Dosing

Calculating the amount of a medicinal substance or preparation to be administered to a patient to obtain the desired therapeutic effect

Calculation of Doses

FS AY 2007-2008

FS AY 2007-2008

Dosing Steps
Locate dosing guidelines Obtain patient variable data Obtain patient-specific daily dosing range Calculate the range for each patient-specific dose Determine an appropriate dosage form for the patient Choose an appropriate strength or concentration Calculate the total amount needed to fill the prescription

Dose and Related Terms

The quantitative amount administered to or taken by a patient for the intended medicinal effect Single Dose the amount taken at one time Daily Dose the amount taken on a daily basis Total dose the amount taken during the time-course of therapy Divided doses the daily dose subdivided and taken several time a day depending on the characteristics of the drug and the illness

FS AY 2007-2008

FS AY 2007-2008

Dose and Related Terms

Dosage Regimen schedule of dosing Usual adult dose the amount that ordinarily produces the medicinal effect intended in adults Usual pediatric dose the amount that ordinarily produces the medicinal effect intended in infants or children Usual dosage range indicates the quantitative range or amounts of the drug that may be prescribed within the guidelines of usual medical practice

Drug Dosage Based on Age

Application and Limitation Pediatric birth to 18 years
Neonate birth to 1 month Infant 1 month to 2 years Child 2 to 18 years

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FS AY 2007-2008

Youngs Rule
age child dose = ------------ x adult dose age + 12

Cowlings Rule
age at next birthday (yrs) x adult dose child dose = -------------------------------------------------24

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FS AY 2007-2008

Frieds Rule for Infants

age (mos) x adult dose infant dose = -----------------------------150

Body weight consideration

Actual body weight (ABW)
Patients real weight Total body weight (TBW)

Ideal body weight (IBW)

Weight of lean body mass (LBM) Lean body weight (LBW) Usually used for medications (hydrophilic) that do not distribute well into fat tissues
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Ideal Body Weight

Male IBW (kg) = 50 kg + (2.3 g) (each inch > 5 ft) Female IBW (kg) = 45 kg + (2.3 g) (each inch > 5 ft) If patient is under 5 ft,
Subtract 0.75 kg for each inch under 5 ft (women) and 0.83 kg for each inch under 5 ft (men)
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Drug Dosage Based on Body Weight

Application and Limitation Ratio between the amount of drug administered and the size of the body influences the drug concentration at its site of action

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Drug Dosage Based on Body Weight

Example: The usual initial dose of chlorambucil is 150 mcg/kg of body weight once a day. How many mg should be administered to a person weighing 154 lb? 150 mcg 1 kg 154 lb 1 mg ----------- x -------- x --------- x -------------- = 10.5 mg 1 kg 2.2 lb 1 1000 mcg

Clarks Rule
weight (lb) x adult dose child dose = ---------------------------------------------150 (average weight of adult in lb) Average weight of adult = 70 kg or 154 lb

FS AY 2007-2008

FS AY 2007-2008

Body Surface Area (BSA)

Based on proposed correlation with physiologic functions (metabolic rate, liver and kidney function, cardiac output) Units are in square meters (m2) Usually used for dosing chemotherapeutic drugs and sometimes for pediatric dosing

Drug Dosage Based on BSA

Universal equation: BSA = H0.3964 x W 0.5378 x 0.024265 Du Bois and Du Bois Method: For adults: BSA = H0.725 x W 0.425 x 0.007184 For children (1-3 years): BSA = (0.1) W 0.67 For neonates (birth 1 month): BSA = (0.103) W 0.67 To check: Adult BSA = 1.4 m2 to 2.4 m2 Children BSA = 0.27 m2 and 1.35 m2 Neonate BSA = not more than 0.22 m2
FS AY 2007-2008

FS AY 2007-2008

Using a Nomogram
Nomogram - table use for determining BSA from weight and height; contains 3 columns: height, body surface area, and weight To use: draw a straight line connecting the height and weight of the patient; the BSA value is the point intersected by the straight line in BSA column.

BSA Dosage with Relation to Weight and Height in Children and Adults
If adult dose is given, child BSA (sqm) child dose = --------------------------------------- x adult dose 1.73 sqm (average adult BSA) If dose per sqm is given, child dose = child BSA x dose per sqm

FS AY 2007-2008

FS AY 2007-2008

BSA Dosage with Relation to Weight and Height in Children and Adults
Example: If the adult dose of a drug is 75 mg, what would be the dose for a child weighing 40 lb and measuring 32 in in height? From the nomogram, the BSA is 0.60 sqm 0.60 sqm ------------ x 75 mg = 26 mg 1.73 sqm

BSA Dosage with Relation to Weight and Height in Children and Adults
Example: The usual pediatric dose of ephedrine sulfate is stated as 25 mg/sqm. Using the nomogram, calculate the dose for a child weighing 18 kg and measuring 82 cm in height. From the nomogram, the BSA is 0.60 sqm 25 mg/sqm x 0.60 sqm = 15 mg

FS AY 2007-2008

FS AY 2007-2008

Tapering
Tapering

Easing Patients Into or Out of Doses

process of easing a patient into or out of a certain medication dose Not starting on a full dose of a drug right away or not discontinuing a medication dose abruptly
Due to unwanted effects

FS AY 2007-2008

FS AY 2007-2008

Titration and Desensitization

Titration
process of easing a patient into a dose of medication over a matter of weeks
to check if a particular dose is working

Sample Problem
A patient brings in a prescription for a prednisone taper as follows: prednisone 30 mg po tonight 20 mg po BID tomorrow and day 3 10 mg po BID days 4 and 5 10 mg po qd days 6 and 7 5 mg po qd days 8 and 9 then off The available prednisone tablets in the pharmacy are in 1-, 5-, 10, 20, and 50-mg. As the pharmacist, what strength and quantity should you dispense? What instructions will you give the patient?
FS AY 2007-2008

Desensitization
process starting a patient with very small doses and then rapidly increasing the dose for the patient to develop tolerance to the immune response caused by the drug
When patient is already immune to the drug for which there is no optimal alternative
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Sample Problem (cont)

The patient will find it easier if he only has to handle 1 type of tablet for all the doses. The tablet strength that may be used for all doses is the 5-mg. A total of 36 tablets of the 5-mg strength will be dispensed. You should give the following instructions to the patient: Day 1: 6 tablets tonight Day 2: 4 tablets twice daily Day 3: 4 tablets twice daily Day 4: 2 tablets twice daily Day 5: 2 tablets twice daily Day 6: 2 tablets once daily Day 7: 2 tablets once daily Day 8: 1 tablet daily Day 9: 1 tablet daily Day 10: off (stop taking tablets)

Calculations in Miscellaneous Dosage Problems

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FS AY 2007-2008

Number of Doses in a Specified Amount of Medicine

total amount number of doses = ------------------size of dose Example: If the dose of a drug is 200 mg, how many doses are contained in 10g? 10 g 10,000 mg Number of doses = --------- = --------------- = 50 doses 200 mg 200 mg

Quantity of an Ingredient in Each Specified Dose

Quantity in total amount Quantity in each dose = --------------------------------Number of doses If the number of doses is not given: Total amount Quantity of ingredient in total ------------------ = --------------------------------------Size of dose Quantity in each dose

FS AY 2007-2008

FS AY 2007-2008

Quantity of an Ingredient in Each Specified Dose

Example: If 0.050 g of Drug A is used in preparing 125 tablets, how many mcg of Drug A are in each tablet? 0.050 g 50,000 mcg Quantity in each = -------------- = ---------------- = 400 mcg dose 125 tablets 125 tablets

Quantity of an Ingredient in Each Specified Dose

Example: If a preparation contains 5 g of a drug in 500 mL, how many g are contained in each tablespoonful dose? 500 mL 5 g ---------- = ---1 tbsp x x = 0.15 g 500 mL 5g ---------- = ---15 mL x

FS AY 2007-2008

FS AY 2007-2008

Intravenous (IV) Injections Intravenous Admixtures and Rate of Flow of Intravenous Fluids
Sterile preparations intended for parenteral administration into the vein Solutions or very fine dispersions of nutrients or therapeutic agents or blood or blood products Small Volume Injection for bolus injections, packaged in ampules for single dose administration and in vials for multiple dose administration Large Volume Parenteral (LVP) for infusion, containing 100 to 1000 mL

Infusions and Admixtures

Intravenous (IV) Infusions

Continuous infusions are LVPs with or without drug are run into a vein uninterrupted Intermittent infusion are administered during scheduled periods in glass or plastic bottles or collapsible plastic bags in volumes of 50, 100, 250, 500 and 1000mL

Administered in critical care, infirm, dehydrated or malnourished patients and to patients prior to, during and/or following surgery Used to extend blood volume and/or provide electrolytes, nutrients and medications

Intravenous Push (IVP)

rapid injection of IV medication, in an emergency or critical care situation Also IV stat Intended to quickly control heart rate, blood pressure, cardiac output, respiration, or other life threatening conditions Administered in less than one minute diluted injection rather than a highly concentrated injection (1 mg/mL vs 5 mg/mL) Depends on precise calculations of dose and rate of administration

Intravenous (IV) Admixtures

Preparation involves the addition of one or more drugs to LVPs e.g. NaCl Injection, Dextrose Injection, Lactated Ringers Injection, etc Additives include electrolytes, antibiotics, vitamins, trace minerals, heparin and insulin
As SVPs packaged in ampuls, vials, piggy bags or sterile solids

Rate of Flow of IV Fluids

LVPs are intended for infusion of medications and/or nutrients in the institutional or homecare setting On medication orders, the physician specifies the rate of flow of IV fluids in mL per minute, drops per minute, amount of drugs (mg/hr), or, more frequently as the approximate duration of administration of the total volume of the infusion Pharmacists may be called upon to perform or check rate of flow calculations
Calculations usually involve the relation of the dosing regimen to the flow rate of the parenteral

Sample Problem 1
A medication order for a patient weighing 154 lb calls for 0.25 mg of amphothericin B per kg of body weight to be added to 500 mL of 5% dextrose injection. If the amphotericin B is to be obtained from a constituted injection that contains 50 mg/mL, how many mL should be added to the dextrose injection? 154 lb 1 kg 0.25 mg 10 mL x ------- x ----------- x --------- = 3.5 mL 2.2 lb 1 kg 50 mg

Sample Problem 2: Delivery of LVP Fluid over a Specified Time

A medication order calls for 1000 mL of D5W to be administered over an 8-hour period. Using an IV administration set that delivers 10 drops/mL, how many drops per minute should be delivered to the patient? 1000 mL 1 hr 10 gtt ----------- x ---------- x ------- = 20.8 or 21 gtt/ minute 8 hr 60 mins 1 mL

Sample Problem 3: Delivery of LVP Fluid over a Specified Time

An IV infusion contains 10 mL of a 1:5000 solution of isoproterenol HCl and 500 mL of a 5% dextrose injection. At what flow rate should the infusion be administered to provide 5 mcg of isoproterenol HCl per minute and what time interval will be necessary for the administration of the entire infusion?

Sample Problem 3
a.) 10 mL of a 1:5000 solution contains 2 mg (2000 mcg) and 2000 mcg are contained in 510 mL 2000 mcg 5 mcg ------------- = --------x = 1.275 mL/min 510 mL x mL b.) 1.275 mL 510 mL ------------ = ----------1 min y mins

Sample Problem 4: Quantitative Amount of Drug in a Specified Period

If 10 mg of a drug are added to a 500 mL LVP fluid, what should be the rate of flow, in mL/hr, to deliver 1 mg of drug per hour? If the infusion set delivers 15 gtt/mL, what should be the rate of flow in drops/min? How many hours should the total infusion last? 10 mg 1 mg ---------- = -------x = 50 mL/hr 500 mL x mL

y = 480 minutes

Sample Problem 4
50 mL 1 hr 15 gtt -------- x ---------- x -------- = 12.5 gtt/min 1 hr 60 mins 1 mL

Sample Problem 5
How many g each of dextrose and NaCl are used to prepare a 250 mL bag of D5 1/2NS for intravenous infusion? 250 mL x 0.05 (5%w/v) = 12.5 g dextrose and 250 mL x 0.0045 (0.45% w/v) = 1.125 g NaCl

50 mL 500 mL -------- = ---------1 hr y hrs

y = 10 hrs

Sample Problem 6
Compare a) the number of drops and b) the length of time, in minutes , required to deliver 50-mL of intravenous solutions, when using a microdrip set at 60 drops/mL, and a standard administration set, at 15 drops/mL, if in each case one drop is to be administered per second.

Sample Problem 6
Microdrip set: a) 60 drops/mL x 50 mL = 3000 drops b) 3,000 drops/60 drops/minute = 50 minutes Standard set: a) 15 drops/mL x 50 mL = 750 drops b) 750 drops/60 drops/minute = 12.5 minutes By dimensional analysis: 50 mL x 15 drops/mL x 1min/60 drops = 12.5 minutes

Sample Problem 7
A physician orders enalaprilat 2 mg IVP for a hypertensive patient. A pharmacist delivers several 1 mL injections each containing 1.25 mg of enalaprilat. How many mL of the injection should be administered? 1.25 mg 2 mg ----------- = ------x = 1.6 mL 1mL x mL 1 mL from one syringe and 0.6 mL from another

Sample Problem 8
A physician orders midazolam HCl 2 mg IV stat. A pharmacist delivers a vial containing midazolam HCl 5 mg/L. How many mL should be administered?

Sample Problem 9
A medication order for an intravenous infusion for a 10 kg child may be stated as dopamine 60 mg/100 mL, IV to run at 5 mL/hr to give 5 mcg/kg/min. At some institutions with standardized drug products and established protocol, the same medication order may be written as dopamine 5 mcg/kg/min IV.

Sample Problem 9
60 mg/100 mL = x mg/5 mL x = 3 mg or 3000 mcg dopamine/hour 3000 mcg /60 mins/hr = 50 mcg/min 50 mcg/10 kg = x mcg/min; x = 5 mcg By dimensional analysis: 60 mg 1000 mcg 5 mL 1 hr -------- x ------------- x ------- x --------- = 50 mcg/min/10 kg 100 mL 1 mg 1 hr 60 min or 5 mcg/min/kg

Sample Problem 10
A medication order for a patient weighing 154 lb calls for 0.25 mg of amphotericin B per kg of body weight to be added to 500 mL of 5% dextrose injection. If the amphotericin B is to be obtained from a constituted injection that contains 50 mg/10mL, how many mL should be added to the dextrose injection? Since 1 kg = 2.2 lb, 154 lb= 70 kg 0.25 mg x 70 = 17.5 mg Constituted solution contains 50 mg/10 mL 50 mg/17.5 mg = 10 mL/ x mL; x = 3.5 mL Solving by dimensional analysis 154 lb x 1kg/2.2 lb x 0.25 mg/kg x 10 mL/50 mg = 3.5 mL

Sample Problem 11
A medication order calls for 1000 mL of D5W to be administered over an 8 hour period. Using an IV administration set that delivers 10 drops/mL, how many drops per minute should be delivered to the patient? 8 hours = 480 minutes 1000 mL/480 min = 2.1 mL per minute 2.1 mL/min x 10 drops/mL = 21 drops/min. By dimensional analysis: 10 drops/mL x 1000 mL/8 hr x 1 hr/60 min = 20.8 or 21 drops/min

Sample Problem 11
By equation: Rate of flow (drops/min) = volume infused (mL) x drip set (drops/mL) -------------------------------------------------------time (minutes) = 1000 mL x 10 drops/mL --------------------------------480 minutes = 20.8 or 21 drops/min

Pharmacokinetic Dosing

FS AY 2007-2008

Pharmacokinetics
Study of drug movement in the body during absorption and disposition
Absorption is when the drug enters the bloodstream Disposition is when the drug leaves the bloodstream

Volume of Distribution, Vd
Indicates how much of an administered drug is present in the bloodstream Expressed in liters Vd = Db Cp
total amount of drug in the body, Db plasma concentration of a drug, Cp

What the body does to the drug

Used in calculating the dose (DL) needed to reach a target concentration (Css) of the drug in the blood
FS AY 2007-2008

FS AY 2007-2008

Sample Problem
A 50-kg woman was given a single IV dose of an antibacterial drug at a dose level of 6 mg/kg. The Cp was determined to be 8.4 mcg/mL. What is the Vd? mcg/mL = mg/L

Vd = Db Cp

FS AY 2007-2008

FS AY 2007-2008

Loading Dose, DL
DL = Vd x Css

Sample Problem
Calculate the oral DL for digoxin for a 70 kg man that would produce a plasma concentration of 1 mcg/L. Assume Vd = 7.3 L/kg DL = Vd x Css

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Clearance, Cl
Indicates how much of an administered drug is removed from the body Expressed as L/hr or mL/min

Sample Problem
If the elimination rate constant k of Drug A is 0.17/hr and the volume of distribution Vd is 25 L, what is its clearance Cl? Cl = kVd Cl = 0.17/hr x 25 L Cl = 4.25 L/hr
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Cl = k Vd
Where k = elimination rate constant

Used to calculate the dose (Dm) needed to maintain a target concentration of the drug in the blood
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Maintenance Dose, Dm
required dose rate to achieve a target plasma drug concentration (Css) Dm = Cl x Css

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FS AY 2007-2008

Sample Problem
Calculate the rate of intravenous administration for aminophylline which would produce a steady state plasma theophylline concentration of 15 mg/L if the estimated theophylline clearance is 2.8 L/hr. Dm = Cl x Css

Parenteral Nutrition Calculation

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Total Parenteral Nutrition, TPN

Nutrition given intravenously to patient who cannot, for various reasons, consume an adequate amount of calories and nutrients by mouth
Bowel surgery Bowel obstruction Inability to swallow Severe malnutrition Inability to adequately absorb food
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Components of a TPN
Water
Solution base for all metabolic processes

Electrolytes
Optimal physiologic function Sodium, potassium, magnesium, phosphate, calcium

Carbohydrates
Main source of cellular energy dextrose

Proteins
Structural building block Amino acids

Vitamins and Trace elements

Cofactors in biochemical processes Vitamins A, B complex, C, D, E, K Zinc, copper, manganese, chromium

Fats
Fuel source, building blocks for hormones
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Mixing TPNs
Preset Volume Method
Involves combining set volumes (500 mL each) of dextrose and amino acids, with fat added or given separately

TPN Calculation
1. Determine the target range of fluid, calories, and proteins for the patient; 2. Choose exact volumes of protein, dextrose, and fat; 3. Calculate doses of electrolytes; 4. Determine the volumes of electrolytes needed
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Pump Method
Involves calculating the amount of fixed concentrations of proteins, dextrose, and fats

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