Registration Assessment Syllabus Part II – Pharmaceutical Aspects of Practice a) Calculations: You must be able to perform accurately all types of calculations relating to pharmacy practice
b) Dilutions: You must be able to demonstrate an
understanding of the correct procedures for the dilution of solid, semi-solid and liquid dosage forms, including selection of the correct diluent Unit Conversions • L / dl / ml • Kg / g / mg / mcg or µg /ng / pg • Km / m / cm / mm • Feet / inches • Pound / stone TIPS: • Ensure all units are the same before commencing a calculation • Ensure your answer has the correct units Unit Conversions Example 1 1. What is 860,000g expressed in micrograms? What do we know? • We know that a quantity in grams multiplied by 1000 = the same quantity in milligrams • A quantity in milligrams multiplied by 1000 = the same quantity in micrograms Therefore… • If we want to get from grams to micrograms we need to multiply the quantity by 1000 and by 1000 again • 860,000g x 1000 = 860,000,000mg • 860,000,000mg x1000 = 860,000,000,000 mcg Unit Conversions Example 2 2. What is 2.5ml expressed in litres? What do we know? • We know that a volume in litres divided by 1000 = the same volume in millilitres Therefore… • 2.5ml /1000 = 0.0025 litres Unit Conversions Example 3 3.Mr AF is 6’5’’ tall. What is his height in metres? Round your answer to two decimal points. What do we know? • We know that 6’5’’ means 6 foot 5 inches • We know that 1 foot is equivalent to 12 inches and 1 inch is equivalent to 25.4mm • We know that to convert a length from mm to m we need to divide by 1000 Therefore… • 6 foot 5 inches = (6 x 12) + 5 = 77 inches • 77 inches = 77 x 25.4mm = 1955.8mm • 1955.8mm / 1000 = 1.9558m • Rounding to two decimal points = 1.96m Unit Conversions Example 4 4. Mrs AG has come to your pharmacy requesting for Alli. In order to decide whether to sell her Alli, you must establish her Body Mass Index (BMI). She weighs 12 stones and has a height of 170 cm. What is her BMI? Round your answer to two decimal points. BMI can be calculated using the following formula: Weight (kg) / Height (m2 ) What do we know? • We know that 1 stone is equivalent to 6.35 kg • We know that to convert a length from cm to m we need to divide by 100 Therefore… • 12 stones = (12 x 6.35) = 76.2kg • 170 cm / 100 = 1.7m • Using BMI = Weight (kg) / Height (m2) = 76.2 / (1.7)2 = 76.2 / 2.89 = 26.36678 = 26. 37 (BMI between 25 and 29.9 – overweight) Prescription Quantities • Read the question carefully! • Write out the steps – per dose change – per day – per interval then total them up Prescription Quantity Example 5. Mr BK presents you with the following prescription for ciprofloxacin: Rx: Ciloxan 0.3% ophthalmic solution, apply eye drops to left eye throughout day and night according to the following regimen: 2 drops every 30 minutes for 6 hours, then hourly for the remainder of day 1 2 drops every hour on days 2 and 3 2 drops every 2 hours on days 4 and 5 2 drops every 4 hours on days 6 to 14 How many 5ml bottles of Ciloxan 0.3% do you need to supply? Assume 1ml = 20 drops What do we know? • 1ml is equivalent to 20 drops • Each bottle is 5ml • Frequency of dosing varies each day so total quantity of opthalmic solution applied to affected eye varies each day • 24 hours in a day Therefore… • 2 drops every 30 minutes for 6 hours, then hourly for the remainder of day 1 = 12 x 2 applications in 6 hours + 18 x 2 applications in 18 hours = 60 drops • 2 drops every hour on days 2 and 3 = 24 x 2 applications in 24 hours + 24 x 2 applications in 24 hours = 96 drops • 2 drops every 2 hours on days 4 and 5 = 12 x 2 applications in 24 hours + 12 x 2 applications in 24 hours = 48 drops • 2 drops every 4 hours on days 6 to 14 = (6 x 2 applications in 24 hours ) x 9 days = 108 drops Therefore… • 60 + 96 + 48 + 108 = 312 drops • 20 drops = 1 mL 312 drops = ? = 15.6 mL • 5mL = 1 bottle 15.6mL = ? = 15.6 / 5 = 3.12 = 4 bottles Formulation Example 6. If the formula for Ferrous sulphate oral solution is: Ferrous sulphate 60mg Ascorbic acid 10mg Orange Syrup 0.5ml Double strength chloroform water 2.5ml Water for preparations to 5ml What do we know? • We know that the formula is for a 5ml preparation • We know that there is 10mg of ascorbic acid per 5ml • We know that to convert a quantity in mg to g we must divide by 1000 Therefore… Using c1 x v1 = c2 x v2 10mg in 5ml X in 160ml • X = 10 x 160 / 5 • = 320mg • = 0.32g Parts Be careful when considering formulae with the word parts. Example: • 1 part with 4 parts = total 5 parts • 1 part to 4 parts = total 4 parts Parts Example 7. This is the formula for a compounded ointment: Betamethasone ointment: 1 part White soft paraffin (WSP): 4 parts What is the quantity of WSP in 600g of the above ointment?
What do we know? • We know that there is a total of 5 parts in this formula • WSP makes up 4/5 of the formulation • The total quantity of ointment is 600g Therefore… Method 1: • Quantity per part = 600/5 = 120g • WSP makes up 4 parts therefore quantity in 600g = 4 x 120 = 480g Therefore… Method 2: • Because the proportion of WSP in the formulation is 4/5, the total quantity of WSP in 600g = 600x4/5 • = 480g Percentage Concentrations % w/v = percentage weight in volume The weight, in grams of solid in 100ml of solution %w/w = Percentage weight in weight The weight in grams of a solid in 100g of product % v/v = percentage volume in volume The volume in mL of a liquid contained in 100ml of product Percentage Concentrations Example 1 8. What is 1 in 80,000 expressed as a percentage? What do we know? • We know that 1 in 80,000 means 1unit in 80,000units • We know that a percentage is an amount out of 100 i.e. 1 in 100 is 1% There are 2 ways you can tackle this calculation. Method 1: c1 x v1 = c2 x v2 1 in 80,000 X in 100 • X = 1 x 100 / 80,000 • = 1/800 • = 0.00125 Therefore the answer is 0.00125% Method 2: • 1 in 80,000 divide each side by 8 • 0.125 in 10,000 divide each side by 100 • 0.00125 in 100 • = 0.00125% Percentage Concentrations Example 2 9. If 500mg of potassium permanganate is dissolved in 5 litres of water, what is the strength of the resulting solution? What do we know? • We know that 500mg has been added to 5L of water • The units of the answer must be % this means 1g in 100ml Therefore… • There is 0.5g in 5000ml of water Method 1: c1 x v1 = c2 x v2 0.5g in 5000ml X in 100ml X = 0.5 x 100 / 5000 = 50/5000 = 1/100 = 0.01 Answer is 0.01% • There is 0.5g in 5000ml of water Method 2: Divide until you get 100ml E.g. Divide both sides by 5 0.1g in 1000ml Divide both sides by 10 0.01g in 100ml Therefore answer is 0.01% Concentration Calculations • There are a number of ways in which the concentration of a drug in a preparation can be expressed • For example: milligrams per millilitre (mg/ml) millimole per millilitre (mmol/ml) units/ml Concentration Example 10. How much solid must be used to make up 3.5 litres of a 3.5% w/v solution? What do we know? • We know that the solution we need has 3.5g per 100ml • We know that we need 3.5L of this solution Therefore… Method 1 Using c1 x v1 = c2 x v2 3.5g in 100ml X in 3500ml X = 3.5 x 3500 / 100 = 122.5g Therefore… Method 2 35g in 1000ml Multiply both sides by 3.5 to get = 122.5g in 3,500ml Therefore answer is 122.5g Concentration Example 2 11. How much solid must be used to make up 250ml of 1:8 solution? What do we know? • 1:8 means 1 part to 8parts • There are a total of 8 parts in 250ml • Answer must be in mg Therefore… Method 1 Using c1 x v1 = c2 x v2 1g in 8ml X in 250ml X = 250/8 = 31.25g = 31,250mg Method 2 Solid takes up 1 out of every 8 parts i.e. 1/8 of the total, therefore… Quantity of solid = 1/8 x 250ml = 31.25g = 31,250mg Dilution Calculations • Dilution of solutions: weight of active ingredient remains the same before and after dilution • However since the volume changes the concentration of the solution also changes • Therefore you can use the formula C1 x V 1 = C 2 x V 2 Dilution Example 12. What volume of a 0.5% w/v stock solution is needed in order to produce 1L of a 1 in 8000 solution? What do we know? • We are using stock solution containing 0.5g per 100ml to produce a final solution containing 1g per 8000ml • We only want 1000ml of the final solution Therefore… First find out how much active ingredient we need… Final solution has 1g in 8000ml, we need 1000ml of this so we need 1/8g = 0.125g Stock solution contains 0.5g in 100ml Method 1 using c1 x v1 = c2 x v2 0.125g in X X = 0.125 x 100 / 0.5 = 25ml Method 2 0.5g in 100ml Divide both sides by 4 0.125g in 25ml Therefore answer is 25ml Chloroform • Single Strength Chloroform water = 0.25% • Double Strength = 0.5% = twice as strong as single strength • Concentrated Chloroform water = 10% = 20 times as strong as double strength and 40 times as strong as single strength Chloroform Example 13. You are asked to prepare 200ml of the following mixture: Potassium Citrate Mixture BP Potassium citrate: 3g Citric acid monohydrate: 500mg Syrup: 2.5ml Quillaia tincture: 0.1ml Lemon spirit: 0.05ml Double strength chloroform water: 3ml Water to: 20ml You have to prepare the double strength chloroform water from the concentrated chloroform water that you have in stock. What volume of concentrated water do you require to prepare required volume of Potassium Citrate Mixture BP? What do we know? • We have concentrated chloroform water in stock • We will make double strength chloroform water from the concentrated chloroform water • We need 3ml of double strength chloroform water per 20ml in the formulation • We need a total of 200ml Therefore… If there is 3ml in 20ml and we need 200ml total this means we need 30ml total of double strength chloroform water (i.e. multiply formula by 10) Method 1 Concentrated chloroform water is 20 times as strong as double strength, therefore we only need 30/20 = 1.5ml Method 2 – using c1 x v1 = c2 x v2 Double strength chloroform water is 0.5% = 0.5g in 100ml, we have 30ml in the formulation X in 30ml, X = 0.5 x 30 / 100 = 0.15 Concentrated chloroform water is 10% = 10g in 100ml 0.15 in Y Y = 0.15 x 100/10 = 1.5ml Mixing Preparations Example 1 14. An ointment contains 1% w/w calamine. What weight of calamine needs to be added to 200g of this ointment to produce a 5% calamine ointment? Round your answer up to two decimal points. What do we know? • We start with 200g of a 1% calamine ointment • We want 5% calamine ointment Therefore… • We need to add an amount to our 200g of 1% ointment to achieve 5%, this translates to… • 2g in 200g (plus “X” amount of calamine) = 5 g in 100ml • i.e. (2g + X) in (200g + X) 5g in 100ml Using c1 x v1 = c2 x v2…cross multiply… (2 +X) x 100 = 5 x (200 + X) 200 + 100X = 1000 + 5X 95X = 800 X = 8.4210… ≈ 8.42g Mixing Solutions Example 2 15. If 150 mL is removed from a bag which contains 500 mL of glucose 5% and replaced with 250 mL of glucose 20%, what is the strength of the resulting glucose solution? What do we know? Step 1: 150ml glucose 5% removed 500ml bag of glucose 5% What do we know? Step 2: Add 250ml glucose 20% 350ml bag of glucose 5% Therefore… Step 3: work out the total amount of active ingredient and total volume 250ml of glucose 20%: 20g in 100ml, means 50g in 250ml 350ml of glucose 5%: 5g in 100ml, means 17.5g in 350ml Total up both sides = 67.5g in 600ml Final concentration = 11.25g in 100ml = 11.25% Mixing Solutions Example 3 16. What volume of 60% ethanol and 20% ethanol should be mixed together to prepare 1.2L of 30% ethanol? What do we know? We have 2 different concentrations of solution that need to be mixed to achieve a specific final concentration and final volume Conclusion: We need to use the “Alligation method” Terminology in the Alligation method • Let the stronger product be called product A and this has a concentration of Ac. Let the weaker product be called product B and this has the concentration of Bc • Let the final concentration be called Fc. Parts of product A (Pa) = Fc-Bc Parts of product B (Pb) = Ac-Fc Total Parts = Ac-Bc Therefore… • Product A is 60%, product B is 20% • Ac = 60, Bc = 20, Fc = 30 • Parts of product A (Pa) = 30-20 = 10 • Parts of product B (Pb) = 60-30 = 30 • Total number of parts = 60-20 = 40 Total volume of final product is 1.2L • 1200ml/40 parts = 30ml per part Of the 60% ethanol need 10 parts = 10 x 30ml (300ml) Of the 20% ethanol need 30 parts = 30 x 30ml (900ml) (Final check: total of both volumes = 1200ml) Molecular Weight Molecular weight of a drug is the sum of all the atomic weights of the individual atoms (in grams) E.g. sodium chloride (NaCl) consists of one atom of sodium and one atom of chlorine so that its molecular weight = 23 + 35.5 = 58.5 aluminium chloride (AlCl3) consists of one atom of aluminium and three atoms of chlorine so that its molecular weight = 27 + (35.5 x 3) = 133.5g Molecular Weight Calculation 17. How many milligrams of lithium are contained in a 500mg tablet of lithium carbonate? (lithium carbonate formula: Li2CO3; molecular weights: lithium = 7, carbon = 12, oxygen = 16) What do we know? • Each molecule of lithium carbonate has 2 atoms of lithium, one atom of carbon and 3 atoms of oxygen • The total weight of lithium carbonate that we have is 500mg Therefore… • First calculate the molecular weight: (2 x 7) + 12 + (3 x 16) = 76g • The proportion of lithium in lithium carbonate is 14g per 74g, therefore the proportion in 500mg should be 14/74 x 500 = 94.59… ≈94.6mg Moles Number of moles = Mass in g Relative Formula Mass in g Number of millimoles = Mass in mg Relative Formula Mass in g Moles Calculation Example 18. Which of the following is the volume of a 40 millimolar solution of drug X that could be made from 3000mg if its relative molecular mass is 50? What do we know? • 40 millimolar solution contains 40 millimoles in 1000ml • One mole of drug X weighs 50g Therefore… • One millimole of drug X weighs 50/1000 = 0.05g • 40 millimoles = 40 x 0.05 = 2g Method 1: Using c1 x v1 = c2 x v2… • 2g in 1000ml 3000mg in X = 3g in X • X = 3 x 1000 / 2 = 1500ml Method 2: divide the total weight to be used with the weight you know the volume for to calculate the relative proportions. • 3000mg / 2g = 1.5 • If 2g is found in 1000ml and we have 3g, the volume we can make would be 1000ml x 1.5 = 1500ml Moles Calculation Example 2 19. Whilst working in the pharmacy aseptic unit you are asked to add 50mmol of Na ions to a batch of intravenous fluids. How many millilitres of sodium chloride injection 0.9% w/v do you need to add? Round your answer to the nearest whole number. Atomic weight of sodium = 23 Atomic weight of chlorine = 35.5 What do we know? • We need a total of 50 millimoles of sodium ions • We will obtain the sodium ions from sodium chloride injection 0.9% w/v injection • Sodium chloride molecular composition is one atom of sodium and one atom of chlorine (NaCl) Therefore… • one mole of sodium chloride = 23+35.5= 58.5g one millimole of sodium chloride = 58.5mg • 50mmol = 58.5 x 50 = 2925mg = 2.9… grams Using c1 x v1 = c2 x v2 • 0.9g in 100ml 2.9…g in X X = 2.9… x 100 / 0.9 = 325ml Displacement Volume • Volume or quantity of solid occupied by the powder (of for example an injection) following the addition of a diluent during reconstitution. • Different for different drugs, different strengths of the same drug and for different brands. Displacement Example 20. Streptomycin is available in 1g vial. A doctor prescribes streptomycin 750mg IM OD. Each 1g vial has a displacement value of 0.75ml. The nurse added 2.25ml WFI to reconstitute the vial. How many ml of the reconstituted solution must the nurse administer? What do we know? Final volume = DV + volume added Therefore… • Final volume = 0.75ml + 2.25ml = 3ml Using c1 x v1 = c2 x v2 • 1g vial contains 1g streptomycin in 3ml 750mg in X 0.75g in X X = 3 x 0.75 / 1 = 2.25ml Displacement Example 2 21. You receive a prescription asking you to prepare 24 Witepsol pessaries (in 2g moulds), each containing 400mg of drug A. What weights of base and medicament are required? (Displacement value of Drug A = 1.2) What do we know? • We need 24 2g pessaries containing Witepsol and drug A • Each 2g pessary contains 400mg of drug A • Displacement value of the drug is 1.2 Therefore… • Quantity required of drug A: 400mg x 24 = 9.6g How much Witepsol is displaced? • If 1.2g of drug displaces 1g of Witepsol, then 9.6g of drug displaces 9.6/1.2 = 8g of Witepsol Therefore weight of Witepsol required… • (24 x 2g moulds) – 8g = 48 – 8 = 40g Pharmacokinetics: Half Life 22. A drug has an elimination half-life of 2 hours. How long will it take for 75% of the administered dose to be eliminated? What do we know? • The half-life of a drug is the time it takes for the initial concentration or amount of drug administered to the body to be reduced by half Therefore… • If a drug has a half-life of 2 hours then the after 2 hours half the initial dose is eliminated i.e. 50% • After another 2 hours half of this half dose is eliminated i.e. a further 25% • Therefore a total 75% is eliminated after 4 hours Pharmacokinetics: Volume of Distribution The Volume of distribution (Vd), is the theoretical volume that would be needed to distribute a drug, if it was found at the same concentration throughout the body as that measured in the serum. Pharmacokinetics: Bioavailability Fraction of the drug that reaches the systemic circulation. Ranges from 0 to 1. Large first pass effect produces a low oral bioavailability. Parenterally administered drugs have a bioavailability of 1. Amount of drug = bioavailability x salt fraction x dose in systemic circulation Bioavailability Example 1 23. Mrs WD is admitted to hospital after suffering from a stroke. She regularly takes digoxin tablets 125 micrograms daily but as she cannot swallow tablets her doctor wants to change her to an equivalent dose of digoxin elixir. What should the daily dose of digoxin be for Mrs WD? The digoxin elixir you have available is a 50mcg/ml formulation. [bioavailabilty of digoxin tablets = 0.7 bioavailabilty of digoxin elixir = 0.8] What do we know? • Digoxin tablets have a bioavailability of 0.7 i.e. 70% of the administered dose is available Digoxin elixir has a bioavailability of 0.8 i.e. 80% of the administered dose is available • Patient used to take 125mcg tablets daily • Digoxin elixir is available as a 50mcg/ml formulation • You need an answer in ml Therefore… Mrs WD normally receives 0.7 x 125mcg = 87.5mcg So to maintain Mrs WD on this dose we need the equivalent amount of digoxin from the elixir: X x 0.8 = 87.5 X = 87.5 / 0.8 = 109.375mcg Using c1 x v1 = c2 x v2 50mcg in 1ml of elixir 109.375mcg in V V = 109.375/50 = 2.1875ml ≈2.2ml Bioavailability Example 2 24. A 3-kg infant has been receiving 7.5mg phenytoin sodium IV bd. If the prescribed formulation is changed to Epanutin oral suspension (30mg/5ml), how many ml of the suspension should be given per dose? Round your answer to one decimal point. [Conversion factor for phenytoin: 92mg phenytoin base = 100mg phenytoin sodium] What do we know? • There is a difference in bioavailability between IV phenytoin sodium and phenytoin suspension (as stated in Section 4.8.1 of BNF/C) • 92mg phenytoin base = 100mg phenytoin sodium • The patient was receiving 7.5mg phenytoin sodium in each dose • Epanutin oral suspension contains 30mg/5ml Therefore… • dose of phenytoin sodium is 7.5mg Using c1 x v1 = c2 x v2 • 92mg phenytoin base equivalent to 100mg phenytoin sodium ? equivalent to 7.5mg phenytoin sodium. ? = 92 x 7.5 / 100 = 6.9mg • 30mg of phenytoin in 5ml Epanutin suspension 6.9mg in X X = 6.9 x 5 / 30 = 1.15ml, round to 1DP = 1.2ml Pharmacokinetics: Loading Dose Loading Dose Calculation Example 25. Calculate a suitable oral loading dose for drug X, given that the doctor wants to obtain a target plasma concentration of 2 micrograms/L. Drug X has an oral bioavailability of 0.7, a volume of distribution of 350L and a salt fraction of 1. What do we know? Loading dose = target concentration x volume of distribution bioavailability x salt fraction Therefore… • Loading dose = 2mcg/L x 350L / 0.7 x 1 • = 700mcg / 0.7 • = 1000mcg • = 1mg Pharmacokinetics: Clearance Clearance is the volume of serum that is cleared of a drug over a set period of time, usually expressed in litres/hour. Clearance Calculation Example 1 26. Mr JT, who weighs 70kg, has taken an overdose of drug X. His serum concentration of drug X is 75mg/L and the clearance rate of the drug is 0.04L/kg/hour. What is the amount of drug X that will be removed from Mr JT’s body in 12hrs? What do we know? • Current serum concentration 75mg/L • Mr JT weighs 70kg • The drug is cleared 0.04L per kg per hour • We need to calculate amount cleared in 12hrs Therefore… • Clearance = 0.04 x 70 per hour = 2.8L per hour There is 75mg of drug X per litre, therefore • 2.8L x 75mg = 210mg drug cleared per hour In 12 hours, the amount of drug cleared = 210 x 12 = 2520mg = 2.52g Body Surface Area Example 1 27. Mr GK is 1.8m tall and weighs 80kg. Calculate his body surface area (m2) What do we know? Therefore… • Convert height to cm: 1.8m = 180cm • Body surface area = √(80 x 180)/3600 • = √14400/3600 • = √4 • = 2m2 Body Surface Area Example 2 28. Drug X has a recommended dose of 25mg/m2. Miss AP and Miss LP are twins who have both been prescribed with Drug X. You measure both their weights and heights to calculate whether there is a difference between the doses they need. Miss AP has a weight of 6.5kg and a height of 0.6m, Miss LP has a weight of 6.3kg and a height of 0.62m. What would be the difference (if any) between their doses of Drug X? Round your answer to two decimal points. What do we know? • Dose of drug 25mg/m2 • Miss AP weight = 6.5kg, height = 0.6m • Miss LP weight = 6.3kg, height = 0.62m • Need to convert m to cm for BSA equation Therefore… • Miss AP BSA = √6.5x60/3600 = √0.1083… = 0.329140…mg • Miss LP = √6.3x62/3600 = √0.1085 = 0.329393…mg Difference: 0.329393…m2 - 0.329140…m2 = 0.0002530…m2 Therefore the difference in dose would be 25mg x 0.0002530… = 0.006326…mg ≈ 6.33mcg Infusion Rate Example 1 29. A patient is receiving a diamorphine infusion over 24 hours. They are currently receiving a dose of 150mg over a 24 hour period using a syringe pump that is calibrated to 36mm/24 hours. You increase the rate of infusion to 54mm/24 hours. What dosage is the patient now receiving? What do we know? • Initially the syringe pump was set to 36mm/ 24hrs to deliver 150mg in 24hrs • Now you have changed the setting of the pump to 54mm in 24hrs Therefore… Using c1 x v1 = c2 x v2 • 36mm delivers 150mg 54mm delivers X X = 150 x 54 / 36 = 225mg Therefore current dose of diamorphine is 225mg per 24hrs Infusion Rate Example 2 30. Master AP is a 10 year old child weighing 32kg. Having undergone surgery he has been prescribed diamorphine infusion with the rate of the pump to be adjusted according to response. If it was initially set to deliver 75mcg/kg/hr and 2 hours later was increased by the paediatric nurse to deliver 0.1mg/kg/hr. How much diamorphine will he have received within 4 hours? What do we know? • Weight = 32kg • Initial rate of infusion = 75mcg/kg/hr • 2 hours later rate became 0.1mg/kg/hr • To calculate total quantity of drug in mg Therefore… • For first 2hrs, Master AP received: 75mcg x 32kg x 2hrs = 4800mcg = 4.8mg of diamorphine • For the next 2hrs, Master AP received: 0.1mg x 32kg x 2hrs = 6.4mg of diamorphine Therefore over 4 hours he received: 4.8+6.4 = 11.2mg of diamorphine