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

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. 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. Effects of alcohol on behaviour

4. Forensic Pharmacology
– There are always TWO sets of considerations:
–Pharmacodynamics
–Pharmacokinetics
Professor Nicholas J.Birch Academic Consultancy Services Ltd

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 receptor
Professor Nicholas J.Birch Academic Consultancy Services Ltd

6. Drug effects and toxicity
Phenytoin
target blood
concentration
range
Ineffective Useful dose range Increasing
toxicity
Professor Nicholas J.Birch Academic Consultancy Services Ltd

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 variability
Professor Nicholas J.Birch Academic Consultancy Services Ltd

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 between
Do s e R a t e and both T h e r a p e u t ic
and 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. Phenytoin dosage
Professor Nicholas J.Birch Academic Consultancy Services Ltd

10. Size does matter
• Dose depends on
– Body size
– Age dependent factors
– Gender dependent factors
– Current physiological state

11. Volume of distribution
Total body water is approximately 60% of lean body mass
Weight =
14.5 kg (3yr) 56kg 70 kg
Total water =
8.7 l 33.6 l 42 l

12. Pharmacokinetics
movement of drug to and from the locality of the receptor
ABSORPTION
–DISTRIBUTION
–METABOLISM
–EXCRETION
ADME controls the concentration of drug
present at the receptor at any precise time
Professor Nicholas J.Birch Academic Consultancy Services Ltd

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. Half life is the time taken for the blood
concentration to decline to one-half of its
HALF LIFE
present 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-life
Professor Nicholas J.Birch Academic Consultancy Services Ltd

15. Multiple doses
Fluoxetine:
Fluoxetine pharmacokinetics
Pharmacokinetic curve, 20mg / day
Single dose. Half life = 72 hours
7
Once daily dosing (Half-life = 72Hr)
6
Blood 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. Phenytoin marginal overdose

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
30
Blood 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. Drug kinetics
Murder + Attempted Murder in which it was alleged that the
victims 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 give
Total 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. 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. 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. 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 related
to 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, Unconsciousness
Professor Nicholas J.Birch Academic Consultancy Services Ltd

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. Common psychotropic drugs
• Hypnotics: sleeping tablets
• Anti-anxiety drugs (anxiolytics)
• Antidepressants
• Antipsychotics
• Major tranquilizers

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. 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. Forensic Pharmacology
How 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 data
Professor Nicholas J.Birch Academic Consultancy Services Ltd