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Pharmacy Calculations

Workshop

Yuxin Qian
090422
Overview:

• Formulas: provided and other important

• Solutions, Compounding, and Dose related

• Pharmacokinetics

• Pharmacy financial assessment

• Statistics
• “give us some examples of the formulas
provided in PEBC information booklet( which are
provided in the EE exam)”
Salt
pH = pKa log
Acid
Base
pH = pKa log
Salt

Rule of nines:
I pH – pKa I = 1 ---- 90 : 10
I pH – pKa I = 2 ---- 99 : 1
I pH – pKa I = 3 ---- 99.9 : 0.1
• What is the pH of the solution containing 0.5 moles of
ephydrine and 0.05 moles of ephedrine HCl per liter of
solution? (pKb = 4.56)

Salt
pH = pKa log
Acid
Base
pH = pKa log
Salt

Base is not in the Basement (bottom) --- it is on the top;


Acid at the bottom

• MANON SHROFF CALCULATIONS


Provided Formulas

• The volume V of isotonic solution that can be prepared from W g of drug


is obtained by solving this equation

• W: the weight of the drug


• E: NaCl equivalent value
• 111.1 = 100/0.9

• How much sodium chloride is required to render 100ml of a 1% solution


of apomorphine hydrochloride isotonic with blood serum? ( Sodium
Chloride Equivalent E = 0.14 )

1. Weight of drug: 100 x 1% = 1.0 g


2. V = W x E x 111.1 = 1 x 0.14 x 111.1 = 15.55 ml
3. Dissolve 1g of apomorphone hydrocloride in 15.5 ml of water and
make up this solution to 100ml with 0.9% sodium chloride solution.
Provided Formulas

• 1st order reaction • 0 order reaction


Provided Formulas

Loading dose

0.693 Vd
t1/2 =
Clt
Estimating drug clearance (Cl):

For linear pharmacokinetic drug clearance and normal renal function


Provided Formulas

IV infusion

Multiple dose: Accumulation Rate

1
If DM is given at a dosage
DL = DM
f = e kT
e kT interval equal to the
1
elimination half-life of the
R = e kT
drug: DL = 2 DM
Fraction remaining in the body
after a dosage interval
Other Important Formulas

Young's Rule (for children >2 years) dose

Clark's rule---weight (child aged 2-17)


Weight in pound x adult dose
Dose f or child =
150 lb (avg wt of adult)

Fried's rule for infants

Child’s dosage based on Body surface area (BSA)

Ideal Gas: PV = nRT P1V1 / T1 = P2V2 / T2


Calculations related to Solutions

• Prepare Desired Concentrations;

• Tonicity Solutions:
– Freezing point

– Sodium chloride equivalents:

• Molarity/Molality

• mEq
Allegation Problems

• Example 1: A pharmacist has a 70% alcoholic elixir and a 20% alcoholic


elixir. He needs a 30% alcoholic elixir to use as a vehicle for medications. In
what proportion must the 70% elixir and the 20% elixir be combined to make
a 30% elixir?
• How many grams of CaCl2 are required to prepare a 480
mL solution that contains 200 meq of Ca2+? (mw CaCl2 =
111 g/mole)

• MANON SHROFF CALCULATIONS


Normality (N) / Molarity (M) / Molality (m)

• Normality (N): the presence of number of gram equivalent weight of


solute in 1000 ml or (1L) solution;
– For example, in a salt such as MgCl2 (1 M), there are two moles of
Cl- for every mole of Mg2+, so the concentration of Cl- is said to be 2
N (read: "two normal").
Molarity (M) vs Molality (m)
• Molarity (M) or molar concentration: the presence of number of
moles of solute in 1000 ml or (1L) of solution;
– A 0.5 molar solution contains 0.5 moles of solute in 1.0 liter of solution.
– This is not equivalent to 1.0 liter of solvent: either slightly more or
slightly less than 1 liter of solvent

• Molality (m): the presence of number of moles of solute in 1000 gm


of solvent
– the number of moles of solute per kilogram of solvent (not solution).
– For instance: adding 1.0 mole of solute to 2.0 kilograms of solvent
constitutes a solution with a molality of 0.50 mol/kg.
Isotonic solutions

• When 1 g mol wt (M-weight) of any nonelectrolyte is dissolved


in 1000g of water, the freezing point of the solution is
depressed by 1.86 ℃;
• Freezing point depression of body fluids: - 0.52 ℃;

• So, the amount needed for preparing isotonic solution:


X = 0.52 × (M-weight) / 1.86 g
Isotonic solutions

Sodium chloride equivalents


• Dissociation values (i) considered as 80% dissociated in weak
solutions: two ions (NaCl) 1.8; three ions (CaCl2) 2.6; four ions
3.4
• 0.9% NaCl is an isotonic fluid;

– Calculated the mass of NaCl represented by all ingredients;


– and the mass of NaCl required to prepare an equal volume of
isotonic solution;

– Based on the difference between those two masses, calculate the


NaCl equivalent for the prescription component.
• How many mg of NaCl are required to prepare 250 mL of 1%
boric acid solution to isotonic with eye tears? (The freezing
point of boric acid is – 0.29 ℃; FP of 0.9% NaCl - 0.58 ℃; FP
of body fluids: - 0.52 ℃)

• MANON SHROFF CALCULATIONS


Compounding and Dose

• W/W
• Parts
• Displacement value: DV in suppositories

• Dose related:
– Abbreviations: tid, bid, qd; o.u., a.s.
– Infusion rate:
How many grams of base are required to dispense 20 suppositories of
boric acid each weighing 2 g and containing 500 mg of boric acid
(Displacement value of boric acid = 1.5)

• MANON SHROFF CALCULATIONS


• Chloroquine can be used for prevention of malaria in areas where
the parasite is still sensitive to this drug. Smith’s family (two adults
and two 8 years old children) are going to central America for 8
weeks and they get a prescription of chloroquine: it should be used
2 week before exposure; continue weekly for 4 week after leaving
the endemic area; 7-10 y (150mg base once/week); adults (300 mg
base once/week). How many chloroquine needed for their trip (mg)?
(Therapeutic choices p1456)

Ans: (2×
×300 + 2×
×150) ×(2 + 8 + 4) = 900 ×14 = 12600 mg
• 250 mg/500 mL Rocephine solution should be administered to
a patient weighing 155 lbs. The recommended adult dose of
drug is 1.5 mcg/kg/min. What would be rate of flow in mL/min?

• MANON SHROFF CALCULATIONS


Pharmacokinetics

• Half-life:
• Shelf-life:
• K: constant rate
• Estimated GFR
• Clearance

• Loading Dose
• Infustion rate
• Css
Provided Formulas

Loading dose For IV infusion

0.693 Vd
t1/2 =
Clt

These formula can help us to solve most of the pharmacokinetic questions


• The initial concentration of a drug is 500 mg/mL, and
turns into 50 mg/mL after 90 mins. What is the rate of
constant if it is followed by first order kinetic?

• MANON SHROFF CALCULATIONS


• The initial concentration of a drug is 0.002M,.
What is the half-life if it is followed by 2ed order
kinetic? (rate of constant K = 7 liter/mole min)

• MANON SHROFF CALCULATIONS


Michaelis–Menten equation
The Michaelis? enten equation describes how the reaction rate v depends on the position
of the substrate-binding equilibrium and the rate constant k2. Michaelis and Menten
showed when k2 is much less than k-1 (called the equilibrium assumption) they could
derive the following equation:

The Michaelis-Menten equation will appear first order when the substrate concentration
[S] << Km;
The Michaelis-Menten equation will appear zero order when Km << [S].

This is the basis for most single-substrate enzyme kinetics.


The Michaelis constant Km is defined as the concentration at which the rate of the enzyme
reaction is half Vmax.
Basic Pharcokinetics

One-compartment model
• Intravenous bolus injection:
– complete absorption; elimination : both followed first-order
• Single oral dose:
– absorption and elimination : first-order; T max depends on kA
and k
• Intravenous infusion:
– zero-order absorption; first-order elimination;
• Css steady-state concentration;
– esp useful for drugs with narrow therapeutic range.
Basic Pharcokinetics

One-compartment model
• Loading dose:
– DL = Css Vd or R/k ( R: the infusion rate; k: elimination rate constant)
• Some oral controlled-release drug:
– zero-order systemic absorption;
• Intermittent intravenous infusions:
– aminoglycoside (gentamicin), no Css
• Multiple doses:
– Dosing rate: D0 / τ (τ: interval between doses, or the frequency of
dosing)
– Certain antibiotics are given by multiple rapid intravenous bolus injections.
Cockcroft-Gault formula
• Estimated creatinine clearance rate (eCcr)

Estimated GFR for Children using Schwartz formula

• ( Height in cm, SCr in mg /dL)


• K: constant that depends on muscle mass varies with a child's age;
• In first year of life, for pre-term babies K=0.33; for full-term infants K=0.45
• For children between ages of 1 and 12 y, K=0.55
• What is the rate of infusion of phenytoin in a patient that
requires steady state plasma concentration of 20
mcg/mL? The elimination half-life of phenytoin is 4 hours
and an apparent volume of distribution is 15 L.

The rate of infusion can be calculated by the following formula:

• MANON SHROFF CALCULATIONS


Multiple IV bolus injections

Linear Plot of Cp Versus Time


Linear Plot of drug concentration Versus Time
Showing Doses Every Six Hours
Provided Formulas

Accumulation Rate Cpmax and Cpmin

f = e kT

R = e kT

Fraction remaining in the body


after a dosage interval
Multiple IV bolus injections

• An example: t1/2 = 4 hr; IV dose 100 mg every 6 hours; V = 10 liter; What


are the Cpmax and Cpmin values when the plateau values are reached?

• Cp fluctuate between 15.5 and 5.4 mg/liter


during each dosing interval when the plateau
is reached.
• A suitable DL: Cpmax • V = 15.5 x 10 = 155
mg as a bolus would give Cp = 15.5 mg/liter
• Followed by 100 mg every 6 hours to maintain
the Cpmax and Cpmin values at 15.5 and 5.5
mg/liter, respectively.
• A subject in whom the renal clearacne of inulin is 120 mL/min is
given a drug, the clearance of which is 18 mL/min. If the drug is 40%
plasma protein bound, what percentage of filtered drug must be
reabsorted in the renal tubules?
A. 10% B. 12.5% C. 25% D. 50% E. 75%

• MANON SHROFF CALCULATIONS


Pharmacy financial assessment

• Inventory turnover,
• Gross Margin,
• Net Profit Margin;
• Price Markup and Elasticity

Reference Guide for Foreign Pharmacy Licensing Exam Questions and Answers,
by Manan H. Shroff, R. Ph, Krisman (1000 Qs)
Efficiency: Inventory Turnover

Inventory turnover rate; calculated by dividing the cost of the goods sold by the average
IN TOR
of beginning and ending inventroy. >6

NS:IN net sales to inventory: calculated by dividing the net sales by the inventory; >8

net sales to net working capital: calculated by dividing the net sales by net working
NS:NWC
capital(current assets minus current liabilities); 4 to 8
net sales to net worth: calculated by dividing the net sales by net worth(total assets total
NS:NW
liabilities); 3 to 8
accounts receivable collection time; calculated by dividing year end accounts receivable by
A/R CT
mean credit sales per day. It is a direct measure of efficient credit management. 30 days
accounts payable remitance time: calculated by year end accounts receivable devided by
A/R RT
mean purchases per day. 21 days
Gross profit margin

• Gross profit margin is a financial ratio used to assess the profitability of a


firm's core activities, excluding fixed costs.
• The general calculation is

• The gross profit margin is related to the net profit margin, which assesses
the profitability of an organization after including fixed costs.

• Indicates the relationship between net sales revenue and the cost of goods
sold. A high gross profit margin indicates that a business can make a
reasonable profit on sales, as long as it keeps overhead costs in control.
Liquidity and solvency

also known as Qucik test ratio; calculated by dividing the sum of cash and accounts
receivable by the current liabilities;
Acid test ratio
Acid test ratio = (Current assets -
see above)
1:1 ratio represents a successful pharmacy; Current assets
Current ratio The current ratio: dividing current assets by current liabilities; minimum standard value
CA:CL would be 2

Inventory to Net working dividing mean inventory (average


of the beginning and ending inventory) by net working
capital capital (unencumbered portion of
current assets);
IN:NWC The higher the value, the lower the liquidity; normall value: 80-100%

Current assets Including Cash, accounts receivable, inventory


Profitability

profitability: net profit to net worth ratio is the best indicator;


"net profit" the acceptable ratio for a 10 year old pharmacy : 15%, target value: 20%

NP:NS net profit to net sales; the acceptable ratio: 5-7%

NP:NW net profit to net worth; For a new pharmacies: 40%; 15% would be acceptable for old
Return on investment pharmcies

NP:TA
net profit to total assets; It is generally useful for a new pharmacies: 10-20%;
Return on asset investment

net profit to inventory; It is generally useful for a new pharmacies: 10-20%; It is also a good
NP:IN
indicator for efficiency of the pharmacy.
Price Markup and Elasticity

• Elasticity: coefficient of elasticity E = Q / P


– Q: % of sales quantities change;
– P: % of price change).
• Pricing:
– Rx: professional fee + cost price
– OTC: retail price = markup + cost price
– markup on cost or markup on retail price;
– Maintained markup = gross margin - cash discounts from suppliers;
Statistics

• Mean / Median / Mode

• Degree of freedom

• Range

( Chapter 2 CPR )
• What is the median of the following values?
120, 135, 140, 118, 175, 105, 115, 190

• Median: a middle value of an experiment;


• If the number of values are even, then the average of
middle values should be considered
• So the first step: arrange the data in order
105, 115, 118, 120, 135, 140, 175, 190
The answer is 127.5
• What is the degree of freedom in a 4 X 3
contingency table in a Chi-square test?

• Equation: (R-1) X (C-1) = 3 X 2 = 6


Statistics

• Standard deviation (SD)

• Relative standard deviation (RSD, precision)

• Standard error of the mean (SEM)

• p value

• Confidence interval and Confidence region


A plot of a normal distribution (or bell curve). Each
colored band has a width of one standard deviation.

• About 68% of values drawn from a normal distribution are within one
standard deviation σ > 0 away from the mean μ (dark blue)
• 2 σ from the mean account for about 95% (medium and dark blue)
• 3 σ account for about 99.7% (light, medium, and dark blue)
• This is known as the "68-95-99.7 rule" or the "empirical rule."
First Aid for the USMLE Step 1 2008
First Aid for the USMLE Step 1 2008
Condition
(as determined by "Gold standard")

Positive Negative

False Positive
Positive True Positive → Positive predictive value
Test (Type I error, P-value)
outcome False Negative
Negative True Negative → Negative predictive value
(Type II error)

↓ ↓
Sensitivity Specificity

First Aid for the USMLE Step 1 2008


First Aid for the USMLE Step 1 2008
Calculator used in the exam
Units Transferring

• 1 gr = 65 mg ( avoir. = apoth.)
• 1 lb (pound) = 454 g (avoir.); 373 g (apoth.)
• 1kg = 2.2 lb (avoir.)
• 1 fluid dram = 1 teaspoonful = 5 ml
• 1 fluidounces = 30 ml
• 1 pint = 480 ml
• 1 cup = 240 ml = 8 fl. oz.
• 1 gallon = 3840 ml = 8 pt = 4 qt
Final Tips

• Using The Provided Formulas to remember related Equations

• Be Careful in calculation;

• Unit transferring: L / hour to mL / min

• Be prepared and take all the marks in this part !!!


References

• MANON SHROFF CALCULATIONS


• CPR chapter 2, 6, 36
• Reference Guide for Foreign Pharmacy Licensing Exam Questions
and Answers, by Manan H. Shroff, R. Ph, Krisman
Thanks

yuxinqian@hotmail.com

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