Presentation on theme: "Instant Clinical Pharmacology E.J. Begg"— Presentation transcript:
1Instant Clinical Pharmacology E.J. Begg Useful revision guideInstant Clinical PharmacologyE.J. BeggUseful information on individual drugs(although a bit old now)Basic Clinical Pharmacokinetics (2nd Edition)M.E. Winter
2Drug dosing Important factors concentration of drug in plasma rate of drug eliminationrate of drug absorption
4Revision of pharmacokinetic terms 1st order eliminationrate of elimination depends on plasma concentrationC = C0e-kt (k= rate constant of elimination)Half life (t1/2)time for plasma concentration to fall by 50%Zero order elimination (pseudo zero order)rate of elimination is constant and independent of plasma concentrationPlasmaConcn(Cp)zero1sttime
5Zero order elimination Half life varies with concentrationPlasmaConcn(Cp)time
6Volume of distribution (Vd) Vd = dose C0 Volume of water in which a drug would have to be distributed to give its plasma concentration at time zero.Can be larger than total body volumefrusemide 7 litresaspirin 14 litrespropranolol 273 litresdigitoxin 38 liters 4 ml min-1digoxin 640 litres 130ml min -1Plasma clearance (ClP)volume of blood cleared of its drug content in unit timeCP= ClM + ClR + ClB + …….
7Area under the curve (AUC) Bioavailability (F)measure of the amount of drug absorbed into the general circulationArea under the curve (AUC)obtained from the plasma concentration v time plotgives a measure of the amount of drug absorbedForal = AUCoralAUCivivClearance = F. doseAUCCporaltime
8Same drug, same dose different formulation different amounts absorbeddifferent peak concentrationdifferent AUCsCptime
9Therapeutic window Same drug, same route, different doses Toxic level Minimumtherapeutic levelCptime
10Different rates of absorption (different routes of administration) Assume the bioavailability is the same (i.e. 1 for all routes)ivscoralCptimeSlower the rate of absorptiontime to peak longeramplitude of peak is lesslonger drug in body
11Two compartment model tissues plasma elimination e.g. thiopentone Redistribution + eliminationPlasmaConcn(Cp)e.g. thiopentoneeliminationtime
12Intravenous infusion C = Css(1- e-kt) At steady state rate of infusion = rate of elimination= Css.ClearanceCss (plateau)CpC = Css(1- e-kt)Time to 90 % of Css = 4 t1/2time
13Half life hours steady state Lignocaine hoursValproate hoursDigoxin daysDigitoxin days
14Rising phase of the infusion curve is governed by therate of eliminationHeight of plateau isgoverned by the rate of infusion2X mg min-1CpX mg min-1time
16Multiple dosing At Steady State amount administered = amount eliminated between dosesCavssCpRising phase of the curve is stillgoverned by the rate of eliminationtime
17Loading dose(s)Loading dose = Cpeak . Volume of distributionCptime
18Tetracycline t1/2 = 8 hours 500mg loading dose followed by 250mg every 8 hours
19Reducing the dose AND reducing the interval Cavss = F . DoseClearance. TT = dosing intervalCavssReducing the dose AND reducing the intervalCavss remains the same but fluctuation in Cp is less
20that have a low therapeutic index Drug plasma concentration monitoring is helpful for drugsthat have a low therapeutic indexthat are not metabolized to active metaboliteswhose concentration is not predictable from the dosewhose concentration relates well to either the therapeutic effector the toxic effect, and preferably boththat are often taken in overdose
21For which specific drugs is drug concentration monitoring helpful? The important drugs are:aminoglycoside antibiotics (plasma or serum)ciclosporin (whole blood)digoxin and digitoxin (plasma or serum)lithium (serum)phenytoin (plasma or serum)theophylline (plasma or serum)paracetamol and salicylate (overdose) (plasma or serum).Other drugs are sometimes measured:anticonvulsants other than phenytoin (eg carbamazepine, valproate)tricyclic antidepressants (especially nortriptyline)anti-arrhythmic drugs (eg amiodarone).
22The uses of monitoring are to assess adherence to therapyto individualize therapyto diagnose toxicityto guide withdrawal of therapyto determine whether a patient is already taking a drug before starting therapy (eg theophylline in an unconscious patient with asthma)in research (eg to monitor for drug interactions in post-marketing surveillance using population pharmacokinetics).