Basic Pharmacokinetics Flashcards
What is Pharmacokinetics ?
Pharmacokinetics is what the body does to a drug
What is volume of distribution ( V )
Volume of fluid in which total amount of drug in body would need to be distributed to give a concentration equal to the concentration measured in plasma
What does the one compartment model show ?
The one-compartment open model is the simplest way to describe the process of drug distribution and elimination in the body. This model assumes that the drug can enter or leave the body (ie, the model is “open”), and the entire body acts like a single, uniform compartment. The simplest route of drug administration from a modelling perspective is a rapid intravenous injection (IV bolus). The simplest pharmacokinetic model that describes drug disposition in the body is the IV bolus model where the drug is injected all at once into a box (the human body) or compartment, and the drug distributes/equilibrates instantaneously and rapidly throughout the compartment. Drug elimination from the compartment also begins to occur immediately after the IV bolus injection.
Refer to BASIC PK 1 PPT
Volume of compartment = Dose / concentration of drug
V = D/C
Magnitude of V
The magnitude of v depends on the drug in plasma vs the drug in tissue .
A small V - more drug in plasma - shows that its more water soluble - plasma protein binding - larger Relative molecular mass meaning its harder for it to pass through the capillaries
A larger V = drug is held more in the tissue - binding to tissue proteins - smaller RMM which shows that it is easier for a drug to pass through the capillaries
What does V tell us ?
Where the drug is distributed in the body
the physiochemical properties of the drug
The amount of drug in the body at a particular time, if the conc of the drug is sampled
Calculation of loading dose of a drug
Patient factors which can be affecting V
Liver, renal or cardiac impairment
Reduced blood perfusion to tissues
Changes in plasma protein binding
Old age
Pregnancy
What is Loading Dose ?
Loading dose is when a higher dose of a drug is given so that therapeutic effects are achieved faster.
When might a LD be given ?
If the drug has a long elimination half life
in acute conditions
in life threatening arrythmias
Calculating Loading Dose
LD = DESIRED C X V
/ S X F
If the patient already received the drug
Incremental LD =
(DESIRED C - MEASURED C ) X V
/ S X F
S = SALT FACTOR OF THE DRUG
F = BIOAVAILABILITY
What is the elimination rate constant K ?
Ct = Co - Kt (Refer to BK2 ppt )
K is fraction of drug dose eliminated from compartment per unit time
Amount of drug eliminated decreases as plasma concentration decreases
But fraction of drug eliminated is constant
What is the clinical importance of K ?
Larger K means faster rate of drug elimination from body
Drugs with rapid elimination have a short duration of effect after a single dose
Drugs eliminated more rapidly would need to be given more frequently
Drugs eliminated more slowly should be given less frequently
What is half life (T 1/2 )
Half life is the time taken for plasma drug conc to fall by half of what it was at beginning of measurement period.
It is another index rate of drug elim along with K
Calculation of half life
A drugs half life is determined by its clearance and volume of distribution
CL=KV
REFER TO BK 2 PPT
What is the steady state ?
Rate or drug going in = rate of drug going out
Time to steady state
time to steady state varies from drug to drug
High K - short half life - steady state reached quicker than lower K and longer half life
Factors affecting half life ?
Volume of distribution
Large v = little drug in plasma = longer half life
Small V - most of drug in plasma = shorter half life
Clearance
High clearance = shorter half life
Lower clearance = Longer half life
Disease can decrease both v and cl
Hepatic or renal failure reduces drug clearance
PPI’S
Have a short elimination half life about 1 hr which indicates they are fast acting. effects of PPI last about 24 hrs
PPIS take 2-3 days to achieve steady state inhibition of acid secretion
increasing dose doesn’t have much further effect once optimal is reached
increasing fq of administration increases effect to 80% inhibition as opposed to 66% of maximal acid output.
What does the area under the curve represent ?
measures how much and for how long a drug stays in the body
can be used to determine pharmacokinetic parameters such as clearance
How do you calculate AUC ?
AUC = Co / K
Refer to BK 3 PPT
What is bioavailability ?
Bioavailability is the fraction of dose reaching the systemic circulation in a chemically unaltered form.
What is clearance ?
Removal of drug from a volume of plasma in a given unit of time
Calculations for rate of elimination.
ROE = CL X C
ROE = K X A
AND C = A / V
THEREFORE CL = K X V
Clinical importance of CL
Decrease in drug clearance means slower rate of elimination
Dosage adjustment may be required in eliminating organ dysfunction
How to calculate Creatinine clearance
Refer to BK 4 PPT
Creatinine clearance bandings
50-20 ml/min = mild
20-10 ml/min = moderate
Less than 10ml / min = severe
Decrease in kidney function results in lower creatinine clearance
Dosage adjustments in renal impairment
Loading dose
Maintenance dose
If half life is prolonged then time to steady state will also be increased
What is hepatic clearance ?
Fraction of drug removed from blood during one pass through the liver
Calculation of hepatic extraction rate
refer to bk 4 ppt
How can liver impairment be assessed ?
Liver function tests
ALT and AST levels
Alkaline phosphatase
clotting studies
dosage adjustment
Calculations of multiple dosing and constant I.V infusions
Refer to BK 4 ppt
