Download Qualitative test

Diagnosis of abuser
By
Prof.Dr: Sherif Mohamed Hassan El-Qannishy
Associate Consultant & Professor
of
Analytical Toxicology and Biochemistry
Emergency Hospital - Analytical Toxicology Unit
Forensic Medicine & Clinical Toxicology Department
Faculty of Medicine - Mansoura University
TOXICOLOGY
TOXICOLOGY

Greek words toxicos and logos is the study of
the adverse effects of chemicals on living
organisms.

It is the branch of medical science, which deals
with poisons with special reference to their
source, character, properties, symptoms they
produce, and of remedial measures.
Substances that cause disturbances to
organisms
 All substances are poisons, there is none which
is not a poison.


PARACELSUS
(1493-1541 )


From ancient Greek "to make numb“
Any psychoactive compound with any sleep-inducing
properties.
1) Abuse

Use of drugs without any medical prescription.
2) Dependence
Continue to take a drug
 In order to avoid discomfort of its absence
( withdrawal symptoms )

Dependence
Psychic dependence
Physical dependence
• It is the desire for
continuous intake of the
drug to experience a
psychological effect.
• Withdrawal symptoms are
mild or slight.
• Slight psychic dependence
known as habituation
• It is an altered physiological
state in which the person is
in a compulsory need of a
drug
• Withdrawal symptoms are
sever .
3)Tolerance
• Tendency to increase the dose of the drug.
What is addiction?

Addiction = Abuse + Dependence + Tolerance

If the Addict attempts to stop drug abuse, a lot of dangerous physical and
psychological symptoms will instantly appear "withdrawal symptoms".
Substance
Morphine
Barbiturates
Alcohol
Benzodiazepines
Alcohol
Cocaine
Cannabis
Physical
dependence
Psychic
dependence
Tolerance
Severe
Severe, occurs rapidly
Marked
Severe
Very severe, occurs slowly
Less marked
Severe
With prolonged heavy use
Present
Present
Present
With prolonged use
Severe
Slight
Present
Slight
Slight & to some actions
only
questionable (?)
Slight
Severe
Present
Reasons for Addiction
:





​Lack of awareness regarding dangers of drug abuse.
Poor religious.
Broken homes.
Bad companionship.
Unemployment.
Signs of Addiction
A
F
Anger
friends
Absence
Fat
L
M
Lifestyle
Mood
Lonely
Money
Dreams of addiction
Reality of addiction
Drug Abuse Prevention and Control Act
Controlled Substances Act (CSA)
1970




regulates the manufacture ,distribution, and dispensation of drugs with a potential
for abuse.
The CSA classifies drugs with the potential for abuse into five schedules
(I–V) to indicate their level of control
Drugs in Schedule I have the highest potential for abuse and addiction.
Drugs in Schedule V have the least potential for abuse and addiction.
Schedul Abuse
e
Potential
Prescription
Requirement
Examples
I
high; no accepted
Medical use
no prescription
permitted
heroin, LSD (lysergic
acid diethylamide),
marijuana, tramadol
II
high; accepted
medical use
Prescription required; no
refills permitted
without a new written
prescription
codeine, morphine, and opium
III
moderate; accepted
medical use
Prescription required; 5
refills permitted in
6 months
certain
barbiturates
IV
low;
accepted
medical use
prescription
required; 5 refills
permitted in
6 months
barbital,
V
low;
accepted
medical use
no prescription
required for
individuals 18
or older unless
quantities are
greater than 4
fluid ounces.
cough syrups with codeine,
atropine sulfate
TOXICOLOGICAL SAMPLES
TOXICOLOGICAL SAMPLES
Urine
 Blood serum
 Vomits (food poisoning)
 Hair
 saliva

A comparison of the types of samples
that can be used in drugs of abuse testing
Sample
Advantages
Disadvantages
Urine
-Non-invasive
-Available in large volumes
-Remains positive 2–3 days
-High adulteration potential when
collection not witnessed
Blood
-Difficult to adulterate
-Short half-life of drugs
-Low drug concentrations
Hair
-Potential for long-term
assessment of drug use
-Requires difficult analytical
procedures (expensive)
Saliva
-Difficult to adulterate
-Low drug concentrations
-Difficult to get large volumes for
confirmation
ACTIVE PRINCIPLES
of Drugs
It depends on:
1) The person.
2) The drug.
Duration of active principles
in urine:
Name
Alcohol
Hashish
Opium / Tramadol
Detect (Days )
Urine
Blood
Hair
3-12
5-30
(sometimes 11w)
1-6
(12h(
2
(1y)
90
(6h)
90
Adulteration of urine sample
Can I beat a drug test and
pass?
The best way to pass the drug testing is
not to do drugs at all
Methods of Samples Adulteration
1) loading up on water before a urine drug test :
urine look pale.
specific gravity >1010.
(Normal: specific gravity 1010 : 1025)
2) Acids (lemon juice, Hydrochloric and nitric acid):
pH >7.
(normal urine pH = 5 : 8 )
3) Bleach (liquid chlorine):
characteristic odour
What is
the most common
method of Adulteration
???
Drug Testing:
Divided into two major categories:
1) screening tests
2) confirmation tests.

THIN LAYER CHROMATOGRAPHY
TLC

Retardation factors (Rf)

Rf = Y/X (always ≤ 1)
Rapid test detection

Antigen antibody reaction = Urine sample
interact with labeled antibody dye.

Automated drug detection
Gas chromatography-mass spectrometry
(GC-MS)
 All positive results on immunoassay
are must be confirmed using GC-MS.

Test
Cut off
Amphetamine
1000 ng/ml
Barbiturates
100 ng/ml
Benzodiazepines
1000 ng/ml
Cocaine
300 ng/ml
Opiates
300 ng/ml
Cannabinoids (THC)
50 ng/ml
Tramadol
200 ng/ml
Drugs of
TOXICOLOGICAL
important
Drugs of important :
A)DAT :
B)TDM :
1) Ethanol
2) Cannabis
3) Opiates
4) Barbiturates
5) Amphetamines
6) Benzodiazepines
7) Tramadol
1) Digoxin
2) Carbamazepines
3) Valproic acid
4) Phenytoin
5) Phenobarbital
�����
Cannabis
A-2)Cannabis :
◙ Other names:
1) In east Africa
Hashish & Bango
2) In America
Marijuana ( a Mexican term means pleasurable feeling )
3) In western Africa
Kaif
◙ Active principle :
∆-9-THC (∆-9-Tetrahydrocannabinol )
◙ Important notes :
- All parts of the plant are poisonous except the coarse stocks.
- THC is fat soluble ,which is rapidly cleared from plasma after
consumption and stored in body fatty tissues.
☼ Clinical picture of cannabis:
1)Small dose:
-
Sense of well being
Hallucination
Euphoria
Laughing
Joking
cheerfulness
2)Moderate dose:
-
Disorientation of place
Disorientation of time
Dilated pupil
4D
Red eyes
Death Fear
3)Large dose:
- Deep coma
- Death (Respiratory Failure.)
Short-term effects of cannabis
Dry mouth "cotton mouth"
 Muscle relaxation
 Increased heart rate

Long-term effects
Mental problems (schizophrenia and
depression).
 Testicular cancer increased risk of 70%
 Increased risk of infertility.

Faces of Cannabis
Effects begin within few minutes,
peak 30 mins.
last 2 hours
25-30% remains in the body
Investigations for Cannabis :
►Qualitative test:
- For urine sample.
► False positive results with
1) Anti-tussive drug (Marinol)
2) Anti-inflammatory/ Anti-rheumatic (Nuprin,Motrin/Aleve)
3) anti-histaminic (Phenergan, Promethegan)
4) Analgesic (Orudis KT)
5) Vitamin B ,Riboflavin (B2, Hempseed Oil)
6) Chemotherapy (Nabilone)
Very important
Strict
Observation
during sampling
Lastly
Longer decision times
Leading to
slower responses to
situations
Impact of cannabis on fertility:
Reduces sperm production.
 Reduces sperm motility.
 Incrases number of abnormal sperm.
 Increases DNA damage (Induce premature labour)
 Plasma of smokers have significant
- lower total testosterone level
- higher FSH and LH concentrations.

Normal Semen Analysis
Parameter
Normal Value
Volume
>=2 cc
Concentration
>=20 million/mL.
progressive motility Class(A) >=25%
or (A+B) >=50%
Motile ratio
(A+B+C) >=60%
Normal Morphology >=15%
CASA
Opiates
A-3)Opiates :
■ source:
Papapaver somniferum plant
Opiates includes :
Codeine
 Morphine
 Heroine ( cause Perforated nasal septum )

ClP of opium:
1) Stimulation stage :




Sense of well being
Euphoria
Hallucination
laughing
2) Depression stage :



Unpleasant sensation
Sleepiness
Fixed PPP
Investigations for Opium :
► Qualitative test:
- For urine sample.
- False positive results with
1) Pain prescriptions for
2) Cough suppressants (containing codeine)
Ethanol
A-1)Ethanol :
C/P: Depends on ethanol bl. Level :-
1)Asymptomatic: <0.05 gm%
2)Mild toxicity: 0.05-0.15 gm%
Drowsiness
Euphoria
Behavioral changes (Real man appear)
Aggressiveness
3)Moderate toxicity: 0.15-0.25 gm%
Flushing ( Alcohol flush)
Hiccough
Ataxia
Emesis
Eye manif. ( blurring of vision )
Ms. Manif. (staggering gait / tremors)
4)Severe toxicity : 0.25-0.35 gm%
5)Death : >0.35 gm%
Alcohol coma
Due to (Resp. Failure in early death )
(Liver cell failure & fatty liver in late death)
In mild and moderate
intoxication hypoglycemia
is commonly present.
Investigations for Ethanol :
1)Qualitative test:
- For urine sample
2)Quantitative test:
-
For blood sample
-
Enzymatic method (Alcohol DH)
#- False positive results :


with other volatile reducing agents
( such as : methanol = found in cheap beverages )
"fermented or decomposed" foods:
- fermentation is the conversion of a carbohydrate such
as sugar into an acid or an alcohol ( ethanol ).
- More specifically, fermentation can refer to the use of
bacteria to create lactic acid in certain foods.
- Many fermented foods, such as soy sauce, contain a
significant amount of alcohol.
Results of food fermentation
Ethanol
 Vinegar, in the form of acetic acid
 Ammonia
 Lactic acid
 Carbonic acid

Methanol

Minimal toxic dose (60 ml) is which can cause
blindness ,due to its metabolization to formaldehyde &
formic acid leading to systemic acidosis (serum pH
drops below 7.2)
N.B: Blindness is not at once.
(Normal serum pH =7,35-7.45).

Formic acid in the urine reduces Fehling's solution , so
gives false positive result of diabetes.
Amphetamine
Amphetamine uses:
1. It is used by students :
To keep them wakeful and alert during exam.,
This may lead to physical dependence on the drug.
2. It is used therapeutically as:
a- Nasal inhalation for decongestion
b- For treatment of obesity
Amphetamine preparations


Amphetamine sulphate (Benzedrine).
Dextroamphetamine sulphate injection
(Dexedrine) (Maxiton forte).
☼ C/P of
Amphetamine:
THE PRIDE-C
Talkativeness
T
Tachycardia
Tachypnea
Hypertension
H
Hyperthermian
Halluciations
E
Euphoria
P
R
I
Palpitations
Rigidity
Insomnia
Dilated pupil
D
Death
(Renal Failure /
Respiratory Failure)
C
Convulsions
Coma
Investigations for Amphetamine :
Qualitative test:
-
For urine sample.
#- False positive results :
Amantadine/Chlorpromazine/Phentermine/
Ranitidine/Thioridazine/Trazodone

BARBITURATES
Therapeutic uses:
Hypnotics
 General anaesthesia


Psycho-analysis (Truth serum).
Classification:
They are classified according to the duration of
action into:




Long acting: (6-8 hours): e.g. phenobarbital "luminal", "veronal".
Intermediate acting: (4-6 hours) e.g. Amobarbital "Amytal".
Short acting: (about 3 hours): e.g. Secobarbital Na "Seconal"
Ultra-short acting: (15 minutes or more) e.g. thiopental Na
"Pentothal".
 CNS:
CNS depression (ranging from mild sedation and hypnosis to coma).
 Respiration:
Respiratory depression .
 Cardiovascular
system:
direct myocardial depression effect
causing decreased force of contraction with reduced cardiac output.
So, a fall in the blood pressure.
 GIT:
decrease motility, tone and secretion.
 Kidney:
oliguria or even anuria due to hypotension.
 Uterus:
Hypnotic doses don't impair the uterine contraction
during labour.
Full anaesthetic doses decrease the force and the
frequency of uterine contraction during labour and may
inhibit the foetal respiration after delivery.
Investigations for BARBITURATES
Qualitative test:
-
For urine sample.
#- False positive results :
Ibuprofen /Naproxen
Benzodiazepines
Benzo. Therapeutic uses:
Anticonvulsant
 Treatment of anxiety states.
 Market names: Rivotril /Apetryl/ Parkinol.

Bullous skin lesions.
Intellectual impairment
Nausea / Vomiting / Vertigo
Headache
Coma
Diplopia / Drowsiness / Dysarthria
Investigations for Benzo
Qualitative test:
-
For urine sample.
#- False positive results :
 Oxaprozin
 Sertraline
Captagon
Captagon
Captagon, the trademark name for the
synthetic
fenethylline.
 Was first produced in the 1960s to treat
depression.

Captagon
Fenethylline = amphetamine + theophylline
Captagon
CNS
Irritability/
Cardiac
Heart rate
Paranoia
Diarheaa
Cocaine
Mode of consumption of Cocaine

Chewing the leaves of coca.

I.V. injection of the drug.
Snuffing of its powder
which may be adulterated
with irritating substances as boric
acid (thus, nasal septum perforation).

Cocaine abuser

Tactile hallucination, the addict feels
as if insects were creeping under his skin
"cocaine bugs or formication".

Dangerous Euphoria
may be unlike the calm morphine abuse.



Tremors and pain in the muscles and joints.
Anorexia, loss of appetite and wasting.
Perforated nasal septum.
► Qualitative test:
- For urine sample.
► False positive results with
 Amoxicillin
 Tonic water
Dilated pupil
Red eyes
Fixed PPP
Blurring of vision
Cannabis
opium
Ethanol
Mydriasis
Amphetamine
Diplopia
Benzodiazepines
TDM
TDM
Digoxin
B-1)Digoxin (lanoxin):
A therapeutic drug used for cardiac patients
with CHF or supraventricular tachycardia.
 It has a cumultive effect & narrow
therapeutic/toxic ratio.
 Therapeutic Dose : 0.25 mg.daily (1x1)
 Fatal dose : 2-4 mg.
 Fatal period : 30 min.- 24 h.

ClP of digoxin toxicity:
GIT symptoms:
Nausea / Vomiting
Abdominal pain
Diarrhea
Cardiac symp.:
Visual symp.:
CNS symp.:
Bradycardia (pulse may fall to 20/min.)
Color vision (yellow &or white vision )
Blurring of vision & diplopia
Headache
Confusion
Investigations for Digoxin :

Serum blood level

When to take blood
Pre-dose preferably
Or at least 6 hours after oral dose to allow distribution
How often to repeat
1 week after initiation or dose change

(Normal 0.8 - 2.1 ng/ml)
Digoxin
Half-life
30-40 hours
Time to steady state sampling
>1 week
Loading dose
IV 10 microgram/kg in 100mL saline over 2hr
oral 15 microgram/kg (750-1,500 micrograms in
divided doses)
Maintenance dose
62.5micrograms – 250micrograms once daily
When to take blood
Pre-dose preferably (at least 6 hours after oral dose
to allow distribution)
How often to repeat
1 week after initiation or dose change
Sampling method
Li-heparin/SST
Signs of toxicity
Anorexia, nausea, vomiting, various arrhythmias,
atrial tachycardia, 10-15mg fatal in adults,
Target range
1-2 microgram/L
Practical issues
125mcg tablet  100mcg liquid (2mL)  80mcg iv
Carbamazepine
B-2) Carbamazepine:





Anticonvulsant & antiepileptic
Seizures.
Mania, mental illnesses & depression.
It works by reducing abnormal electrical activity in
the brain.
Trade names: Tegretol.
What are the hazards during
using Carbamazepin ???

Life-threatening allergic reactions.
These risks are highest in Asian people who have a
genetic (inherited) risk factor.
Anaphylactic shock.
 Decreases the number of blood cells (WBCs &

platelets).
Carbamazepine toxicity:

Dry mouth.
Investigations for Carbamazepine :
Serum blood level
(Normal 4 - 12 ng/ml)
 False positive results with TCA.
 When to take blood
Pre-dose
 How often to repeat
After dose changes (5-7 days)

Carbamazapine
Half-life
30hr then 15hr due to autoinduction
Time to steady state sampling
5-7 days after dose change
Loading dose
Slow titration: 100-200mg bd oral >
increasing by 100-200mg each week
Maintenance dose
200-800mg bd
When to take blood
Pre-dose
How often to repeat
After dose changes (5-7 days)
Sampling method
Heparin
Target range
4-12mg/L
Valproic Acid
B-3)Valproic Acid :
Anticonvulsants drug.
 Seizures.
 Mania.


Trade names: Depakene
Valproic acid IMPORTANT WARNING:
Irregular heart beat.
Difficulty breathing & swallowing.
Blurred or double vision.
Thinking about killing himself or
planning or trying to do so.
Sleepiness / Coma
Investigations for Valproic Acid :

Serum blood level
(Normal: 50-100 mg/ml)
If you have diabetes
Valproic acid can cause false results on urine tests for
ketones
(DKA?)
What is tramadol?
A popular painkiller medication.
 A 4 - phenyl-piperidine analogue of codeine
synthetic agents.
 Centrally acting synthetic opioid analgesic
 It helps to get rid of the pain, by blocking
transmission of pain information for brain
receptors.

Different brands of the drug on the
market
Tamol, Ultram, Ultracet, Ryzolt, Tramal, and
Tramacet.
 Tramadol is excreted in breast milk.

Therapeutic dosage 50–100mg every 4–6 h.
 The total daily dose should not exceed 400mg
with adult.
 A peak blood concentration within 2 hrs.


Once a prolonged use of the drug , it is usually
result in dependence, and resistance to drugs.
Tramadol has been shown to cross the
placenta.
 Tramadol has been shown to cross BBB.
 Tramadol has a cumulative excretion in breast
milk within 16 hours postdose

Tramadol abuse
Swelling
 Sweating
 Tremors

Phenytoin
Phenytoin
Half-life
22 hours but caution: saturable metabolism
Time to steady state sampling
Varies considerably between patients (1-5 weeks)
Loading dose
18mg/kg slow iv infusion for status epilepticus over
30-60mins (ECG recommended)
Maintenance dose
100mg 6-8 hourly iv (convert to od if stable)
200-500mg once daily po
When to take blood
Pre-dose
How often to repeat
Sample within 2-3 days of initiation
Then again 3-5 days later.
If no change, monitor weekly.
Sampling method
Li-heparin/SST
Signs of toxicity
nystagmus, diplopia, ataxia, confusion, slurred
speech, hyperglycaemia, respiratory/circulatory
depression (2-5g lethal)
Target range
10-20mg/L
Lithium
Lithium
Half-life
24 hours
Time to steady state sampling
4-5 days after starting or change in therapy or
sodium/fluid intake
Loading dose
400mg-1.2g daily
Maintenance dose
400mg – 1,200mg od po
When to take blood
pre-dose
How often to repeat
Weekly until dose stable then at least 3-monthly
Sampling method
Plain tube
Signs of toxicity
Hyperreflexia & hyperextension of limbs,
convulsions, psychoses, syncope, renal failure,
circulatory failure, coma, death
Target range
0.4 – 1.0 mmol/L
Practical issues
Slow release brands not interchangeable
Theophylline
Theophylline /Aminophylline iv
Half-life
8 hours
Time to steady state sampling
2 hours post load, then 12 hours into infusion
Oral: 5 days after starting
Loading dose
5mg/kg iv if treatment naïve in 100mL over 20 mins
Maintenance dose
Infusion 0.5mg/kg/hour (500mg in 500mL)
Oral: 200-500mg 12-hourly (slow release)
When to take blood
Infusion : 24 hours after dose
Oral : pre-dose & at least 4-6 hours post-dose
How often to repeat
As required
Sampling method
Li-heparin/SST
Signs of toxicity
Nausea, vomiting and haematemesis, agitation,
restlessness, dilated pupils and convulsions, hypotension
and life-threatening cardiac arrhythmias
Target range
10-20mg/L
Practical issues
Slow release brands not interchangeable
Theophylline 790 mg = Aminophylline 1,000mg
How to write an
analytical toxicology
report
???
2010 /
ANALYTICAL
Site of Sample collection:
Urine Sp. Gr.:
Urine pH :
Urine Nitrite :
/‫د‬0‫أ‬
Referred by Prof. Dr.\
/ ‫نتيجة التحليل المقدم عن السيد‬
/
/ ‫التــــــــــــــــــــــــاريــــــــخ‬
/ ‫السن‬
/ ‫األدويه السابق اخذها‬
TOXICOLOGY
……….
……....
………
...........
Thanks for reference
REPORT
Inside/Outside Lab.
( N.: 1005-1025 )
( N.: 5 – 8 )
( N.: negative )
Signature
►These results are preliminary results & must be confirmed by HPLC or GS/MS
‫يجب اإلحتفاظ بجزأ من‬
‫العينه فى الفريزر‬
Thank You