Drug Dosing You have a 1mL ampule of a drug with a stock concentration of 400µg/mL. You need to administer 120µg of the drug. The volume (in mL) of the stock preparation you would administer is = Answer mL (provide a numerical answer) Application of Bioavailability Based on the bioavaiability of each drug, select the closest equivalent oral dose for each of the following opioid analgesics: Morphine IV dose = 5 mg fh = 0.4 fg = 0.8 Equivalent oral dose: blank mg Codeine IV dose = 50 mg fh = 0.5 fg = 1.0 Equivalent oral dose: blank mg Tramadol IV dose = 100 mg fh = 0.9 fg = 0.9 Equivalent oral dose: blank mg Which drug has the highest bioavailability? blank Options: 100 – 50 – 110 – 6 – 15 – Tramadol 90 190 Morphine 250 120 Codeine 20 Calculating Volume of Distribution Drug A has the following phamacokinetic parameters: Hepatic clearance (CLH): 25L/hr Renal Clearance (CLR): 15L/lr half life (t1/2): 3hr Calculate the volume of distribution (VD) for this drug (Provide answer in liters (L) as a whole number) Answer: Factors that alter drug distribution Drug B is a highly protein bound, lipophilic drug. Determine the impact of the following scenarios on the volume of distribution of Drug B: Scenario 1: Administering Drug B to a severely hypoalbumanaemic patient: Choose…Decrease VdNo effect on VdIncrease Vd Scenario 2: Coadministering a drug that increases the absorption of Drug B: Choose…Decrease VdNo effect on VdIncrease Vd Scenario 3: Coadministering a drug that out competes Drug B for binding to albumin: Choose…Decrease VdNo effect on VdIncrease Vd Scenario 4: Coadministering a drug that decreases the hepatic metabolism of Drug B: Choose…Decrease VdNo effect on VdIncrease Vd Hint: in considering the impact of each scenario, consider the the factors that influence drug distribution and whether the scenario will alter one of these factors. Renal Extraction Active secretion contributes positively to renal clearance by: Select one: a. Actively pumping bound and unbound drug into the nephron through the Glomerulus b. Actively pumping bound and unbound drug into the nephron through the Proximal Tubule c. Actively pumping only unbound drug into the nephron through the Glomerulus d. Actively pumping only unbound drug into the nephron through the Proximal Tubule Determinants of Elimination Drug C has the following phamacokinetic parameters: Renal Clearance: 2.5L/hr Fraction Unbound in Blood: 0.9 Fraction Excreted unchanged in Urine: 1.0 Assuming a glomerular filtration rate of 7.2L/hr (for a healthy individual), which processes MUST be involved in the elimination of Drug C? Select one: a. Filtration and Reabsorption b. Filtration and Secretion c. Metabolism and Secretion d. Filtration and Metabolism IV Infusion Rate You are looking after a patient that your senior partner has suggested should receive an infusion of an opioid analgesic. In making your decision about how to manage the patient you consult a general drug information resource that contains the following phamacokinetic information regarding the drug: Bioavailability (F): 50 % Urinary excretion (fe): 0.08 Fraction unbound in plasma (fu): 0.16 Systemic Clearance (CLs): 60 L/hr Volume of Distribution (VD): 320 L Half life (t1/2): 3.7 hrs Based on this information, calculate the intravenous infusion rate (in ?g/hr) that will be required to maintain a steadystate blood concentration of 15 ?g/L: Answer: Relationship between clearance, volume of Distribution and half life for paramedic drugs Calculate the missing numbers to complete the table. (All answers must be rounded to the nearest whole number) Drug CL (L/h) V (L) (t½) (Hr) morphine (example) 80 230 2 midazolam 28 77 Answer fexofenadine 39.5 Answer 14 amiodarone 8 4620 Answer naloxone Answer 140 1.5 diazepam 1.4 Answer 40 benzylpenicillin Answer 131 3.5 Application of Halflife You attend a call to a patient who is unwell due to an adverse drug reaction resulting from the patient taking an excessive dose of one of their regular medications. You consult a drug information resource and find out the following information about the drug: Systemic clearance (CLS): 10 L/hr Volume of distribution (Vd): 173 hr Target plasma concentration range: 80 to 160 mg/L Patients current plasma concentration: 600 mg/L Based on this information, how long (in hours) will it take for the patient’s plasma concentration to return to within the target range? Answer: Metabolic Drug Interactions Drug D has the following phamacokinetic parameters: Systemic Clearance: 80L/hr Fraction Unbound in Blood: 0.5 Fraction Excreted unchanged in Urine: 0.02 Determine the impact of similtaneously administering a drug that activates the enzymes involved in the metabolism of Drug D on the following pharmacokinetic parameters: Bioavailability: Choose…DecreasedIncreasedEssentially Unchanged Systemic Clearance: Choose…DecreasedEssentially UnchangedIncreased Halflife: Choose…IncreasedEssentially UnchangedDecreased Metabolic Drug Interactions Drug E has the following phamacokinetic parameters: Systemic Clearance: 3L/hr Fraction Unbound in Blood: 0.9 Fraction Excreted unchanged in Urine: 0.02 Determine the impact of similtaneously administering a drug that activates the enzymes involved in the metabolism of Drug E on the following pharmacokinetic parameters: Bioavailability: Choose…DecreasedIncreasedEssentially Unchanged Systemic Clearance: Choose…DecreasedEssentially UnchangedIncreased Halflife: Choose…IncreasedDecreasedEssentially Unchanged Systemic Clearance Extended Calculation A pharmaceutical company is developing a new drug ‘FCP17’ and has just determined the following pharmacokinetic parameters from a Phase I human study: Fraction unbound (fu): 0.5 Clearance by active secretion (CLsec): 5.4L/hr Fraction reabsorbed (FR): 0.2 Hepatic Extraction Ratio (EH): 0.1 Question: Showing all working out, and stating all assumptions, Calculate the total SYSTEMIC CLEARANCE for ‘FCP17’. interIndividual Variability A pharmaceutical company has convinced your paramedic service to add their new orally administered opioid analgesic ‘fucpoaphine’ to their formulary. Fucpoaphine requires hepatic activation in order to elicit an analgesic effect. Studies in healthy volunteers have demonstrated that fucpoaphine is rapidly activated (within 2minutes) following oral administration and that the sole enzyme involved in the activation of fucpoaphine is CYP2C19. Questions: a) Select ONE specific factor (environmental, genetic or physiological) that may contribute to interindividual variability in the activation of fucpoaphine, and explain the potential consequences of this variability in terms of treatment response and tolerability. (200 words) b) Identify a strategy to account for variability in fucpoaphine activation that can be used in a prehospital situation and briefly explain how this strategy could be used to optimise treatment response and tolerability. (100 words)
