IV Bolus Study Reference

What is the parenteral route? Drugs to be administered through one or more layers of skin or mucous membrane What is an intravenous route? -Directly injected into a vein -All of the dose enters systemic circulation What is an IV Bolus route? -Directly injected into a vein -Over a short period (seconds/mins) Which stage of ADME is missing from with IV administration? Absorption -They go straight into the systemic circuWhy does IV administration not get af- lation fected by the hepatic first-pass effect? -They do not enter the hepatic portal vein and get metabolised by the liver What are the two phases in IV Bolus plasma profiles? -Distribution phase -Elimination phase -Assumption where drug instantaneously and uniformly distributes throughout What is the one-compartment model? the body -The body acts as a single homogeneous fluid What does the one-compartment model not account for? -Distribution phase -Assumes it is instantaneous What is the two-compartment model? -Drug rapidly distributes to the central compartment -Takes longer for drug to distribute into the peripheral compartment -Model accounts for distribution and elimination -Volume of compartment = volume of disWhat are the three main assumptions of tribution the one-compartment model of IV bolus -Elimination is a first-order process injections? -Elimination follows linear kinetics (no saturation/plateauing) What is A in pharmacokinetics? Amount 1/5 A = A(initial) x e^-Kt How is the amount of drug in the body calculated, assuming first-order kinetics (one-compartment)? dA/dt = -k x A How is the rate of elimination calculated, assuming first-order kinetics (one-compartment)? What are the units for k in first-order kinetics -Per unit time -e.g. hours^-1 k is proportional to what in the one-compartment model? -Amount of drug present -More drug = greater elimination rate What is the basic equation for k in the one-compartment model? rate of elimination / A -k is the percentage of drug removed Why is k considered as a 'fractional rate from the body per unit of time of drug removal'? -if k is 0.5h-1 -> then 50% of the drug is removed every hour How is the concentration of drug in the body calculated, assuming first-order kinetics (one-compartment)? -C = C(initial) x e ^ -kt -(same as amount just with c substituted) For a plot of Ln(C)/Ln(A), what is the gradient? -k In the one-compartment model, how does the volume of the compartment and volume of distribution numerically relate? They are equal For calculation of volume of distribution, what needs to be true in terms of equilibrium? -Drug distribution in equilibrium -Instantaneously For the one-compartment model, when -As in the one-compartment model there is equilibrium achieved? is no account for distribution 2/5 What is the equation for calculating the volume of distribution, relating to dose and initial concentration? Dose/inital conc = Vd What is Cp in pharmacology? Concentration, plasma What is the equation for rate of eliminaClearance x concentration (plasma) = tion, relating to clearance and concentrarate of elimination tion? What is the equation for clearance, relating the volume of distribution and the rate constant for elimination in the one-compartmental model? Clearance = Volume x k What is the half-life of a drug? The time taken for drug concentration in the body to fall by half How is half-life calculated using k? 0.693 / k Given that k is calculated by Cl/V, how could a half-life equation be derived? 0.693 x V / Clearance What is the equation for calculating the concentration of drug remaining using half life? -Concentraion = inital concentraion x (1/2)^n -(where n is the number of half lives) How can we use AUC and k to calculate clearance? AUC x k = clearance How can we use AUC and dose to calculate clearance? Dose / AUC = clearance Why is using AUC preferred when calculating clearance? Model independent What is the best way to estimate AUC without software? Trapezoidal method What is the equation for the calculation of a trapezium? (B+b)xh/2 For the last proportion of the concentra- 1)AUC = Cn/K (Last concentration meation-time plot, what are the two ways in sured) which AUC is calculated? 2)AUC = Dose / clearance How is the trapezoidal method used to estimate AUC (what is the equation)? (sum of) Areas of all trapezoids 3/5 For extravascular administration, what does AUC represent? Extent of absorption For IV administration, what does AUC represent? Maximum body exposure to the dose given What is the definition of absolute bioavailability? Ratio of AUC obtained intravenously compared with orally What is the equation for the calculation of (AUC,oral / Dose,oral) / (AUC,iv / Dose, absolute bioavailability when comparing iv) an oral and an IV dose? What is the difference between IV and -Bolus is a rapid administration of a dose bolus administration? -IV is prolonged and continuous -Drug plasma levels are easily controlled by adjusting infusion rate (R) What are the advantages of continuous -Constant plasma levels can be achieved infusion? -Less issues of drug levels reaching a toxic level -Requires continual monitoring -Issues with solubility and stability of some drugs -Fluid restricted patients What are the disadvantages of continuous infusion? 1)Elimination = first-order process What are the three main assumptions for 2)Drug input = zero-order process the one-compartment model of IV infu3)Linear kinetics (enzymes don't get satsions? urated) What is the equation for concentration in an IV infusion relating to infusion rate and clearance? R/Cl x (1-e^-kt) What is the equation for rate of elimination relating infusion rate, k and amount of drug? Rate of elimination = R - k x A 1)Accumulation phase 2)Plateau (steady state) What are the three stages of IV infusion? 3)Exponential decline (after the end of infusion) 4/5 During the steady state phase of iv infu- R / Cl (no exponential factor as graph is sion, how is concentration calculated? linear) R / (k x v) x (1-e^-kt) During the accumulation phase of iv infusion, how is concentration calculated? What are the two equations for elimination rate? -Amount x k -Clearance x concentration In the steady state phase, how are elimination rate and input rate related? They are the same What is the equation rate needed to calculate infusion rate, if we know our clearance rate and desired concentration? C,ss x Clearance What is F in pharmacology? Fraction of equilibrium attained at a given time How do we calculate F and explain the equation? -F = C / C,ss -Is the concentration of drug at a given time compared to what it would be at equilibrium (C,ss) What is the equation to calculate F using the half-life equation? ln(1-F) = -0.693 / t,1/2 x t,F What is the equation needed to calculate C = C,inital x e^-kt + C,ss x (1-e^-kt) the concentration of drug following an IV (where blue is from IV bolus and pink if bolus and IV infusion? from IV infusion) C = C,inital x e^-kt + C,ss x (1-e^-kt) What is the equation needed to calculate (where blue is from the initial IV infusion the concentration of drug after a change and pink is from the second IV infusion) in infusion rate of an IV infusion? 5/5