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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

Acid

pH = pKa

pH = pKa

log log  Base

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)

pH = pKa

pH = pKa Salt
Acid
Base
Salt

log log  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. 1 st order reaction

Provided Formulas 0 order reaction

Provided Formulas          0.693 Vd

t 1/2 =

Cl t Estimating drug clearance (Cl): For linear pharmacokinetic drug clearance and normal renal function

Provided Formulas    IV infusion

Multiple dose: Accumulation Rate f =
e k T
R = e k T D L = D M

Fraction remaining in the body after a dosage interval

1

1 If

D M

is given

at a dosage

e k T

 interval equal to the elimination half-life of the

drug:

D L = 2 D M

Other Important Formulas

Young's Rule (for children >2 years) dose Clark's rule---weight (child aged 2-17)

Dose f or child =

Fried's rule for infants Weight in pound x adult dose

150 lb (avg wt of adult) Child’s dosage based on Body surface area (BSA)

Ideal Gas:  PV = nRT

P 1 V 1 / T 1 = P 2 V 2 / T 2

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 CaCl 2 are required to prepare a 480 mL solution that contains 200 meq of Ca 2+ ? (mw CaCl 2 = 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 MgCl 2 (1 M), there are two moles of Cl - for every mole of Mg 2+ , 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 (CaCl 2 ) 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

• Infustion rate

• Css

Provided Formulas     t 1/2 =

For IV infusion  0.693 Vd Cl t

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 2 ed 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;

– esp useful for drugs with narrow therapeutic range.

Basic Pharcokinetics

One-compartment model

– D L = C ss 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: D 0 / 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 drug concentration Versus Time Linear Plot of Cp Versus Time Showing Doses Every Six Hours

Provided Formulas   Accumulation Rate f =
e k T
R = e k T Fraction remaining in the body after a dosage interval

Cpmax and Cpmin Multiple IV bolus injections

• An example: t 1/2 = 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 D L : 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 IN TOR

Inventory turnover rate; calculated by dividing the cost of the goods sold by the average

of beginning and ending inventroy.

>6

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

NS:NWC

NS:NW

net sales to net working capital: calculated by dividing the net sales by net working 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 liabilities); 3 to 8

A/R CT accounts receivable collection time; calculated by dividing year end accounts receivable by mean credit sales per day. It is a direct measure of efficient credit management. 30 days

A/R RT accounts payable remitance time: calculated by year end accounts receivable devided by 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 capital

dividing mean inventory (average of the beginning and ending inventory) by net working 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:

"net profit"

Profitability

net profit to net worth ratio is the best indicator; 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

Return on asset investment

NP:IN

net profit to total assets; It is generally useful for a new pharmacies: 10-20%;

net profit to inventory; It is generally useful for a new pharmacies: 10-20%; It is also a good 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

Test

outcome

Positive

Negative

True Positive

False Negative (Type II error)

Sensitivity

False Positive (Type I error, P-value)

Positive predictive value

True Negative

Negative predictive value

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

• 1 gallon = 3840 ml

= 240 ml = 8 fl. oz.

= 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