Definition: Therapeutic Range - cal tox

1 The Therapeutic Range and DUID efinition: Therapeutic RangeyThe concentration of drug at which the patient will experience the desired clinical effect with a minimum of undesirable or adverse of Range : determined by the toxicity of the Index, Ratio, ConcentrationsyTherapeutic index = LD 50/ED LD 50 if the lethal dose of the drug in 50% of the population and ED 50 is the effective dose of the drug in 50% of the Reference Range Is Not the Same As a Therapeutic : Therapeutic Range : 10 50 ng/ml (NMS).yZolpidem: peak plasma concentrations following single oral 5 mg dose: 29 113 (NMS). This is not a Therapeutic Therapeutic Range Will Vary From Source to SourceyAlprazolam (blood)yPacTox: 5 25 ng/mlyNMS labs:10 40 ng/mlyCarisoprodol/MeprobamateyPacTox;<2 0 /5 20 ug/mLyNMS labs: <25/10 30 ug/mLAbsorption PhaseyDefined as the time required for uptake of the drug across various barrier sites and into certain on route of administration:Patch: very : : : PhaseDistribution PhaseyDrug is distributed via the systemic on several factors:Blood flow to the tissue (cardiac output, arterial health, etc).

2 Partition coefficient between drug of the drug (ionization).Molecular Phase01234567891002468101214 TIMECONCENTRATIONDOSEA bsorption/Distribution Phase OverlapElimination Phase (Clearance)yMost drugs metabolized by the :yTo prepare for occurs ELIMINATION PHASE (CLEARANCE)Half lifeyThe amount of time it takes for the plasma concentration to decrease by 50%, given a first order HALF-LIFES teady StateyThe level at which the amount of drug absorbed is equal to the amount being level of drug achieved after several constant dosages at constant Therapeutic Range is usually steady state, but not necessarily visa StateSubtherapeutic concentrationsDosageIntervalToxic ConcentrationsTherapeutic RangeTIMECONCENTRATIONN arrow Therapeutuc Range : OxycodoneTherapeutic RangeTIMECONCENTRATIONW ider Therapeutic Range : MethadoneTherapeutic RangeTIMECONCENTRATIONT herapeutic RangeDosageIntervalEffect of Increased Dosage Steady StateTIMECONCENTRATIONS teady StateDosageIntervalLengthened Dosage IntervalTherapeutic RangeFrom the PDR.

3 Until You Experience How This Medication Affects You, Do Not Drive a Car or Operate Heavy MachineryAndDo Not Drive a Car or Operate Heavy Machinery Until Such Time You Feel It Is Safe to Do SoTIMECONCENTRATIONT herapeutic RangeImpairment Level: Low Tolerance/New UserTIMECONCENTRATIONT herapeutic RangeImpairment Level: High ToleranceDUI: The Triad of Results IyNature of the driving, including:yDriving behaviors obsd by police and/or of accident or from airbag of witnesses to the : The Triad of Results IIyDriver s condition, including:yPolice and witness descriptions of how the driver appeared and was doing after s and DRE by the driver or : The Triad of Results IIIyToxicology, including:yHistory of ingesting alcohol and/or drugs (prescription or non prescription).yPill bottles or prescriptions found in and urine test records, if report and related , it is defined for a particular Therapeutic benefit, such as pain , most centrally acting drugs carry mfr s warnings that they can adversely affect , Therapeutic ranges are in the eye of the beholder, even for the primary Therapeutic effect, let alone for multiple , such ranges apply to only the drug as sole agent, taken at recommended Which Affect How People Respond to Drugs in a Driving Situation y Pharmacological nature of the drug (depressant, stimulant, etc.)

4 Y Whether this is a new Degree to which the patient is Dose, recency of dose, new , continued Other co administered agents, including alcohol, similar drugs, antagonistic drugs, drugs or food that interfere with metabolism. Physical factors: Tired, sick, in pain. Miscellaneous factors: Distracted, UIC, bad weather, road conditions. How demanding is the driving situation?Illustrative Cases IyNature of AccidentySingle road and unfamiliar to FactorsyTaking Hyc for years in same back prior DUI thousands of miles per Cases I (contd.)yToxicologyyPostmortem = = 29 takes a mg Hyc pill 1 3 X dose 30 RangesyTherapeutic Range (Plasma): 18 32 ~ ~ Cases IIyNature of AccidentyRear impact collision into stopped crossed into opposing lane and struck another when she hit a utility Factorsy37 year old DRE exam at hospital showed impairment by CNS Cases II (contd.)yToxicologyyBlood collect 4 hrs after = = = 70 RangesyChronic Therapy: Carisoprodol: 3 15 ug/mL; Meprobamate: 5 30 Range Hyc(Plasma): 18 32 Cases IIIyNature of AccidentySingle car accidentySurface off bus 4 Factorsy34 year old bloodshot, watery, slurred, FST Cases III (contd.)

5 YToxicologyyBlood collected 1 hour post accidentyAlprazolam = 100 RangesyTherap ranges : 5 25; 10 40 concentration 1 hour after 1 mg dose ~ 12 state after 3 mg daily dose ~ 29 ~ Cases IVyNature of AccidentyHit to stop and render said she knew she hit something .yDriver Factorsy44 year old on face, FST Cases IV (contd.)yToxicologyyBlood collected X hours after = = = 150 RangesyChronic Therapy: Carisoprodol: 3 15 ug/mL; Meprobamate: 5 30 level hours after a single 60 mg dose for Codeine: 110 230 Cases VyNature of AccidentyTurning left at Factorsy42 year old balance & slow, pupils slow to react to B/S, FST sIllustrative Cases V (contd.)yToxicologyyBlood collect 5 hours after the = 480/280 = = 220yNorpropoxy = 470yReference Rangesy60 mg/ day for 1 week, F: 200 531; NF: 103 465 , Caris: 3 15, Mepro: 5 30 100 mg dose, Trazodone: 1300 1900ySS, 195 mg/day, NP: 600 3000 Cases VIyNature of AccidentyVeered into oncoming too fast for Factorsy39 year old Appeared to be asleep at the wheel before the + 100, BP 120/80yProbable meth Cases VI (contd.)

6 YToxicologyyBlood collected 5 hours post = 785 = 45 RangesyTherapeutic Range for methamphetamine (ADHD or narcolepsy): <50 Range for active drug effects in abuse: >100 Cases VIIyNature of AccidentyRear end car caused accident by driving to stop in time when 2 cars came into Factorsy47 year old : Condition Apparently Normal .yNo DRE, No biological samples collected immediately post accident for Cases VII (contd.)yToxicologyyUrine collected 2 days after the = 20000 RangesyUrine level of BZE roughly consistent with a same day dose of 40 120 or other reference ranges can be accepted as a rough guide with blood levels in the Therapeutic Range can still be impaired for people may be unimpaired at elevated drug impairment is not a quantum (contd.)ySome cases will have insufficient information to form a forensically sound opinion on impairment.