L41 - IV Bolus 1

• What is meant by parenteral administration?

  Sterile preparation of drugs injected through 1+ layers of skin/mucous membrane.
• What's meant by intravenous administration?

  
  

  Name the major benefit.

  Drug injected directly into vein via syringe/needle.

  
  

  - 100% bioavailability; ensures ALL dose enters systematic circulation.
• Describe IV Bolus administration.


  Drug solution injected directly into the vein over a short period of time (s to min).

  
• What are some advantages of IV Bolus administration?

  - Get high [drug] conc very fast.

  
  

  Good in emergencies!

  
  

  - No absorption step required.

  
  

  - Bypasses hepatgic first pass.

  
• What are some disadvantages of IV Bolus administration?

  -Toxicitymonitoringrequried.

  -Irritation: lots of drug given in a small amount of time.

  - No dilution of formulation at injection site.

  
• Name the ADME processes that occur following IV administration.

  - Distribution.

  
  

  - Metabolism.

  
  

  - Elimination (metabolism + excretion).

  
  

  - Disposition (distribution + elimination).

  
  

  - Plasma binding.

  
• Describe plasma profiles for IV Bolus.

  
  

  - What is plotted?

  - What does the line look like?

  - What are the 2 main phases?

  - Usually C (mg/L) against time (h).

  
  

  - Rapid decline, then more slow.

  
  

  - Distribution phase and Elimination phase.

  
• What is the decline in [drug] plasma levels primarily due to?

  Distribution of the drugs to the tissues

  
• When does elimination occur?

  - All throughout.

  
  

  - But terminal phase occurs when equilibrium of distribution in plasma-tissues is achieved.

  
  

  - Decline in [drug] plasma levels primarily due to loss of drug from body.

  
• Describe the One Compartment Model

  Drug assumed to rapidly distribute into a homogeneous fluid volume in the body as soon as it's injected.

  
  

  Body is "one compartment".

  
  

  Simplest model as only accounts for elimination.

  
• When can we use the One Compartment Model?

  
  

  What does it account for?

  - When elimination is 1st order: [conc] declines exponentially.

  - Distribution is instantaneous.

  - Linear kinetics.

  - Accounts foreliminationonly.

  
• What is assumed in a TWO compartment model?

  
  

  What does is account for?

  - Central and Peripheral compartments.

  - Drug rapidly distributes to central compartment ( plasma and tissues).

  - Slow to distribute to peripheral compartments (deeper tissues)..

  - Accounts for bothdistributionandelimination.
• What does a ONE compartment model for IV Bolus assume?

  - Compartment volume = Volume of Distribtuion (Vd).

  
  

  - Elimination is a 1st order process (k=rate constant).

  
  

  - Elimination follows linear kinetics.

  
  

  - No saturation of enzymes/transporters.

  
• What are the equations for the Amount of Drug in compartment body with time?

  A = A0 x e^-kt.

  
  

  OR

  
  

  lnA = lnA0 - kt.

  
• What is the rate of elimination proportional to?

  
  

  Eqn?

  - Elimination rate is directly proportional to Amount of drug.

  
  

  k = elimination rate (mass/time) / Amount

  
• Which equation tells us how the conc of a drug has evolved after IV Bolus injection?

  C = C0 x e^-kt.

  
  

  OR

  
  

  lnC = lnC0 - kt

  
• What's the eqn for Volume of Distribution?

  Vd = Amount / C0

  
• What happens to [drug], Cp after injection?

  Declines exponentially sue to 1st order elimination

  
• How do you work out the initial concentration when given dose and Vd?

  C0 = Dose/Vd

  
• How can you find the value of k?

  - Plot lnC against T and find gradient (-k).

  
  

  - Use lnA = lnA0 - kt.

  
  

  OR lnC = C0 - kt.

  
• How can you transform exponential eqns into linear?

  
  

  What do we plot?

  
  

  What's the gradient/intercept?

  Take natural logs (ln) of both sides.

  
  

  If kinetics are linear, plot lnA or lnC by T to give a straight line with a gradient of -k.

  
  

  Intercept = lnA0 or lnC0.

  
• What are the general eqtns describing plasma leveld following IV Bolus administration?


  lnC = C0 - kt.

  
  

  C = Co x e^-kt