linear graph paper with natural log (Ln)

Answer 6

• You may need to extrapolate the line back to get the initial concentration (C₀)
• This will need to be anti-logged (e^x) on the calculator to get the true concentration
• Gradient: The gradient will be -ve; NO NEED TO ANTILOG
• Ignore the negative sign
• Gradient = k (elimination rate)
• K = slope = (C1 - C0) / (t1 - t0)

Question 7

Case study Vancomycin: dosing

Answer 7

• Vancomycin is an antibiotic often used for the treatment of serious bacterial infections
• The minimum effective plasma concentration is 10mg/mL
• When do we need to give a second dose to this patient?-
• About 74 hours

Question 8

Case study 2 Gentamicin: Dosing

What is the concentration after 8 hours in this patient (method 1)

Answer 8

• Gentamicine is another antibiotic often used for the treatment of serious infections
• Convert half life to elimination rate
• t_1/2 = (0.693)/k = Ln2/k
• 0.693/4 = 0.173 h^-1
  *

Question 9

Case study 2 gentamicin: dosing

How to calculate conc after 8 hours

Answer 9

Question 10

The relationship between parameters- everything is related

Answer 10

Question 11

relationship between parameters- What two things change

Answer 11

• 2 things that have changed
  
  • Concentration- what can make the concentration different- Vd
  • Gradient- elimination rate
  • Distribution- more distributed- why gradient is not as steep

Question 12

Impact of changes: Vd

Answer 12

Question 13

Case study 3: impact of changes- volume of distribution

Answer 13

• Concentration- Larger volume; Small concentration
• Elimination rate- Larger volume; More distribution; Longer to eliminate
• Half-life- Larger volume; More distribution; Longer to eliminate

Question 14

Case study 3

Impact of changes: volume of distribution

Answer 14

• V_d is VITAL in determining the right starting dose of a drug
• In this example the Vd of the drug has changed (i.e. during kidney disease and following recovery)

Question 15

Case study 3

Impact of changes- clearance

NB- just check the equations are on the equation sheet

Answer 15

• AUC= how much is the drug exposed to the patient
• Each drug has it’s own CL
• CL can be impacted by
  
  • Drug-drug interactions
  • Ageing (Cardiac output)
  • Disease-induced (renal/liver failure; protein binding)
• Deciding on whether clearance is good or bad, depends on where the therapeutic window is