Pharmacology For Anaesthesiologists

cover next page > Cover title: author: publisher: isbn10 | asin: print isbn13: ebook isbn13: language: subject  publication date: lcc: ddc: subject: Pharmacology for Anaesthesiologists Fee, J. P. Howard; Bovill, J. G. Informa Healthcare 1841842362 9781841842363 9780203499818 English Pharmacology, Anesthetics, Anesthesiology, Pharmacology, Clinical, Anesthesiology--education, Anesthetics, Pharmaceutical Preparations. 2005 RM300.P49 2005eb 615.102461796 Pharmacology, Anesthetics, Anesthesiology, Pharmacology, Clinical, Anesthesiology--education, Anesthetics, Pharmaceutical Preparations. cover http://makolaiwy.blogspot.com next page > page_i next page > Page i Pharmacology for Anaesthesiologists Page ii This page intentionally left blank. Page vi This page intentionally left blank. Page x This page intentionally left blank. γ, the first two terms will decrease faster than the third term and at some time will approach zero and the equation reduces to C(t)=Ce−γt. If the decay curve is plotted on semilogarithmic axes (concentration logarithmic, time linear) this postdistribution phase will be a straight line, with zero time intercept ‘C’ and slope –γ. Subtracting (‘stripping’) this terminal portion from the rest of the curve leaves a bi-exponential curve from which, by the same processes, we can obtain B and β. Repeating the process yields estimates for A and α (Figure 2.5). For obvious reasons this process is referred to as curve stripping or the method of residuals. Note, however, that the results of graphical stripping will only yield rough estimates, that can then be used as starting estimates for a non-linear regression program, which will produce more accurate value of the parameters. Volumes of distribution and clearance Clearance (Cl) and volumes of distribution (VD) are fundamental concepts in pharmacokinetics. Clearance is defined as the volume of plasma or blood cleared of the drug per unit time, and has the dimensions of volume per unit time (e.g. mL·min−1 or L·h−1). An alternative, and theoretically more useful, definition is the rate of drug elimination per unit drug concentration, and equals the product of the elimination constant and the volume of the compartment. The clearance from the central compartment is thus V1·k10. Since e 0=1, at t =0 equation 1 reduces to C(0)=A+B+C, which is the initial concentration in V1. Hence, V1=Dose/(A+B+C). The clearance between compartments in one direction must equal the clearance in the reverse direction, i.e. V1.K 12=V2·k21 and V1·k13=V3·k31. This enables us to calculate V2 and V3.   Clearance can be calculated from the area under the concentration-time curve (AUC; area under the curve) following bolus administration; Cl =Dose/AUC. This can be used for any form of intravenous administration and does not rely on compartmental analysis. The volume of distribution of a drug can be considered as the sum of the volumes of all the tissues into which it becomes distributed. A few compounds, such as indocyanine green, are tightly bound to plasma proteins and are there Page 29 Figure 2.5 Plasma concentration decay (semilogarithmic plot) of a drug with three compartment characteristics, illustrating that the disposition equation, C (t)= Ae −αt+Be −βt+Ce −γt , is the sum of three exponential functions, with y-axis intercepts A, B, and C, and slopes −a, −β, and −γ . fore confined to the circulating blood. They thus distribute into a space that corresponds to the plasma volume. Highly polar drugs, such as some non-depolarising muscle relaxants, are largely confined to the extracellular water (approximately 12 L for a 70 kg individual) and the drug will be diluted by this volume. However, if the volume in which a non-polar drug is evenly dispersed is simpl