Poisons and Drugs

1
Poisons and Drugs

• Prof. Monzir S. Abdel-Latif
• Chemistry Department
• Islamic University of Gaza
• http//www.monzir-pal.net

2
Syllabus

• In this course, it is anticipated to cover the
  following topics
• Introduction to Toxicology
• Epidemiological Studies
• Toxicodynamics and Toxicokinetics
• Toxicokinetics ...... Continued
• Toxicokinetics ... continued
• Risk Assessment and Management
• Review of Analytical Methods
• Drug Testing Methodologies and Possible Pitfalls

3

• Methods of Analysis
• Gas Chromatography
• Liquid chromatography
• Mass Spectrometry
• Hyphenated Techniques
• AAS and AES
• Spectrophotometry and Fluorometry
• Sample Preparation
• Classes of drugs and poisons
• According to site of action
• Grouping of drugs

4

• Drug Classification
• Amphetamines
• Lysergic acid and LSD
• Other Hallucination Drugs
• Cannabis
• Opiates and Cocaine
• Therapeutic Drug Monitoring
• Pesticides
• Illicit Drugs Analyzed by the Forensic Lab in
  Gaza

5

• We will follow presentation chapters from several
  textbooks including Fundamantal Toxicology by
  John Duffus and Howard Worth, published by RSC in
  2006, Poisoning and Toxicology handbook, 4th Ed.,
  A Guide to Practical Toxicology, 2nd Ed, Woolley,
  Toxicological Chemistry and Biochemistry, 3rd
  Ed., as well as others .
• However, other books in Instrumental Analysis and
  related research papers will be found very
  helpful.
• Ill try to maintain a web page for the course
  and regularly post reading material for you to
  look at.

6
Introduction to Toxicology

• Toxicology is the fundamental science of poisons.
• A poison is a substance that can cause severe
  injury or death as a result of interaction with
  living tissue.
• Therefore, in principle, all chemicals can be
  considered as potential poisons causing injury or
  death upon excessive exposure. At the same time
  all chemicals can be regarded as safe if exposure
  to chemicals was kept below a tolerable limit.

7

• Exposure to toxins
• Exposure is a function of the following factors
• Amount or concentration of the target chemical
• Time of interaction of the chemical with the
  target organ
• Frequency of interaction of the chemical with the
  target organ
• Organ exposed
• For humans, age and health of the subject are
  also important factors
• For highly toxic chemicals, the tolerable
  exposure is close to zero

8

• Determination of tolerable exposure
• In fact, this constitutes a problem since we do
  need reliable data relating exposure to injury or
  adverse effect in humans.
• Unfortunately, what can be considered as an
  injury or an adverse effect is not well defined
  and debatable. We will look at this problem later

9
Adverse effects

• An adverse effect can be defined as an abnormal,
  undesirable, or harmful change of people or
  organs following exposure to the potentially
  toxic substance
• Although the ultimate adverse effect is death,
  the following are definite adverse effects
• Altered food consumption
• Altered body or organ weight
• Altered enzyme or hormone levels, ..etc

10
Harmful effects

• An effect is considered harmful if it causes a
  functional damage to an organ, irreversible
  change in homeostasis or increased susceptibility
  to chemical or biological stress including
  infectious diseases.
• One should consider the degree of alteration from
  normality and the relation of the altered
  property to the total well-being of the person
• In some cases, a person can adapt to the
  irreversible alteration and practice normal life

11
In some cases of immune reactions leading to
allergy

• The first exposure may not cause an adverse
  effect of allergy, however, it may sensitize the
  organism to respond adversely (badly) to future
  exposures even at lower levels

12
Amount of exposure

• The amount of exposure to a chemical that causes
  injury varies over a very wide range depending on
  the type of chemical and its form (liquid, solid,
  or gas)
• This can be quantified using the median lethal
  dose (LD50) concept or lethal concentration LC50

13
Median Lethal Dose (LD50), mg toxin/kg body weight

• LD50 is a statistically derived single dose of a
  chemical that can be expected to cause the death
  of 50 of organisms of a given population, under
  a defined set of experimental conditions.
• LD50s when reported for human beings are
  obtained by extrapolation from studies on
  mammals, or observations following accidental or
  suicidal exposures.

14
(No Transcript)
15

• The LD50 is used to classify and compare toxicity
  of chemicals, although it is of limited merits.
  For example, the LD50 classification orally to
  rats are
• Very toxic less than 25 mg/kg
• Toxic from 25 -199 mg/kg
• Harmful from 200 - 2000 mg/kg
• However, it is not convincing to label a
  substance as toxic because its LD50 is 199, while
  labeling another as harmful since its LD50 is
  200. That is why the LD50 values need more
  refinements.

16

• In addition, when using LD50 values, there is no
  simple relationship between lethality and sub
  lethal toxic effects.
• In other words also, it is not informative to
  what is the minimum dose that can be lethal, and
  thus no indication of what can be considered a
  safe exposure level.

17
Toxicity versus Risk

• With regards to chemical safety, risk assessment
  can be more important than actual toxicity of
  chemicals.
• Risk can be regarded as the probability that a
  substance would impart unacceptable harm or
  unacceptable effects to an organ or to ecosystems
  upon exposure.

18
Safety

• It is possible to define safety as the practical
  certainty that injury will not (high probability)
  result from exposure to a hazard under defined
  conditions.
• Practical certainty is a numerically specified
  low risk (or socially acceptable risk).
• Assessment of risk depends on scientific data,
  but acceptability is influenced by social,
  economic, political and benefits arising from a
  chemical or a process.

19
Uncertainty (safety) factors

• A threshold of exposure above which an adverse
  effect can occur and below which no such effect
  is observed, is obtained from available data.
• The threshold of exposure is then divided by a
  factor (uncertainty or safety factor) to lower it
  to a new value that toxicologists can regard as
  safe beyond doubt.

20
(No Transcript)
21

• US National Academy of Sciences safe drinking
  water committee proposed the following guidelines
  for selecting the safety factors, to be used with
  no observed effect level (NOEL) data.

22

• Safety Factor Selection
• An uncertainty (safety) factor of 10 is used when
  valid human data based on chronic exposure is
  available
• An uncertainty (safety) factor of 100 is used
  when human data is inconclusive or limited to
  acute exposure, but reliable data on animals is
  available
• An uncertainty (safety) factor of 1000 is used
  when no human data is available and experimental
  animal data is limited

23
Exposure to potentially toxic substances

• Toxins can cause injury when they reach sensitive
  parts of an organism at a sufficiently high
  concentration.
• Exposure can occur through
• Skin (dermal or percutaneous) Absorption
• Inhalation
• Ingestion

24
Skin absorption

• Among the chemicals that are absorbed through the
  skin are aniline, hydrogen cyanide, some steroid
  hormones, organic mercury compounds,
  nitrobenzene, organophosphate compounds and
  phenol. Some chemicals, such as phenol or
  methylmercury chloride, can be lethal if absorbed
  from a fairly small area (a few square
  centimeters) of skin. If protective clothing is
  being worn, it must be remembered that absorption
  through the skin of any chemical that gets inside
  the clothing will be even faster than through
  unprotected skin because the chemical cannot
  escape and contact is maintained over a longer
  time.

25
(No Transcript)
26
Inhalation

• Gases and vapors are easily inhaled but
  inhalation of particles depends upon their size
  and shape. The smaller the particle, the further
  into the respiratory tract it can go. Dusts with
  an effective aerodynamic diameter of between 0.5
  and 7 µm can persist in the alveoli and
  respiratory bronchioles after deposition. Peak
  retention depends upon the aerodynamic shape but
  is mainly of those particles with an effective
  aerodynamic diameter of between 1 and 2 µm.

27
(No Transcript)
28

• Physical irritation by dust particles or fibers
  can cause very serious adverse health effects but
  most effects depend upon the solids being
  dissolved. Special consideration should be given
  to asbestos fibers which may lodge in the lung
  and cause fibrosis and cancer even though they
  are mostly insoluble and therefore do not act
  like classical toxicants care should also be
  taken in assessing possible harm from man-made
  mineral fibers that have similar properties.
• Some insoluble particles such as asbestos, coal
  dust and silica dust will readily cause fibrosis
  of the lung

29
Ingestion

• A chemical may accumulate if absorption exceeds
  excretion this is particularly likely with
  substances that combine a fairly high degree of
  lipid solubility with chemical stability. Such
  chemicals are found in the group of persistent
  organic pollutants (POPS), including several
  organochlorine pesticides, which are now largely,
  but not entirely, banned from use

30

• Divalent lead ions accumulate in bone where they
  replace the chemically similar calcium ions.
  While in the bone, they cause little harm but
  when bone breaks down, or during pregnancy or
  illness, the lead ions enter the blood and may
  poison the person who has accumulated them or, in
  the case of pregnancy, the unborn child.