Calculations Flashcards
Define glomerular filtration rate
Rate of formation of filtrate. Volume/Time
Define clearance
The volume of plasma from which the substance is completely removed/cleared in a unit of time (volume/time)
Largest source of error in a clearance measurement?
Accuracy of timed urine collection (using mL implies an unrealistic degree of accuracy - L to 2 sig figs would be better)
Define tubular reabsorption (TR)
Proportion (fraction) of filtered substance that is reabsorbed. By definition, TR = 1-FE
Cockroft Gault equation
Creatinine clearance (mL/min) = [(140-age) x Body wt (kg) x 1.3]/plasma creatinine (umol/L)
Multiply by 0.85 for women (to correct for muscle mass)
Least significant change equation
2.77 x CV (including assay and within subject variation)
Bioavailability
dose reaching circulation / dose administered
Salt conversion factor
MW free (parent) drug / MW drug administered (salt of the drug)
Bioavailability taking into account salt conversion factor
Dose of drug reaching circulation / (salt conversion factor x dose of drug administered)
Volume of distribution
amount of drug in body / plasma concentration
Clearance of a drug
Cl (r) + Cl (m) where Cl(r) = renal clearance and Cl(m) = hepatic metabolism
In practice, hepatic metabolism hard to quantify and most dosage calcs take into account impairment of renal fn only
What is first order kinetics?
When the rate of drug clearance changes in proportion to the remaining drug concentration in plasma. Rate decreases as concentration decreases. Exponential decay.
What is zero order kinetics?
When the rate of drug clearance is constant and independent of plasma drug concentration. Inverse linear relationship between drug concentration and time.
What is k(d)?
The elimination rate constant.
decrease in plasma concentration of drug / unit time is proportional to plasma concentration
The elimination rate constant is a proportionality constant introduced such that the above relationship can be written:
decrease in plasma concentration of drug / unit time = k(d) x Cp(t)
ie decrease in plasma concentration of drug / Cp(t) = k(d) x d(t)
where Cp(t) = plasma concentration of drug at any point in time
What is e and what is its approximate value?
e = a universal constant encountered in nature whenever we are dealing with exponential growth or decay.
Approximately equal to 2.718
What equation is used to find concentration at time, t, if we know concentration at time, 0 and the elimination rate constant, for a drug that follows first order kinetics?
ln Cp(t) = ln Cp(0) - k(d).t
Express the elimination rate constant in terms of half lives of a drug
k(d) = 0.693 or ln2 divided by t(1/2)
where t(1/2) = half life of the drug
If we know the half life of a drug, t(1/2) and it’s initial concentration, Cp(0), what equation can we use to determine the plasma concentration at time, t?
Substitute for k(d):
lnCp(t) = lnCp(0) - 0.693/t(1/2) x t
OR
lnCp(t) = lnCp(0) - 0.693t/t(1/2)
Rate of elimination, R(E), of a drug?
Amount of drug removed per unit time
R(E) = clearance x plasma concentration at steady state, Cp(ss)
Rate of administration, R(A), of a drug?
Dose x salt conversion factor x bioavailability (amount that reaches plasma) / interval between doses (tau)
How do rate of elimination and rate of administration compare when a drug is at steady state?
R(A) = R(E)
T or F: For a drug that is eliminated by glomerular filtration alone, clearance = GFR
True
How can k(d) be expressed using clearance and volume of distribution?
k(d) = Cl/V(d)
The fraction of total body drug eliminated from the body per unit time
ie R(E) / amount of drug in body
ie [Cl x Cp(ss)] / [V(d) x Cp(ss)]
Cp(ss) term cancels, leaving Cl/V(d)
Composition of body fluids
- TBW = 60% body wt
- ECF = 20% body wt
- plasma = 1/4 ECF (5% body wt)
Main difference between plasma and interstitial fluid?
Absence of protein in interstitial fluid
T or F: for practical purposes, concentration of glucose and elytes in interstitial fluid is considered the SAME as that in plasma
True
Average daily insensible water losses
400mL
Average initial total body water (for calculating fluid loss from osmolality)
42L (70kg male)
Average initial osmolality (for calculating fluid loss from osmolality)
285 mmol/kg
Average initial plasma sodium concentration (for calculating fluid loss from [Na+])
140 mmol/L
What assumptions are required for enzymatic reaction rate to be proportional to enzyme concentration?
The assay conditions are carefully chosen such that factors affecting enzyme activity are held constant
Define international unit
Quantity of enzyme that catalyses the reaction of 1umol of substrate per minute
Steps for calculating enzyme activity
- Take physical measurements (eg absorbances) at one or several time points
- Convert absorbances into substrate concentrations at each time point
- Calculate rate of change in substrate concentration
- Convert to international units of enzyme activity
- Correct for any dilution of the sample that occurs during the reaction (multiply by total volume of reaction mixture then divide by volume of sample)
Define katal
The amount of enzyme that catalyzes the reaction of 1 mol of substrate in 1 second.
Michaelis - Menten equation
v = V(max) [S] / (Km +[S])
where v = reaction velocity
V(max) = [E]total x K(+2)
Km = Michaelis -Menten constant
[S] = substrate concentration
[E]total = total enzyme concentration [E] + [ES]
K(+2) = rate constant of [ES] –> [E] + [P]
What is skewness?
When the distribution around a median is no longer symmetrical. Skewness to the right means there are more values greater than the mode and skewness to the left means there are more values less than the mode.
How to correct for skewness
Take logarithms of data
What is kurtosis
How curves differ in how peaked or flat they are
What is the T test?
Comparison of 2 means - if the means are different, the standard errors of the means will not overlap. Good for assessing differences between runs
What is the paired T test?
Comparison of 2 groups of results - if there is no difference between each pair of results, the mean difference between results should be zero. Good for assessing differences between methods.
What is the F test?
Variance ratio - eg could be used to compare if the precision of an assay has changed. s1^2 / s2^2
Utility of ANOVA?
When you have multiple sets of data and you want to know if there is a difference between any of them. If there is, you can then perform t-tests between the most likely two sets to determine if there is a difference. If no difference is detected by ANOVA, then no further statistical testing need be done.
Define sensitivity
The proportion of patients with disease that are identified correctly by the test
Define specificity
The proportion of patients WITHOUT disease that are identified correctly by the test
Define efficiency of a test
The proportion of all results which are true (either positive or negative) and is equal to (sensitivity + specificity) / 2
What is the false negative rate?
The proportion of patients with disease who have a false negative result
What is the false positive rate?
The proportion of patients without disease who have a false positive result
What is the positive predictive value?
The probability that you have the disease if your test result is positive. TP / (TP + FP)
What is the negative predictive value?
The probability that you do not have disease if your test result is negative. TN / (TN + FN)
What is the likelihood ratio positive?
The ratio of the probability of a positive test in the presence of disease (sensitivity) to the probability of a positive test in the absence of disease (1-specificity)
What is the likelihood ratio negative?
The ratio of the probability of a negative test in the presence of disease (1-sensitivity) to the probability of a negative test in the absence of disease (specificity).
Utility of likelihood ratio positive?
Converting pre-test odds to post-test odds
What is the pre-test odds?
prevalence / (1-prevalence)
What is the post-test odds?
Pre-test odds x likelihood ratio positive
Post-test probability?
post-test odds / (1+post-test odds)
