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CPD Lecture Forensic Pharmacology

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Professional Dev elopment seminar given to a number of Barristers\' Chambers in UK

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CPD Lecture Forensic Pharmacology

  1. 1. Forensic Pharmacology: the relevance of medicines and drugs to some criminal cases How can the pharmacologist help the legal team to maximize the value of the evidence?Professor Nicholas J. Birch Academic Consultancy Services Ltd
  2. 2. Forensic Pharmacology• Basic tenet of pharmacology: – there is always an ordered relationship between the concentration of a drug acting in the body and the magnitude of its effect Professor Nicholas J.Birch Academic Consultancy Services Ltd
  3. 3. Effects of alcohol on behaviour
  4. 4. Forensic Pharmacology – There are always TWO sets of considerations: –Pharmacodynamics –PharmacokineticsProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  5. 5. Pharmacodynamics = response of the body to the presence of a drug• The actions of a drug at a receptor or receptors response proportional to drug concentration at receptorProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  6. 6. Drug effects and toxicity Phenytoin target blood concentration range Ineffective Useful dose range Increasing toxicityProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  7. 7. Drug response may be influenced by: naturally occurring substances present at receptor e.g. neurotransmitters, hormones other drugs or xenobiotics present at receptor factors affecting number, structure or function of receptors •disease, exercise, abnormal environment, starvation, obesity dehydration, age, sex, previous drug or dietary history  genetic variabilityProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  8. 8. D rug D os a g e R e g im e n• O b je c t iv e : To prescribe a dose, the size and timing of which will provide the maximal THERAPEUTIC effect at the minimal cost in ADVERSE effects•A s s u m e s : Orderly relationship betweenDo s e R a t e and both T h e r a p e u t icand T o x ic effects•B o u n d a r i e s : Ineffective¦ Effective ¦ Toxic Professor Nicholas J.Birch Academic Consultancy Services Ltd
  9. 9. Phenytoin dosageProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  10. 10. Size does matter• Dose depends on – Body size – Age dependent factors – Gender dependent factors – Current physiological state
  11. 11. Volume of distribution Total body water is approximately 60% of lean body massWeight = 14.5 kg (3yr) 56kg 70 kg Total water = 8.7 l 33.6 l 42 l
  12. 12. Pharmacokineticsmovement of drug to and from the locality of the receptor ABSORPTION –DISTRIBUTION –METABOLISM –EXCRETIONADME controls the concentration of drugpresent at the receptor at any precise timeProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  13. 13. Drug distribution & kinetics Blood Lorazepam vs Time log10 concentration vs time Approximation from urine analysis: minimum blood concentration compatible with urinary detection limit of 1mg / litre. t0.5 = 14.0 hr, Vd= 1.3 l/kg, Body weight 44.5 kg, Clearance = 1.1ml/min/kg* linear 6 Projected Blood Lorazepam (Ctem) 5 4 C(Lorazepam)concentration vs time 3 log C(Lorazepam) exponential (mg/l) 2 1 0 -36 -24 -12 0 12 24 36 48 60 72 -1 * = pharmacokinetic data from Hardman et al (1995) -2 Time before (-) or after (+) urine sample (hours) Professor Nicholas J.Birch Academic Consultancy Services Ltd
  14. 14. Half life is the time taken for the bloodconcentration to decline to one-half of its HALF LIFEpresent value Dose at time zero = 16 t0.5= 1 hours. Residual dose vs time t 15 Residual dose 10 = ½ 5 0 0.00 1.00 2.00 3.00 4.00 5.00 Time after dose (hours) •characteristic range of values for each drug –long-acting drugs have long half-lifeProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  15. 15. Multiple doses Fluoxetine: Fluoxetine pharmacokinetics Pharmacokinetic curve, 20mg / day Single dose. Half life = 72 hours 7 Once daily dosing (Half-life = 72Hr) 6Blood fluoxetine (arbitary units) concentration 5 35 4 30 3 2 25 Blood concentration 1 (arbitrary units) 0 20 0 2 4 6 8 10 12 14 16 18 20 15 Days •Equilibrium occurs between four and five Half- 10 5 Lives after first dose 0 0 2 4 6 8 10 12 14 16 18 20 22 days
  16. 16. Phenytoin marginal overdose
  17. 17. Fluoxetine pharmacokinetics Effect of triple dose after equilibration to single dose (Once daily dosing, half life = 72hr) Pharmacokinetic curve, 45 Once daily dosing (Half-life = 72Hr) 40 Blood concentration 35 35 arbitrary units 30 30Blood concentration (arbitrary units) 25 25 20 20 15 15 10 10 5 5 0 0 0 1 2 3 4 5 6 7 8 9 10 12 13 11 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 17 18 23 15 19 20 21 22 days days Effects of additional dose?
  18. 18. Drug kineticsMurder + Attempted Murder in which it was alleged that thevictims had been drugged prior to lethal assault with machete Total Body Temazepam (mg) Victim A Blood Temazepam vs Time (Victim A) based on one blood determination (KAH2) (based on t0.5 = 11.0 hr) 6 5 4 80 Blood sample 3 Ctem Recalcd to giveTotal Body Temazepam (mg) 2 body load log Ctem (mg/l) Blood sample Estd. Blood Temazepam (Ctem) 1 0 0 -36 -24 -12 0 12 24 36 48 -1 0 12 24 36 -2 Time before (-) or after (+) blood sample (hours) Alleged time of dose 29th Sept Time 30th Sept Professor Nicholas J.Birch Academic Consultancy Services Ltd
  19. 19. Drug interactions• Drugs may interact: – Pharmacodynamically • affect each other’s response at the same receptors • block or modify biochemical action of receptor – Pharmacokinetically • alter rate of absorption or distribution • prevent access to receptors • alter each other’s metabolism or excretion Professor Nicholas J.Birch Academic Consultancy Services Ltd
  20. 20. Drug interactions• Pharmacokinetic interaction between Prozac and diazepam (Valium) – these drugs are both metabolised in the liver by a single enzyme, cytochrome P450-cyp2D6. – presence of Prozac will cause the rate of removal of Valium to be decreased and vice versa • Valium effects will be prolonged • Prozac effects will be prolonged Professor Nicholas J.Birch Academic Consultancy Services Ltd
  21. 21. Pharmacological issues in criminal cases• Those in which the drug is the main issue •Illicit drugs, possession or dealing •Driving offences: •Alcohol by definition, Other drugs by implication• Those in which drug effects are relatedto the offence •Behaviour alleged to be modified by presence of drug •Intent, memory, ability to comprehend, ability to perform •Behaviour triggered by drug: •Aggression, Confusion, Amnesia, Consent, UnconsciousnessProfessor Nicholas J.Birch Academic Consultancy Services Ltd
  22. 22. Psychopharmacology• Drugs affecting the mind are the most widely prescribed of all drugs•About 50 % of all GP’s consultations have a psychiatric component •10 % of the population will be treated for serious psychiatric disease at some stage in their life
  23. 23. Common psychotropic drugs • Hypnotics: sleeping tablets • Anti-anxiety drugs (anxiolytics) • Antidepressants • Antipsychotics • Major tranquilizers
  24. 24. Other drugs which may also have psychiatric effects • Alcohol • Anaesthetics • Antihistamines • Calcium channel blockers • Anticonvulsants • Drugs leading to dependence: – analgesics, stimulants, hallucinogens, solvents
  25. 25. Psychotropic drugs and crime • Drugs may be used in the performance of criminal acts: e.g. murder, abduction • Drugs may be themselves the main issue of the crime: e.g. drink driving, drug dealing • Drugs may precipitate the criminal act: e.g. psychiatric patient who commits theft whilst confused, drug interaction leading to uncharacteristic disinhibition
  26. 26. Forensic PharmacologyHow can a pharmacologist assist the legal team? • Pharmacologist can: – interpret drug actions –evaluate the likely interplay between drugs and related disease processes –evaluate potential interactions between drugs –make estimates of the timescale of events based on the properties of drugs involved –confirm other evidence by providing collateral dataProfessor Nicholas J.Birch Academic Consultancy Services Ltd

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