Principles of

Clinical Toxicology

Edited by
Staff Members of Forensic Medicine and
Clinical Toxicology Department

Faculty of Medicine
Ain Shams University
 ‫‪i‬‬

‫الرؤية‬
‫تصبب ك يبب الطبب جامعبب عببي شببم إلبب أ تكبب‬
‫اأ ل ب منط ب الش ب اأ سببط لتخ ب ي أط ببا ذ ى قببا ا‬
‫تنافسي أ ت ا اإصاح في التع ي الط ي‪.‬‬
‫الرسالة‬
‫تهاف ك ي الط جامعب عبي شبم إلب إعبااا خب ي‬
‫مببا ذي مهببا تنافسببي ع ب المسببت ى المح ببي العببالمي‬
‫قببباا ع ببب التع بببي البببتع التبببا مببباى الحيبببا م تببب‬
‫معايي الخام الط ي اأخا المهني ‪.‬‬
‫تسبببببع الك يببببب إلببببب التطببببب ي المسبببببتم ل ببببب ام‬
‫الم بب ا اعبب تطبب ي ال حبب الع مببي مبب الت سبب فببي‬
‫اأ حببا الع مي ب التط ي ي ب ب ام ال عاي ب الصببحي لخام ب‬
‫احتياجا المجتم تنمي ال يئ ‪.‬‬
‫كمببا تهبباف الك ي ب إل ب ت ب في كبب اا متميبب أكاايميبباً‬
‫حثيببباً مببب أعضبببا هيئببب التبببا ي اعببب الجهبببا اإاا ي‬
‫اا ت ببا ببالن المؤسسببي ت ب في الم ب ا ا الذاتي ب لتح ي ب‬
‫الغايا اأهااف‪.‬‬
‫القيم‬
‫عم نبا صبا التميب لبي لمجب ا اأاا‬ ‫نح نمبا‬
‫الصببا فببي كبب مبببا نفعبب نسببع اائمببا لتح يببب‬ ‫نمببا‬
‫التببب ا بببي الحببب ال اجببب مببب‬ ‫المسبببا ا فبببي الح ببب‬
‫ااحت ا المت اا نح نعم معاً لمص ح الف ا المجم ع‪.‬‬
 ii

The Vision, Mission and Values

Our vision…
To be the first in the Middle East to produce doctors
with a competitive edge and lead the development of medical
education.

Our mission…
To prepare a graduate having competitive skills on the
local and international level, capable of teaching, learning and
training for life and is committed to the standards of medical
service and professional ethics.
The College also seeks continued development of
programs and courses, supports and develops scientific
research with the expansion of applied scientific research and
health care programs to serve the needs of society and
environment development.
The College also aims to provide excellent academic
staff and research faculty members, to support the upgrading
of administrative and institutional systems and to provide its
own resources in order to achieve the goals and objectives.

Our values…
We carry out our job aiming at excellence and not just
performance, we practice honesty in everything we do, we
always strive to achieve equality of rights and the balance
between the right and duty, with mutual respect and we work
together for the benefit of one and all.
 iii

Preface

This book is the fruit of the cooperation between the

staff members of Forensic Medicine and Clinical Toxicology
Department, Faculty of Medicine, Ain Shams University.

We acknowledge their extraordinary efforts and to all

who participated in this book our appreciation and
gratefulness.

Finally, we hope that Principles of Forensic Medicine will

be useful to students and will find it a valuable aid to learning
and success.

Staff members of Forensic Medicine and

Clinical Toxicology Department
 iv

Objectives of the Clinical Toxicology Course

By the end of this course, the student should be able to:

1. Evaluate an intoxicated patient, pick up critical
conditions for immediate intervention.
2. Think of toxicological causes as a part of differential
diagnosis of medical and surgical emergencies.
3. Write an informative complete sheet for an intoxicated
patient containing all required data including history,
examination and investigations.
4. Be aware with steps of management of toxicological
emergencies, and be initially trained on supporting
respiration, CPR, endotracheal intubation and
venepuncture.
5. Diagnose and show competency in decision making
regarding the treatment of commonly encountered
acute toxicity of some household, medical and
environmental poisons.
6. Display good communication skills, attitudes and
working in a team during sessions of case studies and
preparing assignments.
7. Display general and transferable skills and self learning
through problem based studying and preparing
assignment.
 v
Notes and Instructions to the Students
I- Learning resources:
A) Books:
1- Department book. It should be known that not all
subjects the student will be evaluated in are included in
the department book. This means that some of the
examination topics will not be included in the
department book.
2- Textbooks of Clinical Toxicology:
a) Emergency Toxicology (Peter Viccellio)
b) Goldfrank's Toxicologic Emergencies (Lewis S. Nelson,
Neal A. Lewin, Mary Ann Howland and Robert S.
Hoffman)
c) Poisoning and Drug Overdose (Kent R. Olson)
d) Medical Toxicology (Richard C. Dart)
B) Lectures
C) Handouts
D) Electronic resources (e-learning). These will be included in
the evaluation and will be considered in the distribution of
marks.
Link to the official e-learning site:
http://www.medicaleducationonline.org/smf/index.php?boa
rd=23.0
Other useful links:
www.toxnet.com
http://emedicine.medscape.com/emergency_medicine#toxic
ology
II- Subjects for e-learning in the Clinical Toxicology curriculum are:
A) Gastric Lavage Technique
B) Button Batteries
C) Naphthalene
D) Anticoagulants
E) Nitrates, Nitrites, and Methemoglobinemia
F) Lithium
G) Ethylene Glycol
H) Mercury
I) Cocaine
J) Performance Enhance Drugs
III- Nobody will be permitted to change his/her group.
 vi
IV- Attendance: at least 75% is required. Absenteeism for any
reason will diminish the attendance score, while absenteeism for
more than 25% will exclude the absentee from examinations.

 The whole forensic and toxicology course is appreciated by

V- Evaluation

200 marks:
1- At the end of the course the student will be evaluated by
80 marks distributed as follows:-
a) 10 marks for 2 research assignments for every
student
b) 10 marks assigned to weekly exams (questions will be
about the lectures topics given in the preceding
week).
c) 20 marks for an MCQ exam held out in the computer
lab.
d) 40 marks for the end of the round practical
examination that includes:
i. Answering questions on data show illustrations.
ii. Skills demonstration: e.g CPR.
2- End of the year final exam 120 marks:
a) 100 marks MCQ and written exam.

 Missing any examination will waste its assigned marks, unless

b) 20 marks oral exam in two sessions.

an acceptable medical excuse is offered; and in such case

marks will be redistributed to the remaining examinations.
VI- Guide to Problem Oriented Sessions (POS)
You have two PO sessions per week in one day

 Your group will receive one or two problems and is

A) A Problem Presentation Session

required to discuss various aspects in them. During this

session, you will be guided by a tutor who will regulate

 During the session you will:

the session.

a) Conduct a meeting within the group

b) Discuss the case
c) Participate actively

 Output of the session: by the end of the session you are

d) Assess yourself at the end of the session

expected to:
a) Identify points of interest in the case
 vii
b) Identify the baseline knowledge you will need to
solve the case
c) Assign roles and duties among the team
d) Outline recommended studies to solve the case

 Your group will hold another meeting with one of the

B) A Discussion session

 During the session you will:

faculty members to discuss the problem.

a) Present the challenges met to solve the problem

b) Discuss the case
c) Listen to faculty inputs and comments on the case

 Output of the session: by the end of the session you are

d) Assess yourself at the end of the session

expected to:
a) Outline a valuable solution to the case
b) Write down a case discussion
c) Master the tricky points in the problem
C) Assignment work
Each student has to prepare 1 assignment in toxicology and 1
assignment in forensic topics. The assignments should be
presented in a written form for evaluation. Topics of
assignment will be selected interactively by the student, his
colleagues and the supervisor staff member. 5 marks will be
assigned for each assignment. Evaluation will be carried out
by the supervisor staff member.
VII- Teaching places
A) Lectures and practical sessions will be held in lecture Hall 2 at
the ground floor.
B) Skills sessions will be held at the Laboratory, Amphitheatre,
Demonstrators Room, Room 1, and Room 2 at the
underground floor.
C) POS (Problem Oriented Sessions) and assignment will be held
in staff rooms in floor 1.

VIII- Clinical Toxicology course specifications and weights:

Teaching and Learning

Methods
Topics
Total
L T P/ C O
%
[1] Diagnosis Of Poisoning (8%)
 viii
1.1Toxic Syndromes, General Signs and Symptoms of
Intoxication and Role of The Laboratory
1.2 Assessing a Case of Intoxication
1.3.General Examination of an Intoxicated Patient
1.4. Required Investigations to Reach to a Provisional 5.5 1.5 - 4 -
Diagnosis
1.5Writing a Sheet For an Intoxicated Patient

[2] Common Toxicological Emergencies (11%)

Toxic Causes, Diagnosis, Treatment of:
2.1.Respiratory Failure
2.2 Coma
2.3.Convulsion
2.4 Acute pulmonary edema 7 3 - 4 -
2.5.Shock and hypotension
2.6.Rhabdomyolysis

[3] Decontamination of Poisons (11%)

3.1 Elimination of Ingested Poisons (Emesis-Gastric
Lavage-Activated Charcoal –Catharsis)
3.2 Elimination Of Poisons Administered By Other
7 3 - 4 -
Routes (Dermal, Eye And Inhalation)
3.3 Enhancement Of Excretion Of Poisons (Diuresis,
Hemodialysis, Hemoperfusion)
[4] Household Poisons (13%)
Pathophysiology, Clinical Picture Treatment of Acute
Overdose of :
4.1 Corrosives
8.5 4.5 - 4 -
4.2 Insecticides and Rodenticides
4.3 Hydrocarbons
4.4 Non Toxic Exposure
[5] Volatiles poisoning (5.5%)
Pathophysiology, Clinical Picture Treatment of Acute
Overdose of :
5.1 Ethyl alcohol 3.5 3 - 0.5 -
5.2 Methyl alcohol
5.3 Ethylene glycol
[6] Substance Of Abuse intoxication (12.5%)
6.1 Definitions and General Considerations
6.2 Doping
6.2 Pathphysiology, Clinical Picture and Treatment of
Acute Overdose of
- Opiates 8 4.5 - 3.5 -
- Alcohol dependence
- Cannabis
- Amphetamine
- Cocaine
 ix
- Sedative Hypnotics (barbiturates,bnzodiazepines)
- Nicotine
- Volatiles
[7] Metallic Poisons (6%)
Pathphysiology, Clinical Picture and Treatment of
7.1 Iron Toxicity
4 3 - 1 -
7.2 Lead Toxicity
7.3 Mercury Toxicity
[8] Toxicities of analgesics (5.5%)
Pathphysiology, Clinical Picture and Treatment of Acute
Overdose of:
8.1 Salicylates 3.5 1.5 - 2 -
8.2 Paracetamol
8.3 Non steroidal anti-inflammatory drugs
[9] Poisoning with cardiovascular System Acting Drugs (7%)
Pathphysiology, Clinical Picture and Treatment of Acute
Overdose of:
9.1 Digitalis
4.5 3 - 1.5 -
9.2 B- Blockers
9.3 Calcium channel blockers
9.4 Nitrites
[10] Intoxications with central Nervous System Acting Drug (7.5%)
Pathphysiology ,Clinical Picture and Treatment Of Acute
Overdose Of:
10.1 Sedative Hypnotics
10.2 Theophylline 5 3 - 2 -
10.3 Antidepressants
10.4 Antipsychotics
10.5 Aniconvulsants
[11] Toxic Gases Exposures (5.5%)
Pathophsilogy, Clinical Picture and Treatment of:
11.1 Carbon Monoxide
3.5 1.5 - 2 -
11.2 Cyanide
11.3 Hydrogen Sulphide
[12] Natural Poisons (7.5%)
Pathophsilogy, Clinical Picture and Treatment of:
12.1 Food Poisoning
12.2 Botulism
5 3 - 2 -
12.3 Scorpion Sting
12.4 Snake Bite
12.5 Spider Sting
65+5
Total 34.5 - 30.5 5
(100%)
L: lecture, T: Tutorial, P: Practical, C: Clinical, O: Other
Directed Self Learning includes:
- Department museum
- Explanatory posters for curriculum
 x
- Practical teaching materials in department computers
- Progress of research.

IX- Clinical Toxicology Course Objectives

Module
1 1. State the toxic causes and clinical picture of
Diagnosis of poisoning
1.1Toxic syndromes, general
signs and symptoms of
intoxication .and role of the lab.
1.2. Appropriate questions and
information required for
assessing a case of intoxication
1.3.General examination of an
intoxicated patient
1.4. Required investigations to
reach to a provisional diagnosis.
1.5. Writing a sheet for an
intoxicated patient.
2 1. Diagnose the critical conditions from the
Common toxicologic
emergencies
Toxic causes ,diagnosis
,treatment of:
2.1. Respiratory failure
2.2. Coma.
2.3. Convulsion.
2.4. Acute pulmonary edema,
2.5. Shock and hypotension.
2.6. Rhabdomyolysis
3 1. State the uses, indications precautions and
Decontamination of poisons
3.1. Elimination of ingested
poisons (emesis-gastric lavage-
activated charcoal –catharsis).
3.2. Elimination of poisons
administered by other
routes.(dermal, eye and
inhalation).
3.3. Enhancement of excretion
of poisons ( diuresis
,hemodialysis, hemoperfusion).
4 1. State the types , pathophysiology, clinical
Household poisons
Pathophysiology ,clinical picture
,treatment of acute toxicity of :
4.1. Corrosive alkali, and acids.
Objectives
the common toxic syndromes(cholinergic
,anticholinergic, sympathetic, opiate)
2. Ask the appropriate questions required to
help reach to a diagnosis.
3. Pick up the threats and recognize the
critical abnormalities in a critically
intoxicated case
4. State and interpret the required
investigations to reach to a provisional
diagnosis
5. State all these data on a sheet.
6. Perform and interpret some bed side tests
for common poisons.
given clinical data.
2. Decide the appropriate management and
care that should be done for each case.
3. When given mannequin the learner should be
able to perform correctly steps of CPR,
venepuncture , endotracheal intubation ,O2
mask application ,mouth to mouth
respiration.
complications of methods of
decontaminations.
2. Decide the appropriate method of
contamination to be used in a given clinical
case.
3. When given the instruments used in
decontamination procedures the learner
should be able to define it and mention its
uses.
picture and treatment of toxicity of
commonly encountered corrosives (acids,
alkalis, hypochlorite, oxalic and phenol)
2. Diagnose from a given clinical data the

4.2. Phenol, carbolic and oxalic
acids.
4.5 Insecticides.
4.6 . Kerosene.
4.7 . Non toxic exposure
5 1. State the types, pathophysiology, clinical
Substance of abuse.
5.1 Definitions and general
considerations.
5.2.Pathphysiology ,clinical
picture and treatment of acute 2. Diagnose from a given clinical data the
overdose of:
5.2 1. Opiates.
5.2.2 Cannabis.
5.2.3 Amphetamine
5.2.4 Cocaine.
5.2.5. Sedative hypnotics
(barbiturates, benzodiazepines).
xi
causative poison and decide the required
investigations and treatment for this
particular case.
3. When given a commercial household sample
the learner should be able to identify the
possible poisonous substances and their
effects and differentiate non toxic materials.
picture and treatment of acute toxicity of the
listed substances of abuse (opiates, cannabis,
amphetamines, cocaine ,and sedative
hypnotics)
causative poison and decide the required
investigations and treatment for this
particular case.
3. When given a commercial medical or plant
sample the learner should be able to identify
the possible poisonous substance and its
effect.

6 1. State the types, pathophysiology, clinical

Metallic poisons
6.1. Pathophysiology ,clinical
picture and treatment of acute
overdose of iron intoxication:
6.2. Chronic lead toxicity
6.3. Chronic mercury and
phosphorus toxicity.
7 1.
Analgesics
7.1. Pathophysiology ,clinical
picture and treatment of acute
overdose of:
-Salicylates
-Paracetamol
8 1.
C.V.S. acting drugs
8.1Pathphysiology ,clinical
picture and treatment of acute
overdose of:
-Digitalis
-Beta blockers
picture and treatment of acute toxicity of
iron medication.
2. State the important hazards,
environmental sources and lines of
treatment of chronic toxicity of lead,
mercury and phosphorus.
3. From a given data of an acute iron
poisoning, the learner should be able to
diagnose, and state the line oft treatment.
1. State the types, pathophysiology,
clinical picture and treatment of acute
toxicity of salicylates and paracetamol.
2. 2. Diagnose from a given clinical data the
causative poison and decide the required
investigations and treatment for this
particular case.
3. 3. Show skills of performing gastric lavage
on mannequin.
1. State the types, pathophysiology,
clinical picture and treatment of acute
toxicity of digitalis and B-blockers.
2. 2. Diagnose from a given clinical data the
causative poison and decide the required
investigations and treatment for this
particular case.
 xii
9 1. State the types, pathophysiology, clinical
C.N.S. acting drugs picture and treatment of acute toxicity of
Pathophysiology ,clinical picture listed drugs.
and treatment of acute overdose 2. Diagnose from a given clinical data the
of: causative poison and decide the required
-Theophylline. investigations and treatment for this
-Antipsychotic phenothiazines) particular case.
-TCA.and MAO inhibitors)
-Lithium
-Anticonvulsants
10 1. State the types, pathophysiology, clinical
Toxic gases picture and treatment of acute toxicity of
Pathophysiology, clinical picture listed toxic gases.
and treatment of acute toxicity 2. Diagnose from a given clinical data the
of causative poison and decide the required
-Carbon monoxide investigations and treatment for this
-Cyanide particular case.
-Hydrogen sulphide.
11 1. State the types, pathophysiology, clinical
Natural poisons picture and treatment of acute toxicity of
Pathophysiology, clinical picture listed natural poisons.
and treatment of: 2. Diagnose from a given clinical data the
-Food poisoning. causative poison and decide the required
-Botulism investigations and treatment for this
-Animal poisoning: particular case.
-Scorpion sting
-Snake bite
 xiii

TABLE OF CONTENTS
General Toxicology _________________________________ 1
INTRODUCTION _____________________________________ 1
GENERAL APPROACH TO THE POISONED PATIENT _____________ 4
TOXIC SYNDROMES (TOXIDROMES) ______________________ 11
GENERAL MANAGEMENT OF POISONING __________________ 12
MANAGEMENT OF COMMON TOXICOLOGIC PRESENTATIONS ____ 24
HOSPITAL DISPOSITION ______________________________ 35
NON-TOXIC EXPOSURE _______________________________ 37
MEDICOLEGAL ASPECTS OF POISONING ___________________ 37
Household Toxicity ________________________________ 39
CORROSIVES ______________________________________ 39
HYDROCARBONS ___________________________________ 51
INSECTICIDES _____________________________________ 56
NAPHTHALENE ____________________________________ 64
RODENTICIDES ____________________________________ 64
Atropine _______________________________________ 66
Analgesics ______________________________________ 70
SALICYLATES ______________________________________ 70
PARACETAMOL ____________________________________ 76
Cardiovascular Drugs ______________________________ 81
DIGITALIS ________________________________________ 81
BETA BLOCKERS____________________________________ 85
NITRITES, NITRATES AND METHEMOGLOBINEMIA ____________ 87
Theophylline ____________________________________ 87
Psychotropic Drugs ________________________________ 91
ANTIPSYCHOTICS ___________________________________ 92
ANTIDEPRESSANTS _________________________________ 94
Sedative Hypnotics ________________________________ 98
BARBITURATES ____________________________________ 99
BENZODIAZEPINES __________________________________ 102
Anticonvulsants _________________________________ 106
PHENYTOIN ______________________________________ 106
CARBAMAZEPINE __________________________________ 107
Toxic Gases ____________________________________ 109
CARBON MONOXIDE ________________________________ 109
CYANIDE ________________________________________ 116
HYDROGEN SULPHIDE (H2S) ___________________________ 119
Metals ________________________________________ 123
LEAD ___________________________________________ 123
IRON ___________________________________________ 127
MERCURY ________________________________________ 130
 xiv
Food Poisoning __________________________________ 132
FOOD POISONING ASSOCIATED WITH ACUTE GASTROENTERITIS __ 134
FOOD POISONING ASSOCIATED WITH NEUROLOGICAL SYMPTOMS 136
Animal Poisons __________________________________ 143
SNAKE ENVENOMATION ______________________________ 144
SCORPION ENVENOMATION ___________________________ 151
SPIDER ENVENOMATION _____________________________ 154
Alcohols_______________________________________ 156
ETHYL ALCOHOL ___________________________________ 157
METHYL ALCOHOL __________________________________ 160
ETHYLENE GLYCOL __________________________________ 163
Drug Dependence and Drug Abuse ____________________ 165
OPIATES AND OPIOIDS _______________________________ 171
ALCOHOL DEPENDENCE ______________________________ 178
AMPHETAMINE ____________________________________ 180
BENZODIAZEPINES DEPENDENCE ________________________ 183
CANNABIS _______________________________________ 184
NICOTINE ________________________________________ 187
VOLATILE ABUSE ___________________________________ 187
Cocaine _________________________________________ 188
Performance enhancing drugs __________________________ 188
Role of Laboratory in Clinical Toxicology ________________ 191
References _____________________________________ 195

Normal Vital data

Systolic Diastolic Respiratory

Pulse
Age BP BP rate
(beats/min)
(mm Hg) (mm Hg) (breaths/min)
Adult 90-140 <90 60-100 8-14
12 years 110 70 85 15-20
6 years 100 60 100 20-25
1 year 95 60 120 25-30
Newborn 60 40 125 35-40
 1

CHAPTER 1
General Toxicology
INTRODUCTION
Intended Learning Outcomes (ILOs):
By the end of this section the student should be able to:
K1: Define what is meant by the science of toxicology.
K2: Explain factors affecting toxic responses.
(K: Knowledge)
Definitions:
Toxicology is the study of the harmful effects of
chemicals on living systems, (human, animal, plant or microbe).
These effects can range from a life threatening injury to
something that might be considered a minor effect.
Toxicology is a growing science that covers many areas, for
example:
Environmental toxicology: it is the science that deals with
Pollution of contaminants into an environment that causes
instability, disorder, harm or discomfort to the ecosystem i.e.
physical systems or living organisms.
Forensic toxicology: is the use of toxicology and other
disciplines such as analytical chemistry, done to various kinds
of samples, to aid medical or legal investigation of death,
poisoning, and drug use.
Industrial toxicology: is a science that deals with potential
harmful effects of materials, products and wastes of industry
on health and environments.
Experimental toxicology: is the science that integrates the
principles and methods of many fields: chemistry, biology,
pharmacology, molecular biology, physiology and medicine. It
combines both of observational studies (i.e. looking at what
effects result from exposure to a particular substance) and
mechanistic studies,(i.e. understanding and explaining the
 2
basis for such effects. It takes place in the lab or occasionally in
the field of exposure.
Clinical Toxicology: is the application of toxicological
principles to deal with the diagnosis and treatment of
poisoning. This area of toxicology is typically practiced by a

 Historical background: the earliest writings in toxicology

clinician and a nurse:

were found on the Egyptian papyrus Ebers (1552B.C.)

where many recopies for poisons were described such
as antimony, lead, hyocyamus and opium. The first
poison centers established was in 1949 when a
specialized medical unit devoted to treatment of
poisoned patients in the cities of Copenhagen and
Budapest.

When to suspect a toxicological case:

1. Sudden deterioration in conscious level in previous
healthy patient.
2. Sudden development of excessive vomiting without
history of food poisoning.
3. Presence of psychiatric problem.

Factors Affecting the Toxic Response

Factors related to the poison Factors related to the patient
• A ou t take . •“to a h.
• Route of ad i istratio . • Age.
• For of the poiso . • Disease.
• Cu ulatio . • Tolera e.
• H perse siti it .
Factors related to the poison:
1. Amount taken: The greater the poison dose taken, the
more serious are the symptoms.
2. Route of administration: the quickest and most dangerous
route is the intravenous injection, followed by inhalation,
intramuscular injection, subcutaneous injection, , absorption
through mucus membranes (as from the rectum, or vagina),
 3
ingestion and lastly the lowest route is absorption through the
skin. However, skin absorption is rapid in organo-phosphorous
insecticides, carbolic acid, and tetraethyl lead.
3. Form of the poison: Poisons in the gas form are most
rapidly absorbed. Liquid poisons are more rapidly absorbed
than solids. Fine powders are more rapidly absorbed than
tablets.
4. Cumulation: occur with repeated small doses of certain
drugs(that have slow metabolism) produce an effect similar
to a single large dose leading to poisoning as in case of
digitalis.
Factors related to the patient:
1. Stomach: a quicker and more serious action is obtained if
the stomach is empty before ingestion of the poison.
However, some poisons are more rapidly absorbed in the
presence of a fatty meal as in case of chlorinated
insecticides, and yellow phosphorous.
2. Age: as a general rule, infants and old people are more
susceptible to toxicity than adults due to decrease the
detoxification power.
3. Disease: cirrhosis and renal insufficiency leads to
diminished excretion of poisons.
4. Tolerance: after repeated intake of addicting drug as
opiates, benzodiazepines, alcohol, and cocaine, the patient
can withstand larger doses, without serious effects.
5. Hypersensitivity: very small harmless doses can produce
severe symptoms in sensitive patients.
 4
GENERAL APPROACH TO THE POISONED PATIENT
ILOs:
By the end of this section the student should be able to:
K1: Discuss the general approach to the poisoned patient
including initial assessment, history taking, clinical
examination and investigations.
K2: Discuss the appropriate steps required to help reach a
diagnosis.
K3: Diagnose the threats and the critical abnormalities in a
critically intoxicated case.
K4: State and interpret the required investigations to reach a
provisional diagnosis.
A1: Realize the importance detailed history taking and
appropriate examination to reach the correct diagnosis in
intoxicated patients.
A2: Realize the value of quick assessment and maintenance of
vital functions.
(A: Attitudes)
Evaluation of the Patient
The management of any toxicological emergency follows
regular steps including the following:
I- Initial Assessment and Stabilization
Establish and maintain vital functions.
1- Airway:
o Ensure airway patency.
o Breathing.
o Asses ventilation and if necessary assist with oxygen-
mask and/or endotracheal intubation. Administer 100%
oxygen if needed. All unconscious or shocked patients
will benefit from intubation.
2- Circulation:
o Take the pulse and assess the volume, rate and rhythm.
Take the blood pressure, place patient on ECG monitor.
Insert a venous cannula and obtain blood specimens.
3- Neurological status:
o Asses level of consciousness by Reed coma scale.
 5
o Determine pupil size and reactivity to light.
II- Reassessment and measures to identify the poison
This is achieved by:
History
If there are no immediate life threatening
manifestations, or after stabilization a careful history is
obtained.
A- Personal history:
1. Name.
2. Age & sex (menstrual history in female).
3. Marital status.
4. Address (residence).
5. Occupation (metal toxicity, insecticide poisoning).
6. Special habits (e.g. smoking and drug abuse).
B- History of present illness (intoxication history):
If there is history of intoxication ask about: The 5W’s
of toxicology.
Who:
1. As in personal history
What:
2. Name and dose of medication (ingredient, regular
form or slow release or enteric coated).
3. Co-ingestants if other drugs are taken.
4. Amount ingested or duration of exposure to a gas.
When:
5. Time of intoxication (delay).
6. Relation between time of ingestion and symptoms.
Where:
7. Route of ingestion (Inhalational, oral, I.V., skin
contamination).
8. also the geographical location of poisoning.

 Pre-consultation treatment i.e. if the patient received

Why: intentional (suicidal) or unintentional (accidental)

any treatment before reaching the emergency room.

 6
 Ask about other symptoms:
1. Respiratory symptoms: cough-wheeze-chest pain-
breathing-sputum (bloody or not).
2. GIT symptoms: nausea -vomiting characteristics of
vomitus (odor, color, blood, tablets)-diarrhea-pain.
3. CVS symptoms (dyspnea, pain, tightness, cough,
palpitation).
4. Neurological symptoms (irritability, seizures,
weakness, numbness, rigidity).
5. Genitourinary symptoms (menstrual history, urine).
C- Past history (Medical history):
1. Drug therapy- recent medication.
2. Preexisting disease (hepatic, renal, psychiatry).
3. Trauma.
4. Operations – blood transfusion.
D- Family history:
1. Any familial disease (allergy-blood diseases).
2. Psychological troubles (addiction-suicidal attempts).
Examination
A- General Examination
1- Consciousness and mental status:
 Grading of coma (Reeds classification).see later.
 Hallucinatioin (e.g. in cannabis and anticholinergics)
 Agitation and restlessness (e.g.sympathomimetics,

 Disorientation to time: ( e.g. cannabis or sedatives).

anticholinergics, scorpion sting).

2- Pupils:
a- Mydriasis produced by agents listed in SHAW:
S= sympathomimetics, H= hallucinogens A=
anticholinergics W= withdrawal from opioids, sedative-

 N.B.: anticholinergics produce dilated irriactive pupils.

hypnotics and ethanol.

b- Miosis in: opiate overdose, organophosphorus,

carbamate (pin pointed pupils).
 7
 N.B. pin point pupil may also occur in pontine
hemorrhage and can be differentiated from toxic
causes by not responding to nalloxone (as in opiate
overdose), MRI and CT scan can confirm its
diagnosis.

3- Vital Signs:
A- Pulse:
1) Bradycardia: e.g. in toxicity by B- blockers, Anticholine
esterases, Digoxin, opiates, barbiturate.
2) Tachycardia: e.g. in toxicity by anticholinergics,
(atropine, TCA, antihistamincs), sympathomimetics,
scorpion and theophilline.
N.B. General systemic conditions as hypoxia and
hypoglycemia may result in tachycardia.
3) Irregular pulse: (produced by drugs causing
arrhythmias as digoxin, TCA sympathomimetics and
carbon monoxide).
N.B. systemic conditions as hypoxia, metabolic
disturbances (electrolyte, glucose, acid-base) may
cause dysrythmias and their correction may cure the
problem.
B- Blood Pressure:
1) Hypertension: It is usually initial and transient may be
followed by life threatening hypotension. It may be

 Sympathomimetics.
due to:

 Anticholinergics.
 Scorpion sting.
 Phencyclidine.

 Decreased peripheral vascular resistance: (e.g. B-

2) Hypotension:

 Hypovolemia: e.g. GIT fluid loss as in food

blockers, Ca channel blockers, antipsychotics).

poisoning and organophosphates. Severe

sweating as in salicylates or blood loss as in
snake bite and corrosives.
 8
 Decreased myocardial contractility as in B-
blockers, Ca channel blockers.
C- Body Temperature:
1) Hyperthermia:
Temperature elevation associated with
toxicological causes may be due to excess muscle
activity, impaired thermoregulation, hypermetabolic
state, interference with oxidative phosphorylation,
and impaired dissipation of heat. Toxicological
temperature elevations require external cooling
measures and control of excess muscular activity such
as convulsions. Antipyretics are not useful. It occurs in
overdose of:
• Salicylates, Sympathomimetics, Anticholinergics,
Antidepressants.
2) Hypothermia:
It is frequently associated with hypoglycemia. It

 Carbon monoxide.
may occur in overdose of: (COOLS)

 Opiates.
 Oral hypoglycemics/insulin.
 Ethanol.
 Sedative hypnotics.

 Normal rate 12-20/min (pulse: respiration ratio is 4:1).

D- Respiratory Rate:

 Toxic hypoxia( CO, Cyanide and H2S).

1) Tachypnea: (increased resp, rate)

 Metabolic acidosis in methanol and salicylate.

 Associates dyspnea occurring in aspiration pneumonia
and irritant gas inhalation.

 Caused by CNS depressants (opiate, ethanol, sedative

2) Bradypnea: (decreased resp. rate)

hypnotic, psychotropics or anticovulsants).Paralytic

agents, e.g., neuromuscular blockers, paralytic plant
toxin, botulism, and paralytic shell fish.
4 -Skin examination:
 Burns – erythema (corrosives).
 9
 Sweating (salicylate, organophosphorous or

 Dry –flushed (anticholinergics).

hypoglycemia).

 Cold & clammy ( sedative hypnotics).

 Skin bullae (due to skin hypoxia, prolonged coma,

 Needle tracts (drug users or addict).

barbiturates, or carbon monoxide).

B- Systemic Examination
 Respiratory, cardiovascular, neurological and abdominal
systems are examined individually to reach for accurate
diagnosis of the specific signs of each poison.
C- Investigations
I- Laboratory studies The lab. In toxicological practice should be
equipped to perform:
1. Regular and emergency investigations e.g. (arterial
blood gas analysis, electrolytes, blood sugar, liver and
renal function tests, CBC and hemoglobin and
coagulation profile.
2. Specific toxicological tests (diagnostic): e.g.:
a. Toxicological screening: using patient's urine, blood,
vomitus or gastric wash. However its value is
diagnostic and has no quantitative value to deicide
steps of management.
b. Blood levels of: ethanol, Methanol, Ethylene glycol
acetaminophen, salicylate, digoxin, carbamazepine,
phenobarb, phenytoin, valproate, theophylline, Iron,
and Lithium.
c. Pseudocholinesterase (organophosphate and
carbamates insecticides).
II- Other Investigations (follow up complications):
1. ECG.
 10
2. Plain chest X-ray (aspiration pneumonia, pulmonary
edema or endotracheal tube placement).
3. Plain abdominal X-ray (radiocontrast poisons as iron,
phenthiazines), disk batteries or (corrosives to exclude
gastric perforation).
4. CT or MRI for coma of unexplained etiology.
 11
TOXIC SYNDROMES (TOXIDROMES)
ILOs:
By the end of this section the student should be able to:
K1: Define a toxidrome.
K2: State the types, toxic causes and clinical picture of
toxidromes.
K3: Compare between anticholinergic and sympathomimetic
toxidromes.
K4: Solve problems revolving around virtual cases presented
with toxidromes.
A1: Realize the value of using toxidromes to quickly reach a
provisional diagnosis of a toxicological case.
Definition:
Toxidromes are collections of integrated data provided
by both the vital signs and clinical examination to elicit
manifestations specific to a toxic agent. Toxidromes may help
in diagnosis when the agent is unknown.
Types:
1. Anticholinergic syndrome:
Clinical picture: Dry skin and mucus membranes, dilated
irreactive, hyperthermia, hallucinations, urinary
retention, decreased bowel sounds and tachycardia.
Causes: Atropine, Tricyclic antidepressents,
antihistaminics (H2 blockers) and some mushrooms.
2. Cholenergic syndrome:
Clinical picture: muscarenic and nicotinic effects.
DUMBLES: defecation, urination, miosis, bronchospasm,
excessive salivation, lacrimation and seizures.
Causes: carbamate and organophosphorus insecticides,
nicotine, and some mushrooms.
3. Symathomimetic syndrome:
Clinical picture: Convulsions, hyperthermia,
hypertension, mydriasis, psychosis, and tachycardia.
Causes: amphetamines, cocaine.
4. Opioid syndrome:
 12
Clinical picture: Miosis, CNS depression,
hypoventilation, hypotention, bradycardia and
hypothermia.

Comparison between anticholinergic and sympathomimetic

toxidromes

Anticholinergic Sympathomimetic
Skin Dry Diaphoresis
Bowel sound Inhibited Hyperactive
Urine retention Present Absent
Pupil Dilated irriactive Dilated reactive

GENERAL MANAGEMENT OF POISONING

ILOs:
By the end of this section the student should be able to:
K1: Discuss the steps of the general management of an
acutely poisoned patient.
K2: Describe the details of the emergency evaluation and
support of intoxicated critically-ill patient.
K3: State the uses, indications, precautions, contraindications,
technique, dose and complications of methods of
decontamination depending on the route of exposure.
K4: Describe the indications, precautions, contraindications,
technique, dose and complications of the methods of
enhancing excretion of poisons.
K5: Decide the appropriate method of decontamination to be
used in a given clinical case.
A1: Realize the importance of time factor in treating cases
with acute intoxication.
A2: Realize the value of deciding the appropriate method of
toxin elimination in different cases of intoxication.
In any toxicological emergency and after initial
evaluation, and while diagnosis is proceeding,
management should start following regular steps:
I- Emergency Measures (ABCD):
 13
The goal is to maintain respiration by:
A. Clearance of Airway:
1. The patient is placed on his back with the head tilted
and chin lifted (to establish an aligned airway passage).
2. Suction of accumulated upper airway secretions, and
regurgitated food and stomach contents.
3. Removal of foreign bodies, removable dentures or
mucous from the mouth.
4. Prevent falling back of the tongue in comatose patients
by using oropharyngeal tube.
5. Endotracheal intubation and mechanical ventilation
(better used with inflatable cuff) if patient cannot
breathe spontaneously.
6. Tracheostomy may be needed in laryngeal obstruction.
B. Breathing (to deliver oxygen to respiratory passages):
1. Artificial respiration is done by mouth to mouth
breathing before arrival to hospital.
2. The rescuer places the patient on his back with head tilt
chin lift.
3. The rescuer rapidly takes a deep breath and breaths into
the mouth of the patient after good sealing between
their lips.
4. After arrival to the hospital, oxygen mask is used if the
patient breathe spontaneously, or endotracheal
intubation with the use of mechanical ventilation if
apnea occurs.
C. Circulation:
1. Cardiac monitoring of the patient.
2. Correction of hypotension by IV fluids. Inotropic drugs
may be used if no response occurs.
3. Treatment of arrhythmias.
D. Drugs:
Any patient with undiagnosed coma should empirically
receive the following drugs (coma cocktail) for immediate
treatment of rapidly reversible causes of coma:
 14
1. 100 ml glucose 50%: to correct hypoglycemia.
2. 100 mg thiamine: to correct Wernike's encephalopathy
in alcohol toxicity.
3. 0.4-2 mg naloxone: to revert coma of opiate overdose.
II- Decontamination (Elimination):
The aim of these procedures is to reduce the absorption
of poisons before approaching the systemic circulation. Early
intervention is recommended for these methods to be
efficient.
A. Dermal Exposure:
 Many poisons are absorbed through the skin & produce
systemic toxicity e.g. Organophosphates and phenol.
 Avoid secondary exposures by wearing protective
(rubber or plastic) gowns, gloves, and shoe covers. Cases
of serious secondary poisoning have occurred in
emergency personnel after contact with xenobiotics such
as organic phosphorus compounds on the victim's skin or
clothing.
 Remove all clothing.
 Wash the skin with soap and copious amount of water
for at least 15 minutes.
 Avoid rubbing or scrubbing of skin for fear of increasing
absorption of the poison.
 In scalp exposure to organophosphate insecticides, it is
advisable to cut the hair for rapid control.
B. Eye Exposure:
 The eyes should be irrigated with lids fully retracted for

 Solid corrosives should be removed first by forceps and

no less than 20 minutes.

washed with running tap water for at least 20 minutes.

C. Pulmonary Exposure:
Many poisons are toxic by inhalation such as carbon

 Remove the patient to fresh air.

monoxide and cyanide.
 15
 Care of respiration is started after clearing the mouth,

 Steroids may be given in case of laryngeal or glottic

oxygen, and tracheostomy or ETT intubation.

edema
D. GIT Exposure:
Gut Emptying
The aim of gastric emptying is to remove the poison
from the stomach before it gets absorbed to minimize its toxic
effects. However it is described to be aggressive and multiple
studies revealed that patients could be successfully managed
without its use.

Causes of limitations of gastric emptying:

1) Time factor: In order for gastric emptying to be efficient,
the patient should present to ER within one hour of
ingestion. Demographic studies revealed that majority of
patients arrive to the hospital within 3-4 hours of ingestion.
2) If small doses of poison is ingested not expected to produce
significant morbidity.
3) If significant vomiting prior to presentation had occurred.
4) If other methods of decontamination are efficient such as
activated charcoal or whole bowel irrigation.
Indications for gastric emptying:
1) If the patient had ingested potentially highly lethal doses of
the poison.
2) If the poison is not adsorbed on activated charcoal or if not
amenable to treatment by other measures as hemodialysis
or effective antidote.
Methods of gastric emptying:
1) Induction of emesis.
2) Gastric lavage.
I- Induction of Emesis
 16
Only a few groups of patients are considered
appropriate candidates for induction of emesis, it may be
helpful in particular in poisons that does not produce rapid
altered mental status as acetaminophen and salicylates also in
poisons known to produce delayed gastric emptying or in slow
release preparations.
Contraindication:
Emesis is absolutely contraindicated in the following
conditions:
1- Substances ingested:


Corrosives (acids & alkalis): risk of perforation.


Convulsants: may precipitate fits.


Hydrocarbons: risk of inhalation.


Foaming agents: Froth may block respiratory passages
Sharp objects (needle, pin razor).
2- Patient:
 Unconscious, or comatose: risk of inhalation

 Decreased gag reflex: as in Antiemetic poisons.

pneumonia.

 Severe CVS disease or emphysema or ARDS.

 Recent surgical intervention especially in GIT.
 Expected to deteriorate rapidly (coma, convulsions).
 Hemorrhagic tendencies (cirrhosis, varices, active

 Spontaneous vomiting before attending ER.

peptic ulcer and thrombocytopenia).

 Less than 6 months of age (gag reflex not well

developed).
3- Time Factor:
Emesis is less effective if time passed since ingestion of
the poison is more than 1 hour, as it is suggested that the
poison is passed from the stomach to the intestine.
Methods of induction of emesis:
Syrup of Ipecac:

 Early phase: within 3 min due to direct GI stimulation.

It causes vomiting through 2 phases:
 17
 Late phase: After 30 min through its central action on

 Dose: 30ml for adults and 15ml for children.

chemoreceptor trigger zone.

 Water can be offered but not essential for success.

 Give another dose if emesis does not occur within 30
minutes. For children (6-12 months), syrup of Ipecac

 If the second dose of Ipecac does not induce vomiting,

should be limited to a single dose of maximum 10ml.

 Adverse effects: Syrup of Ipecac should no longer be

do not give a third dose and perform gastric lavage.

used as a routine for its adverse effects such as:

1. Aspiration of gastric contents.
2. Vagally mediated bradychardia.
3. Persistent vomiting.
4. Intracerebral hemorrhage.

Never use salty water as an emetic as it may lead to fatal

hypernatremia.
II- Gastric Lavage
The goal of the procedure is to remove poisons by
washing the stomach by saline or warmed tap water via a
specific tube.
Contraindications:
1. In corrosives poisoning for risk of perforation of the
esophagus or the stomach (except in carbolic acid).
2. Froth producing substances (liquid soap & shampoo).
3. The patient is at risk of hemorrhage or gastrointestinal
perforation if there is an underlying pathology, e.g: recent
surgery or other medical condition that could be further
compromised by the use of orogastric lavage.
4. Coma or Convulsions (for risk of aspiration). The use of an
endotracheal tube (ETT) with inflatable cuff is
recommended to avoid aspiration of the gastric wash.
5. Petroleum distillates (as kerosene) except if ETT is used.
6. Time factor. Lavage is less effective if time passed since
ingestion of the poison is more than 2 hours. However a
 18
delayed lavage may be useful with certain poisons that are
eliminated in the GIT (opiates, alcohol), form concretions
(salicylates, meprobamate), have delayed gastric emptying
as drugs with anticholinergic action (tricyclic
antidepressants 'TCA' atropine, and phenothiazines),
sedative hypnotics (barbiturates).
Technique: e- learning
Complications of gastric lavage:
1. Bradycardia during the introduction of the gastric tube
especially with OP insecticides and digoxin poisoning.
2. Faulty passage of the gastric lavage tube in the trachea
3. Laryngospasm and cyanosis.
4. Aspiration of gastric contents leads to aspiration
pneumonia particularly if the airway is unprotected by
cuffed ETT.
5. Hypertension, tachycardia in conscious patients (stress
reaction).
6. Hyponatremia if GL is performed with tap water especially
in children in whom normal saline is preferable.
7. Mechanical gut injury.
III- Activated Charcoal (AC)
1. It is an extremely effective adsorbent of nearly all poisons
from the gastrointestinal tract.
2. It is prepared by destructive distillation of wood pulp.
3. It has small particles with large surface area; each particle
adsorbs many particles of poison.
4. It is available in the form of tablets or black powder that is
mixed with water, and has an inedible taste.
5. It is claimed to be more effective than emesis or gastric
lavage, but is usually given after emesis or lavage is
performed.
6. Some poisons are not adsorbed by activated charcoal such
as iron, alcohols, cyanide, lead and mercury.
 19
Dose: 1gm/Kg body weight if the amount of poison is not
known. If known, activated charcoal is given 5-10 times the
weight of the ingested poison.
Multiple Dose Activated Charcoals (MDAC):
It is the administration of repeated doses of activated
charcoal to enhance poison elimination.
Indications:

 Slow release preparations as theophylline

1. Adsorption of drugs remaining in the gut for long time:

 Drugs producing concretions e.g. Salicylates,

phenobarbitone
2. Adsorption of drugs having enterohepatic circulation
e.g. dapsone, quinine, digoxin, TCA, glutethimide.
3. Drugs diffusing passively from the blood to the lower GI
lumen as theophylline and salicylate.
Dose: 0.5-1gm/kg every 4 hours.
Contraindications of AC:

 It worsens mediastinitis & peritonitis in case of

1. Corrosives:

 It masks the view in endoscopy.

perforation.

 It is not effective.
2. Hydrocarbons: It may precipitate vomiting with the high risk
of aspiration.
3. Intestinal obstruction, perforation or ileus.
Complications of AC:
1. It may adsorb oral medication making it not effective such as
syrup of Ipecac, oral antidotes as N-acetyl cysteine (antidote
of paracetamol poisoning.
2. Constipation and gastrointestinal obstruction

IV- Whole Bowel Irrigation (WBI)

 A newer method for decontamination.
 20
 Effective well tolerated process for evacuating intestinal
tract and safe in pregnancy.
Principle of action:
 Fluid used is (PEG) polyethylene glycol (non absorbable
and does not cause electrolyte and water imbalance) to

 Its value in poisons that does not adsorb on activated

hasten removal of poisons and prevent its absorption.

 Dose: 0.5 L/h for children and 1.5-2L/h for adults of PEG is
charcoal and in slow release preparations.

given by nasogastric tube or orally over 3-4 hours or till

passage of clear rectal effluent can be combined with
antiemmetics to reduce nausea and vomiting.
Adverse effects:
- Vomiting with rapid PEG administration.
- Abdominal fullness and cramps and pruiritis.
Contraindications:
- Current or expected diarrhea.
- Volume depletion.
- Significant GIT pathology: ileus-perforation-colitis-
hemorrhage-obstruction.

V- Catharsis
Cathartics should never be considered part of routine
management of poisoning and overdose in either children or
adults. a single dose of a cathartic may be given with AC.

Enhancement of Excretion
Certain methods are applied to enhance excretion of the
poison from the blood after being absorbed. They include the
following:

I. Multiple doses Activated Charcoal (MDAC):

It is described as gastro–intestinal dialysis for poisons
that are rexcreted in the lower GIT (previously discussed).
 21
II. Diuresis:
It is a simple method for enhancing excretion of some
poisons. It is efficient only in poisons with the following
pharmacokinetic properties:
1. The kidney is the main route of their excretion.
2. Have a small volume of distribution.
3. Have low protein binding.
a. Fluid diuresis: Dextrose 5-10% or a mixture of glucose and
normal saline.
b. Osmotic diuresis: Mannitol 20% is given in a dose of 1-2
gm/kg. It is excreted in renal tubules leading to increase
its osmotic pressure and diuresis. It is usually given as a
part of alkaline diuresis.

III. Manipulation of Urine pH:

 Definition: It is the change of the urine pH in order to
turn the drug to its ionized form. Drugs can be weak
acids or bases. If they are rendered ionized, they are
trapped not reabsorbed easily by the renal tubules, so
they are readily excreted.
A- Alkalinization of urine:
Used for weak acidic toxins as salicylates and
phenobarbitone which have greater ionization and better
excreted at urine pH of 7.5-8.
Indications:
1. Overdose of salicylates.
2. Long acting barbiturates overdose as they are excreted
mainly through the kidneys and have low volume of
distribution.
3. Poisons producing hemolysis and rhabdomyolysis.
Method: It is produced by repeated cycles of IV fluids in the
following sequence:
IV fluids
10-15ml/kg Dextrose 5%
1-2meq/kg Sodium Bicarbonate as 1.26% Over
1-2gm/kg Mannitol 20% 4 hours
KCl may be added to avoid hypokalemia
 22
Precautions:
1. Keep urinary pH at 7.5-8
2. Keep urine output at 300-500 ml/hour closely observing
input / output chart.
3. Normal renal functions should be ascertained before the
start of diuresis.
4. Blood pH and electrolytes should be monitored in the
blood esp. serum K as the infusion of Na HCO3 may lead
to hypokalemia.
5. Auscultate the lung bases for the possibility of
pulmonary edema.
B. Acidicfication of urine:
Formerly used for basic drugs as amphetamine. Now
it is obsolete because it does not significantly enhance
removal of xenobiotics and is complicated by systemic
metabolic acidosis.
Complications of dieresis:
1. Acid-base and electrolyte imbalance.
2. Fluid overload with pulmonary and cerebral edema.
IV. Dialysis:
The principle of dialysis is to allow blood to circulate in
contact with a semi-permeable membrane to remove
substances from the blood by concentration gradient, i.e. to
allow particles to pass from higher concentration to the lower
concentration. Dialysis is of value when renal function becomes
impaired.
Dialyzable drug should be:
1. Of small volume of distribution.
2. Have low protein binding.
3. Have small molecular weight.
Examples of dialyzable drugs: alcohols, barbiturates, lithium,
and salicylates.

A. Hemodialysis:
A cellulose membrane (smipermeable membrane) in
the hemodialysis apparatus is used. Heparinized blood is
extravasated and allowed to circulate in the apparatus to
 23
pass against the semi-permeable membrane. Exchange of
toxic materials from the blood to a special fluid (dialysis
fluid) takes place (according to concentration gradient). In
addition to removal of toxins, it can correct acid-base and
electrolyte disturbances, and extracellular fluid volume
overload.
Complications:
1. Hypotension (extravasations of blood)
2. Elimination of therapeutically administered drugs.
3. Bleeding tendency (due to heparin).
4. Air embolism.
5. Electrolyte imbalance.
6. Infection, hepatitis.
Contraindications:
1. Non dialyzable toxic agents.
2. Patients with coagulopathy.
3. Patients with uncorrected hypotension.
B.Peritoneal dialysis:
The peritoneum acts as the semi-permeable which is an
easy but less effective method.
V- Hemoperfusion:
This method allows blood derived from radial artery to
pass through a cartridge coated with activated charcoal to
adsorb poisons existing in the plasma. It can be done for toxins
with high protein binding, or for those having big molecular
weight, and also in lipid soluble drugs.
The poison must be absorbable to charcoal.
Complications:
1. Trapping of white blood cells and platelets causing a
reduction in the platelet count.
2. Reduction in serum calcium, glucose.
3. Hypotension.
4. Adsorption of therapeutically administered drugs.

N.B. methods of enhancing elimination with extravasation of

blood are called extracorporeal methods
 24
MANAGEMENT OF COMMON TOXICOLOGIC
PRESENTATIONS

ILOs:
By the end of this section the student should be able to:
K1: Describe the common toxicological presentations (coma,
respiratory failure, acute pulmonary edema, acid-base
disturbance, convulsions and rhabdomyolysis), their
toxic causes, mechanism and management.
K2: Diagnose the common toxicological emergencies from
the given clinical data.
K3: List the different grades of coma according to Reed's
classification.
K4: Discuss the interpretation of blood gases in acute
poisoning.
K5: Explain the electrolytes and acid-base disturbances in
acute intoxication.
K6: Explain the clinical sequelae of rhabdomyolysis.
K7: Discuss the guidelines for hospital admission and
discharge for intoxicated cases.
K8: Discuss the non-toxic ingestions.
K9: Describe the medicolegal aspects of handeling an
intoxicated patient.
K10: Solve problems revolving around virtual cases
presenting with different toxicological emergencies.
A1: Realize the importance of urgent appropriate treatment
in cases of acute intoxication.
A2: Realize the importance of working in groups.

Poisoning can be associated with certain emergency

problems that can be misdiagnosed as medical or surgical
problems. It should be promptly differentiated and treated.
These may include:
 25
Coma
Coma is a state in which the patient is unresponsive to
stimuli, unable to communicate in any manner and from which
he cannot be aroused. It is maintained by the normal
functioning of the brain stem reticular activating system and its
bilateral projections to the thalamus and cerebral
hemispheres. Unresponsiveness may occur in varying grades. A
comatose patient should be graded using scales as REEDs
classification scale.
Toxic causes of coma:
I- Coma due to direct CNS depression:
1. Alcohols.
2. Opiates.
3. Barbiturates.
4. Benzodiazepines.
5. Anticonvulsants.
6. Antidepressants e.g. MAO inhibitors and TCA.
7. Tranquilizers e.g. phenothiazines.
II- Coma secondary to hypoxia:
1. Carbon monoxide (COHb).
2. Causes of methemoglobinemia.
3. Displacement of oxygen in the atmosphere e.g. CO2
III- Coma secondary to acidosis:
1. Methanol
2. Salicylates
3. Iron
IV- Coma secondary to hypoglycemia:
1. Hypoglycemic drugs.
2. Alcohols.
3. Salicylates.
Reed's classification of coma
Conscious Response to
Grade Reflexes Respiration Circulation
level pain
0 Asleep Arousable Intact Normal Normal
I Comatose Withdrawal Intact Normal Normal
II Comatose None Intact Normal Normal
III Comatose None Absent Normal Normal
IV Comatose None Absent Cyanosis Shock
 26

Management:

 Concurrently with the "ABCs", (airway, breathing,

Emergency measures include:

circulation), the clinician must search for and treat

hypoglycemia, hypoxia, drug overdose and electrolyte

 Arterial Blood Gas (ABG), glucose, urea, electrolytes.

imbalance.

 Supplemental oxygen.
 Administer IV Glucose (adults: D50W; children D25W 2-4
cc/kg). Glucose should be given immediately to all persons
with suspected hypoglycemia even if the glucometer

 Naloxone may be given to all undiagnosed patients (the

reading is normal (since false negatives can occur).

 Flumazenil, a benzodiazepine antagonist should not be

initial is 2mg).

routinely administered. Reversal of benzodiazepine effect in

a mixed drug ingestion involving cyclic antidepressants may
result in seizures or arrhythmias with fatal outcomes.
Care of comatose patient:
 Cardiovascular monitoring and pulse oximeter.
 Urinary catheterization and evaluate input and output of

 Mouth, eyes, and skin care.

fluids.

 Protect against deep venous thrombosis by prophylactic

doses of heparin 5000U. SC /12h or low M.W. heparin

 Protect against stress ulcerations of the stomach give H2

10.000USC once/day.

 Protect against infection prophylactic antibiotics.

blockers.

 Physiotherapy for chest, muscles and joints.

 Frequent positioning of the body to avoid bed sores on
bony prominences and recumbent pneumonia 2ry to non

 Nutrition and proper hydration either by Ryle tube or total

drained lung lobes.

parental nutrition.
 27
 Daily clinical examination and monitoring of electrolytes,
glucose, hematocrit and urea.
Respiratory Failure
Respiratory failure is the inability of the lungs to
perform their basic task of gas exchange, the transfer of
oxygen from inhaled air into the blood and the transfer of
carbon dioxide from the blood into exhaled air. Respiratory
failure can be defined with as a partial pressure of oxygen
(Pao2) < 60 mm Hg (hypoxemia) or a partial pressure of carbon
dioxide (Paco2) > 45 mm Hg (hypercapnia).
Respiratory failure may be due to:
a) Failure of the exchange of oxygen and carbon dioxide
within the alveoli e.g. pulmonary edema, aspiration
pneumonia.
b) Failure of the muscles required to expand the lungs e.g.
paralytic syndromes as botulism, cobra snake
envenomation.
c) Failure of the brain centers controlling respiration. e.g.
central CNS depressants, narcotics, hypnotics,
psychotropics, alcohol, toxic cerebral edema, cerebral
hypoxia CO.
Symptoms and Signs:
a) Cyanosis due to hypoxemia.
b) Confusion, sweating and sleepiness caused by high carbon
dioxide levels.
c) Deteriorating consciousness and abnormal heart rhythms
(arrhythmias) due to tissue hypoxia, which can lead to
death.
Diagnosis:
A. Arterial blood gas: The following determinants should be
initially determined and reassessed repeatedly. These
include: pH, PO2, PCO2, SaO2 (Oxygen saturation).
B. Chest X Ray is essential in any clinical condition presenting
with respiratory failure for assessment and diagnosis of the
cause e.g. aspiration pneumonia, pulmonary edema,
pneumothorax, atelectasis.
 28
C. ECG and cardiac monitoring: May manifest signs of tissue
hypoxia and or arrhythmias.
D. Other investigations directed towards the cause of
poisoning and effects on other systems.
Management:
A. Oxygen: it is almost always given initially by nasal prongs or
mask. The amount of oxygen should be properly adjusted in
patients with chronic rise of PCO2 as high oxygen flow
precipitate hypoventilation with a more rise of PCO2. If
cyanide or CO are suspected oxygen is given at the highest
flow rates.
B. Ensure upper airway patency by suction of secretions,
oropharyngeal airway, bronchial toilet, head positioning.
C. The underlying cause of the respiratory failure must also be
treated.
D. Antibiotics are used to fight infection.
E. Bronchodilators are used to open the airways. In OP
poisoning atropine is given while theophylline is
contraindicated as it may reduce the AChE.

 Hypoxemia not responding to oxygen high flow rates.

F. Mechanical Ventilation: It is indicated in the following:

 Altered conscious level (Coma or stupor) interfering with

normal breathing and normal respiratory function as

 Respiratory muscle paralysis or exhaustion.

with all CNS depressants.

 Peripheral toxic lung injury (NCPE, aspiration pneumonia,

ARDS) interfering with normal respiratory function
without support.
Pulmonary Edema
Pulmonary edema is the accumulation of exudate in
alveolar lumen with edema of alveolar wall and thickening of
respiratory membrane. There is impaired gas exchange
between alveoli and capillary blood.
Two types are met with in clinical toxicology practice
depending on the cause:
I. Cardiogenic Pulmonary Edema:
 29
Left ventricular dysfunction is responsible for the
development of acute pulmonary edema. Usual triggering
factors are acute ischemia, myocarditis, rhythm or
conduction abnormalities, high blood pressure, infection,
physical stress.
Toxic causes:
This may occur in poisoning with calcium channel blockers,
beta blockers, tricyclic anti-depressants, poison-induced
arrhythmias or scorpion myocarditis.
II. Non-Cardiogenic Pulmonary Edema (NCPE):
It is pulmonary edema that results from disruption of
alveolar capillary membrane resulting in fluid leak in the
interstitium then in the alveoli. Destruction of pneumocytes
II lining of alveoli responsible for surfactant synthesis may be
responsible for disruption of capillary alveolar membrane.
Toxic causes:
This results from direct toxic effect on the pulmonary
capillary membrane as in corrosive fumes, heroin,
barbiturates, salicylates and OPC.
Clinical picture:
1) Severe dyspnea, rapid respirartion and even cyanosis.
2) Coughing of pink, frothy sputum.
3) Excessive sweating, anxiety, and pale skin.
4) Pulmonary crepitations (basal in cardiogenic and
scattered in non cardiogenic).
Investigations:
1. ABGs: assess severity of respiratory dysfunction.
2. ECG and cardiac monitoring.
3. Chest x-ray shows: increased vascular shadowing, (butter
fly appearance) in cardiogenic type.
Treatment


Put the patient in semi-sitting position.


Ensure airway patency.


Give 100% O2 by masks or nasal prongs.
Mechanical ventilation if PO2 cannot be maintained
above 60 mmHg or if there is progressive hypercapnea
(PCO2 is rising).
 30
 PEEP (Positive End Expiratory Pressure) mode may be
needed in NCPE to avoid alveolar collapse and improve

 Morphine SC, IM or IV: to relieve anxiety, and decrease

oxygenation.

 IV aminophylline to minimize bronchoconstriction.

tachypnea for to better chance for gas exchange.

 In addition; Cardiogenic pulmonary edema is treated

with I.V. nitrates, and loop diuretics (frusemide). These
improve both preload and afterload, and aid in

 Digitalis In severe associated heart failure.

improving cardiac function.

 Treatment of the underlying toxic cause.

Shock
Shock is a state of inadequate perfusion of vital organs.
Hypotension means that systolic blood pressure is less than
90mmHg or mean arterial blood pressure 65mmHg. Shock and
hypotension frequently occur together however tissue
perfusion can be maintained by vascular resistance.
Toxic causes:
A- Cardiogenic causes:
Drugs producing decreased cardiac contractility as B-
blockes, Calcium Channel blockers, Carbon monoxide, Tricyclic
antidepressants and drugs causing bradycardia as B-blockers
and Calcium Chanel blockers, digoxin and organophosphates,
acidosis and hypoxia.
B- Decreased peripheral vascular resistance:
Barbiturates, benzodiazepines, nitrites, TCA.
C- Volume loss:
Acute gastroenteritis, corrosives, iron, salicylates due to
sweating and vomiting, and in blood loss as with anticogulants ,
vipers coagulopathy and corrosives.
Clinical picture:
1) Altered mental status.
2) Decreased urine output.
 31
3) Low blood pressure and the pulse may be slow, normal
or fast depending on the pharmacologic action of the
poison.
4) Ischemic change in ECG and skin may be cold.

Treatment:
1) Correction of hypoxia and respiratory support.
2) Fluids: aggressive intravenous fluids are recommended
in shock (e.g. 1 liter normal saline bolus over 10
minutes or 20ml/kg in a child).
3) Vasopressors may be used if blood pressure does not
improve with fluid.
4) Inotropics are used if blood pressure not improved
with vassopressors.
5) Treatment of the cause of shock.
Acid-base Disturbances

 The pH is a measurement of the acidity or alkalinity of the

Overview:


blood.
The pH of a solution is measured on a scale from 1 (very
acidic) to 14 (very alkalotic). A liquid with a pH of 7, such


as water, is neutral.


The normal blood pH range is 7.35 to 7.45.
When the pH is below 7.35, the blood is said to be acidic.
Effects of Acidosis:
1. Decrease in the force of cardiac contractions.


2. Decrease in the vascular response to catecholamines.
When the pH is below 7.35, the blood is said to be
alkalotic.
Effects of Alkalosis:
1. Interferes with tissue oxygenation.


2. Affects neurological and muscular functioning.
Significant changes in the blood pH above 7.8 or below 6.8
will interfere with cellular functioning, and if uncorrected,
will lead to death.
Normal ABGs Values
 32
 PH: 7.35-7.45
 PaCO2:35-45 mmHg
 PaO2: 80-100 mmHg
 HCO3:22-26 meq/L
 SaO2:> 95%
1- Metabolic acidosis


pH: < 7.35


HCO3: < 22 meq/L
PaCO2: variable
Causes:
1. Renal Failure.
2. Diabetic ketoacidosis.
3. Alcoholic ketoacidosis.
4. Lactic acidosis.

 Salicylates
5. Poisonings:

 Ethylene glycol
 Methanol
 Iron
Calculation of anion gap may help in diagnosing the
cause of metabolic acidosis:
Anion gap= ([Na+] +[K+])- ([Cl-]+[HCO3-]) .It is normally
12± 2 , high anion gap acidosis occurs in poisons including
ethanol, methanol, ethylene glycol, metformin, cyanide,
isoniazide and salicylates.
Treatment:
1. Treating the cause.
2. NaHCO3 administration if PH < 7.1.
2- Metabolic alkalosis:
 pH: > 7.45
 HCO3: > 28 meq/L
Causes:
1. Gastric acid loss: vomiting.
2. Excessive bicarbonate intake.
Treatment:
1. Treating the cause.
 33
2. Breathing in closed bag.

 pH;<7.3
3- Respiratory acidosis:

 pCO2>45 mm Hg
Causes:
1. Hypoventilation from any cause results in retention of
CO2 e.g: (CNS depressant drugs).
2. Acute respiratory distress e.g: (hydrocarbon induced
pneumonia).
Treatment:
1. Treating the cause.
2. Oxygen supply if failed mechanical ventilation.

 pH: > 7.45

4- Respiratory alkalosis:

 PaCO2: < 35 mmHg

 HCO3: Variable

Causes:
1. Acute hyperventilation e.g. early salicylate toxicity and
early theophylline toxicity.
2. Anxiety.
Treatment:
1. Treating the cause.
2. Sedations.
Convulsions
 Toxic seizures are often transient, in which case no long


treatment will be required.
Do not attempt emesis. Gastric lavage is performed after
controlling convulsions and protecting the airway by ETT


and oropharyngeal airway to avoid biting.


Restrain the patient to prevent injuring himself.
Maintain adequate airway and aspirate secretions and


food debris from pharynx and mouth cavity.
Supplement with oxygen mask or prongs.
 34
Anticonvulsants: should be given without delay:
1. Diazepam: Drug of choice; as it is efficient and safer on
respiration. It enters the brain rapidly and acts within
seconds to 1-2 minutes. Its effect lasts for 15-30
minutes. Given at a dose of 5-10 mg /15-30 minutes
maximum of 30 mg by direct IV injection for adults. If
convulsions not stop administrate barbiturate.
2. Phenobarbital: It has the disadvantage of being slowly
acting. If no response to barbiturate administrates
phenytoin.
3. Phenytoin: Continuous monitoring of the patient's
electrocardiogram (ECG), blood pressure, and
respiration is essential. If no response so general
anesthesia is indicated.
4. General anesthesia, muscle relaxants and mechanical

 IV fluids administration and control of acidosis that may

ventilation may be required in resistant cases.

result from prolonged or repetitive seizures.

Rhabdomyolysis
The syndrome of rhabdomyolysis is the result of
skeletal muscle injury which occurs due to excess energy and
inadequate oxygen to skeletal muscles. This causes myocyte
breakdown and release of cellular toxic contents into the
plasma; myoglobin, creatinine phosphokinase (CPK >3-10
times normal), lactic dehydrogenase (LDH), potassium,
phosphates, uric acid, aspartate aminotransferase (AST).
Clinical sequelae of rhabdomyolysis:
1. Hypovolemia (due to sequester of water within injured
myocytes).
2. Hyperkalemia (due to release of cellular K+ into
circulation).
3. Metabolic acidosis.
4. Acute renal failure in 25% (deposition of myoglobin
pigment in renal tubules).
5. Disseminated intravascular coagulation (DIC).
Toxic causes include:
1. Substance abuse (alcohols, heroin, methadone,
 35
barbiturates, cocaine, amphetamine, ecstasy, LSD).
2. Drugs increased muscular activity as Antihistamines,
salicylates, caffeine, (neuroleptics malignant hyperthermia
syndrome), theophylline, cyclic antidepressants, selective
serotonin reuptake inhibitors (the serotonin syndrome).
3. Drugs causing hypoxia as Carbon monoxide and toluene.
4. Direct toxic effect to muscles as spider (e.g. black widow
spider), and massive bee envenomations.
Diagnosis:
1. History of previous causes exposure.
2. Edema, pain and tenderness in a group of muscles.
3. Elevated CPK, LDH, K+, AST, ALT and Uric acid.
4. Metabolic acidosis.
Treatment:
1. Good hydration.
2. Urinary alkalanization to trap acidic pigment of myoglobin
in urine.
3. Control of hyperkalemia (by NaHCO3, Insulin/ Glucose and
Calcium) and diuretics when blood volume is expanded.
HOSPITAL DISPOSITION
A history of significant toxic exposure usually requires
observation for at least 6 hours. Any patient who is already
symptomatic should be considered for admission, careful
monitoring, and if intentional exposure, one-to one suicide
precautions.
If symptoms are present, hospitalize until free of toxic
effects and not at risk of sequelae.
Guidelines for hospital admission:
1. Exposure to corrosive substance.
2. Exposure to an amount sufficient to anticipate
manifestations.
3. Exposure to a substance that produces delayed
symptomatology.
4. When symptoms are already present.
5. Suspicion of chemical maltreatment of children or
intentional overdose.
 36
Guidelines for admitting patient to an ICU
1. Need for intubation.
2. Seizures.
3. Unresponsive to verbal stimuli.
4. Arterial carbon dioxide pressure > 45mmHg.
5. Any rhythm except sinus arrhythmia.
6. Second or third degree A-V block.
7. QRS > 0.12 s, in TCA poisoning, or >0.1 s (and) signs of
toxicity.
8. Systolic blood pressure less than 80 mmHg.
Indications for patient discharge from hospital
 When the patient state does not request specialist care
and monitoring, i.e. symptom free, awake, alert and

 Psychiatric patient are referred for psychiatric

orientated and has no organ failure.

assistance.
 37
NON-TOXIC EXPOSURE
 An exposure to a substance that is not dangerous to life or

 No product is entirely safe and all can produce symptoms if

health in the amount ingested.

 Knowledge of nontoxic ingestions helps avoid

a large enough concentration is consumed.

overtreatment and its risks.

You must insure the following:
 Product should be absolutely identified (material, amount,

 Only 1 product was surely ingested and no signal warning

and time of ingestion).

 Victim is free of symptoms or signs that can be associated

word on the container.

 The ability to call back at intervals to determine that no

with the ingestion.

 Time elapsed must be known and must be longer than the

symptoms have developed.

longest predicted interval between ingestion and possible

toxicity.
Common non-toxic Ingestions:
1. Antibiotics- Usually nontoxic unless massive amounts.
2. Cosmetics.
3. Household soft cleaners.
4. Vitamins without iron.
5. Antacids.
6. Bleach 5%.
7. Ink, pencils, crayons, clay, perfumes, chalk, deodorizers and
disinfectants.
8. Plants- most household plants are nontoxic or cause only
mild oral burn.
9. Hormonal contraceptives.
MEDICOLEGAL ASPECTS OF POISONING
Mentally competent adult patient has the right to refuse
examination and treatment even if such decision carries risk of
 38
death. Detailed documentation and witnessing of the patient
refusal of treatment is a must before discharge is allowed.
Mentally competent patient is the person who shows
complete understanding and retaining information about the
manage benefits and effects of non treatment. Also he should
be capable of judging up this information.
Treatment can be given without consent in order to
maintain patient life in mentally incompetent or in comatose
patient.
1. No scope for professional secrecy.
2. Collect and preserve evidence of poisoning e.g. sealed
samples biological fluids.
3. If a case dies Do not issue death certificate , notify the
police who may require autopsy.
4. Detailed written reports of the case and keep in a safe
custody.
5. Facing a case of food poisoning from a public eatery,
notify the public health authority concerned.
Summary:
This chapter discussed the toxic response, toxidromes,
initial evaluation of intoxicated patients, different methods of
toxin elimination and management of common toxicological
presentations. In addition, non-toxic exposure with some
examples of common non-toxic ingestions was enlightened as
well as the medicolegal aspects in the field of Clinical
Toxicology.
Questions:
1. List the factors affecting the toxic response.
2. Discuss the important points in history taking for an
intoxicated case.
3. Enumerate types and toxic causes of different
toxidromes.
4. List contraindications of gastric lavage.
5. Discuss indications of multiple dose activated charcoal.
6. Describe different ways of enhanced elimination
regarding their indications and complications.
 39
7. Describe the measures of treatment of toxicological
coma.
8. Discuss types of pulmonary edema.
9. Enumerate toxic causes of convulsions.
10. List the different toxic causes of rhabdomyolysis.

CHAPTER 2
Household Toxicity
CORROSIVES
ILOs
By the end of this chapter the student should be able to:
K1: List the different types of corrosives.
K2: State the pathophysiology of different types of
corrosives.
K3: Enumerate the different stages of local lesions caused by
corrosives.
K4: Discuss the local and systemic manifestations of
corrosive injuries.
K5: State how to diagnose a case with corrosive exposure.
K6: Describe the different lines of treatment in cases of
corrosive injury.
K7: State the different complications due to corrosive
exposure.
K8: Discuss button batteries regarding their effects, clinical
presentation, diagnosis and treatment.
K9: Discuss carbolic acid regarding its effects, clinical
presentation, diagnosis and treatment.
K10: Discuss oxalic acid regarding its effects, clinical
presentation, diagnosis and treatment.
K11: Solve problems revolving around virtual cases exposed to
different types of corrosives.
A1: Realize the importance of urgent treatment of cases with
corrosive exposure.
 40
A2: Realize the magnitude of the problem of corrosive
poisoning and the need for educational measure for its
limitation.
A3: Realize the importance of notification to the authorities
of cases with recurrent exposure to corrosives.
Introduction:
A corrosive (caustic substance) is a substance that
causes both functional impairment and histologic damage on
contact with tissue surfaces. Corrosives are typically classified
as acids or alkalis.
Classification and Sources:
There are many corrosive agents available in industrial
products as well as in home products. They are of solid or
liquid forms with different viscosities and concentrations.
- Acids are found in toilet bowl and drain cleaners, car
batteries, metal cleaners and disinfectants.
- Alkalis are found in paint removers, drain cleaners, hair
dyes, glass cleaners, antirust products and bleach.
Acids Alkalis
Types Source Types Source
Inorganic
-Sulfuric acid - ‫ما النا‬ - KOH -Potash ‫ال تا‬
-Hydrochloric - Drain and toilet - NaOH -Detergents
acid bowel cleaner. -Ammonia and bleachers
-Nitric acid - Disinfectant and in -Toilet bowel
Organic polish cleaner
-Oxalic acid
-Carbolic acid
-Acetic acid
Pathological effects:
1- Acids cause an immediate coagulative necrosis that
creates an eschar, which tends to self-limit further
damage.
2- Alkalis cause a liquefactive necrosis with saponification
and continued penetration into deeper tissues, resulting in
extensive damage.
 41
3- Other agents may act by oxidizing, reducing, or denaturing
cellular proteins.
N.B: Most corrosives have only local effects but some like
organic acids have local and systemic effects.
Phases of lesions:
1- Inflammation phase and cellular necrosis (24-48 hours).
2- Sloughing phase: necrotic tissues fall down by 4-7 days
leaving ulcers or perforating lesions.
3- Granulation tissue and collagen deposition continue for 2
weeks.
4- Cicatrisation phase: dense fibrous tissue is formed in 2-4
weeks.
Corrosives with local action
These are mainly inorganic acids, alkalis, salts of heavy
metals and button batteries. Toxicity occurs after ingestion,
inhalation, and skin or eye exposure.
1- Ingestion of corrosives
Site of lesion:
Common sites of lesions after ingestion:
Acids: Lesions are located in esophagus and stomach.
Alkalis: Lesions are usually located in the esophagus.

Clinical presentation:
The patient is commonly a severely irritated child
presenting with:
1- Severe pain: oropharyngeal, epigastric and retrosternal.
2- Oropharyngeal burns: light grayish to black ulcers in
addition to edema of the tongue, lips, gums, pharynx
and epiglottis. These lesions do not reflect the severity
of esophageal or gastric lesions.
3- Dysphagia and drooling of saliva. These effects are due
to edema, burns and inflammation of the mouth cavity
and pharynx.
4- Hoarseness of voice if edema and burns extend to
larynx.
 42
5- Stridor denotes significant edema of the vocal cords. It
results from vomiting and aspiration or inhalation of
corrosives fumes.
6- Spontaneous vomiting is very common. Patient should
not be forced to drink or feed to avoid vomiting.
7- Hematemesis and or melena suggest significant
gastroesophageal ulceration.
Complications of corrosive ingestion:
I- Acute complication:
1. Upper respiratory tract obstruction (laryngeal edema –
severe stridor).
2. GIT hemorrhage (hematemesis or even regurgitation of
fresh blood from esophageal severe corrosion).
3. Esophageal and gastric perforation.
4. Shock which could be hemorrhagic, neurogenic or
hypovolemic (secondary to corrosion which leads to
impaired feeding and water drinking or due to vomiting).
5. Septicemia.
6. Dissiminated intravascular coagulation (DIC) ( coagulatve
due to septicemia and hemoconcenteration).
7. Renal failure (secondary to dehydration ).
8. Acute pulmonary edema and Adult respiratory distress
syndrome (ARDS) (in inhalation of corrosive fumes ,or due to
aspiration).
II- Delayed complications:
These could be divided into:
a- Complications due to sloughing of the devitalized
esophageal wall:
These occur by the end of the first week or later.
1. Mediastinitis.
2. Pericarditis.
3. Tracheoesophageal fistula.
4. Pleurisy.
b- Complications due to scarring and stricture formation
(chronic complications):
These occur after weeks.
 43
1. Esophageal obstruction secondary to stricture
formation (as shown in the x-ray Fig 1).
2. Pyloric stenosis and pyloric obstruction secondary
to fibrous tissue deposition.
3. Malnutrition, dehydration and cachexia secondary
to dysphagia.
Investigations:
1- To diagnose the GIT lesions:

 Endoscopy is recommended for all patients

A. Endoscop:.

regardless of symptoms and should be undertaken

 It is contraindicated in:
within the first 12 hours.

- Airway obstruction.

 It reveals different grades of severity:

- The presence of signs of perforation.

- Grade I: Erythema.
- Grade II: Destruction of mucosa.
- Grade III: Destruction of all layers of the gut
beyond the mucosa.
2- To diagnose complications:

 Chest x-ray: will demonstrate air in the

A. Radiography :

 Abdominal x-ray (in upright position): will

mediastinum in cases of esophageal perforation.

demonstrate free abdominal air in cases of gastric

 X ray with Barium to demonstrate the site of

perforation.

stenosis (done after 21 days post ingestion).

 44

Fig. (1): Post corrosive esophageal stricture

B. CT scan
It provides accurate detection of site of perforation.
C. Laboratory studies
These include CBC (|HB and hematochrite),
electrolytes, glucose and arterial blood gases.

Treatment of corrosive ingestion:

I- Emergency treatment and first aid measures:
1- No oral interventions: e.g.(neutralization (i.e giving alkali
for acids ingestion or acids for alkali ingestion, as heat is
produced by the chemical reaction with more tissue
damage), emesis, gastric lavage, activated charcoal and
cathartics).
2- Secure the patient's airway in respiratory distress by:
a. Oxygen and ventilator support.
b. Oro-tracheal intubation may be attempted only if it
can be performed under complete visualization.
c. Tracheostomy should be performed if vocal cords
edema prevents intubation.
 45
N.B: Only severe cases of airway edema could be
treated by steroids but with caution.
3- Dilution therapy: It minimizes damage to oral,
esophageal and gastric tissue. Perforation should be
excluded first then 1-2 glassful of milk or water may be
administered to the adult patient within 30 minutes (half
this dose is administered to children).
4- Anti-shock measures: According to hydration status,
fluids and caloric requirements and blood loss. These
include:
 IV fluids.
 Blood transfusion.
 Crystalloids.
5- Strong pain killers: Both local and systemic e.g. pethidine.
6- Monitor vital signs and follow up for complications.
II- Supportive treatment:
1- Total parentral nutrition (TPN) for at least 3 weeks for
grades II and III.
2- H2 blockers (ranitidine) or proton pump inhibitors
(lansoprazole) to minimize acid secretion.
3- Antibiotics to guard against infection.
4- Steroids to prevent fibrosis were used in the past but
they proved to be ineffective and even dangerous in
cases with deep perforating lesions and bleeding.
III- Surgical interference:

 Severe uncontrolled hemorrhage.

Emergency surgery in

 Perforation of the GIT.

 Post corrosive strictures as Dilatation

Elective surgery in
of
esophageal strictures (as shown in figure 2).
2- Inhalation of corrosives
Inhalation of corrosive gases (e.g: chlorine or ammonia
in industries) may cause upper respiratory tract injury, with
cough, dyspnea, stridor, hoarseness, wheezing, noncardiogenic
pulmonary edema (NCPE) and chemical pneumonitis. Chlorine
 46
gas is released also at home when sodium hypochlorite
(Clorox) is mixed with acidic or alkaline detergents. Treatment
consists of removal of the patient from exposure, stabilization
and giving supplemental oxygen.
3- Skin exposure to corrosives
Skin exposure to corrosive agents usually results in
immediate pain and redness, followed by blistering. Serious full
thickness burns can occur. Sulfuric acid causes black slough,
nitric acid causes yellow discoloration and alkalis cause
bleaching of tissues. The condition could be complicated by
scar formation or infection. It is treated by removal of clothes
and copious washing with water or saline for 30 minutes.
4- Eye exposure to corrosives
Eye exposure to corrosive agents causes pain, redness,
conjunctivitis and lacrimation. Serious full-thickness burns and
blindness can occur. It is treated by copious irrigation with
water or saline for 30 minutes.

Button Batteries (e-learning)

Phenol (Carbolic Acid)
It is one of the oldest antiseptic agents. It was used in
wound dressing in the past but its toxicity limited its use. Now
it is used as a disinfectant. It is found in many commercial
products like dettol, cresol and phenol detergent. ( ‫(الفني‬
Pathophysiology:
It acts as a general protoplasmic poison. Toxicity is due
to its ability to cause cell wall disruption, protein coagulation
and coagulative necrosis.
Route of toxicity:
1- Ingestion: either intentional or accidental.
2- Inhalation: usually in industry (accidental).
3- Skin exposure: results in serious skin burns as well as
systemic toxicity.
4- Eye exposure.
 47
5- Intravenous administration (very rare, 1 gram is fatal).
Clinical manifestations:
A- Local symptoms:

 Smell of phenol.
1- Ingestion

 Nausea & vomiting.

 Bloody diarrhea.
 Abdominal pain.
 White patches in the oral cavity.

 Respiratory irritation and chemical pneumonitis.

2- Inhalation

 Painless skin lesions which are white patches

3- Skin exposure

which turn red then brown.

 Eye irritation.
4- Eye exposure

 Corneal damage.
B- Systemic manifestations:

 Seizures.
1- CNS symptoms:

 Lethargy.
 Coma.

 Tachycardia followed by bradycardia.

2- Cardiac symptoms:

 Hypotension.

 Acute glomerulonephritis with oliguria and

3- Other systemic symptoms:

 Hypothermia.
anuria.

 Metabolic acidosis.
 Methemoglobinemia.
 Hemolysis leading to hemolytic anemia and
jaundice.

 Early within 48 hours CNS depression

C- Cause of Death
 48
 Late more than 48 hours toxic
glomerulonephritis.
Investigation:
 Blood: methemoglobinemia, decreased hemoglobin

 Urine contains high levels of phenol. Urine turns dark

level and RBCs count

green due to the oxidation of the excreted products of

phenol (hydroquinone). Albuminuria and renal casts

 Kidney function tests: urea and creatinine.

may be present in renal affection.

Treatment:

 Care of respiratio , o a, o ulsio s…et .

A- Emergency treatment:

 If corrosive injury to the gastrointestinal tract is

suspected, endoscopy should be done.

 For ingestion: Do not induce emesis (for fear of CNS

B- Decontamination:

depression).
Gastric lavage is possibly performed as phenol
produces thick coagulative layer so perforation is not

 For inhalation: Remove victims from exposure and

likely to occur.

 For skin or eye exposure: Remove contaminated

administer supplemental oxygen.

clothing and wash exposed skin with soapy water.

Immediately flush exposed eyes with copious water
or saline.

 If methemoglobinemia occurs, administer methylene

C- Symptomatic treatment:

 Dialysis in case of renal failure.

blue.

Oxalic Acid
Oxalic acid and oxalates are used as bleaches, metal
cleaners, and rust removers and in chemical synthesis and
 49
leather tanning. Soluble and insoluble oxalate salts are found in
several species of plants.
Pathophysiology:
Oxalic acid is highly irritating and corrosive. Ingestion
and absorption of oxalate cause acute hypocalcemia resulting
from precipitation of the insoluble calcium oxalate salt.
Calcium oxalate crystals may then deposit in the brain, heart,
kidneys, and other sites, causing serious systemic damage.
Route of toxicity:
Toxicity may occur as a result of ingestion, inhalation,
skin or eye exposure.
Clinical manifestations:
A- Local symptoms:

 Irritation and swelling in the oropharynx and

1- Ingestion:

 Abdominal pain.
esophagus.

 Sore throat, cough and wheezing.

2- Inhalation:

 Chemical pneumonitis and/or pulmonary edema.

 Irritation and burning.

3- Skin or eye exposure:

 Corrosion of the skin or eye.

B- Systemic manifestations:

 Weakness.
1- Symptoms due to hypocalcemia.

 Tetanic convulsions.
 Arrhythmias and cardiac arrest.

 Dysuria and hematuria.

2- Renal symptoms:

 Oliguria and anuria.

 Blood: serum electrolytes, serum calcium, blood

Investigations:

 Urine contains calcium oxalate crystals.

urea nitrogen (BUN) and serum creatinine.
 50
 ECG monitoring.
Treatment:

 Care of respiratio , o a, o ulsio s…etc.

A- Emergency treatment:

 Monitor the ECG and vital signs for at least 6 hours

after significant exposure, and admit symptomatic

 Administer 10% calcium solution (chloride or

patients to an intensive care unit.

gluconate) slowly to counteract symptomatic

hypocalcemia.

 For ingestion: Do not induce emesis. Perform

B- Decontamination:

 For inhalation: Remove victims from exposure and

gastric lavage.

 For skin or eye exposure: Wash with copious water

administer supplemental oxygen.

or saline.
Summary:
This chapter introduced some examples of the different
types of corrosive substances, either with local effects or with
both local and systemic effects. The pathophysiology, routes of
toxicity, clinical presentation, diagnosis, treatment as well as
different complications were discussed.
Questions:
1- Enumerate the different phases of local lesions caused by
corrosives.
2- Discuss the local and systemic manifestations of corrosive
injuries.
3- State how to diagnose a case with corrosive exposure.
4- Describe the different lines of treatment of cases of
corrosive injury.
5- State the different complications due to corrosive exposure.
6- Give a short account on the hazards caused by button
batteries and their management.
7- Discuss carbolic acid regarding its effects, clinical
presentation, diagnosis and treatment.
 51
8- Give an account on toxicity with oxalic acid.
HYDROCARBONS
ILOs:
By the end of this chapter the student should be able to:
K1: Define Hydrocarbons and list their types
K2: Describe the mode of toxicity with kerosene.
K3: Discuss the pathophysiology and clinical presentation of
acute kerosene toxicity.
K4: Enumerate the possible causes of death in acute kerosene
toxicity.
K5: Discuss the lines of management of acute kerosene
toxicity.
K6: Discuss the possible preventive measures to decrease the
incidence of kerosene toxicity.
K7: Solve problems revolving around virtual cases presenting
with acute kerosene toxicity.
A1: Realize the magnitude of the problem of kerosene toxicity
and how we are in need for educational and limiting
measures.
A2: Realize the importance of notification of cases of children
with recurrent exposure to household poisoning.
A3: Realize the value of time factor in treating cases with
acute intoxication.
Introduction:
A hydrocarbon is an organic compound made up
primarily of carbon and hydrogen atoms. These products
derived from plants (pine oil, vegetable oil), animal fats (cod
liver oil), natural gas, petroleum, and coal tar. Petroleum
distillates hydrocarbons, used as fuel, solvent and lighter fluid.

Kerosene
Mode of Toxicity:
These are frequently stored at home or garage in
unmarked container or soft drink bottles. Most intoxicated
cases involve accidental ingestion by young children.
 52
Some insecticides and other toxic chemicals are often
mixed with kerosene, and it should be noted that these
additives can be more dangerous than kerosene itself.
Pathophysiology:
Pulmonary injury:
The principal pathologic finding is respiratory tract injury
due to aspiration and spread of the liquid in the lung. The
aspiration depends primarily on two physical properties:
viscosity and volatility. Kerosene has low viscosity and low
volatility. This leads to a high risk of aspiration with
increasing rate of penetration into the terminal bronchioles
and alveoli. Kerosene will destroy the surfactant lining the
alveoli rather than direct parenchymal injury that occurs.
Acute chemical pneumonitis will develop. Hemorrhagic
pulmonary edema, interstitial inflammation, affection of
hyaline membrane and alveolar collapse may occur.
Neurologic Injury:
CNS toxicity occasionally observed following kerosene
ingestion appears to be indirect and secondary to
pulmonary involvement with resulting hypoxia. If large
amount ingested direct CNS depression may occur.
Cardiac Manifestations:
Sudden death has been associated with kerosene
inhalation. Severe arrhythmias have been proposed to be
the result of sensitization of the heart to circulating
catecholamines. This also makes the heart more susceptible
to hypoxia-induced arrhythmias.
GIT:
Direct local irritation
Cutaneous Injury:
Injury appears to be due to irritant effects and fat
solubility properties of kerosene.
Occular Exposure : Slight irritation
Clinical picture:
1-GIT:
Nausea, vomiting with smell of kerosene in vomitus.
Diarrhea, abdominal pain and distension are less common.
 53
2-Pulmonary:
1. Characteristic smell of kerosene.
2. Cough.
3. Cyanosis.

 Intercostal retraction.
4. Chemical pneumonitis with:

 Dyspnea, tachypnea.
 Ronchi and wheezes and decreased breath sound.
 Fever.
5. Bronchopneumonia.
6. Pulmonary edema.

 CNS depression with dizziness, stupor, hyporeflexia,

3-Neurological:

 Rarely convulsion.
coma and central respiratory depression.

 Mild erythema.
4-Cutaneous:

 Dermatitis with redness, itching and inflammation

may be seen.

 Tachycardia.
5-Cardiac:

 Atrial & ventricular arrhythmias.

N.B.: if other toxins as pesticides are present clinical picture
may be atypical to kerosene.
Causes of death:
1. Death may occur in 24 hours from central respiratory
failure and sudden arrhythmias.
2. If late in few days, death is secondary to broncho-
pneumonia and pulmonary edema.
3. Toxic additives may cause death secondary to CNS or
cardiac toxicity.
Investigations:
1. Arterial blood gases (ABGs).
2. ECG monitoring.
3. Chest x-ray early, every 2-3 days and two weeks later
4. Lab. investigations for toxic additives.
Prevention:
 54
 Storage in labeled container with Safety closure.
 Education of parents.
Treatment:

 In mild cases emesis and gastric

A- Mild cases:
lavage are

 Observation and follow up.

contraindicated for fear of aspiration.

B- Severe cases:
Showing CNS manifestations, systemic manifestations,
or amount ingested more than 1ml/kg, or in combination with
insecticides.
I- Emergency measures ABCD.

 Contaminated clothes should be removed and skin

II- Elimination:

 If ocular exposure occurs: prolonged irrigation with

should be washed with soap and water.

 Evacuation of the stomach:

sterile saline or tap water.

Gastric lavage is done after introduction of cuffed

 Activated charcoal and hemodialysis are not effective

endotracheal tube to prevent aspiration.

and may be harmful.

 Care of coma and treatment of pulmonary

III-Symptomatic treatment:

oedema.

 No specific antidotes.
IV- Drug therapy:

 Corticosteroids may be used cautiously to treat chemical

pneumonitis as they may affect the immunity of the

 Although kerosene causes chemical pneumonitis,

patient predisposing to infection with other organisms.

antibiotics may be used if bacterial pneumonia

develops.
Summary:
 55
Acute kerosene toxicity is one of the common
toxicological emergencies. It affects mostly the lungs. Effective
preventive measures should be done to decrease its incidence.
Questions:
1. Discuss the clinical picture of acute kerosene toxicity
and correlate it with the pathophysiology of kerosene.
2. Enumerate the possible causes of death in cases of
acute kerosene toxicity.
3. Mark √ or × :
-Gastric lavage is essential in treatment of kerosene
aspiration ( )
 56
INSECTICIDES

ILOs:
By the end of this chapter the student should be able to:
K1: List the different types of insecticides.
K2: Describe the mode of toxicity and route of exposure of
organophosphates.
K3: Discuss the pathophysiology and clinical picture of
organophosphates poisoning.
K4: Discuss the diagnosis of organophosphates poisoning.
K5: Describe the investigations and treatment of
organophosphates poisoning.
K6: Explain the possible complications of organophosphates
poisoning.
K7: Compare between organophosphates and carbamates
poisoning regarding the clinical picture and management.
K8: Solve problems revolving around virtual cases presenting
with organophosphates and carbamates poisoning.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
Introduction:
These are chemicals widely used in our life. An
estimated 1000 or more chemicals are available in a variety of
professional exterminating compounds agricultural chemicals
and non licensed preparations available to the general
population.
Types:
1. Organophosphates.
2. Carbamates.
3. Chlorinated (obsolete).
4. Pyrethroids.
5. Dipyridyls.
6. Fumigants: CN, phosgene, methyl bromide.
7. Others: Dioxins, nitriles, nitrophenol, surfactant.
 57

Organophosphates Insecticides (OPCs)

Mode of toxicity:
Poisoning usually occurs accidental during agricultural
applications or suicidal attempt rarely homicidal.
Route of exposure: oral, inhalation or through the skin
(dermal).
Pathophysiology:
Organosphosphates (OPCs) inhibit the ability of
Acetylcholine Esterase enzyme to hydrolyze acetylcholine (Ach)
which in turn accumulates profusely and stimulates muscarinic
and nicotinic receptors as well as the central nervous system
(CNS) directly. This inhibition is irreversible after 24-36 hours
without initiation of specific treatment. As a result, the victim
will manifest a classic cholinergic syndrome that, depending on
exposure and treatment, range from simple miosis to a
fulminating cholinergic crisis progressing within minutes to
respiratory arrest and death, commonly preceded by twitches
and convulsions.
Diagnosis:
A) Clinical picture:
The classical presentation of OPCs toxicity is the
cholinergic crisis; however other syndromes may follow the
cholinergic crisis and complicate the condition in some
patients.
1. Cholinergic stimulation (crisis): with episodes of
relapses in between episodes of control due to
reactivation of acetyl cholinesterase E. (AchE). It may
persist for days or weeks with good treatment.
2. Intermediate syndrome: may occur 2-3 days after
exposure.
3. Delayed neuropathy: may occur 3-4 weeks post
exposure.
4. Cardiotoxicity may overlap and complicates the picture
since early episodes.
 58
Cholinergic stimulation (crisis):
It starts shortly after ingestion and corresponds in
intensity to the degree of cholinesterase inhibition.
Relapses are caused by redistribution in the body or
delayed absorption from the gut where it may be adsorbed
to the gut wall. It consists of muscarinic, nicotinic and
central effects. The signs and symptoms of a particular
organophosphate depend on the balance between
stimulation of muscarinic and/or nicotinic receptors.
1. Muscarinic effects (S&S):
Best remembered with the mnemonic DUMBELS:
1. Diarrhea.
2. Urination.
3. Miosis (pin pointed pupil).
4. Bradycardia, hypotension, bronchospasm,
bronchorrhea.
5. Emesis.
6. Lacrimation.
7. Salivation, sweating.
2. Nicotinic effects (S&S):
Best remembered with the mnemonic MATCH:
1. Muscle fasiculations: typically starts around eyelids
and peri-oral region followed by weakness and
respiratory paralysis.
2. Adrenal medullary hyperactivity with transient
hyperglycemia.
3. Tachycardia, arrhythmias.
4. Cramping of skeletal muscles.
5. Hypertension.
3. Central effects (S&S):
Vertigo, confusion, tremors, agitation, convulsions
and coma due to inhibition of brain A.Ch.E. which
coincides with true (RBCs) cholinesterase.
B) Investigations
1. ABG, electrolytes, glucose, urea or creatinine.
2. ECG and cardiac monitoring.
 59
3. Assessment of true (in RBCs) and pseudo (in plasma)
A.Ch.E. enzymes.

 50% of normal: subclinical or mild poisoning.

Interpretation of their levels.

 30-40% of normal: mild to moderate toxicity.

 Less than 20-25% of normal: severe poisoning.
N.B.: True A.Ch.E: is present in brain and RBCs.
Inhibited only by OPC and require 5wk - 4 months to
recover.
Pseudo A.Ch.E.: present in plasma inhibited both by
OPC and carbamates and require 4 wk to recover.
4. Chest X-ray: evidence of aspiration pneumonia and
bronchospasm.
Complications:

 Characterized by relapse of muscle weakness including

1. Intermediate syndrome:

cranial nerves, palsies, respiratory, neck and proximal

limb muscles weakness resulting in respiratory muscle
paralysis frequently necessitating treatment with

 It occurs between the acute cholinergic crisis and the

controlled ventilation.

usual onset of organophosphate induced delayed

 The weakness is due to muscle fiber necrosis and begins

neurotoxicity.

shortly after the initial decline in A.Ch.E. activity.

Maximal muscle involvement occurs within the first 2-5

 Its intensity is correlated with the degree of fall of True

days of poisoning.

 Early treatment with oximes may prevent the

A.Ch.

occurrence of intermediate syndrome.

2. Delayed neuropathy:
1. It usually occurs 2-3 weeks after exposure to some OPC
even after a skin contact.
2. It is a mixed sensory-motor neuropathy.
 60
3. It usually begins in the legs, causing burning or tingling
sensations, and then followed by weakness of the legs
and feet. Thighs and arms also become involved.
4. It is due to nerve demyelination and is usually
permanent.

 Parasympathetic cardiomyopathy: foci of myocardial

3. Cardiotoxicity:

necrosis which correlate with the degree of

 Increased QT interval favoring ventricular tachycardia.

accumulated acetylcholine.

Treatment:
A- Emergency treatment:
ABC, assisted ventilation and immediately start atropine
(life saving) and oxygen therapy.

 As early as possible after stabilization. Use cold then hot

B- Decontamination:

water to the whole body. If hair is still smelly it may be cut

to avoid relapses from continuous absorption. Gastric
lavage with cuffed endotracheal tube should be
performed as early as possible after initial stabilization and
use of atropine to control muscarinic effects that

 Emesis better to be avoided for fear of aspiration due to

compromise respiration.

muscle weakness and many OPC are in petroleum

 Activated charcoal is administrated.

distillate vehicles.

C- Antidotes:
1. Atropine:
It is a competitive antagonist of A.Ch. at muscarinic
receptors. The patient must be well oxygenated to minimize
the risk of atropine induced ventricular irritability. 2-5 mg IV
every 15 minutes until relief of bronchospasm and dryness of
chest secretions as this is the greatest life threat. Do not rely
on HR and papillary size titrates and keep patient atropinized
for 1-2 days to avoid possible relapses of cholinergic crisis.
Atropine antagonizes muscarinic but not nicotinic effects.
 61
Diagnostic test:
Atropine 1 mg IV. If it produces general signs of
atropinization, this suggests other diagnosis.
Failure of this dose to revere the patient's symptoms of excess
cholinergic activity provides indirect evidence of OPC.

 They reactivate the inhibited A.Ch.E; hence correcting all

2. Cholinesterase reactivators: Oximes:

signs of Ch.E inhibition including muscarinic, nicotinic

 They protect against subsequent skeletal and respiratory

and central effects.

 They rapidly replenish True and Pseudo Ch.E. enzymes.

muscles necrosis.

 Atropine premedication is essential.

 Pralidoxime (PAM): 1-2 mg IV or infusion as loading

Dose:

doses, followed by half this dose every 6-8 hrs for 2

days. It is a quaternary amine thus it reverses both

 Obidoxime (DAM): 250 mg amp. IV/d for 3 days. It is

nicotinic and muscarinic effects but not central effect.

preferred than pralidoxime for its ability to cross the

BBB (tertiary amine) and better control of the central

 Reload and re-maintain with oximes in case of relapse.

manifestation as it is a tertiary amine.

D- Symptomatic treatment:
1. Management of arrhythmias.
2. Diazepam: to control convulsions and reduce
cardiomyopathy.
3. Avoid: succinylcholine for rapid intubation as it is
metabolized by plasma ChE - theophylline -
phenothiazines and antihistaminics.

 Intermediate syndrome: assisted ventilation.

E- Treatment of complications:

 Patients who intentionally ingest OPC should go

 Evaluation for peripheral neuropathy and other long term

psychiatric evaluation.

effects.
 62
Carbamates
They are reversible inhibitors of cholinesterase enzyme
A.Ch. Carbamylation of A.Ch enzyme results in accumulation of
Acetylcholine with muscarinic and nicotinic receptors
stimulation. Their duration of action is relatively short. They
are commonly used for domestic uses (Baygon), have low
dermal toxicity and their toxicity is rarely fatal. The most
potent types, aldicarb (temik) and carbofuran (lannate) are
used as rodenticide.
Clinical picture and management:
Is similar to organophosphates insecticides poisoning with the
following differences:
1. Onset of symptoms may be more rapid that with OPC.
2. Picture is milder.
3. Recovery is rapid. Poisoning seldom exceeds 1-2 days.
4. Pseudo-cholinesterase enzyme is rapidly replenished
within few hours.
5. No intermediate syndrome, delayed neuropathy or
cardiotoxic effect.
6. Carbamates produce little or no CNS toxicity because of
their inability to penetrate the BBB.
7. Atropine is required in smaller doses than that used in
OPC.
8. Oximes are not required to the spontaneous
regeneration of Ach.E.
Summary:
Acute poisoning with OPC is a global public health
problem.
The diagnosis can be made using four criteria:
1. History of exposure to an insecticide.
2. Signs and symptoms of excessive muscarinic or nicotinic
stimulation.
3. Decreased plasma and RBC Ch.E. levels.
4. Response to atropine and oximes therapy.
 63
N.B.: IV atropine is the life saving measure in acute OPC
poisoning and should be given until dryness of chest
secretions.

Question:
1. The life saving measure in acute OPC toxicity is:
a) IM atropine b)IV-obidoxime
c) IV atropine d)Oxygen 100%
2. The sign of full atropinization in acute OPC toxicity is:
a) Mydriasis b) Tachycardia
c) Dryness of chest secretions d) Dry mouth
3. All the following are muscarinic effects of OPC poisoning
EXCEPT
a) Urination b) Bradycardia
c) Bronchospasm d) Muscle fasiculations
4. OPC insecticides induced toxidrome is:
a) Cholinergic b) Sympathomimetic
c) Anticholinergic d) Opioid

5. OPC leads to:

a) Reversible inhibition of both true and pseudo Ch.E.
enzyme.
b) Irreversible inhibition of true A.Ch.E. enzyme.
c) Irreversible inhibition of pseudo A.Ch.E. enzyme.
d) Irreversible inhibition of both true and pseudo A.Ch.E
enzyme
6. Oximes are:
a) Cholinesterase inhibitors
b) Given IM
c) Ineffective in carbamate poisoning.
d) Life saving in OPC poisoning
* Give a full account on:
- Antidotes of OPC toxicity.
Complete
1. The classical prese tatio of OPC to i it is the ……
ho e er other s dro es as …….. , ………… a d …….. a
follow.
 64
2. E posure to OPC leads to ………… ith resulta t
sti ulatio of ……….., ……………. a d …………..
3. Car a ate i to i atio o urs through…………
4. Carbamates differ from OPC in ………. a d …………

NAPHTHALENE
(E-learning)

RODENTICIDES
ILOs:
By the end of this chapter the student should be able to:
K1: List the types of rodenticides.
K2: Explain the pathophysiology of zinc phosphide and
coumarins poisoning.
K3: Describe the clinical picture of zinc phosphide and
coumarins poisoning.
K4: Discuss the management of zinc phosphide and coumarins
poisoning.
K5: Solve problems revolving around virtual cases presenting
with zinc phosphide and coumarins poisoning.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
Introduction:
These are substances used to kill rodents as rats and mice.
Types:
1. Zinc phosphide and yellow phosphorus, thallium,
arsenic.
2. Anticoagulants.
3. Carbamates.
4. Strychnine.
Zinc Phosphide
Pathophysiology:
 65
A potent rodenticide with a fishy odor, which is
absorbed orally, through broken skin or may be by inhalation.
On contact with water or gastric acids, phosphine gas
(PH3) is liberated which inhibits cytochrome oxidase enzyme
leading to inhibition of aerobic metabolism which in turn leads
to lactic acidosis and cell death.
Diagnosis:
A- Clinical picture:
1st phase (1-24 hours):
1. Irritability and restlessness are the earliest symptoms.
2. Vomiting, diarrhea and dehydration.
3. Metabolic (lactic) acidosis with respiratory
compensation.
4. Toxic cardiomyopathy (direct effect) with arrhythmias
and shock.
5. Pulmonary edema due to liberation of phosphine gas.
2nd phase (24-48 hrs):
Phase of apparent recovery: this phase may last for few
hours or may be totally absent.
3rd phase (36hrs-7 days):
Phase of severe toxic hepatitis.
1. Right hypochondrial pain and enlarged tender liver.
2. Jaundice
3. Elevation of liver enzymes, bilirubin and prothrombin
time are more significantly affected and are prognostic
markers to the development of liver cell failure and
hepatic coma.
4. Anuria and renal tubular damage complicate the picture.
B- Investigations:
1. ECG.
2. ABG.
3. Liver functions (particularly, PT).
4. kidney functions.

Treatment:
A- Emergency treatment: ABC.
 66
B- Elimination: emesis or gastric lavage is done using sodium
bicarbonate.

 IV fluids and electrolytes to correct dehydration and

C- Symptomatic treatment:

 Inotropics and antiarrythmics for toxic myocarditis.

electrolyte imbalance.

 Liver support.
 Hemodialysis.
Anticoagulants
(E-Learning)
Summary:
This chapter discussed rodenticides poisoning namely
zinc phosphide regarding its pathophysiology, clinical
presentation and treatment.
Questions:
* The affected enzyme in zinc phosphide poisoning is:
a) Alkaline phosphatase .
b) Cholinesterase.
c) Cytochrome oxidase.
d) Glucose phosphate dehydrogenase.
* Liver is the target organ of toxicity in:
a) OPC.
b) Sulphuric acid.
c) Naphthalene .
d) Zinc phsophide.
* To i it ith zi phosphde o urs due to li eratio of ………..
hi h leads to ………
CHAPTER 3
Atropine
ILOs:
By the end of this chapter the student should be able to:
K1: Enumerate the origin and sources of atropine.
 67
K2: Discuss the action, clinical picture, Uses and management
of atropine poisoning.
A1: Realize the importance of urgent appropriate treatment of
cases with acute intoxication.
Origin & sources:
- In all parts of the following plants: Atropa Belladonna,
Datura Fastiosa, and Datura Stramonium. It is present
with hyoscine and hyoscyamine and it is sold by herbalists
for colic and asthma.
- Anticholinergic medications (antispasmodics).
Actions:
1. Central: atropine and hyoscyamine cause stimulation of
the CNS followed by depression; while hyoscine causes
CNS depression.
2. Peripheral: anticholinergic effect, it blocks the muscarinic
action of acetylcholine at the cholinergic nerve endings.
Uses and Indications:
Life saving antidote in organophosphorus toxicity and in
chemical warfare (nerve agents' toxicity).
Mode of toxicity:
1. Intentional overdose of anticholinergic medications.
2. Abuse of hallucinogenic plants or herbs for colic.
3. During treatment of organophosphate insecticides
poisoning with large doses of atropine.
Clinical Picture:
A. Peripheral manifestations:
1. Dry mucous membranes due to inhibition of secretions
from salivary glands, vasodilatation.
2. Increased body temperature due to altered CNS
regulation and inability to sweat.
3. Tachycardia is one of the earliest and most reliable signs.
Sinus tachycardia is the most common arrhythmias in
atropine and other anticholinergic poisoning.
4. Increased respiratory rate (tachypnea).
 68
5. Eye effects including (a) dilated fixed pupil (mydriatic,
cycloplegic), (b) blurring of vision and photophobia, and
(c) diplopia.
6. Relaxation of all smooth muscles causing urinary
retention and constipation due to decreased peristalsis
which may result in reduced drug absorption.
B. Central manifestations:
Usually occur in combination with peripheral signs:
1. Delirium, disorientation, agitation, incoherent speech,
purposeless movement and visual hallucinations.
2. Seizures are not frequent manifestations.
Cause of death:
- Respiratory depression.
- Arrhythmias.
Investigations:
1. Arterial blood gases (ABGs).
2. ECG.
Treatment:
I. Emergency measures (ABCD).
II. Elimination:
1. Induction of emesis.
2. Gastric lavage may be useful up to 12 hours or even 24
hours as atropine delays emptying of the stomach.
3. Activated charcoal.
III. Antidote:
Physostigmine:
- It is a short acting reversible cholinesterase inhibitor that
increases acetylcholine at the sites of cholinergic
neurotransmission.
- It acts centrally and peripherally as it crosses blood brain
barrier (BBB).
- It should be given in hospital and under continuous ECG
monitoring for fear of arrhythmias and fatal bradycardia.

IV. Symptomatic treatment:

- Cold compresses (for hyperthermia).
 69
- Catheterization (for urine retention).
- Enema (for constipation).
- Benzodiazepines (for seizures).
Summary:
This chapter discussed atropine regarding its source,
clinical picture and management of its acute intoxication.
Questions:
1. Describe the clinical picture of acute atropine overdose.
2. Give an account on physostigmine.
 70

CHAPTER 4
Analgesics
ILOs:
By the end of this chapter the student should be able to:
K1: Describe the toxicokinetics of salicylates and paracetamol.
K2: Explain the pathophysiology of acute toxicity of salicylates
and paracetamol.
K3: List the factors affecting the risk of toxicity and the toxic
dose of paracetamol.
K4: Discuss the clinical picture of acute toxicity of salicylates
and paracetamol.
K5: Describe the lines of management of acute toxicity of
salicylates and paracetamol.
K6: Discuss chronic salicylates toxicity.
K7: Enumerate the differential diagnosis of acute salicylates
toxicity.
K8: Solve problems revolving around virtual cases presenting
with toxicity of salicylates and paracetamol.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
Introduction:
An analgesic (also known as a painkiller) is any member
of the group of drugs used to relieve pain (achieve analgesia).
Analgesic drugs act in various ways on the peripheral and
central nervous systems; they include paracetamol (also known
as acetaminophen), the non-steroidal anti-inflammatory drugs
(NSAIDs) such as the salicylates, and opioid drugs such as
morphine.
SALICYLATES
Salicylic acid and its derivatives are active ingredients in
a wide variety of readily available preparations used for the
treatment of pain, warts, and acne. Salicylates have analgesic
 71
anitpyretic and antiinfammatory actions and exert their effects
by inhibition of synthesis of prostaglandin.
Salicylate toxicity has decreased since the
introduction of alternative analgesics, but it still remains a
serious clinical problem. The incidence of salicylate poisoning
in children has declined because of the use of alternative
analgesics and the use of child-resistant containers.
Forms of salicylates:
Salicylates are found in hundreds of over-the-counter
(OTC) medications and in numerous prescription drugs. Aspirin
or aspirin-equivalent preparations (in milligrams) e.g. children's
aspirin (80-mg tablets), adult aspirin (325-mg tablets).
Route of exposure:
The prevalence of aspirin-containing analgesic products makes
these agents, found in virtually every household, common
sources of both unintentional and suicidal ingestion.
Toxicokinetics:
 Salicylate is readily absorbed in the stomach and small
bowel. It forms concretions in large doses withgreater

 Salicylates (water soluble) appear with high

amount available for absorption.

concentrations in blood, liver and renal cortex. Lesser

concentrations are present in the CNS . In severe toxicity,
acidosis increases salicylate passage to CNS. In overdose,
peak serum concentrations may not be reached for 4-6

 Approximately 80% of small doses of salicylic acid is

hours or longer.

metabolised in the liver (first order kinetics). These

metabolic pathways have only a limited capacity.
Salicylates are excreted mainly by the kidney Renal
excretion of salicylate becomes importantwhen the
metabolic pathways become saturated.
Pathophysiology:
 72
Salicylates directly or indirectly affect most organ
systems in the body by uncoupling oxidative phosphorylation
causing a variety of metabolic abnormalities:
1. Salicylates uncouple oxidative phosphorylation resulting
in hyperthermia, increased metabolic rate and
hyperpnea. This hyperactive state leads to increased
insensible fluid losses. The increased energy demand will
lead to increased tissue glycolysis and gluconeogenesis
that may result in hyperglycemia.
2. Salicylates directly inhibit certain enzymes in Kreb's cycle
leading to increased amounts of organic acids (lactate and
pyruvate) that contribute to metabolic acidosis.
3. Salicylates stimulate lipid metabolism leading to
increased levels of ketones.
4. Salicylates inhibit aminotransferase resulting in increased
levels of circulating aminoacids and amnoiaciduria.
Acid-base disorders in salicylate toxicity:
Acid-base disturbances vary with age and severity of the
intoxication.
A. Initially, a respiratory alkalosis develops secondary to
direct stimulation of the respiratory center. This may be
the only consequence of mild toxicity. The kidneys
excrete potassium, sodium, and bicarbonate, resulting in
alkaline urine.
B. severe metabolic acidosis with compensatory respiratory
alkalosis may develop with severe salicylate intoxication
due to:
1. Uncoupling of oxidative-phosphorylation 
accumulation of organic acids (lactic and pyruvic)
2. Increased levels of circulating amino acids due to
inhibition of amino acid transferases.
3. Increased levels of ketones due to stimulation of
lipid metabolism.
C- In severe toxicity CNS and respiratory depression occurs 
CO2 retention  respiratory acidosis.
Clinical picture of acute salicylate toxicity:
 73
The earliest signs and symptoms of salicylate toxicity
without hearing loss.

 Nausea and vomiting, common ( due to GIT irritation).

I- Gastrointestinal:

 Epigastric pain &pylorospasm.

 GI hemorrhage (most common with chronic

 Hepatitis (generally in chronic toxicity, rare in acute

intoxication).

toxicity).

 Tinnitus.
II- Auditory:

 Mild to moderate reversible hearing loss.

 Hyperventilation (common).
III- Pulmonary:

 Hyperpnea.
 Noncardiogenic pulmonary edema.
 Apnea.

 Tachycardia.
IV- Cardiovascular:

 Hypotension.
 Dysrhythmias (eg, ventricular tachycardia, ventricular
fibrillation).

 Toxic doses of salicylates first stimulate and then

V- Neurologic:

depress the CNS. Confusion, dizziness, delirium,

psychosis, and then ultimately stupor and coma may
occur.

 Acute renal failure may occur due to severe

VI- Genitourinary:

dehydration.
VII- Hematologic:
 Hematologic effects may include prolongation of the
prothrombin and bleeding times and decreased platelet
adhesiveness.
VIII- Dermatologic:
 74
 Diaphoresis is a common sign in patients with salicylate
toxicity.

 Rhabdomyolysis can occur because of dissipation of

IX Musculoskeletal Effects:

energy resulting from oxidative phosphorylation

uncoupling.

 Dehydration.
X- Electrolytes:

 Hypocalcemia(due to initial respiratory alkalosis).

 Acidosis.
Investigations:
I- Laboratory Studies:
1. Serum salicylate concentration (should be done
repeatedly). Levels from 15-30 mg/dL are considered to
be in therapeutic range. Signs and symptoms of toxicity
begin to appear above 30 mg/dL. Salicylate level >100
mg/dL is considered potentially lethal and is an
indication for hemodialysis.
2- Arterial blood gases: Repeat approximately every 2
hours until metabolic acidosis improves.
3- Serum electrolytes (K, Na).
4- Blood urea nitrogen (BUN).
5- Liver function tests.
6- Blood picture and coagulation profile ( bleeding time
and prothrombin time.

 A chest x-ray for detection of pulmonary edema.

II- Imaging Studies:

 Abdominal x-ray for detection of gastric salicylate

concretions.
III- Other Tests:
 The ferric chloride test but rapid nonspecific screening
tests that may be available in the emergency
department.
o If acetylsalicylic acid is present, combining 1 mL
of urine and a few drops of 10% ferric chloride
causes a purple color change.
 75
Treatment:
I- Emergency measures.

 Do not induce vomiting for salicylate ingestion.

II- Elimination:

 When recent large ingestion is suspected, gastric lavage

may be performed .Presence of concretion may make it

 Gastric lavage may be done up to several hours due to

effective few hours after ingestion.

 Activated charcoal. (MDAC) is preferred and may

concretions formation and delayed absorption.

probably reduce the concentration of initially absorbed

salicylates.
III- Enhancement of elimination:

 Salicylic acid is a weak acid, it will be ionized in the

A- Alkalinization of urine:

alkaline medium in the renal tubules. This prevents renal

reabsorption of the drug to the blood (urine pH is
maintained 7.5-8).
Alkalinization is done by I.V. administration of sodium

 It is indicated if serum salicylate concentration exceeds

bicarbonate.

 Monitor the serum pH keep it between 7.3-7.5. and

35 mg/dL.

 Monitor serum K+ as hypokalemia may occur. This is

avoid alkalemia.

because K+ ion is excreted by the kidney in exchange

with H+ ion to compensate for the alkalanization state,
also it is shifted intracellularly with extracellular shift of
H+ ion.
A- Hemodialysis:
Is indicated in cases of deterioration in spite of proper
management: e.g.
1. Salicylate concentration >100 mg/dL.
2. Renal failure.

 Cooling for hyperthermia.

IV- Symptomatic treatment:

 Milk is used as demulcent.

 76
 Cimetidine for peptic ulcer.
 Vitamine k or fresh blood transfusion for
hypoprothrombinemia.

PARACETAMOL
Paracetamol or acetaminophen is a popular analgesic
and antipyretic drug that is used for the relief of fever,
headaches and other minor pains. It is a major ingredient in
numerous cold and flu medications and many prescription
analgesics. It is remarkably safe in standard doses, but because
of its wide availability, deliberate or accidental overdoses are
not uncommon. Paracetamol, unlike other common analgesics
such as aspirin and ibuprofen, has no anti-inflammatory
properties. Paracetamol exerts its analgesic effect through
inhibition of prostaglandin synthesis.
Toxicokinetics and pathophysiology:
1. Even after overdose, the majority of paracetamol
absorption occurs within 2 hours.
2. Peak plasma concentrations generally occur within 4
hours.
3. Paracetamol is mostly converted to inactive compounds
by conjugation with sulfate and glucuronide, with a small
portion being metabolized via the cytochrome P450
enzyme system (CYP). The cytochrome P450 system
oxidizes paracetamol to produce a highly reactive
intermediary metabolite, N-acetyl-p-benzo-quinone
imine (NAPQI). Under normal conditions, NAPQI is
detoxified by conjugation with glutathione.
4. In cases of paracetamol toxicity, the sulfate and
glucuronide pathways become saturated, and more
paracetamol is shunted to the cytochrome P450 system
to produce NAPQI. Subsequently, hepatocellular supplies
of glutathione become exhausted and NAPQI is free to
react with cellular membrane molecules, resulting in
widespread hepatocyte damage leading to acute hepatic
necrosis.
 77
Toxic dose:
A single dose above 7.5 grams in adults or 150 mg/kg in
children have a reasonable likelihood of causing toxicity.
However, unintentional paracetamol overdose in children
rarely causes illness or death. This may be due in part to the
immature cytochrome P450 enzyme system in children.
Clinical picture of paracetamol toxicity:
The course of paracetamol toxicity generally is divided into 4
phases. Clinical evidence of end-organ (hepatic
or occasionally renal) toxicity is often delayed 24-48 hours
postingestion.
 Phase 1 (0-24 h) hepatic injury has not yet occurred and
laboratory indices of liver function are normal.
o The patient may be asymptomatic or has non specific
symptoms as:
o Anorexia.
o Nausea or vomiting.
o Malaise, pallor, diaphoresis.
 Phase 2 (24-72 h) represents the onset of liver injury
o Phase 1 symptoms become less evident or may
resolve.
o Aspartate aminotransferase (AST) elevation which
always precedes evidence of actual liver
dysfunction.
 Phase 3 (72-96 h) defined as the time of maximal
hepatotoxicity
o Abdominal pain.
o Jaundice.
o Coagulopathy.
o Hepatic encephalopathy.
o Nausea and vomiting.
o Renal failure.
o Oliguria.
o Laboratory indices of liver functions continue to
deteriorate.
 78
Fatalities from fulminant hepatic failure generally occur
between 3 and 5 days after an acute overdose.
 Phase 4 (4 d to 3 wk) defined as the recovery phase
o Complete resolution of symptoms and hepatic
regeneration.
Investigations:
I- Laboratory Studies:
1- Serum Paracetamol concentration: Should be measured
4 hours after a SINGLE ingestion after it reaches its peak
level.
2- Liver function tests:
1- Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) begin to rise within 24 hours
post ingestion and peak at about 72 hours. Toxicity
is defined as serum AST or ALT levels greater than
1000 IU/L.
2- Bilirubin level, Serum glucose, Prothrombin time
(PT) and international normalized ratio (INR)
3- Electrolytes and arterial blood gases: pH <7.3 is a bad
prognostic sign.
4- Kidney function tests.
Treatment:
I- Emergency measures ABCD.
II- Gastric decontamination:
o In general, however, gastric emptying is not a
consideration for patients with isolated paracetamol
overdose because of the very rapid GI absorption of
paracetamol and the availability of an effective antidote.
o Oral activated charcoal (AC) adsorbs paracetamol and
may be effective if the patient presents within 1-2 hours
of ingestion .antidote should be given at least half an
hour after the charcoal.
III- Antidote :
N-acetylcysteine (NAC) :
 79
o Is the drug of choice for the prevention and treatment
of paracetamol-induced hepatotoxicity.if given within 8
hour of ingestion.
Indications:
1) Ingestion of high toxic dose of the drug.
2) High serum toxic levels.
3) Elevated liver enzymes.
Oral Dose:
1. Loading dose: 140 mg/kg once; follow with maintenance
dose followed by maintainance dose of 70mg/Kg every 4
hours)
Continuous IV administration:
1- Loading dose: 150 mg/kg IV infused over 15 min
(diluted in 200 mL D5W) followed with maintenance
doses(50mg/kg over 4 hours follwed by 100mg/kg
over 16 hours.
Intravenouse NAC should be preferentially used in
cases of fulminant hepatic failure or intractable
vomiting and in pregnant patients.
IV- Supportive treatment:
1. Antiemetics: Emesis frequently is associated with
paracetamol toxicity.
2. Managing the hepatic injury, renal dysfunction, and
other manifestations.
3. Vitamin K may produce some improvement in
coagulopathy.
V- Liver transplantation.
Summary:
This chapter discussed salicylates and paracetamol
toxicity.
Salicylates are found in hundreds of over-the-counter
medications and in numerous prescription drugs. If aspirin
overdose is suspected, using a combination of symptoms,
signs, laboratory studies, and characteristic ABG findings, the
clinician can rapidly confirm significant salicylate ingestion.
Signs and symptoms of toxicity begin to appear when salicylate
 80
serum level is above 30 mg/dL. For treatment, institute
immediate alkalinization with sodium bicarbonate, achieve
gastric decontamination by orogastric lavage (if indicated), AC,
or MDAC (if indicated), and consider the need for hemodialysis
early in the course of management. As with all significant
overdoses, the airway, breathing and circulation should be
evaluated and stabilized as necessary. Dehydration and
concomitant electrolyte abnormalities must be immediately
corrected.
Paracetamol is remarkably safe in standard doses, but
because of its wide availability, deliberate or accidental
overdoses are not uncommon. Toxic dose of paracetamol is
150mg/kg.When managing paracetamol overdose,
measurement of serum concentration should be considered as
part of the patient's initial evaluation. Treatment with NAC
should be initiated as soon as possible and ideally within 8
hours from the time of ingestion.

Questions:
1. Explain the pathophysiology of acute salicylates toxicity.
2. Describe the clinical stages of acute paracetamol
toxicity.
3. Discuss the clinical picture of acute salicylates toxicity.
4. Give an account on the differential diagnosis of acute
salicylates toxicity.
5. Describe the needed investigations in a case of acute
salicylates toxicity.
6. Discuss the management of acute paracetamol toxicity.
 81

CHAPTER 5
Cardiovascular Drugs
ILOs:
By the end of this chapter the student should be able to:
K1: Enumerate the different modes of digitalis toxicity.
K2: Discuss the pathophysiology and the clinical picture of
toxicity of digitalis, beta blockers, nitrites and nitrates.
K3: Describe the management of toxicity of digitalis, beta
blockers, nitrites and nitrates.
K4: Solve problems revolving around virtual cases presenting
with toxicity of digitalis, beta blockers, nitrites and
nitrates.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
DIGITALIS
Introduction:
 Digitalis glycosides are found in Digitalis purpurea and

 Digoxin is the most commonly used digitalis preparation.

Digitalis lanata.

 It is used in the management of congestive heart failure

and atrial fibrillation.
Mode of toxicity:
1. Accidental in children
2. Suicidal
3. Chronic digoxin poisoning usually follow long standing
treatment in elderly patients with preexisting renal and
cardiac disease usually. It results from large doses of
digoxin relative to age, changing renal function,
concurrent diuretic administration which may produce
hypokalemia and hypomagnesemia.
Mechanism of toxicity:
 82
1. Cardiac glycosides produce reversible inhibition of
sodium-potassium (Na+-K+)-ATPase pump, which causes
increased intracellular sodium and decreased
intracellular potassium. Inhibition of Na+-K+-ATPase in
skeletal muscle results in increased extracellular
potassium and contributes to hyperkalemia.
2. At therapeutic doses, cardiac glycosides increases
inotropy.
3. Vagotonic effects, resulting in bradycardia and heart
blocks with toxic doses.
4. Prolongation of refractory period in AV node, shortening
of refractory periods in atria and ventricles, and
decrease resting membrane potential (increased
excitability) leading to various types of arrhythmias
whether atrial or ventricular, bradyarrhythmias, or
tachyarrhythmias.
Clinical Picture:
1. Cardiac manifestations (the most frequent) include
palpitations, bradycardia, any degree of heart block,
atrial and ventricular arrhythmias. Hypotension and
shock may ensue.
2. Gl symptoms (the first symptoms to evolve) include
nausea, vomiting, abdominal pain, diarrhea, and
anorexia.
3. Visual effects include blurred vision, abnormal color
perceptions of yellow or yellow-green halos may occur.
4. Others: headache, fatigue and weakness.
5. Hyperkalemia may occur in acute toxicity. (in chronic
toxicity hypokalemia may be seen due to the
concomitant use of K+ losing diuretics).
Investigations:
1. Electrolytes:
- Hyperkalemia is an early predictor of need for
antidotal therapy.
- Hypokalemia exacerbates chronic toxicity.
 83
- Hypercalcemia and hypomagnesemia exacerbate
cardiac glycoside toxicity.
2. Digoxin level:
- Therapeutic blood level is 0.6 – 2.1ng/ml.
- Concentrations exceeding 15ng/ml carry a serious
prognosis.
3. Renal functions:
- Renal impairment impairs elimination of glycosides.

 Look for bradycardia, heart block, atrial or ventricular

4. Electrocardiogram (ECG) and continuous cardiac monitor

 Nonspecific ST segment sagging and T wave

tachyarrhythmias.

 Peaked T waves may occur in hyperkalemia.

abnormalities are consistent with digitalis treatment.

Treatment:
I. Emergency measures (ABCD).
II. Prevent further exposure: Stop digoxin medications.
III. Continuous cardiac monitoring.

 Gastric lavage is of limited value. Gastric lavage

IV. Elimination:

increases vagal tone and may precipitate or worsen

arrhythmias. Consider pretreatment with atropine if

 Activated charcoal. Because of the enterohepatic

gastric lavage is performed.

circulation of digoxin and digitoxin, multiple-dose

 Cholestyramine will interrupt the enterohepatic

charcoal (1 g/kg) may be beneficial.

circulation.
V. Antidote (Digibind):
 84
Digoxin specific monoclonal antibodies (Fab
fragments) are effective for digoxin. Dose depends on
digoxin blood level or amount ingested and body weight.
The onset of action of Fab fragments may take 30-60
minutes. Monitor potassium level as hypokalemia may
occur due to reactivation of Na-K-ATPase.
Indications:
1. Serum digoxin level above 10 ng/ml in adults (>
5ng/ml in children)
2. Ingestion more than 10 mg in adults (4mg in children).
3. Hyperkalemia (> 5 mEq/L).
4. Heart block even 1st degree.
5. Life-threatening supraventricular and ventricular
arrhythmias.
6. Hemodynamically significant bradycardia
unresponsive to atropine.

 Atropine may be used in bradyarrhythmias.

VI. Treatment of complications:

 Phenytoin or Lidocaine for ventricular arrhythmias.

 Magnesium sulfate reverse digoxin-induced

 Cardiac pacing (temporary pacemaker) in serious

arrhythmias.

heart block if Fab fragments are not immediately

 Glucose, insulin, sodium bicarbonate,may be used to

available.

facilitate redistribution of potassium intracellularly in

life-threatening hyperkalemia (> 6.5 mEq/L) if Fab
fragments are not immediately available.
Avoid the following:


Calcium preparations.


Quinidine and procainamide.


Calcium channel blockers, beta-blockers.
Because of the large volume of distribution, diuresis,
hemodialysis and hemoperfusion do not increase
clearance. These procedures may lead to fluid
imbalance and exacerbate CHF.
 85
BETA BLOCKERS
They are used for the treatment of hypertension,
arrhythmia, coronary artery heart disease and management of
migraine.
Mechanism of action:
 They decrease adenylate cyclase and cAMP and leads to
decreased influx of sodium and calcium ions and

 Membrane stabilizing effects: results in depression of

produce negative inotropic and chronotropic effects.

myocardial contractility and conduction ( quinidine like

 High degree of lipid solubility: increases CNS

action).

penetration of drug and can result in CNS depression

and seizure activity.
Clinical effects:
1. Hypotension and bradycardia are common. Arrhythmias
PR interval prolongation with AV Block and prolongation
of QRS interval, cardiogenic shock, asystole may occur in
serious overdoses.

First degree heart block

Second degree heart block

2. Seizures, coma, respiratory depression or arrest.
3. Hypoglycemia may occur.
4. Hyperkalemia may occur.
5. Bronchospasm in asthmatic patients.
Investigations:
 86
1. ECG.
2. Serum electrolytes especially K level.
3. Serum glucose.
4. Arterial blood gases (ABGs).
5. Renal function tests.
6. Cardiac enzymes.
Treatment:
I- Emergency measures ABCD.

 Gastric lavage may be beneficial if the patient presents

II- GI Decontamination:

to the ED within 1-2 hours of ingestion. Pretreat with

 Activated charcoal should be administered routinely

atropine before lavage to avoid severe bradycardia..

after lavage.
III- Antidote (Glucagon):
It increases inotropic and chronotropic effects through a
non-adrenergic mechanism. Glucagon activates myocardial
adenylate clyclase which results in increased cAMP and
enhanced cardiac contractility. Dose: Initial adult dose: 50
µg/kg IV bolus over 1-2 minutes, followed by an infusion of 1-
5 mg/hr. beneficial effects can be seen within one minute of
dosing. However, larger doses may be needed to produce the
desired effect.

 Fluids: for hypotension.

IV- Specific management:

 Atropine is the first line treatment of clinically important

bradycardia and hypotension (e.g., symptomatic patients

 Catecholamines: Epinephrine and isoproterenol are of

with hypotension, confusion despite use of fluids).

very limited usefulness as beta blockers are extremely

 Sodium bicarbonate for treatment of ventricular

tightly bound to beta receptors.

dysrhythmias that occur with drugs with membrane-

 B- blockers should be differentiated from Ca channel

stabilizing effects.

blockers by the following:

 87
1) Ca channel blockers are agents that block slow Ca
channels of vascular smooth muscles and cardiac
muscles .They are mainly used for treatment of
hypertension and angina.
2) Acute toxicity is similar to B- blockers in which there is
bradyarrythmia, (sinus bradycardia) or any degree of
AV block. There is myocardial depression and
hypotension which is more frequent than in B-
blockers. Cardiogenic shock, seizures and coma are
end stage of acute poisoning. Unlike B-blockers
hyperglycemia may occur in Ca channel blockers
toxicity.
3) Treatment is as in B-blockers in addition; Ca chloride
10% 10-20 ml very slowly I.V. should given for
treatment of hypotension and myocardial depression.

NITRITES, NITRATES AND METHEMOGLOBINEMIA

(e-leaning)
CHAPTER 6
Theophylline
ILOs:
By the end of this chapter the student should be able to:
K1: Enumerate the different modes of theophylline toxicity.
K2: Discuss the mechanism of action and the clinical picture of
acute theophylline toxicity.
K3: Describe the management of acute theophylline toxicity.
K4: Solve problems revolving around virtual cases presenting
with theophylline toxicity.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
Introduction:
 Theophylline is derived from methylxanthines alkaloids.
 88
 It is used in many preparations for treatment of asthma
(Epicophylline – Theo. SR – aminophylline).
Mode of toxicity:
 It has narrow therapeutic margin (10-20 µg/ml) chronic
patients develop toxicity at lower serum level than acute

 Accidental: mainly iatrogenic or parent error. Serum

patients.

 Suicidal.
level monitoring during treatment is a must.

Mechanism of action:
1. Relaxation of smooth muscles(notably bronchial
muscle).
2. Stimulation of central nervous system.
3. Induction of dieresis.
4. Increases serum catecholamines.
5. Vasodilatation except for cerebral circulation.
6. Increases contractility of skeletal muscles.
7. Increases GIT secretions of HCL & pepsin.

Clinical picture of acute toxicity:

 Nausea, vomiting, diarrhea, abdominal pain and may be

I- GIT:

upper GIT bleeding.

 Agitation, restlessness.
II- CNS:

 Generalized seizures are the most concerning because

they are associated with increased mortality. Prolonged

 Coma may follow.

seizures can contribute to rhabdomyolysis.

 Tachyarrhythmias, sinus tachycardia is the most

III- Cardiovascular:

common, all other types of tachyarrhythmias may be

 89
present. Ventricular arrhythmias as ventricular

 Hypotension occurs in 25% overdoses.

fibrillation and cardiac arrest may occur.

 Hypokalemia (intracellular shift of K as a result of

IV- Metabolic:

increase level of catecholamines leading to activation of

 Hypophosphatemia.
NA. K ATPase).

 hypomagnesemia, and metabolic acidosis).

 Hyperglycemia.
 Metabolic acidosis.
These changes are due to theophylline-induced increase in
catecholamine releas.
Investigations:
1- Serum Theophylline level(Therapeutic level 10-20 µg/ml).
2- Serum electrolytes especially K level.
3- Serum glucose.
4- Arterial blood gases (ABGs) may show:
- Metabolic acidosis.
- Respiratory alkalosis due to stimulation of respiratory
center (early).
5- ECG.

Treatment:
I- Emergency measures (ABCD).
II- Elimination:
1- Induction of emesis is better avoided as it may lead to
intractable vomiting and delay administration of
activated charcoal.
2- Gastric lavage. It may be delayed in case of sustained
release preparations.
3- Activated charcoal given in multiple doses 20 g/2 hs to
40 gm/ 4 hours) decreases serum theophylline.
4- Hemodialysis or hemoperfusion in severe cases.
III- Symptomatic measures:
 90
 Treatment of arrhythmias: verapamil & beta blockers.
 Seizures (difficult to manage) 1st by diazepam if no
response, Phenobarbital and if no response use Na

 Treatment of hypokalaemia must not be aggressively

thiopental.

treated because redistribution of K occurs with decrease

of theophylline level.
Summary:
This chapter discussed acute theophylline toxicity
regarding the clinical picture and management.
Questions:
1- Describe the mechanism of action and the clinical
picture of acute theophylline toxicity.
2- Discuss the management of acute theophylline toxicity.
 91

CHAPTER 7
Psychotropic Drugs
ILOs:
By the end of this chapter the student should be able to:
K1: List the different types of psychtropic drugs.
K2: Discuss the pathophysiology and clinical picture of acute
intoxication with antipsycotics, antidepressants and
lithium.
K3: Explain the needed investigations and the different lines
of treatment of acute intoxicated cases with
antipsychotics, antidepressants and lithium.
K4: Discuss the new antidepressants.
K5: Solve problems revolving around virtual cases presenting
with acute intoxication with antipsychotics,
antidepressants and lithium.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
Definition:
They are group of drugs that exerts their effect on the
higher function of CNS. They change the mood, thinking,
behavior and emotions.
Classification:
I. psychotherapeutics:
1. Drugs used in the treatment of psychosis called neuroleptic
or antipsychotics e.g. phenothiazines (major tranquilizers is
the old name).
2. Drugs used in the treatment of anxiety called anxiolytic e.g.
benzodiazepines, meprobamate (minor tranquilizers in old
classification).
3. Drugs used in mood disorders: mood stabilizing drug
(lithium) and antidepressants (TCA, MAOI).
II. Psychostimulants:
Drugs increase the level of motivation e.g. amphetamine.
 92
III. Psychodysleptics: (hallucinogens): e.g. LSD, cannabis.
ANTIPSYCHOTICS
(Neuroleptics)
Uses:
1. Management of psychiatric illness.
2. Antiemetic.
3. Sedation.
4. drug-induced psychosis.

Mode of toxicity:
1. Accidental.
2. Suicidal.

Mechanism of action:
I. Receptor blockade:
1. Dopamine receptors blockade in the CNS (limbic system,
basal ganglia and hypothalamus).
2. Alpha adrenergic receptors blockade.
3. Cholinergic (muscarinic) receptors blockade (atropine
like action).
4. Histamine (H1) and 5HT receptors blockade (with
increase serotonin).
II. Cardiovascular effects:
Cardiovascular toxicity may occur during
therapeutic use and after overdose. These
manifestations are dose related and reversible.

 Dire t α lo ki g effect
1. Hypotension caused by:
peripheral

 Depression of the central vasomotor reflex.

vasodilatation.

 Direct myocardial depression.

2. Na+ channel blocking (Quinidine like action) and K+
channel blocking of the myocardium leading to
impairment of myocardial conduction and depressed
contractility. This is recorded as prolonged PR
 93
interval, QRS complex duration and QT interval with
resultant ventricular arrhythmias.

Clinical picture:
I. Acute toxicity:
A. CNS manifestations:
1. CNS depression, drowsiness, ataxia, stupor, coma and
respiratory depression.
2. Convulsions may occur.
2. Extrapyramidal manifestations:
a. acute dystonia: spasm of the muscles of tongue,
face, neck (torticollis) and back (opisthotonos)
b. Parkinsonism: mask face, rigidity, static tremors.
4. Hypothermia.
B. Cardiovascular manifestations:
1. Hypotension.
2. Sinus tachycardia secondary to hypotension and
anticholinergic effects.
3. Conduction abnormalities.
4. Arrhythmias e.g. premature ventricular contraction, V.
tachycardia or V. fibrillation
C. Anticholinergic effects:
Dry mouth, blurred vision, mydriasis, tachycardia
decrease intestinal motility and urine retention.
D. Eye manifestations:
Miosis (alpha adrenergic receptors blockade) or may
produce blurred vision due to mydriasis (cholinergic
receptors blockade).
E. Neuroleptic malignant syndrome:
It is a rare life-threatening adverse reaction to
antipsychotic agents. It is not a result of overdose but an
idiosynchratic reaction due to blockade of 5HT receptors.
Manifestations: - Hyperthermia.
- Stupor or coma.
- Muscular rigidity.
- Increased CPK level.
 94
- Myoglobinuria.
High mortality rate > 20%.
Investigations:
1- Arterial blood gases..
2- ECG.
3- Toxicological screen tests (for detection of
phenothiazines in urine).
Management:
I. Emergency measures (ABCD).

 Induction of emesis or gastric lavage (could be effective

II. Elimination:

for few hours after ingestion due to its delayed gastric

 Activated charcoal.
emptying effect.

 Hypotension: I.V. fluids and vasopressor e.g

III. Symptomatic treatment:

 Arrhythmias:
norepinephrine

1- Sodium bicarbonate ( 1-2 mEq/Kg) infusion is the first

line therapy for arrhythmias and is recommended for
patients with QRS complex duration greater than 100
ms.
2- Lidocaine, or DC chock, are second line
antiarrhythmics.

 Extra pyramidal manifestations respond to:

1. antihistaminics as Diphenhydramine (Benadryl).
2. Benzatropine (Cogentol).

 Parkinsonism: antiparkinsonian agents.

3. Diazepam.

 Neuroleptic malignant syndrome: diazepam (first choice as

it is effective) cools the patient, dantrolene (or any other
muscle relaxant).
ANTIDEPRESSANTS
These are drugs used for:
 95
1- Treatment of depression as they cause mood elevation
however in normal persons they cause sedation.
2- Treatment of enuresis.
They include: Monoamine oxidase inhibitors (MAOI) or tricyclic
antidepressants e.g. amitryptyline and imipramine.
Mode of toxicity:
- Accidental.
- Suicidal.
Route of intoxication through oral ingestion.
Tricyclic Antidepressants (TCA)
Mechanism of action:
I. Inhibition of neurotransmitter reuptake:
They decrease the reuptake of norepinephrine,
serotonin or both at presynaptic nerve terminal
II. Receptor blockade:
1- Muscarinic receptors: anticholinergic (atropine like)
effects central and peripheral.
2- Histamine (H1) receptors: sedation
3- Peripheral alpha1 adrenergic receptors: orthostatic
hypotension
III. Cardiovascular effects:
1- Conduction defects and arrhythmias as it has a direct
quinidine like effect
2- Hypotension due to direct myocardial depression,
peripheral vasodilatation and increased capillary
permeability
Clinical picture:
1. CNS:
Restlessness, agitation and seizures occur early in
the course of the disease due to atropine like effect
followed by depression delirium, confusion and coma
2. Anticholinergic effects:
Dry skin, dilated pupil, sinus tachycardia, urinary
retention, decreased bowel movement, constipation
and hyperthermia.
3. CVS:
 96
 Sinus tachycardia.
 Conduction defects and A.V block.
 Arrhythmias e.g. ventricular tachycardia, V.

 Hypotension.
fibrillation.

 ECG showed prolonged QRS complex > 100msec. The

QRS interval is a sensitive indicator of toxicity
(convulsions and arrhythmias).
Investigations:
1- Arterial blood gases.
2- ECG monitoring.
3- Toxicological screen test for detection of TCA in urine.
Management:
I. Emergency measures (ABCD).
II. Continuous cardiac monitoring.

 Gastric lavage (may be useful after many hours

III. Elimination:

 Activated charcoal (MDAC) as they have

of ingestion for its anticholinergic effect).

enterohepatic circulation if no ileus is present.

IV. Specific measure:

 It is the 1st line of treatment for TCA induced conduction

Alkalinization of serum:

defects, arrhythmias, hypotension and to correct the

acidosis. It is recommended for QRS duration more than

 1-2 mEq/kg of NaHCO3 is given as a bolus over several

100 msec.

minutes followed by repeated doses or NaHCO3 drip

till disappearance of manifestations of cardiotoxicity.
V. Symptomatic treatment:
1- Arrhythmias: (alkalinization followed by lidocaine, DC
shock).
2- Heart block: alkalinization and pacemaker for 3rd
degree H.B.
3- Hypotension: IV fluids + pressor agents with direct
alpha adrenergic activity e.g. norepinephrine.
 97
4- Hyperthermia: cool the patient.
New Antidepressants
These newer antidepressants have become the most
commonly used antidepressants replacing the older TCAs as first
line treatment of depression due to their selective action and less
side effects.
Examples of Specific serotonin reuptake inhibitors (SSRIs):
Fluoxetine (Prozac), sertraline, paroxetine and fluvoxamine
Lithium
(E-learning)

Summary:
This chapter discussed psychotropic drugs regarding
their different types. It also discussed the pathophysiology,
clinical presentation and management of some examples of
psychotropic drugs namely antipsychotics, antidepressants.
Questions:
1. Enumerate the different types of psychotropics.
2. Discuss the mechanism of action of antipsychotics.
3. Describe the management toxicity with tricyclic
antidepressants.
4. Give an account on new antidepressants.
 98

CHAPTER 8
Sedative Hypnotics
ILOs:
By the end of this chapter the student should be able to:
K1: List types, clinical uses, mode and route of toxicity of
barbiturates and benzodiazepines.
K2: Describe the pathophysiology of acute toxicity with
barbiturates and benzodiazepines and correlate it with
the clinical picture.
K3: Describe the clinical picture and differential diagnosis of
acute toxicity with barbiturates and benzodiazepines.
K4: Discuss the proper management procedure of cases of
acute toxicity with barbiturates and benzodiazepines.
K5: Enumerate the possible complications of acute
barbiturates toxicity.
K6: Solve problems revolving around virtual cases presenting
with acute barbiturates and benzodiazepines toxicity.
A1: Realize the importance of urgent appropriate treatment
in cases of acute intoxication.
A2: Realize the importance of working in groups.
Introduction:
 Sedative-hypnotic agents are commonly prescribed drugs
used for a variety of indications including the treatment of
restlessness, insomnia, seizures, alcohol withdrawal and
induction of anesthesia. Some members of this group are

 Sedative – hypnotic group can be divided into barbiturate

used as well, as muscle relaxants, anti-epileptics.

and nonbarbiturates (benzodiazepines, chloral hydrate,

meprobamate)
 99
BARBITURATES
They act as hypnotic, antiepileptic or anesthetic
depending on their liposolubility, distribution, binding to tissue
proteins and metabolism.
Tissue Duration
Binding of action
Generic and Onset
Type & Lipid in Uses
Trade names (h)
Solubilit therapeuti

 Hypnotic
y c doses (h)

 Antiepilepti
Phenobarbit
 Mixed with
c
Long acting al
Least 2 -4 12 -18
Barbiturate (Sominal -
other
Gardenal)
medications

 Hypnotic
.

Intermediat  Mixed with

e Amobarbital + other
acting medications

 Hypnotic
.

 Mixed with
Pentobarbita
l (Nembutal )
Secobarbital other
Short acting ++ 1/4-1/2 2-4
( Illegally medications
sold as .


Farawla )
Induct
Ultra-short Thiopental Immediat Few
+++ ion of
acting ( Pentothal) e minutes
Anesthesia.

Mode of toxicity:
1. They are common suicidal agents.
2. Accidental over-dosage may occur in children.
3. Overdose by dependent subjects.
4. They lead to automatism (where the patient repeats the
ingestion several times till toxic levels).
Metabolism:
1. Phenobarbital and Barbital (long acting) have the least
lipid solubility and tissue protein binding explaining the
comparatively less intense and less rapid hypnotic
action. They are minimally metabolized in the liver and
 100
are excreted unchanged in the urine, hence a relatively
longer duration of action.
2. On the opposite, short and ultra short acting BBI have a
rapid and high lipid solubility and tissue protein binding,
hence a rapid and intense action with short duration of
action. They are highly metabolized in the liver, and only
metabolites will appear in urine.
Pathophysiology:
Barbiturates inhibit neuronal depolarization by
potentiating and prolonging the actions of GABA leading to:
1. CNS Effects: Direct effects include sedation and
hypnosis at lower dosages. The lipophilic barbiturates
(thiopental) will cause rapid anesthesia because of their
tendency to penetrate brain tissue quickly.
2. Depression of the medullary respiratory center and
respiratory depression.
3. Hypotension follows depression of the medullary
vasomotor centers.
Clinical picture of acute toxicity:

 Very rapid (15 min) after short acting barbiturates.

Onset:

 Delayed (1-2 h) after long acting barbiturates.

 Confusion and decreased deep tendon reflexes.

Manifestations:

 Coma: It is the major sign of acute massive

intoxication. Grading of coma is correlated with the

 Respiratory depression: Results in hypoventilation and

blood level of barbiturates.

apnea especially with short acting barbiturates. It may

be of very rapid onset (half an hour) and may cause

 Hypotension: severe shock may occur following

death if the patient is late in reaching hospital.

 Hypothermia.
prolonged anoxia or delayed CPR.

Complications:
 101
1. Respiratory arrest followed by hypoxic encephalopathy
or irreversible brain damage or death.
2. Renal Insufficiency: severe dehydration or following
shock. Barbiturates per se are not nephrotoxic but
renal insufficiency will follow complications.
3. Mendelson's Syndrome: It follows spontaneous
vomiting or regurgitation of the acidic fluid contents of
the stomach and its aspiration in the respiratory tract
in deeply comatose patients. It results in extensive
destruction of the alveolar membrane. Clinically the
patient develops non cardiogenic pulmonary edema
and may progress to ARDS ( Adult Respiratory Distress
Syndrome ).
4. Rhabdomyolysis: Ischemic lysis of compressed muscles
and overlying skin over the pressure points in deep
prolonged coma.
5. Cutaneous blisters in severe cases. These are bullous
lesions that are typically found on the dependant part.
Differential diagnosis:
All agents inducing C.N.S depression.
1. Sedative hypnotics.
2. Opiates.
3. Alcohol.
4. Co intoxication.
Investigations:
1. Arterial blood gases (ABGs).
2. Renal functions.
3. Serum barbiturate concentrations (phenobarbital)
should be quantified to determine treatment and its
efficacy once initiated (e.g., urinary alkalinization,
multi-dose charcoal, and hemodialysis).
4. Urine drug screen for diagnosis of barbiturate and
other drugs.
Treatment:
I- Stabilization of the patient (ABCD).
II- Elimination:
 102
1. Emesis should be avoided as patient is in impaired
consciousness.
2. Gastric lavage with protected airway by cuffed ETT.
Delayed gastric lavage may be useful if there is
decreased bowel movement.
3. Activated Charcoal: as a single dose. Or MDAC increase
the efficacy of adsorption of residual drug should be
avoided in ileus .
III- Enhancement of excretion:
1. Alkalinization of urine: It helps elimination of long
acting barbiturates. It is also of great help in
Rhabdomyolysis. It is of no value in intermediate
and short acting barbiturates.
2. Hemodialysis (HD): It is 4 - 6 times more effective
than urinary alkalinization. It is of particular
interest in associated acute renal failure.
However HD is not useful in short acting
Barbiturates.
3. Hemofiltration: Is more effective than HD and is
recommended in patients with heart failure with
or without pulmonary edema or renal
insufficiency.

 Treatment of rhabdomyolysis.
IV- Supportive measures:

 Treatment of pulmonary complications.

BENZODIAZEPINES
Introduction:
 This group of drugs has greatly expanded over the last
two decades and has replaced the older sedatives. They
are of variable potency and are responsible for millions of

 They are used as sedatives (Anxiolytics), hypnotics,

cases of misuse and dependence all over the world.

muscle relaxants, antiepileptics as well as anesthetics

depending on the rapidity, intensity and duration of
action.
 103
 Children and geriatric patients are particularly vulnerable
to the effects of Benzodiazepines.
Mode of toxicity:
1. Suicidal is usual in adolescents.
2. Criminal to facilitate robbery and rape (short acting
drugs).

 Overdose by inexperienced drug users.

3. Accidental:

 In elderly with low tolerance to CNS depressants.

Route of toxicity:
 Benzodiazepines are usually taken in pill form, also can
be injected into the veins or muscles.
Pathophysiology:
 They stimulate GABA b receptors (GABA = Gamma
Amino Butyric Acid) of nerve cells reducing potential
difference across cell membrane , hence blocking cells
ability to conduct nerve impulse.
Common Benzodiazepines:
Generic name & Therapeutic dose ( mg ) Trade name
Diazepam 10 Valium
Chlordiazepoxide Librax
Alprazolam 0.25 – 0.5 Xanax
Bromazepam 1.5 Lexotanil
Lorazepam 1 Ativan
Clonazepam 2 Rivotril
Flunitrazepam 1 – 2 Rohypnol (Abou saliba)
Midazolam 5 Dormicum

Clinical picture:
 Less severe toxic effect than barbiturates and the
patient presents with disturbed conscious level
associated with less likely affected vital signs.
Treatment:
I- Emergency measures (ABCD).
II- Elimination.
III- Antidote:
Flumazenil (Anexate):
 104
 It is a nonspecific competitive antagonist for
Benzodiazepine acting on GABA receptor. It reverses

 Dose: 1 – 2 mg IV slowly given under monitoring.

coma and amnesia.

 Contraindications
o Mixed overdose with antidepressants or anti-
asthmatic preparations (serious seizure may occur).
o Benzodiazepine dependence as flumazenil is
arrythmogenic.

Summary:
CNS drugs are a common component of home drug
cabinets and thus are common toxic agents in children and in
suicide victims. Barbiturates and benzodiazepines are drugs
hi h depress or slo do the od ’s fu tio . O er dosage
causes C.N.S depression and leads to coma and respiratory
failure.

Questions:
1) Anesthetic action of barbiturate depends on:
a) Metabolism.
b) Liposolubility.
c) Distribution.
d) All the above.
2) Hypotension result from barbiturate toxicity occur due to:
a) Direct action on blood vessels.
b) Depression of the medullary vasomotor centers.
c) Direct inhibition on C.V.S.
d) All the above.
3) Barbiturate toxicity induced renal insufficiency due to
except:
a) Severe dehydration.
 105
b) Shock.
c) Nephrotoxicity.
d) All the above.
4) Bullous lesions are found in poison due to:
a) Diphenyl hydantoin.
b) Benzodiazepine.
c) Barbiturates.
d) Carbamazepine.
5) Forced alkaline dieresis (F.A.D) Is helps in elimination of:
a) Long acting barbiturate.
b) Ultra- short acting barbiturate.
c) Benzodiazepine.
d) All the above.
6) Role of Flumazenil in acute B.Z.D toxicity is:
a) Reverse respiratory center depression.
b) Reverse C.N.S depression.
c) Improve glucose metabolism.
d) Used as primary management of comatose patient.
7) All the following statements are true about B.Z.D except:
a) They are the single most widely used group of C.N.S
sedatives.
b) B.Z.D selectively depress polysynaptic pathways within
the C.N.S.
c) Effects of B.Z.D overdose are more prominent on
cognition than on motor function.
d) Cross-tolerance with ethanol and barbiturates may
occur.
8) Flumazenil can cause convulsions if:
a) Taken with cyclic antidepressants.
b) Patient addict on B.Z.D.
c) Patient with history of epilepsy.
d) All of the above.
 106

CHAPTER 9
Anticonvulsants
ILOs:
By the end of this chapter the student should be able to:
K1: List the uses of phenytoin and carbamazepine.:.
K2: Discuss the clinical presentation of acute toxicity of
phenytoin and carbamazepine.
K3: Explain the lines of management of acute toxicity of
phenytoin and carbamazepine.
K4: Solve problems revolving around virtual cases presenting
with acute and chronic toxicity of phenytoin and
carbamazepine.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
PHENYTOIN
Uses:
1. Oral phenytoin is used to treat grand mal epilepsy.
2. Intravenous phenytoin is used to treat status epilepticus
and arrhythmias.
Clinical picture of acute toxicity:
I- Oral toxicity:
Nystagmus, ataxia and dysarthria.
1. GIT irritation may be seen.
2. Hyperglycemia due to inhibition of insulin release.
3. Convulsions (if occur, they are most probably due to co-
existing factor as anoxia or other co-ingestions).
4. Stupor, coma and respiratory arrest.
II- Intravenous toxicity:

 Profound hypotension, bradycardia and cardiac arrest

Rapid intravenous injection leads to (cardiac effects):

(these effects are caused by the propylene glycol

diluent that is used with phenytoin, so IV infusion must
 107
be done slowly at a maximum rate of 50mg/min and
patients must be observed continuously especially
blood pressure and ECG monitoring.
Investigations:
1. Serum level monitoring (therapeutic serum level is 10-
20 mg/L).
2. ECG monitoring (during intravenous infusion).
3. Electrolytes, glucose, liver and kidney function tests.
Treatment:
I- Emergency measures (ABCD).
II- Elimination:
1. Induction of emesis.
2. Gastric lavage.
3. Activated charcoal MDAC (due to prolonged
absorption).
III- Supportive treatment.
CARBAMAZEPINE
Carbamazepine "Tegretol" is related structurally to TCA.
Uses (only oral preparations are available):
1. Trigeminal neuralgia.
2. Antiepileptic.
3. Manic depressive patients.
4. Drug withdrawal reactions.
Clinical picture of acute toxicity (Unpredictable clinical
course):
1. Nystagmus, ataxia and dysarthria followed by lethargy,
coma and respiratory arrest.
2. Fluctuations in level of consciousness are common.
3. Seizures in non-epileptic patients and seizure
deterioration in epileptic patients.
4. Tachycardia, hypotension and cardiac conduction
abnormalities.
5. Anticholinergic manifestations.
6. In children: higher incidence of dystonic reactions,
choreoathetosis and seizures with lower incidence of
 108
ECG changes.
Investigations:
1. Serum level monitoring (therapeutic serum level is 4-
12 mg/L).
2. ECG monitoring.
3. CBC, electrolytes and glucose.
Treatment of Acute toxicity:
I- Emergency measures (ABCD).
II- Elimination:
1. Induction of emesis or gastric lavage
2. Activated charcoal MDAC (due to slow absorption
caused by the anticholinergic effect of the drug,
enterohepatic circulation and formation of
concretions).
3. Hemoperfusion.
III- Symptomatic treatment:
1. Cardiac monitoring and management of arrhythmias
2. Convulsions are treated by benzodiazepines.

Summary:
This chapter discussed two examples of anticonvulsant
drugs, namely phenytoin and carbamazepine. They both have
acute and chronic toxicities. MDAC is the main line of
elimination as they are both slowly absorbed.
Questions:
1. Describe the clinical presentation of acute and chronic
phenytoin toxicity.
2. Discuss the management of acute carbamazepine
toxicity.
 109

CHAPTER 10
Toxic Gases
ILOs:
By the end of this chapter the student should be able to:
K1: List the different sources of carbon monoxide, cyanide
and hydrogen sulphide.
K2: Enumerate the factors affecting carbon monoxide toxicity.
K3: Explain the pathophysiology of carbon monoxide, cyanide
and hydrogen sulphide poisonings.
K4: Discuss the clinical picture of acute carbon monoxide,
cyanide and hydrogen sulphide poisonings as well as the
delayed clinical manifestations.
K5: Describe the management of carbon monoxide, cyanide
and hydrogen sulphide poisonings.
K6: List the differential diagnosis of acute carbon monoxide
poisoning.
K7: Solve problems revolving around virtual cases presenting
with carbon monoxide, cyanide and hydrogen sulphide
poisonings.
A1: Realize the importance of time factor as well as the
appropriate treatment in managing acutely intoxicated
patients.
A2: Realize the importance of working in groups.
Introduction:
Toxic gases tend to interfere with one or more of the
four phases of oxygen delivery. Toxic gases include chemical
asphyxiants which are gases that prevent oxygen use by the
body's tissues, even though enough oxygen is inhaled. Carbon
monoxide, hydrogen sulphide and cyanide are chemical
asphyxiants
CARBON MONOXIDE
Carbon monoxide (CO) is a significantly toxic gas with
poisoning being the most common type of fatal poisoning in
many countries.
 110

Physical properties:
Carbon monoxide is colorless, odorless, tasteless and
nonirritating, making it difficult for people to detect "Silent
Killer". Its density (0.968 relative to air) allows it to disperse
homogeneously within a room as it is released
Sources:

 Normally the body produces small amount of CO

1. Endogenous:

 Carboxyhemoglobin (COHb) normally dose not

during catabolism of protoporphyrin ring of Hb.

exceed 4-6%.

 Incomplete combustion of carbonaceous materials:

2. Exogenous:

Carbon monoxide is a product of combustion of

organic matter under conditions of restricted oxygen
supply, which prevents complete oxidation to carbon
dioxide (CO2) .Carbon monoxide poisoning, occurs

 Motor vehicle exhaust.

after the inhalation of carbon monoxide gas.

 At home, defective oil and gas heaters, kerosene

 Tobacco cigarette smoking.

heaters charcoal grills all emit CO.

 Fires: CO is the most common hazard to smoke

inhalation victims.
Factors affecting CO Toxicity:
1. Physical factors: CO is tasteless, odorless, colorless and
non-irritating so not noticed.
2. Duration of exposure.
3. Concentration of the gas in the inspired air.
4. Muscular activity of the person.
5. Decreased PO2 as in high altitude.
6. Individuals with cardiovascular or pulmonary disease
tolerate CO intoxication poorly.
7. Lowered Hb% as in anemia.
 111
8. Neonates and fetus are more vulnerable to CO toxicity
because fetal Hb has increased affinity to CO.In addition;
fetal elimination of CO is much slower than that of the
mother. Also there is a natural leftward shift of the
oxyhemoglobin dissociation curve which causes
decrease in O2 delivery to tissues.
9. Smokers will have higher carboxyhemoglobin levels than
non-smokers and therefore facing higher risk from
carbon monoxide exposures.
Mode of Poisoning:
 Accidental.
 Suicidal.
Pathophysiology:
1. CO binds to Hb with affinity 200-250 times greater than

 CO causes leftward shift of the oxyHb dissociation

that of O2.

curve, thus decreasing unloading of O2 from Hb to

 The net effect of these processes is the decreased

tissues.

ability of the blood stream to carry O2 and release it

to cells. Organs with increased O2 demands, as brain

 CO toxicity cannot be attributed solely to COHb

and heart, are more susceptible.

mediated hypoxia as there is poor correlation

between COHb levels and clinical effects or delayed
neurological deficits.

 Myoglobin functions as short O2 reservoir. In

2. Myoglobin impairment:

addition, myoglobin facilitates O2 transport and

 Myoglobin affinity to CO is 40 -60 times greater than

diffusion from blood stream to mitochondria.

that to O2. Also, in cases of CO poisoning, there is

 In the heart, carboxymyoglobin causes direct

leftward shift of oxymyoglobin dissociation curve.

myocardial depression and arrhythmias.

3. Binding to cytochrome oxidase:
 112
 This leads to inhibition of cellular respiration with
ineffective tissue utilization of oxygen leading to
tissue anoxia

 NO is a potent smooth muscle relaxant and causes

4. Nitrous oxide (Endothelial derived relaxation factor):

vascular dilatation and hypotention.CO causes

displacement of NO from heme containing proteins

 This effect of CO is transient and explains the

in the platelets.

transient nature of hypotension occurring with CO

syncope. So, CO induced vasodilatation and
carboxymyoglobin induced cardiac depression result

 The neurological effects of CO correlate with the

in hypotension.

degree of hypotension.
Clinical picture:
I- Acute toxicity:
The earliest symptoms of carbon monoxide poisoning,
especially from low level exposures, are often non-specific and
readily confused with other illnesses, typically flu-like viral
syndromes with the most frequent exposures occurring during
winter, it is not surprising that influenza is the most common
misdiagnosis. If suspected, the diagnosis can be confirmed by
measurement of blood carboxyhemoglobin.
The main manifestations of poisoning develop in the
organ systems most dependent on oxygen use: the central
nervous system and the heart.

 Symptoms are directly related to the level of cerebral

A. Neurological effects:

hypoxia and hypoperfusion and not necessarily to the

 Symptoms of mild intoxication include throbbing

level of carboxyhemoglobin

headache (due to reflex cerebral vasodilatation 2ry to

 More significant intoxications result in cognitive

hypoxia) dizziness and nausea

impairment, ataxia, visual and auditory abnormalities,

confusion, convulsions, and coma.
 113

 Tachycardia, hypotension, arrhythmias, conduction

B. Cardiovascular complications:

 Patients with cardiac disease show manifestations at

abnormalities, angina up to myocardial infarction.

lower levels of COHb.

 Tachypnea and pulmonary edema (either cardiogenic

C. Pulmonary complications

or non-cardiogenic).

 Cherry-red skin coloration rarely occurs after excessive

D. Dermatologic complications:

exposure due to CO-induced vasodilation with

 Coetaneous bullae following severe exposures. These

concomitant tissue ischemia.

bullae due to pressure necrosis and direct CO effects

in the epidermis.

 Blurred vision decreased light sensitivity, decreased

E. Ophthalmologic complications:

dark adaptation and retinal affection.

 Rhabdomyolsis (hypoxia of muscles) which may lead to

F. Effect on muscles:

myoglobinuria and rarely renal failure.

 It is a severe form of secondary deterioration

G. Delayed neuropsychiateric sequel:

characterized by appearance of signs of neurological

 Delayed neuropsychiatric sequaelea: may be preceded

or psychiatric impairment.

by a lucid period of 2-40 days after the initial CO

 C/P- Dementia, memory problems, psychosis, gait

poisoning.

disturbance, Parkinsonism, paralysis, chorea,

peripheral neuropathy and incontinence. Other
neuropsychiatric problems include depression,
emotional liability, hallucinations, and personality

 Children may show behavioral changes and learning

changes.

difficulties after severe poisoning.

 114
 Age>30 years, loss of consciousness and neurological
abnormalities in the acute phase of toxicity may
indicate a greater chance of developing delayed

 Recovery only occurs in 50% of patients.

symptoms.

II. Chronic low level exposure to CO:

Long term, repeated exposure represent a greater risk
to persons with coronary heart disease, atherosclerosis,
cerebral changes and pregnant patients. Chronic exposure may
increase the incidence of cardiovascular symptoms in some
workers, such as motor vehicle examiners, firefighters and
welders. Patients often complain of persistent headache,
lightheadedness, depression, confusion and nausea. Upon
removal from exposure the symptoms usually resolve.
Investigations:

 This is the most useful diagnostic test in suspected

1. Carboxy hemoglobin(COHb) level in blood:

CO poisoning (normal range 0-5%, smokers may

have range up to 10%.

 Early it shows respiratory alkalosis.

2. Arterial blood gases (ABG):

 Metabolic acidosis which is more reliable index for

severity than COHb.
3. ECG and cardiac monitoring are essential to detect
ischemia and dysrhythmias.
4. Cardiac enzymes (CPK, Troponin, LDH and SGOT).
5. Chest x-ray (pulmonary edema in severe cases).
6. Others: CBC (to rule out the occurrences of hemolytic
anemia) and renal function.
7. CT brain and MRI especially in patients with CO
exposure that resulted in loss of consciousness.
Abnormal findings indicate poor prognosis.
Treatment:
1. First aid for carbon monoxide poisoning is to
immediately remove the victim from the exposure
 115
without endangering oneself, call for help, and begin
CPR if needed.
2. The main medical treatment for carbon monoxide
poisoning is breathing 100% Oxygen by a non
rebreathable tight fitting oxygen mask or endotracheal
tube. Oxygen hastens the dissociation of carbon
monoxide from hemoglobin decreasing CO half life from
mean of 5hrs to about 1hr.
3. Hyperbaric Oxygen (2 Atmospheric pressure) is also
used in the treatment of CO poisoning; hyperbaric
oxygen also increases carboxy-hemoglobin dissociation
and does so to a greater extent than ambient oxygen.
Hyperbaric Oxygen decreases CO half life to about 20
min.It may prevent delayed neurological sequaelae.It
may also facilitate the dissociation of CO from
cytochrome oxidase.
Indications of hyperbaric oxygen
o Altered mental status or confusion.
o Carboxy-hemoglobin >25%.
o Fetal distress in pregnancy.
4. Specific treatment for other complications such as
seizures , cardiac abnormalities (e.g. antiarryhthmic
drugs), pulmonary edema, cerebral edema
(prednisolone 1mg/kg IV every 4 hours + Mannitol 20%
1 mg /kg over 20 minutes ) , coma and acidosis may be
required
5. Consider associated exposure to other toxic gases (as
cyanide) in cases of smoke inhalation.
Differential diagnosis:
There are many conditions to be considered in the
differential diagnosis of carbon monoxide poisoning. The
earliest symptoms, especially from low levels of exposures are
often non-specific and readily confused with other illnesses,
typically flu-like viral syndromes ,food poisoning ,depression
,chronic fatigue syndrome, chest pain and migraine or other
headaches. Carbon mono ide has ee alled a great
i i ker due to the prese tatio of poiso i g ei g di erse
 116
and non-specific. Other conditions included in the differential
diagnosis include acute respiratory distress syndrome, altitude
sickness, lactic acidosis, diabetic ketoacidosis, meningitis,
methemoglobinemia, or opioid or toxic alcohol poisoning.
Prevention:
1. Public education on the safe operation of appliances,
heaters, fireplaces and internal combustion engines.
2. Installation of CO detectors.
3. Early diagnosis prevents much of the morbidity and
mortality associated with CO poisoning.
CYANIDE
Sources, forms and exposure:
 Cyanide gas inhalation occurs mainly due to smoke

 Exposure to cyanide may occur in industry such as metal

inhalation in fires

 Rarely suicidal cyanide ingestion by lab workers and

trade, mining, jewelry manufacturing.

 Cyanogens are substances that release cyanide during

health care providers.

 Cynide can bne absorbed by all routes

metabolism, as sodium nitroprusside

Pathophysiology:
 Its principal toxicity results from inactivation of
cytochrome oxidase, the terminal enzymes involved in
aerobic metabolism. Inhibition of this enzymes results in
the shift of cellular metabolism from aerobic to
anaerobic and inhibiting cellular respiration, even in the
presence of adequate oxygen stores (histotoxic
anoxia).The most sensitive organs to hypoxia are the
heart and the brain.
Clinical picture:

 There is no reliable pathognomonic toxic syndrome

Acute toxicity:

associated with cyanide poisoning (Diagnosis is easier if

 117
related to the setting of poisoning e.g. sudden collapse

 Onset of symptoms is Seconds in inhalation of gaseous

in laboratory or industrial worker).

cyanide, or delayed (3-24 hours): in cyanogenic

chemicals that require bioconversion to cyanide before
the onset of effects.

 Symptoms reflect progressive hypoxia including

A. Neurological effects:

headache, confusion, lethargy, convulsions and coma.

 Initially cardiovascular responses to cyanide include

B. Cardiac effects:

bradycradia and hypertension followed by

 The terminal event is consistently bradycradia and

hypotension and reflex tachycardia.

hypotension.

 Initial centrally-mediated tachypnea followed by

C. Pulmonary effects:

 Cardiogenic pulmonary edema & acute lung injury.

bradypnea.

 Gastritis, nausea, vomiting and abdominal pain occurs

D. Gastrointestinal effects:

due to ingestion of corrosive cyanide salts.

 Production of an odor of bitter almonds (this is not

E. Miscellaneous effects:

reliable finding and unrecognizable by many

 Venous oxygen saturation due to decreased tissue

personnel even chemist)

extraction may be manifested by red colored veins of

the fundus and rarely cherry red coloration of the
skin.

 Survivors of serious acute poisoning may develop

F. Delayed clinical manifestations:

 Parkinsonian symptoms including dystonia, rigidity,

delayed neurologic sequaelae.

dysarthria and bradykinesia typically develop over

 118
weeks or months and these symptoms may progress
or resolve.
Investigations:

 Metabolic acidosis and elevated lactate due to

1. Arterial blood gases:

 Oxygen saturation is not altered except when

blockade of aerobic metabolism.

 Elevated venous oxygen saturation.

respiratory failure occurs.

 Can confirm exposure, but it is not usually rapidly

2. Cyanide determination in the blood:

available.
Treatment:
1. First aid airway patency, ventilator support, and
oxygenation 100% oxygen. If CPR is needed, do not give
mouth-to-mouth resuscitation without a barrier.
2. Cyanide antidote:
Nitrites + thiosulfate ± hydroxycobalamin (cyanide kite).
Mechanism of action of antidote: Sodium nitrite
works by inducing methemoglobinemia. The ferric iron
in methmoglobin combines with cyanide producing
cyanomethemoglobin. This drives the reaction towards
cyanomethemoglobin and liberates cyanide from
cytochrome oxidase.

 Thiosulfate provides sulfur which binds to cyanide

3. Detoxification of circulating cyanide:

producing thiocyanate (mediated by rhodanese

enzyme). Thiocyanate is a minimally toxic substance

 Hydroxycobalamin provides cobalt which combines

which is eliminated renally.

to cyanide to form relatively non-toxic

cyanocobalamin.

 Acidosis: adequate ventilation

4. Specific treatment for complications:
and sodium
bicarbonate administration.
 119
 Hypotension: I.V. crystalloids and vasopressor.
 Seizures.
 Arrhythmias.
HYDROGEN SULPHIDE (H2S)
Introduction:
Hydrogen sulphide is colorless gas, with an irritating
odor of rotten eggs. It is highly lipid soluble (allowing easy
penetration through biological membranes).
Hydrogen sulphide poisoning is not common.
Sources:
It is product of bacterial decomposition of proteins
(decay of organic matter) and from mixture involving sulphur
acids. It is also produced by industrial activities such as
petroleum distillation, leather industry. It is a common risk in
sewage workers.
Pathophysiology:
Systemic toxicity results from inhibition of cytochrome
oxidase even with higher affinity than cyanide but this is
spontaneously reversible.

Clinical picture:
A- Acute toxicity:
Diagnosis should be suspected whenever a person is
found unconscious in a closed space especially with the odor of
rotten eggs.
The primary target organs are central nervous system
and respiratory system.

 Headache, dizziness, convulsions, and coma.

A. Central nervous system

B. Cardiovascular
 120
 Hypotension, tachycardia, arrhythmias then
bradycardia and arrest.

 Nausea and vomiting.

C. Gastrointestinal

 Dyspnea, respiratory depression, cyanosis and may be

D. Respiratory

pulmonary edema.

 Erythema and cyanosis.

E. Dermal

 Involves memory failure, disorientation, delirium,

F. Delayed neuropsychiatric sequelae

dementia, transient hearing impairment, visual loss,

 Motor symptoms resulting in ataxia, tremors and

and anosmia.

muscle rigidity due to basal ganglia damage.

Diagnosis:
H2S toxicity should be suspected in any person found
unconscious in an enclosed space especially if the odor of
rotten eggs is noted.
Investigation:

 Metabolic acidosis and elevated lactate due to

1. Arterial blood gases:

 Oxygen saturation is not altered except when acute

blockade of aerobic metabolism.

 Elevated venous oxygen saturation.

lung injury occurs.

 Can confirm exposure.

2. Sulphide determination in the blood:

 Not readily available.

 Whole blood sulphide greater than 0.05 mg /l is
considered abnormal.

 Chest radiography
3. Imaging Studies:

Chest radiographic findings initially may be

normal, but up to 20% of patients present with
evidence of acute lung injury (ARDS).
 121
Treatment:
1. First aid is to move victim to fresh air and focus
attention to airway patency, ventilator support,
administer high flow oxygen as soon as possible.
2. Cyanide antidote: nitrites
Mechanism of action of antidote: Nitrite-induced
methemoglobin binds to sulfide ions removing them
from cytochrome oxidase.

 Acidosis: adequate ventilation and sodium

3. Specific treatment for complications:

 Hypotension: I.V. crystalloids and vasopressor.

bicarbonate administration.

Summary:
 Unintentional exposure to CO can easily be
misdiagnosed. CO should be suspected in any patient
with coma, acidosis, or signs of cardiac ischemia,
especially if attempted suicide is suspected. Fire victims,
in addition to suffering airway problems and potential
cyanide toxicity, may die of CO toxicity. COHb blood

 In all these cases, the mainstay of treatment is good

level is the main diagnostic test.

supportive care with early oxygenation to increase CO

 Both cyanide and hydrogen sulfide are high-risk

elimination.

industrial agents. Industrial precautions are essential to

limit worker risk. Cyanide is of great concern with regard
to homicide and suicide. There are particular metabolic
risks and concerns with regard to exposure to both
agents because they bind specifically to the ferric
moiety of the cytochrome oxidase complex. Odor
recognition is unreliable and is not a definitive approach
to diagnosis. The laboratory evaluation usually is not
timely for diagnostic purposes. Decontamination,
removal from the site of exposure, and oxygen are
essential.

Questions:
 122
1. Enumerate the factors affecting toxicity with carbon
monoxide.
2. Compare between the pathophysiology of carbon
monoxide and cyanide poisonings.
3. Describe the clinical picture of acute carbon monoxide
poisoning.
4. Give an account on the delayed neuropsychiatric
sequelae of carbon monoxide poisoning.
5. Discuss the role of ABG analysis in the diagnosis of
carbon monoxide and cyanide poisonings.
6. List the differential diagnosis of acute carbon monoxide
poisoning.
7. Describe the investigations needed in case of carbon
monoxide poisoning.
8. What is the role of hyperbaric oxygen in treatment of
carbon monoxide poisoning?
9. Discuss the management of cyanide poisoning.
10. Describe the lines of management of hydrogen sulphide
poisoning.
 123

CHAPTER 11
Metals
ILOs:
By the end of this chapter the student should be able to:
K1: List the sources and the methods of exposure to lead,
mercury and iron.
K2: Explain the pathophysiology of lead, mercury and iron.
K3: Discuss the clinical picture and management of acute
toxicity of lead, mercury and iron.
K4: Discuss the clinical picture and management of chronic
toxicity of lead and mercury.
K5: Solve problems revolving around virtual cases presenting
with lead, mercury and iron toxicity.
A1: Realize the importance of urgent appropriate treatment in
cases of acute intoxication.
A2: Realize the importance of working in groups.
LEAD
Poisoning by lead is the most common metallic poison.
It is probably the most important chronic environmental
illness. Its salts occur in organic and inorganic forms. Its toxic
effects on humans are well documented in history.
Methods of Exposure:
1- Water and Food contamination: drinking water from lead
pipes or storage tanks, and eating contaminated food
grown near factories may lead to poisoning.
2- Inhalation of lead from motor vehicle exhaust when
leaded gasoline is used. Occupational exposure in lead
workers, glassmakers, scraps metal workers, plumbers,
and workers in battery factories.
3- Dermal exposure: alkyl lead (organic lead salts) is easily
absorbed through the skin.
Pathophysiology:
Absorption of ingested lead is 10% in adults while it is
 124
50% in children, thus children are at greater risk of toxicity,
especially the developing brain.
Lead disturbs multiple enzyme systems. As in most
heavy metals, it binds to –SH group of metabolic enzymes such
as those of the heam synthesis and Kreb's cycle. Chronic lead
poisoning is more common than acute exposure producing the
following manifestations:
I- Hematoloogical Effects:
The effects of lead on hemopoietic system are:
A- Anemia:
It is either normochromic or hypochromic microcytic. It
occurs more in children in comparison with adults. The
mechanisms included to cause anemia are:
1- Defective hemoglobin synthesis:
a. Lead i hi its o ersio of δ a i ole uli i a id
(DALA) to porphobilinogen.
b. Lead inhibits conversion of coproporphyrinogen III
to protoporphyrin.
DALA and coproporphyrin accumulate in urine and
are used as toxicity markers.

 Lead interferes with Na-K ATPase pump and attacks

2- Increase of RBC fragility:

RBC membrane causing increased fragility and

decreased RBC survival (hemolysis).

 This results from the toxic effects of lead on renal

3- Erythropoietin deficiency:

tubules.

 This is due to decreased ability of the RBCs to rid

B- Basophilic stippling of RBCs:

off RNA degradation products followed by

aggregation of ribosomes.

 Response of the bone marrow to anemia.

C- Reticulocytosis:

 Due to increased RBCs fragility.

II- Renal Effects:
Chronic toxicity may cause chronic interstitial nephritis.
III- Nervous Effects:
 125
Direct effect on CNS causing lead encephalopathy
especially in children. Other effects include delayed or
reversed development, permanent learning disabilities.
Peripheral neuritis: presenting as wrist drop and foot drop.
Optic neuritis may occur.
IV- Reproductive System Effects:
1. Lead crosses placenta and may cause abortion, stillbirth,
and neurodevelopmental problems.
2. Lead may cause decreased sperm count, and increased
number of abnormal sperms.
V- Bone Effects:
Lead triggers hypermineralization, which is reflected in
metaphyseal and growth plate densities, the classic lead
lines are observed on radiographs. They reflect bone
growth arrest and not deposition. Their width is related to
the duration of exposure.
VI- Other manifestations:
1. Nonspecific: vague body aches, anorexia, constipation
and abdominal colic.
2. Blue lines on the gums caused by bacterial action on blood
lead at these sites precipitating lead sulfide.
Acute toxicity:
Uncommon and results from accidental or suicidal
ingestion of lead oxides may present with:
1- GIT: metallic taste, vomiting, anorexia, abdominal colic,
constipation.
2- CNS: lead encephalopathy, behavioral changes, lethargy,
fatigue, seizures, and coma.
Investigations:
 126

 Blood levels more than 30 µg/dl is abnormal.

1. Blood Levels of Lead & Erythrocyte Protoporphyrin:

 Erythrocyte protoporphyrin (EP) level more than

50µg/dl is abnormal.
2. CBC.
3. Urinary DALA can be used as screening test for those
exposed to lead.
4. Renal functions, liver functions, and serum uric acid.
5. X-ray on long bones to reveal lead lines.
Treatment:
Acute toxicity:
I- Emergency measures (ABCD).

 Induction of emesis or gastric lavage if ingested.

II- Elimination:

III- Chelation: (see below)

 IV fluids for dehydration.

IV- Symptomatic treatment:

 Ca gluconate for lead colic.

 Encephalopathy: care of coma and convulsions and
mannitol to decrease ICT.
Chronic Toxicity

 Prophylactic measures to decrease exposure as masks,

A. Prophylactic:

 Periodic medical examination of workers.

gloves, ...etc.

B. Curative:
I- Stop further exposure.
II- Chelation therapy drugs:
These are drugs that act by binding to the metal
forming metal- chelator complex which easy to excrete in
the bile or urine.

 It is the first chelator used in encephalopathic

1- Dimercaprol (BAL):

individuals.
2- Calcium disodium EDTA (Ca Na2 EDTA):
 127
 Once started CaNa2EDTA should be given in full 5-
day course. The first dose begins removing lead
from extracellular fluid in bone, if not followed by
next doses the free lead can redistribute to cause

 In cases of lead encephalopathy, BAL should be

lead neurotoxicity.

given first to avoid redistribution of lead mobilized

by CaNa2EDTA to CNS.

 Effective orally and has few adverse effects.

3- D-Penicillamine:

 It is the best for lead chelation in children with

4- Dimercaptosuccinic acid (DMSA):

a lead level higher than 45g/dL. Has been

shown to be an effective oral chelator.

 It has become antidote for most heavy metal

5- Dimerval (DMPS):

intoxications. It is available in the oral form and in

a water-based parenteral form.
III- Symptomatic:
1. Treatment of anemia: blood transfusion
2. Renal affection: hemodialysis.
3. Splint and physiotherapy for wrist and foot
affection.

IRON
Iron preparations are very common therapeutic drugs
used as a pediatric or prenatal vitamin supplement and for
treatment of anemia.
Iron poisoning is one of the most common poisoning
emergencies in young children. It is the leading cause of death
from accidental ingestion in children under age of five years.
Pathophysiology:
 Iron exerts both local and systemic effects. It has both

 The corrosive toxic effect is exerted mainly on the

corrosive and cellular toxic effects.

gastric and intestinal mucosa. The damage to the

 128
gastrointestinal mucosa allows irregular iron absorption
which reaches toxic serum levels. It also allows invasion

 Cellular toxic effects occur due to absorption of

by bacteria causing infection and fever.

excessive quantities of ingested iron and result in

systemic iron toxicity. Severe overdose causes impaired
oxidative phosphorylation and mitochondrial
dysfunction, which can result in cellular death. The liver
is one of the organs most affected by iron toxicity, but
other organs such as the heart, kidneys, lungs, and the

 Deposition of excess iron in the soft tissues due to

hematologic systems also may be impaired.

exceeding the total iron binding capacity causes multiple

organ toxicity with liver necrosis, renal failure,
cardiovascular collapse and coma.

Acute Iron Toxicity:

Mode of poisoning:
Iron intoxication remains a common and serious for
of accidental poisoning especially in children. It is
common toxic ingestant because it is available in home
and present in attractive colored sugar coated
preparations.
Clinical picture:
Typically, iron poisoning is described in 4 sequential
stages.

 Onset: 1-6 hours from ingestion.

Stage I: (Direct local gastrointestinal corrosive effects

 GIT irritation due to direct corrosive action on mucosal

surfaces with nausea, vomiting, abdominal pain, GIT
bleeding (which may be severe), diarrhea, and shock.
Necrosis may be severe and lead to perforation and

 In severe cases CNS depression may occur at this stage

peritonitis.

leading to lethargy and coma.

 129

 Onset: up to 24 hours from ingestion.

Stage II: (Quiescent phase)

 Apparent (false) improvement in most cases.

 Onset: 12-48 hours from ingestion.

Stage III: (Metabolic and cellular toxic phase)

 Metabolic acidosis due to:

1. Hypoperfusion due to significant volume loss,
vasodilatation, and negative inotropic effect of iron
will result in lactic acidosis.
2. The inhibition of oxidative phosphorylation will
promote anaerobic metabolism.
3. Releasing of hydrogen ion from conversion of ferrous
iron to ferric iron in the blood.
4. Interference with Krebs cycle leading to

 Fever and leucocytosis (due to invasion of the damaged

accumulation of organic acids (citric and lactic).

 Hepatic necrosis, liver cell failure (jaundice,

intestinal mucosa by bacteria).

hypoglycemia and coagulation defect), and renal failure

(all due to deposition of excess iron exceeding total

 Bowel ulceration and perforation.

iron binding capacity (TIBC) in the soft tissues.

 Coma and cardiovascular collapse.

 Onset: 4-6 weeks from ingestion.

Stage IV: (GIT scarring)

 Intestinal scarring with or without obstruction.

 Hepatic cirrhosis may complicate the case.
Investigations
1. Serum iron level (normal serum level ranges between
80-180g/dl-Action level >500ug/dl).
2. Electrolytes.
3. Renal function tests e.g. BUN and creatinine.
4. ABGs.
5. Hepatic profile: transaminases, bilirubin, and coagulation
profiles.
6. X-Ray abdomen to detect radio-opaque shadows.
 130
Treatment:
I- Emergency measures (ABCD).
II- Elimination:
1- Induction of emesis (not used if there spontaneous
vomiting).
2- Gastric lavage.
3- Whole bowel irrigation using polyethylene glycol has
been used to speed the passage of undissolved iron
tablets through the GI tract.
4- Exchange transfusion may be useful in removing iron
from the blood stream in advanced cases.
N.B.:Activated charcoal cannot adsorb iron so it is not
used.
III- Antidote:
Deferoxamine (Desferal®):
Is the iron-chelating agent. It binds absorbed iron from
tissues, and free iron from plasma. The iron-deferoxamine
complex (ferrioxamine) is water soluble and is excreted in
the urine. It turns urine color to, vin ros. Desferoxamine
does not bind iron in hemoglobin, myoglobin, or other iron
carrying proteins. It is safe to administer to children and
pregnant women.
Indications:
1. Serum iron level >500g/dL or estimated dose
greater than 60 mg/kg of elemental iron.
2. Shock.
3. Altered mental status.
4. Persistent GI symptoms.
5. Metabolic acidosis.
6. Serum iron level is not available with presence of
symptoms.
IV- Symptomatic treatment:
IV fluids, liver support, dialysis, correction of acidosis.

MERCURY
(E-learning)
 131
Summary:
This chapter discussed some examples of toxicity caused
by metals. Acute and chronic toxicity of lead and mercury as
well as acute iron toxicity were described regarding their
clinical presentations and management.
Questions:
1- List the different methods of exposure to lead.
2- Explain the effects of lead on blood.
3- Describe management of acute lead toxicity.
4- Give an account on Plumbism.
5- Explain the pathophysiology of mercury.
6- Discuss the clinical picture of acute mercury toxicity.
7- Describe the different lines of treatment of chronic
mercury toxicity.
8- Discuss the clinical picture of acute iron toxicity.
 132

CHAPTER 12
Food Poisoning
ILOs:
By the end of this chapter the student should be able to:
K1: List the different causative agents of food poisoning.
K2: Discuss the clinical picture of food poisoning presented
by acute gastroenteritis.
K3: State how to diagnose a case of food poisoning
presented by acute gastroenteritis.
K4: Describe the different lines of treatment in cases of food
poisoning presented by acute gastroenteritis.
K5: State the different complications caused by food
poisoning presented by acute gastroenteritis.
K6: Discuss the differential diagnosis of vomiting.
K7: Compare between toxigenic and invasive bacterial
gastroenteritis.
K8: Discuss botulism regarding its pathophysiology, clinical
presentation, diagnosis and treatment.
K9: Discuss ciguatera and scombroid poisoning regarding
their clinical presentation and treatment.
K10: State the differential diagnosis of paralytic syndromes.
K11: List the different presentations of food poisoning.
K12: Solve problems revolving around virtual cases exposed to
different types of food poisoning.
A1: Realize the importance of urgent treatment of cases with
food poisoning.
A2: Realize the importance of notification to the authorities
of cases with mass food poisoning.
Introduction:
Food poisoning is a condition resulting from ingestion of
food contaminated by microbes, microbial toxins or chemicals
or ingestion of special kinds of poisonous food. This causes a
variety of symptoms depending on the causative agent.
 133

Causative agents:
A- Microbes:
1- Bacteria:

 Staphylococcus aureus.
- Toxigenic:

 Enterotoxigenic Escherichia coli.

 Clostridium botulinum.
 Clostridium perfringens.
 Vibrio cholera.
 Group A streptococcus.

 Salmonella.
- Enteroinvasive:

 Shigella.
 Campylobacter jejuni.
 Enteroinvasive E coli.

 Rotavirus.
2- Virus:

 Norwalk virus.
 Hepatitis A, E, F and G.

 Giardia lamblia.
3- Parasites:

 Entamoeba histolytica.
 Trichinella spiralis.
B- Chemicals:
Pesticides, heavy metals, monosodium glutamate
(Chinese restaurant syndrome) and methemoglobin-
induced poisoning.
C- Endogenous:
Ciguatera and scombroid fish poisoning and mushroom
poisoning. Here the toxic material is a constituent in the
plant or the fish.
 134
FOOD POISONING ASSOCIATED WITH ACUTE
GASTROENTERITIS
This is mainly caused by microbes and to a lesser extent
by some chemicals. Food-borne bacteria and bacterial toxins
are the most common causes of epidemic food poisoning.
Gastroenteritis may be caused by invasive bacterial infection of
the intestinal mucosa or by a toxin elaborated by bacteria.
Bacterial toxins may be pre-formed in food that is improperly
prepared and improperly stored before use, or may be
produced in the gut by the bacteria after they are ingested.
Clinical picture:
There is commonly a delay or "incubation period"
before the onset of symptoms. It is less than 6 hours in
toxigenic types and between 8-24 hours in invasive types. The
condition is self limited and lasts for a day or more in toxigenic
types (less than 24 hours in staphylococcal food poisoning),
while it persists for several days in invasive types. The clinical
picture differs according to the type as follows:
Comparison between toxigenic and invasive bacterial
gastroenteritis
Toxigenic Invasive
Incubation period Short 2-6 hours Longer 8-24 hours
Self-limited, less than 24 Lasts several days (3-11
Duration of illness
hours days)
Clinical picture
- Vomiting Prominent and profuse Less prominent
Profuse and watery
- Diarrhea +ve Mucoid and bloody
- Abdominal pain -ve +ve
- Fever -ve +ve
- Bloody stools +ve
Investigations

  IV Fluids
- Pus cells in stool -ve +ve

  Antibiotics
Fluids replacement
Treatment No antibiotics are are
needed frequently needed

Diagnosis:
1- History of food consumption which could be shared by a
group of persons.
 135
2- The clinical presentation of food poisoning
3- Investigations:
- Complete blood count (CBC) may show severe
leucocytosis in enteroinvasive types.

 Fecal leucocytosis denotes microbial invasion of

- Stool analysis and stool culture and sensitivity test:

 Stool culture is diagnostic and of epidemiological

the gut.

concern.
- Serum electrolytes, renal function test and blood
glucose levels.
- Food samples should be saved for bacterial culture
and toxin analysis for use by public health
investigators.
Complications:
1- Dehydration, hypotension and prerenal acute renal
failure may occur in neglected cases of severe vomiting
and diarrhea especially in children affected with
toxigenic food poisoning.
2- Shigella and enteroinvasive E coli can cause acute
hemorrhagic colitis complicated by hemolytic-uremic
syndrome and renal failure.
3- Extraintestinal complications as gram negative
septicemia, peritonitis and arthritis are serious but rare
complications of neglected enteroinvasive food
poisoning.
Differential diagnosis of vomiting:
Individual cases:
1- Acute abdomen (pancreatitis, intestinal obstruction,
appe di itis, pepti ul er…(.
2- Initial manifestation of another more serious illness e.g
systemic viral or bacterial disease, migraine, septicemia
or conditions associated with increased intracranial
tension, benign positional vertigo.
Collective cases:
 136
1- Carbon monoxide poisoning( may simulate food
poisoning as it presents with vomiting and can affect a
group of patients).
2- Methemoglobinemia.
3- Botulism.
Treatment:
1- Emergency and supportive measures:
- Rehydration with saline and correction of
electrolytes imbalance.
- Antiemetics and antispasmodics.
2- Specific drugs:
- Antibiotics are indicated only in enteroinvasive
types of food poisoning.
- Different antibiotics are given according to the
result of the stool culture which reveals the specific
bacteria responsible.
- Emperic treatment with ciprofloxacin or
trimethoprim-sulfamethoxazole is commonly given
while awaiting culture results.
3- Notification to the health authorities if occurs in
epidemics.

N.B: The Chinese restaurant syndrome is induced by ingestion

of monosodium glutamate. Individuals present with burning
sensation on the back, neck, shoulders and abdomen. There is
also nausea, vomiting, headache, flushing, chest pain and
rarely life-threatening bronchospasm. It is self-limited and
symptoms usually last approximately 1 hour.

FOOD POISONING ASSOCIATED WITH

NEUROLOGICAL SYMPTOMS
This is caused by either the toxigenic bacteria
clostridium botulinum or the endogenous poisons in some
kinds of fish or mushrooms.
 137
Botulism
Botulism is caused by ingestion of the pre-formed
exotoxin in improperly preserved food (canned, fermented or
smoked). In Egypt, outbreaks are caused by ingestion of the
salted fish "fesikh
The exotoxin is produced by clostridium botulinum, a
spore forming anaerobic gram +ve bacillus that releases 8
types of toxins, the most important are A, B and E. Clostridium
botulinum spores grow everywhere in the soil, seawater and
air.
They are dormant and highly resistant to damage by boiling.
The spores germinate in food with low acidity and salt content
and they produce the toxin in anaerobic media with
temperature above 27°C. Although the toxin is considered the
most potent toxin ever known to man, it could easily be
destroyed by boiling.
Pathophysiology:
The toxin binds irreversibly to peripheral neuromuscular
junction so prevents the release of acetyl choline and produces
block. The toxin does not cross the blood brain barrier.
Clinical picture:
Time delay "incubation period" ranges from few hours
to 8 days but typically it is between 18-36 hours.
1- Initial GIT manifestations: nausea, vomiting and
abdominal pain.
2- Anticholinergic picture: dry mouth, constipation, urine
retention, dilated sluggish pupils and tachycardia.

 Gradually progressive cranial nerve paralysis (squint,

3- Neurological picture:

ptosis, d sarthria, d sphagia…( follo ed :

 Progressive symmetric descending paralysis and

 There is no sensory affection and no coma.

finally respiratory arrest with loss of cough reflex.

Diagnosis:
1- History of ingestion of improperly preserved food.
 138
2- Clinical picture of dry throat, descending paralysis and
gastroenteritis.
3- Investigations:
 Toxin assay and anaerobic culture for samples of
serum, stool, vomitus, gastric contents or suspected

 Tensilon test (used to differentiate between botulism

food.

and myasthenia gravis): Tensilon (edrophonium) is an

anticholinesterase which causes dramatic
improvement in case of myasthenia gravis but not in

 Mouse neutralization bioassay test: Samples of stool,

botulism.

serum or suspected food are injected into the mouse

peritoneum and subsequent paralysis and death of
the mouse are considered to be a positive test.

Treatment:

 Maintain an open airway and assist ventilation if

I- Emergency and supportive measures:

 Tracheostomy in bulbar paralysis.

necessary.

 Obtain arterial blood gases and observe closely for

respiratory weakness.
II- Antidote:
Botulinum antitoxin (trivalent ABE) is given. One vial
is administered every 4 hours for at least 4–5 doses. The
antitoxin binds the circulating free toxin and prevents the
progression of illness; however, it does not reverse
established neurologic manifestations. It is most effective
when given within 24 hours of the onset of symptoms.

 Induction of vomiting if recent ingestion of known or

III- Decontamination:

 Gastric lavage and catharsis to remove spores from the

suspected contaminated material has occurred.

 Administration of activated charcoal

gut.
 139
IV- Symptomatic treatment.
V- Notification to health authorities.
Other forms of botulism:
Infant botulism:
It is not caused by ingestion of preformed toxin but by in
vivo production of toxin in the immature infant gut (which
lacks gastric and bile acids). Infants 1 week to 6 months old,
breast-fed infants and those given honey may have a higher
risk of developing the disease, which is characterized by
hypotonia, constipation, tachycardia, difficulty in feeding, head
lag, and diminished gag reflex. It is rarely fatal, and infants
usually recover strength within 4–6 weeks. Treatment consists
mainly of respiratory support.
Wound botulism:
Occurs in crush injuries where the wound is dirty and
associated with inadequate debridement and in intravenous
drug abusers who inject the drug subcutaneously rather than
intravenously. The organism germinates and produces toxin in
vivo. Typical manifestations of botulism occur after an
incubation period of 4–14 days. Treatment consists of
botulinum antitoxin, antibiotic (penicillin) and wound
debridement and irrigation.
Therapeutic botulism:
This is either botulinum toxin type A (Botox) or type B
(Myobloc) which is injected in muscles to induce temporary
weakness to treat cases of blepharospasm, squint, facial nerve
disorders, torticollis and to eliminate frown lines. The affected
muscles then weaken by atrophy over a 3-week period, but
recover within 2–4 months as nerve transmission is restored
through new nerve endings and functional connections at
motor endplates.
Ciguatera Poisoning
Ciguatoxin originates from tiny organisms eaten by small
herbivorous fish which is then eaten by larger carnivorous fish
and the toxin becomes concentrated in their flesh, adipose
 140
tissue and viscera. The toxin does not harm the fish which is
normal in smell, taste and consistency. There are more than
500 fish species involved and the common factor is the large
size of the fish.
Clinical picture:
Time delay "incubation period" ranges from 2-6 hours after

 Initial GIT manifestations: nausea, vomiting, abdominal

ingestion.

 Headache, myalgias, numbness in mouth and

pain and watery diarrhea. This is followed by:

extremities, temperature inversion (hot feels cold),

 Hypotension and bradycardia.

itching, vertigo and ataxia.

Treatmen:t
 Symptomatic. It is a self limited intoxication.
Scombroid Poisoning
Scombrotoxin is a mixture of histamine and other
histamine-like compounds produced when histidine in fish
tissue decomposes by the effect of enzymes of bacteria on
their body surface when they are not refrigerated. Fish types
include tuna and mackerel.
Clinical picture:
Time delay ranges from few minutes to 3 hours after

 Numbness tingling or burning sensation in the mouth.

ingestion.

 Headache, erythema of the face, neck and upper part of

 Nausea, vomiting and abdominal pain are not common.

the body.

Treatment:
 Symptomatic with H2 blockers. It is a self limited
intoxication.
Differential diagnosis of paralytic syndromes:
1- Guillian-Barre syndrome: Difference is paralysis starts in
the limbs i.e. ascending.
 141
2- Organophosphorus insecticide poisoning: SLUD,
fasiculations and diminished cholinesterase.
3- Cerebrovascular accidents: focal asymmetric findings,
diagnosed by CT.
4- Ciguatera: sensory affection, vertigo.
5- Myasthenia gravis: +ve history of episodic ptosis, +ve
Tensilon test.
6- Encephalitis: fever, coma and abnormal CSF.
7- Poliomyelitis: fever, bulbar involvement but ascending
paralysis
Different clinical presentations of food poisoning:
1- Acute gastroenteritis: toxigenic or invasive bacterial
food poisoning.
2- Neuromuscular weakness: botulism or ciguatera.
3- Parasthesia: monosodium glutamate, ciguatera.
4- Cholinergic syndrome: organophosphorus or
carbamates insecticides.
5- Allergic-like rash and headache: scombrotoxin.
6- Cyanosis: methemoglobinemia(meat preserved with
nitrites)
7- Chest pain: monosodium glutamate.

Summary:
This chapter discussed the different causes of food
poisoning, the clinical presentations, diagnosis, treatment and
the possible complications.

Questions:
1- Compare between toxigenic and invasive bacterial food
poisoning.
2- Discuss the differential diagnosis of vomiting.
3- Discuss the clinical picture and treatment of botulism.
4- Give a short account on ciguatera and scombroid
poisoning.
5- List the different presentations of food poisoning.
142
 143

CHAPTER 13
Animal Poisons
ILOs:
By the end of this chapter the student should be able to:
K1: List the commonly encountered snake, scorpion and
spider species in Egypt.
K2: State the composition of snake and scorpion venoms and
their actions.
K3: Discuss the clinical picture of envenomation by snakes,
scorpions and spiders.
K4: State how to diagnose a case with snake bite
envenomation.
K5: Describe the different lines of treatment in cases of
envenomation by snakes, scorpions and spiders.
K6: Solve problems revolving around virtual cases
envenomated by snakes, scorpions and spiders.
A1: Realize the importance of time factor in saving critical
cases of envenomations by snakes, scorpions and spiders.
Introduction:
Envenomations caused by animal poisons are common
toxicological emergencies. Common animals causing
envenomation include:
1- Reptiles (‫)ال احف‬: e.g snakes and lizards.
2- Arthropods ) ‫(المفص يا‬: e.g scorpions, spiders, ticks, bees
and ants.
Some important facts about envenomation by animal
venoms:
 All animal venoms are mixtures of proteins and enzymes

 Accidents predominate in summer, rare in winter

with various actions that affect most body systems.

 The onset of symptoms and the clinical picture are

(hibernation).

variable as they depend on many factors like the

 144
amount and type of injected venom, the age, size and
edi al state of the i ti ,…..et .
 Prognosis: the condition is always severe in young aged
victims (infants and young children), when bites or
stings are produced in a central location (neck, back,
face) and when victims receive more than one bite or


sting.
Diagnosis consists of history, local and systemic


manifestations as well as investigations.
Treatment consists of local treatment, antivenom and


treatment of symptoms and complications.
Skin sensitivity test should be done before
administration of the antivenom. If the test is positive
and there is severe envenomation, the antivenom is
given with premedication to guard against
hypersensitivity reactions (hydrocortisone and


adrenaline).
The dose of antivenom administered to neutralize the
venom is the same for children and adults as the
amount of venom needed to be neutralized is the same
in both.
SNAKE ENVENOMATION
 Snakes are reptiles with a worldwide distribution.
 Only about 15% of the 3000 species of snakes are

 They have poor vision and hearing but they have a

venomous.

powerful smell sensation and their bodies are very

 Cobra lives in a humid environment (around the Nile

sensitive to vibrations.

 Vipers distribute in most of the Egyptian desert.

valley).

 Venom is injected in the victim through 2 fangs situated

on both sides of the upper jaw. These fangs are
connected to a pair of glands by narrow ducts.
 145
 Dry bite: it occurs when venom is not injected during the
bite by venomous snakes. It represents about 50% of
bites and results in no envenomation.
 146
The common venomous snakes in Egypt:
I- Viperidae (Vipers):

Cerastes cerastes Cerastes vipera

)‫الحية المقرنة (الطريشة‬ )‫الحية القرعاء (الطريشة‬

Pseudocerastes Echis carinatus

(‫الحية المقرنة الكاذبة (الطريشة‬ ‫الحية الغريبة السمراء‬

Echis coloratus
‫الحية الغريبة الحمراء‬
 147

II- Elapidae:

Naja Haje Naja Nigricolis

‫الكوبرا المصرية‬ (black spitting cobra)
‫البخاخ‬

Walterinnesia Aegyptia
‫الثعبان اأسود‬
Venom composition and effects:
The major groups of venom toxins are:
- Coagulotoxins: these include phospholipase A2,
metalloproteinases, fibrinolytics and platelets factors.
They attack hemostasis and vascular integrity resulting
in coagulopathy, hemorrhage and shock.
 148
- Neurotoxins: these are peptides and phospholipase A2,
they lead to flaccid paralysis of skeletal muscles (causing
respiratory failure).
- Cardiotoxins and nephrotoxins and they are mainly
peptides.
- Myotoxins: these are mainly phospholipase A2. They
cause myolysis of skeletal muscles.
- Necrotoxins: These are mainly proteolytic enzymes.
They cause local tissue injury varying from mild effects
to major necrosis.
Effects and clinical manifestations:
A- Viper envenomation:
1- Local effects (they are so severe and the condition may

 Fang marks: one or two.

extend to gangrene):

 Local pain and bleeding from the fang marks.

 Edema which appear within few minutes and may

 Enlarged tender regional lymph nodes.

progress to involve the whole limb.

 Ecchymosis: extravasation from damaged

 Blistering.
capillaries

 Skin necrosis and dry gangrene.

 Anxiety which may induce sweating, nausea,

2- General manifestations:

 Coagulopathy which occur mainly due to rapid

vomiting, rigors, tachycardia and chest tightness.

fibrin formation then fibrinolysis leading to

consumption of fibrin, and to a lesser extent due
to inhibition of portions of the clotting cascade
and the decrease in platelets count. This leads to
bleeding from all body orifices and presents as:
o Persistent bleeding from the bite site or
venipuncture.
o Bleeding gums and epistaxis.
o Hematemesis and melena.
o Hematuria.
 149

 Hemorrhage due to venom-induced capillary

o DIC (dissiminated intravascular coagulopathy)

 Hemolysis due to the effect of the venom on red

damage.

cell membranes. This presents as:

o Hemolytic anemia.

 Cardiac and circulatory effects: usually secondary

o Hemolytic jaundice.

to hemorrhagic disturbances leading to the

 Myotoxicity due to myolysis of skeletal muscles.

occurrence of hypotension and shock.

This presents as:

o Muscle pain, tenderness and weakness.
o Secondary renal failure due to
myoglobinuria.
o Hyperkalemia which may result in cardiac
arrhythmias.
B- Cobra envenomation:

 Fang marks: one or two.

1- Local effects:

 Minimal local pain and edema around the fang

marks.

 Anxiety which may induce sweating, nausea,

2- General manifestations:

 Systemic symptoms usually occur within a few

vomiting, rigors, tachycardia and chest tightness.

 Fasciculation of face and neck muscles which is

hours but may be delayed up to 12 hours.

 Weakness up to paralysis of skeletal muscles of

usually followed by paralysis.

the whole body including respiratory muscles and

muscles supplied by cranial nerves. This presents
as:
- Diplopia, ptosis.
- Dysarthria.
- Generalized muscle weakness.
- Respiratory arrest
 150
 Consciousness and sensation are spared.
 When the whole body is paralysed and cranial
nerve palsy occurs, the patient looks as if
comatosed.
Diagnosis:
 History of a bite accompanied by seeing or capturing the

 Examination: the presence of fang marks and the

snake.

 Investigations: in cases of viper envenomation the

clinical manifestations.

laboratory findings are anemia, thrombocytopenia,

hypofibrinogenemia, increased fibrin degradation
products and prolongation of PT and PTT (lab tests also
help to follow up treatment).
Treatment:
I- First aid treatment (pre-hospital care):
Rest, reassurance and immobilization of the affected
limb and removal of any constricting object like rings or
bracelets. A light tourniquet could be used but it is proved to
be of limited value. Other measures like incision and suction,
cryotherapy or electric shock are proved to be harmful and
they are now obsolete.
II- Hospital treatment:

 Sometimes needed especially in cases of respiratory

A. Emergency treatment ABCD:

paralysis in elapids envenomation where mechanical

ventilation is needed.

 Antivenom is indicated in all systemic

B - Polyvalent antivenom:

 It is best given within the first 2 hours to prevent

envenomation.

local injury but it's never too late to give the

 It is given by slow intravenous injection or

antivenom.

intravenous infusion.
 151
 Initial dose is 3-5 vials to be repeated according to
severity and the follow up of the patient. 10 vials
could be given after the initial dose if the condition
is still progressing. More vials could be given
according to the evolution of the clinical condition
and response to antivenom.

 Hypotension is treated by I.V fluids.

C- Treatment of complications:

 Hemostatic abnormalities: are treated by fresh

whole blood, fresh frozen plasma, platelets

 Tetanus prophylaxis is given to non-immune

concentrates and fibrinogen infusion.

 Treatment of local complication in the form of

persons.

debridement of necrotic tissue at the bite site.

SCORPION ENVENOMATION
Scorpions are small arthropods yellowish, brown or
black in color. They live in deserts, hide by daytime under rocks
and stones and emerge at night for hunting. They attack man in
its habitat in proximity with desertic places. Scorpions detect
their prey by air and ground vibrations not by sight.
Accidents are common in Cairo suburban regions and
are more frequent in Upper Egypt.
Common scorpions found in Egypt:

 Brownish black
Leiurus quinquestriatus: Androctonus australis:
 Yellow with a black trunk, small in
size and is considered the world's
deadliest scorpion.
 152

 Black
Buthus bicolor:

Scorpion venom composition and effects:

Scorpion venom is a potent autonomic stimulant
resulting in a sudden pouring of endogenous catecholamines
and acetyl choline into the blood stream. The massive release
of these mediators in the circulation results in a severe
autonomic storm which is responsible for most of the systemic
signs and symptoms of scorpion envenomation. The venom
consists of:
1- Neurotoxins which release neurotransmitters and huge
amounts of catecholamines (causing hypertension &
tachycardia) and acetyl choline (causing cholinergic
syndrome).
2- Phospholipase A2.
3- Hyalurinidase.
4- Acetyl cholinesterase.
5- Serotonin and histamine (responsible for stridor).
Clinical picture:

 Intense local pain and numbness.

I. Local manifestation:

 Tender regional lymph nodes.

 Erythema, local edema and sting marks are not
common.
II. Systemic manifestations:

 Fever,
1. General manifestations:
conjunctival congestion, sweating,
dehydration, peripheral cyanosis and cold extrimities
 153
(2ry to peripheral vasospasm caused by
catecholamines) and priapism.

 Tachycardia
2. Cardiovascular manifestations:
(less commonly bradycardia),
hypertension (severe and very characteristic of
scorpion envenomation), arrhythmias, acute heart
failure and shock in severe cases.

 Tachypnea, respiratory distress and failure, stridor,

3. Respiratory manifestations:

wheezes and crepetations. Acute pulmonary edema

which could be either cardiogenic (secondary to
cardiac failure caused by sudden severe afterload
effect) or non-cardiogenic (due to chemical mediators
liberation).

 Agitation, tremors, convulsions, fasiculations, rigors,

4. Neurological manifestations:

hyperthermia, hypertensive encephalopathy,

confusion, coma (irresponsive to anti-hypertensives)
cranial nerve palsy (usually 6th nerve, reversible).

 Excessive salivation, vomiting, diarrhea and acute

5. Gastrointestinal manifestations:

erosive gastritis.

 Hyperkalemia, hypocalcemia, stress hyperglycemia

6. Metabolic effects:

and metabolic acidosis.

Management of scorpion envenomation:
A protocol of six hours surveillance in the emergency
department is followed, and only patients who develop
systemic manifestations should be hospitalized.

 Control convulsions (by barbiturates and diazepam),

I- Emergency measures:

shock (by I.V fluids), pulmonary edema, cardiac or

respiratory failure.

 Pain is treated by non-steroidal anti-inflammatory drugs

II- Symptomatic treatment:

or local infiltrative anaesthesia.

 154
 Hypertension is treated by vasodilators (in particular
hydralazine, prazocin, sodium nitroprusside, nifedipine

 Cholinergic manifestations are treated by anticholinergic

and captopril).

 Vomiting is treated by antiemetic drugs (particularly

drugs (particularly atropine).

 Hyperpyrexia is treated by antipyretics (mainly

metoclopramide)

 Heart failure is treated by dobutamine.

paracetamol) and cold compresses.

 Dehydration resulting from sweating, vomiting and

diarrhea is treated by IV fluids.

 Indication: it is given to all children and senile adults

III- Antidote: scorpion antivenom:

presenting with any of the systemic manifestations as

well as patients with previous cardiovascular disease,

 It is best given in the first 4 hours but can still be given

hypertension or diabetes.

 Dose: 3-5 ampoules as initial dose are given by slow IV

as late as 24 hours.

or IM route. More ampoules are given every 30 minutes

if signs still progress or do not regress.
SPIDER ENVENOMATION
Spider species with clinical significance found in Egypt:

Black widow spider Brown recluse spider

North America, Europe, Asia and Africa. worldwide distribution
 155
Clinical picture of spider bite:

 Severe local pain.

1- Black widow spider:

 Painful cramping and muscle fasiculations in the

affected extremity which then spreads to the chest,

 Weakness and dyspnea

back and abdomen and can produce board like rigidity.

 Headache and restlessness

 Tachycardia and hypertension
 Nausea and vomiting
 Symptoms may mimic myocardial infarction or acute

 Symptoms often persist for 1 – 2 days.

abdomen.

 Painful burning sensation at the bite site.

2- Brown recluse spider:

 The bite area then bleeds and ulcerates.

 The necrotic ulcer takes a month or more to heal.
 The clinical presentation may mimic many
dermatological conditions.
Treatment:

 Analgesics.
1- Black widow spider bite:

 Spider antivenom administered only to severe cases.

 Calcium IV and muscle relaxants are given to treat
muscle cramping.

 Analgesics.
2- Brown recluse spider bite:

 Antibiotics and tetanus prophylaxis.

Summary:
Envenomation by the common species found in Egypt of
snakes, scorpions and spiders were discussed with highlighting
the venom composition and actions, the clinical picture of
envenomation and the different lines of treatment.
Questions:
 156
1- Enumerate the composition and the different actions of
snake venom.
2- State the criteria for diagnosis of a case of snake
envenomation.
3- Compare the systemic effects of viperids and elapids
envenomation.
4- Discuss the different lines of treatment of scorpion
envenomation.
5- Describe the clinical presentation of envenomation by
black widow spider.

CHAPTER 14
Alcohols
ILOs:
By the end of this chapter the student should be able to:
K1: Enumerate the uses and the toxic dose of ethyl alcohol.
K2: Describe the mode of toxicity of alcohols (ethyl alcohol,
methyl alcohol and ethylene glycol).
K3: Explain the pathophysiology and kinetics of alcohols.
K4: Describe the clinical presentation of acute toxicity of
alcohols.
K5: Discuss the differential diagnosis of acute toxicity of
alcohols.
K6: Discuss the management of acute toxicity of alcohols.
K7: Solve problems revolving around virtual cases acutely
intoxicated with alcohols.
A1: Realize the importance of urgent and aggressive
treatment of cases of acute toxicity of alcohols.
A2: Realize the importance of working in groups.
 157
ETHYL ALCOHOL
(Ethanol)
Ethyl alcohol is a clear colorless liquid with characteristic
odor. It is the most widely abused psychoactive agent
worldwide dating back to antiquity. Beer contains 3-6% weight
by volume of alcohol; Wine contains 10-14% w/v; Fortified
wines as campari, martini and vermouth contain 22-25%w/v;
Whiskey, brandy, gin and vodka contain 40-55%w/v.
Beer and wine are products of fermentation, while other
hard liquors are product of distillation processes where alcohol
has been fortified.
Uses:
1. Alcoholic beverages consumed for its pleasant and
euphoriant properties.
2. Sterilizing solutions as 70% or with tincture iodine in
medical uses.
3. Solvent and vehicle of many household and industrial
products
4. Cosmetic products.
Mode of Intoxication:
1. Overdose by inexperienced young adult seeking pleasure
and cheerfulness
2. Acute toxicity can also occur in addicts after ingestion of
large amount or ingestion of more concentrated type of
alcohol.
-Fatal dose of ethyl alcohol: nearly 150 ml of absolute
alcohol. However addicts can tolerate higher doses.
Pathophysiology:
 Ethanol is a dose dependent CNS depressant. It affects a
number of excitatory and inhibitory neurotransmitters. The
effect on the cortex reaches its peak while the blood level

 Alcohol in large quantities affects not only the cortex but

is increasing.

continues to the medulla as well as exerting a strong

 158
depressant action on the respiratory centers resulting in

 Ethanol metabolism affects NAD/NADH ratio with

acidosis and respiratory failure.

 Alcohol metabolism affects NADH/NAD ratio in the cell;

excessive consumption of NAD leading to hypoglycemia.

blocking conversion of lactate to glucose leading to

 Vasodilatation increases cutaneous blood flow together

metabolic lactic acidosis.

with impaired central thermal auto regulation may lead to

profound hypothermia.

Pharmacokinetics:
25% of ingested alcohol is absorbed from stomach, the
rest is absorbed from the intestine. It is detected in blood 5
minutes after ingestion. It is widely distributed to all organs &
body fluids. Peak level is reached after 30-180 min. 10%
excreted unchanged in urine, sweat and expired air.
Ethanol is mostly metabolized in the liver. It is normally
oxidized by alcohol dehydrogenase to form acetaldehyde
which upon further oxidation by aldehyde dehydrogenase is
converted to acetic acid. Oxidation is then completed with the
formation of carbon dioxide and water. If some chemical such
as antabuse or another enzyme inhibiting agent interfered with
the cycle involving the oxidation of the alcohol, the
intermediate products will accumulate and produce their own
effect.

Alcohol dehydrogenase
Ethanol ----------------------------------------acetaldehyde
NAD--- NADH
aldehyde
dehydrge-
nase
Acetic acid

Water & CO2

 159

Clinical Picture of acute alcohol intoxication:

1- Higher cortical depression  Release of inhibition:
 Euphoria, cheerfulness and talkativeness
 Increased appetite in non-addicts

 Staggering gait, tremors and slurred speech.

2- Cerebellar ataxia with:

3- Cutaneous vasodilatation  flushing, sweating and false

4- In Severe cases CNS depression  Coma with:

feeling of warmth with actual hypothermia.

 Hypothermia, hypotonia and hyporeflexia

 Hypotension and slow respiration.
 Irregular acidotic breathing
5- Conjunctival injection and Diplopia.
6- Vomiting and hiccough.
Investigations:
1. Arterial blood gases (ABG), glucose and electrolytes.
2. Blood alcohol level.
DD:
High Anion gap and high osmolarity gap, ketoacidosis,
hypoglycemia.

Treatment:

 Correct hypoglycemia, acidosis, water and

1. Emergency measures ABCD:

electrolyte imbalance.

 Mild cases should be left undisturbed and observed

2. Gut decontamination and Elimination:

 Stupor and coma may benefit from careful gastric

 Charcoal is not useful. Avoid emesis

lavage

 Hemodialysis if severe intoxication more than

400mg/dl or severe acidosis pH< 7
3. Symptomatic treatment and drug therapy:
 160
 Thiamine 100mg IV or IM if coma is related to

 Warming if there is hypothermia

Wernicke's encephalopathy.

METHYL ALCOHOL
(Methanol-Wood Alcohol)
Methyl alcohol is an alcohol produced by distillation of
wood. It is similar to ethyl alcohol in its odor, color and taste. It
is cheap, less expensive than ethyl alcohol.
It is used as cleaner and solvent. For this commercial
reason, it is denatured by adding pyridine giving the
commercially available methanol a rosy color, characteristic
odor and bad taste. However non denatured methanol will
produce the same euphoriant effect produced by ethanol.

Mode of Toxicity:
Methyl alcohol is added to ethyl alcohol as adulterant.

Pathophysiology and kinetics:

 Methanol is well absorbed from GIT, evenly distributed in
whole body water, 3-5% excreted via lungs and12%
excreted unchanged via kidneys. The rest is slowly

 Methanol is metabolized in the liver by alcohol

metabolized in the liver.

dehydrogenase, an enzyme that preferentially uses

ethanol as substrate. The enzyme will metabolizes
methanol to formaldehyde, when no ethyl alcohol is

 Formaldehyde is then metabolized to formic acid by the

available. This process is slow.

effect of aldehyde dehydrogenase. Formic acid is

responsible for metabolic acidosis. Its local accumulation
in the CNS and optic nerve accounts for the optic atrophy

 Formic acid inhibits cytochrome oxidase resulting in

and other central neurological sequelae.

cellular ischemia and obligatory anaerobic metabolism

exaggerating acidosis by lactic acid
 161
Alcohol dehydrogenase
Methanol ------------------------formaldehyde
Slow (12 hr)

aldehyde dehydrogenase
----------------------------------------- formic acid

folate dependent mechanism

-------------------------------------------- CO2+H20

Lethal dose: 1-2 mg/kg (80 mg/dl)

Clinical presentation:
A latent period of 12 - 36 hours results from the slow
metabolism of methanol to the toxic metabolites and from the
preferential metabolism of ethyl alcohol by alcohol
dehydrogenase enzyme
1. Visual: Visual blurring, ocular pain, papilledema, optic
atrophy and blindness.
2. Metabolic acidosis: Moderate to severe, is secondary to
the toxic metabolites of methanol. It is responsible for
the tachypnea (air hunger), confusion, headache and
weakness. Severe metabolic acidosis may produce life-
threatening hyperkalemia.
3. Gastrointestinal: vomiting, abdominal cramps and
dehydration may occur.

 Disorientation, Stupor and Coma: It is caused by

4. Neurological:

 Convulsions (serious).
acidosis and accumulation of formic acid in the CSF.

 Encephalopathy.
 Delayed necrosis of basal ganglia accounts for the
frequent muscle spasticity and dyskinetic
movements following severe methanol poisoning.
5. Respiratory depression follows air hunger It is correlated
with severity of acidosis and coma.

 Cardiogenic: follow myocardial ischemia, acidosis

6. Shock
 162
and hyperkalemia-induced depressed myocardial

 Vasoplegic: Depression of VMC (vasomotor center)

contractility.

occurs 2ry to cerebral edema caused by local

 Hypovolemia 2ry to severe vomiting may produce

accumulation of metabolites in the CNS.

hypotension
Investigations:
1. Arterial blood gases and Electrolytes to monitor
acidosis, respiratory depression and hyperkalemia.
2. Random Blood Sugar.
3. Kidney function tests.
4. Methanol blood level: Levels above 25mg/dl are
indications for antidotes and hemodialysis.
5. ECG and Monitoring to rule out ischemia and arrhythmias.
6. 6.Fundus Examination and Visual Evoked Potential :
Initial and serial examinations are essential to assess
optic nerve affection
D.D:


*Diabetic ketoacidosis


*Pancreatitis


*Retinal detachment
*Other toxins that cause acidosis
Treatment:
1. Emergency measures (ABC):
• Oxygen, Airway, Breathing, Circulation support
• Control acidosis (if pH is less than 7.15) and
hyperkalemia by slow infusion of Na Bicarbonate. In
addition it keeps formic acid in its anionic form to
decrease its entry to CNS.
2. Gut decontamination and elimination:
• Gastrointestinal decontamination is rarely
indicated because of its rapid absorption and
limited binding to activated charcoal.
• Hemodialysis is indicated if methanol level
exceeds 25-30mg/dl, in aggressive acidosis
 163
refractory to treatment or in precipitation of
renal failure.
3. Antidotes:
a) Ethyl alcohol 1gm/kg followed by 0.5gm/kg/4 hours
to maintain blood ethanol at 100mg/dl.

 Both compete with methanol for alcohol

b) 4-Methyl pyrazole

dehydrogenase enzyme, blocking its metabolism

to toxic metabolites, and allowing methanol to be
excreted as parent compound. 4-Methyl pyrazole
has no inhibitory effect on CNS.
c) Folinic acid: It helps oxidation of accumulated
formates.
4. Symptomatic treatment:
• Diazepam or anticonvulsant for convulsions
• Steroids are early indicated for optic neuritis or
later for cerebral edema.

ETHYLENE GLYCOL
(E-Learning)

Summary:
This chapter discussed acute alcohols toxicity. Ethyl
alcohol causes initial loss of inhibition followed by decrease
level of consciousness, ataxia, vomiting and possibly the odor
of ethanol. Hypoglycemia and respiratory depression may
occur. Methanol toxicity is diagnosed by the clinical picture, lab
findings which may include elevated level of methanol, and
high anion gap metabolic acidosis. Optic nerve atrophy and
blindness are the major complication.

Questions:

Mark √ or × :
-Ethanol acute toxicity may lead to profound hypothermia.
 164
-Methanol ingestion may induce severe metabolic acidosis.

 4- methyl pyrazol is preferable than ethyl alcohol in ttt

CHOOSE THE CORRECT ANSWER:

of methyl alcohol toxicity because

- It is more rapid.
- It has stimulant effect on CNS.

 In case of methyl alcohol intoxication shock may be

- It has no depressant effect on CNS.

- Cardiogenic.
- Vasoplegic.
- Hypovolemic.

 Folate is used in methyl alcohol toxicity in order

- All the above.

- To prevent wernickes encephalopathy.

- To enhance formate oxidation.
- To compete with methanol at alcohol
dehydrogenase enzyme level.
 165

CHAPTER 15
Drug Dependence and Drug Abuse
ILOs:
By the end of this section the student should be able to:
K1: Define drug abuse and habituation dependence and
describe their characteristics.
K2: Discuss how drugs of abuse are controlled in a country..
K3: Describe factors affecting the development of
dependence.
K4: List the types of addicts.
K5: Describe the classification of drugs of abuse.
K6: Describe clinical picture and treatment of acute and
dependence toxicity of addicting drugs (opiates ,
cannabis, benzodiazepine and volatiles)
K7: Describe generally how an illicit drug is tested for..
K8: Solve problems revolving around virtual cases presenting
with drug dependence or doping.
A1: Realize the importance of urgent treatment of cases with
acute intoxication.
A2: Realize the magnitude of the problem of drug
dependence and doping and the need for educational
measures for its limitation.
Introduction:
The problem of drug dependence and drug abuse is as
old as civilization itself; every society has used drugs to
produce effects on mood, thought and feeling. Over the last 20
years addiction has become a major health problem affecting
youth all over the world including Egypt. The abuse of drugs
costs millions in lost productivity and medical expenses and
more millions in efforts of law agents to arrest users and
distributers of drugs.
Definitions:
Drug Abuse: It is the use of a drug for non medical purpose,
usually for altering consciousness and or mood e.g. the use of
 166
medically prescribed opiate analgesic for inducing euphoria
and cheerfulness or to improve sexual performance.
Occasional or recreational user: He is the person who
irregularly uses the drug (in a party or in a gathering with
friends) and is still not totally bound to it.
Drug Dependence: It is a state of chronic intoxication produced
by repeated taking of the drug and is characterized by:
1- Overpowering or compulsive desire (craving) to
continue taking the drug and to obtain it by any mean.
2- Tolerance a tendency to increase the dose or frequency
of administration to produce the same effect. This is

 Decreased sensitivity of the receptors or their

may be due to:

 Increased metabolism and excretion of the drug

responses.

Tolerance may be complete or partial (as in cases of

Opiate that produces tolerance to euphoric and sedative
effects but not to miotic or constipating effects.

 Means that the metabolism of the cells become

3- Physical dependence

dependent on the drug, so that if the drug is

abruptly stopped, withdrawal manifestations will
result and it typically involves tolerance and
dosage escalation.

 Means that the person seek the drug for its

4- Psychological dependence

desirable effects (without drug, user’s life ill e

unsatisfactory.
5- Detrimental effects
Har ful effe ts o the addi t’s; ph si al a d
mental health, which are reflected on; his family, work,
and on the community, to which he belongs. He neglects
his work, lies, steals, passes his time tying to procure the
drug, becomes violent and may even commit crimes to
get his supply.
How drugs of abuse are controlled in a country?
 167
The possession, use and sole of illicit drugs have been
the subject of governmental control since the early part of the
twentieth century. Drugs of abuse (termed controlled
substances) are put in one of five schedules. These schedules
are extremely flexible in that the authorities can add, delete, or
reschedule a drug as more information becomes available.
The criminal penalties for the illegal manufacture, sale
or possession of controlled dangerous substances are related
to the schedules. The most severe penalties, are associated
ith drugs listed i s hedule Ι a d ΙΙ. The controlled substance
act, includes severe penalties for a person who possesses a
listed precursor chemical with the intent to manufacture a
controlled substance (designer drug).
Schedule of controlled substances
Schedule Criteria Examples
No medical use. Heroin (Diacetyl morphine), Ecstasy (3, 4
Very high abuse Methylenedioxymethamphetamine), China
Ι
potential white (methylfentanyl), N-ethyl
amphetamine, LSD.
Medical use and Morphine, Opium, Methadone, Cocaine,
ΙΙ high abuse Amphetamine, Pethidine, Pentobarbital,
potential Secobarbital, Fentanyl.
Medical use, have Codeine with paracetamol, compounds of
an abuse pento, seco, or amobarbital with other
ΙΙΙ potential less than compounds, Chloral hydrate and anabolic
those in schedule steroids.
Ι a d ΙΙ.
Medical use, have Benzodiazepines, Meprobamate,
an abuse Dextropropoxyphene and diethylpropion.
IV potential less than
those listed in
s hedule ΙΙΙ
The drug has Some over the counter drugs like cough
accepted medical medications containing codeine.
use and low abuse
V
potential relative
to the substances
i s hedule Ιν

Cannabis (bango, hashish, marijuana) and khat are

o sidered s hedule Ι o trolled su sta es i U“A. Anabolic
steroids, which are abused by athletes, have been classified as
 168
s hedule ΙΙΙ i so e A eri a states. Dronabinol a synthetic
equivalent to active ingredient of cannabis has been placed in
s hedule ΙΙ due to its gro i g edi al use i treati g glau o a
and chemotherapy side effects.
Drug Habituation:
It is a state resulting from repeated consumption of a

 A desire is present but without compulsion to take the

drug and is characterized by the following:

 Some degree of psychological dependence (no physical

drug for the sense of well being.

 Little or no tendency to increase the dose.

dependence and no withdrawal manifestations).

 Detrimental health effects primarily on the patient

rather than on the society.
Examples of drug habituation include caffeine in coffee and
tea. Cannabis is considered drug of dependence. It is a false
belief to consider it a drug of habituation.
Classification of drugs of abuse:
Besides putting the drugs in schedules, there are other
ways to classify them. The most common method of classifying
drugs of abuse is the systems affected under this scheme,
there are four major classes of illicit drugs.
1. CNS stimulants e.g. cocaine, amphetamine and
methamphetamine
2. CNS depressants e.g. barbiturates
3. Hallucinogens e.g. LSD, marijuana and phencyclidine
4. Narcotics e.g. heroin, morphine, codeine and other
opiods.
Tests for drug abuse:
 Tested drugs: most testing programs include screen on
opiates, cannabis, amphetamine, barbiturates,

 Biological samples: Blood, urine, hair (except alcohol) or

benzodiazepines and alcohol.

saliva.
 169
 Urine is the specimen of choice for drug tests as it is
easily available in adequate volume, non-invasive and

 Positive Preliminary tests by immunoassay should be

contains reasonable concentration.

confirmed by confirmatory tests with thin layer

chromatography or gas chromatography for medicolegal
purpose.
Medical hazards of drug abuse:
1. Overdose due to inappropriate calculation by
inexperienced users, or users who abstained, regained
drug sensitivity and used previously tolerable doses.
2. Withdrawal manifestations
3. Malnutrition, loss of weight and avitaminosis.
4. Anaphylactic reactions: due to intravenous injection of
impurities.
5. Psychiatric diseases as cannabis psychosis or depression
.
6. Mental changes and consequences: Early dementia, it
follows episodic mental changes related to drug effects.
Lack of concentration, disorientation, amnesia and
impaired skills and performance expose addicts to road
traffic accidents, legal punishments, and loss of
employment and failure of education.
7. Behavioral changes (aggression, lie, stealing, crimes and
sexual perversion).
8. Pulmonary and peripheral embolism, by adulterants as
talc and starch.
9. Infectious diseases due to lack of sterilization and
sharing contaminated needles and it includes viral
hepatitis B and C, AIDS, sexually transmitted diseases,
meningitis, osteomyelitis, pneumonia, abscesses, or
infective endocarditis.
10. Impaired immunity, with repeated infections, AIDS and
increased risk of cancer.
11. Cotton Fever: a febrile reaction due to suspension of
drugs filtered through cotton. It begins 10-20 minutes
 170
after IV infusion producing headache, chills, dyspnea,
palpitations and fever (40 degrees).
12. Pregnancy related hazards: abortion, congenital birth
defects, congenital addiction and sudden infant death
syndrome (SIDS). Abortion may follow previous
sensitization of Rh –ve females when exposed to Rh +ve
blood through contaminated syringes. Intravenous
preg a t fe ales’ a users a tra s it iruses to her
offspring.
13. Sexually transmitted disease.
14. Automobile and high way accidents may lead to death
in case of alcohol, marijuana, cocaine and
benzodiazepine addiction as they impair driving skills.

General management of drug dependence:

1- Hospitalization.

 Sudden withdrawal or gradual withdrawal according

2- Detoxification:

 Substitution is favored in certain instances.

to the addicting agent.

 Supportive treatment during detoxification.

3- Treatment of co-existing medical disease and healthcare
(nutrition and vitamins).
4- Treatment of co-existing or resulting psychiatric diseases
5- Psychotherapy and rehabilitation.
6- Continuous toxicological clinical and analytical follow up
for long periods to trace possible relapses and
subsequently manage.

Substances of abuse
ILOs:
By the end of this section the student should be able to:
K1: List the different routes of intake of substances of abuse.
K2: State the pathophysiology of abused substances.
K3: Enumerate the different opiate and opioids preparations.
 171
K4: Describe the mechanism of opiate and opioids
dependence.
K5: Discuss the clinical picture, diagnosis and treatment of
acute overdose of amphetamine, cannabis, cocaine,
nicotine and opiates.
K6: Discuss the clinical picture and treatment of abused
substances dependence (alcohol, amphetamine,
barbiturates, benzodiazepines, cannabis, cocaine,
nicotine, opiates and volatile substances).
K7: List the differential diagnosis of pin-point pupils.
K8: Solve problems revolving around virtual cases exposed to
acute overdose of amphetamine, cannabis, cocaine,
nicotine and opiates or chronic dependence of abused
substances.
A1: Realize the importance of urgent treatment of cases with
acute intoxication.
A2: Realize the magnitude of the problem of abused
substances dependence and the need for educational
measures for its limitation.
OPIATES AND OPIOIDS
Introduction:
Opiates and opiods are substances that have medical
uses as analgesics but they are also abused for non medical
causes to induce euphoric effects
Route:
Street users commonly use heroin and morphine by
sniffing, SC and IV injection. Raw opium is usually eaten or
smoked and sometimes, the powder is sniffed ("snorted").
Transdermal opioid patches, such as fentanyl, may also
produce toxicity.
Mode of toxicity: Accidental overdose.
Pathophysiology:
1. The physiological effects of opioids are mediated
principally through mu and kappa receptors in the CNS
 172
and peripheral nervous system. Sigma and delta receptors
may be activated as well.
2. Activation of opiate receptors results in inhibition of
synaptic neurotransmission in the CNS.
3. The opiate antagonists (e.g., naloxone, nalmefene,
naltrexone) antagonize the effects at all 4 opiate
receptors.
Preparations:
1. Opium ( a mixture of alkaloids extracted from papver
somnifarum fruit containing morphine and codeine.
2. Opiods are synthetic products that have opium like
effects:
A) Heroine (diacetylmorphine):
It is a synthetic product, of high liposolubility and
of better bioavailability. It is 5-10 times more toxic
than morphine and its action is immediate because it
enters the brain so rapidly.
B) Tramadol (tramal).
C) Pethidine (Meperidine).
D) Methadone, Buprenorphine, Nalbuphine (Nubain).
E) Antidiarrheal: diphenoxylate (lomotil) & loperamide
(imodium). Antitussive: codeine (broncholase),
codethyline (ethylmorphine).

Clinical picture of acute opiates overdose:

1- Depressed level of consciousness, stupor or coma which
may be preceded by anxiety, agitation, euphoria or
dysphoria, depression and hallucinations.
2- Respiratory depression: Rates as slow as 4-6/min are
often seen with moderate to severe intoxication with a
resultant hypoxia.
3- Pin-point pupils (miosis), opiate toxicity should be
suspected when the clinical triad of CNS depression,
respiratory depression and pin-point pupils are present.
However, reliance on pupillary miosis to diagnose opioid
intoxication can be misleading. Pupillary dilation may be
 173
present due to CNS hypoxia which may be accompanied
with hypertension.
4- Sinus bradycardia. Ventricular arrhythmias may occur 2ry
to hypoxia.
5- Hypothermia.
6- Orthostatic hypotension due to peripheral vasodilation.
Pruritis, flushed skin and urticaria may be seen due to
histamine release.
7- Pink frothy sputum, cyanosis, dyspnea, tachypnea,
crepitation and bronchospasm srtongly suggest non
cardiogenic pulmonary edema (especially heroin) due to
hypoxic alveolar damage or inhalation pneumonia.
8- Cardiac arrest is an indication of severe hypoxia and poor
neurological outcome.
9- Skin boils, cellulitis and needle tracks are occasionally
observed in IV users due to use of contaminated needles,
phlebitis and fibrosis of the veins.
10- Distal cyanosis or gangrene of hand or forearm is
frequently seen in IV drug users accidentally injected
arterially, provoking reactive distal arterial vasospasm or
particulate embolism.
N.B. Tramadol is a synthetic analog for codeine, Overdose: can
produce convulsions in susceptible individuals.
Causes of death:
Include respiratory depression, pulmonary edema,
arrhythmias and irreversible brain damage 2ry to prolonged
hypoxia.
DD:
Diffrential diagnosis of pin point pupils:
1- Pontine hemorrhage or brainstem cardiovascular
accident.
2- Organophosphorous insecticide poisoning. In both these
conditions pin-point pupils associated with coma and
respiratory insufficiency confuse the diagnosis.
3- Carbamate toxicity.
Diagnosis:
 174
A- History: A detailed history may be obtained from family
or friends. Finding pill bottles or eye witness may assist
in the diagnosis.
B- Clinical picture.
C- Investigations:
1- ABG, electrolytes, glucose (Random Blood Sugar),
urea and creatinine.
2- Drug screens in urine and in gastric lavage fluid to
confirm or to discard diagnosis and to detect
associated abused drugs.
3- Chest X-rays are obtained if pulmonary edema is
suspected.
4- Abdominal X-Rays may be helpful when evaluating a
suspected body stuffer (i.e., a patient who swallows
drugs in an effort to hide evidence from police) or
body packer (i.e., patients who seal large amounts of
drugs in condoms and then swallow them for
transport across borders).
5- An ECG to detect hypoxia effects and arrhythmia.
Treatment:
I- Emergency measures (ABCD).

 Naloxone is a pure competitive antagonist of opioid

II- Antidote: Naloxone (Narcan)

 Given in a dose of 1-2mg in adults & 0.1mg/kg in child

receptors and lacks any agonist activity.

 Naloxone can be given by the following routes: IV.ET (in

up to 2mg.

Endotracheal Tube), IL (Intralingual) or IM, a second

dose can be repeated if no response is noted after 3-5

 Side effects are rare at therapeutic doses. Administer

min.

the lowest practical dose because precipitation of

withdrawal is potentially determintal and
unpredictable. The onset of action is often within 5 min

 Initial lowest successful dose should be followed by a

and subsides in 1-2hr.

continuous infusion of naloxone in saline or dextrose

 175
as a drip to avoid relapses because naloxone has

 Naloxone may be given to unknown possibly toxic

shorter duration of action than opiates.

coma associated with respiratory depression in a dose

of 2mg IV. Good response is strongly suggestive of
opiate intake.
N.B: Nalmefene (Revex) is a newer opioid antagonist
with longer half life (4-8 hours) as compared to
naloxone. It is helpful in acute intoxication.

 Gastric lavage or whole bowl irrigation is done after

III- Elimination:

oral ingestion. Delayed gastric lavage may be usefull

because opiates delay gastric motility and it is also
done in body packers who swallow heroin bags to hide

 Activated charcoal. Due to impairment of gastric

the drug from police.

emptying and GI motility produced by opiate

intoxication, charcoal may still be effective when
patients present late following ingestion.

 IV fluids for dehydration and daily fluids need.

IV- Supportive treatment:

 Antiarrhythmics if rhythm disturbances develop.

 Anticonvulsants if seizures.
 Management of pulmonary edema.
 General management of coma

Opioid Dependence
Definition:
It is a state of chronic intoxication produced by repeated
intake of opiates for their euphoric effects and to escape
reality (conflicts and suffering in human life).
 176
Tolerance is a characteristic feature of opiates which
may be due to adaptation of the neuron to opiate intake. No
tolerance occur for miosis and constipation.
Mechanism of dependence:
Four types of opiate receptors (Mu, Kappa, Sigma and
Delta) are present in the CNS. They are involved in pain
perception and transmission. High concentration of biologically
active peptides have been found in these areas e.g.
endorphins, encephalins and dynorphins. Such peptides are
believed to function as neurotransmitters and known as
endogenous opioids. Exogenous narcotic agonists and
endogenous opioids decrease sodium permeability in opiate
receptors. The use of exogenous narcotic agonists decreases
the need for endogenous opioids. Sudden cessation of
narcotics does not allow enough time for regaining adequate
endorphin production. This results in sodium permeability with
subsequent neuronal hyperexcitability and withdrawal
manifestations.
Clinical picture:
1. Mental change: lack of concentration, amnesia and
decreased mental powers.
2. Mood changes: Patient becomes careless, lack of interest
in everything except getting the narcotic by any mean
with wide mood swings (period of depression, anger and
irritability alternating with euphoria).
3. Moral changes: the patient becomes dishonest, forced to
crime to obtain the drug with absence of social
integration.

 Anorexia, malnutrition, weight loss.

4. Physical effects:

 Always miosis and constipation.

 Evidence of multiple injections (called needle tracks)
which may be septic and found along veins.
5. Withdrawal manifestations: Signs and symptoms of acute
opiate withdrawal can emerge within hours of cessation of
short acting drugs (such as heroin), peak within 36 to 72 hours
and subside over a period of 7 to 10 days.
 177
Manifestations:
 Rhinorrhea, salivation, sweating, lacrimation and

 Vomiting, colic, diarrhea, urinary incontinence and

yawning.

 Irritability, tremors and agitation.

dehydration.

 Insomnia, pains allover the body and muscle aches

 Shivering and cold sensation.
 Hypertension, tachycardia, tachypnea and dilated pupils.
 Death may occur from dehydration and collapse.
Diagnosis:
1- History.
2- Clinical picture.

 Urine screen. Remember that positive urine screen does not

3- Investigations:

necessarily mean dependence.

Treatment:

 It should be individualized according to dependence

I- Detoxification:

status, general condition of the patient, intensity and

duration of dependence and co-existing other drug

 Good will from the patient's side helps to a great extent

dependence or other medical conditions.

 The procedure necessitates hospitalization and strong

the detoxification and the following steps of treatment.

 It may be performed by gradual detoxification which is

supervision.

completed in one month using easily adjustable doses

of opiate drugs of long half life. The ideal drug would be
methadone in gradually decreasing doses until it can be
stopped. Patients are not allowed to take their

 Drugs used in detoxification

methadone home.

1. Alpha2 adrenergic agonists as clonidine or lofoxidine

to block most of withdrawal signs. Clonidine acts by
releasi g e doge ous opioid a d α ago ist effe t
 178
decreasing c.AMP and all manifestations of
withdrawal. These drugs carry the risk of
hypotension.
2. Supportive care and drugs for pain relief and control
of vomiting, diarrhea and anxiety without restoring
to drugs of abuse.
3. Naltrexone, a long acting opiate antagonist given as
an outpatient treatment aiming to block the opiate
receptors and block any opiate agonist effect in case
of reuse of the drugs in moments of craving. It
should be used once detoxification is complete as
50mg tablet once daily for 3 months.
4. Sedatives.
II- Psychotherapy and rehabilitation.
III- Follow up.
ALCOHOL DEPENDENCE
Mechanism of Alcohol Dependence:
Alcohol enhances the actions of the inhibitory neuro-
transmitter GABA, which are mediated by the GABA receptor.
Repeated consumption of alcohol produces a decrease of
endogenous GABA. Stopping alcohol will initiate sudden
withdrawal manifestation due to the reduction of GABA
production.
Effects:

 Cardiomyopathy and arrhythmias.

1. Heart:

 Tremors,
2- Neurological:
cerebellar ataxia and cerebellar

 Peripheral neuropathy.
degeneration.

 Increased risk of cerebro-vascular accidents

 Wer i ke’s e ephalopath : distur ed e tal state,
ataxia, nystagmus, confusion and paralysis of eye

 Korsakoff’s ps hosis: a esia to re e t e e ts a d

movement.

confabulation.
 179
 Depression, suicides.
 Violence.

 Recurrent severe acute gastritis with ulcerations.

3- Gastrointestinal:

 Pancreatitis.
 Fatty liver early stages.
 Liver cirrhosis.

 Muscle
4- Muscle:
pain and weakness (myopathy),
Rhabdomyolysis and increased CPK.

 Anemia, leucocytosis, thrombocytopenia (easy

5- Blood:

bruising) and bleeding.

Alcohol Withdrawal Syndrome:
 Delirium tremens (DTs) begins after 2-3 days, lasts 3-5
days and consists of profound confusion, incontinence,
tremor and frightening hallucinations. It may precipitate

 Alcohol withdrawal syndrome resolve after 5 days.

violence and aggression, suicide or homicide.

Investigations:
1. CBC.
2. Liver function tests.
3. Amylase.
4. ECG.
5. Imaging studies: ultrasound or CT abdomen is useful to
screen and evaluate hepatitis, cirrhosis, ascites and
chronic pancreatitis with cysts.
Treatment:
1. Hospitalization of severe withdrawal states.
2. Evaluation and management of associated medical
complications.
3. Abrupt withdrawal should be covered by benzodiazepine
anxiolytics and antidepressants.
4. Good nutrition and vitamins especially Vitamin B1
(Thiamine 100 mg/d) to prevent Wernicke,s
 180
encephalopathy, Vitamin B2, Folic acid, Ascorbic acid and
Vitamin K.

 This drug blocks the aldehyde dehydrogenase enzyme

5. Disulfiram (Antabuse):

 accumulation of acetaldehyde. Alcohol ingestion 

severe but harmless reaction (malaise nausea,

 Antabuse is started 24 hrs after the last alcohol dose

vomiting, palpitations, sweating, and tachycardia.

at which time patient should be on benzodiazepine

sedation.
6. Psychotherapy and group therapy.
AMPHETAMINE
Introduction:
The most common type of amphetamine is Ecstasy
named methylene dioxy metamphetamine (MDMA) or named
hallucinogenic amphetamine.

 Induce euphoria.
It is used to:

 Decrease fatigue (athletes).

 Anorexogenic.
 Induce alertness.
Route of intake:
1- Inhalation.
2- Injection.
3- Ingestion.
Mechanism of action:
I- Sympathomimetic action due to:
a- Increase release of catecholamines especially dopamine
and serotonin.
b- Prevention of reuptake of catecholamines.
c- Inhibition of MAO enzyme which destroys

 Amphetamine releases high levels of the

catecholamine.

neurotransmitter dopamine, which stimulates brain

cells, enhancing mood and body movement. It also
 181
appears to have a neurotoxic effect, damaging brain
cells that contain dopamine and serotonin.
ІІ- Vasospasm of blood vessels due to increased level of
serotonin.

Acute Amphetamine Overdose

Clinical picture:
І- Sympathomimetic action:

 CNS stimulation followed by depression with

A- Central:

euphoria, delayed fatigue, restlessness, irritability,

insomnia, tremors, hallucinations, agitation,
convulsions (which may result in hyperthermia and
rhabdomyolysis) then confusion, drowsiness, coma,

 Anorexia (serotonin induced)

respiratory center depression and VMC depression.

 IV rush: It is intense pleasurable sensation lasts for

few minutes that occurs during injection.

 Tachypnea, tachycardia, hypertension, arrhythmia,

B- Peripheral:

 Hypertension may be so severe causing: subarachnoid

dilated reactive pupils and diaphoresis.

hemorrhage, intracranial (intraparenchymal)

hemorrhage with neurological sequelae.
IІ- Vasospasm of blood vessels:
 Renal vasospasm leading to renal infarction and acute

 Coronary vasospasm leading to myocardial ischemia and

renal failure.

even infarction which is aided by increase heart work

 Cerebral vasospasm leading to cerebral infarction.

and oxygen demand due to sympathomimetic effect.

IIІ- Needle marks, cellulitis, abscesses, and phlebitis.

IV- Loss of weight.
N.B. Rhabdomyolysis caused by amphetamine is due to:
 182
1. Direct toxic effect.
2. Vasospasm of BV.
3. Convulsions.
Treatment:
I- Emergency: ABC.
II- Elimination: Gastric lavage is very effective in cases of oral
intake then activated charcoal is administered.

 Agitations: Benzodiazepines.
III- Symptomatic treatment:

 Hypertension: Benzodiazepine is the first choice, if no

response; the best antihypertensive agent used is IV

 Hyperthermia: Cooling.
Na nitroprusside or nitroglycerine (vasodilators).

 Rhabdomyolysis: Fluids, alkaline dieresis or

 Arterial vasospasm: Phe tola i e )α a tago ist( or

hemodialysis.

Nitroglycerine may be used also for coronary

vasospasm.
Amphetamine Dependence
Dependence on amphetamine occurs to prevent sleep,
decrease fatigue, increase athletic performance, induce
euphoria, increase self confidence, induce anorexia (to
decrease weight) and increase mental abilities.
Clinical picture:
І - Physical changes:
 Anorexia and loss of weight.
 Euphoria, tachycardia, hypertension, and dilated
reactive pupils, tremors, insomnia, irritability and

 Parkinsonism due to dopamine depletion and damage of

delayed fatigue.

 Needle marks, cellulitis and abscesses.

cells.

ІІ- Mental changes:

 Amphetamine psychosis due to prominent
dopaminergic effect.
 183
ІІІ- Psychological changes:
 Social isolation and lack of personal hygiene.
 Hallucinations (visual, auditory, olfactory and tactile)

 Criminal or antisocial acts to obtain the drug.

IV- Moral changes:

 Tendency to violence and aggressiveness.

 Fatigue, somnolence, confusion, apathy, depression and

V- Withdrawal manifestations:

increase appetite.
Treatment:


Hospitalization of the patient.


Sudden withdrawal.


Sedation.


Dopamine agonist (amantadine or bromocriptine).


Serotonin reuptake inhibitor (fluoxetine).


Psychological treatment.
Good diet, vitamins and health care.
BENZODIAZEPINES DEPENDENCE
Benzodiazepine is an addictive drug with tolerance,
psychological and physical dependence. Tolerance develops
rapidly to its sedative effect. Dependence occurs if it is
continuously administrated for more than 4 months.
Street name: ‫ا ص ي‬
Clinical picture:
1- Mental changes: confusion, lack of concentration and
amnesia.
2- Mood changes: depression, hallucination and paranoid
reaction.
3- Moral changes: aggressiveness and hostility.
4- Physical changes: nystagmus, ataxia, drowsiness, slurred
speech and postural hypotension.
5- Withdrawal manifestations: occur if Benzo is withdrawn

 Anxiety, insomnia, tremors, agitation, myalgia,

and starts within 24 hrs with:-

nightmares, headache, seizures and psychosis.

 184
Treatment:
Withdrawal of short acting Benzo and replacing it by a
long acting one, then gradual withdrawal of the long acting
one.
CANNABIS
The various forms of cannabis come from the plants
Cannabis Sativa and Cannabis Indica, which grow throughout
the world including Egypt.
Cannabis is available in three main forms, as a dried
herb (composed of top leaves and buds - usually known as
bango), as a resin (usually known as hash or hashish) which is
extracted from the buds and flower tops, and less commonly as
a sticky liquid (hashish oil) which is prepared from the resin.
Absorption and Metabolism:
Cannabis is most commonly smoked. Usually by mixing it
with tobacco and rolling it up into a cannabis cigarette.
Cannabis is strongly lipophilic and it passes rapidly to brain and
adipose tissues where it is stored. It is metabolized in the liver
to several inactive metabolites.
Pathophysiology:
Cannabinoids act on CB1 and CB2 receptors on
dopaminergic neurons increasing the release of dopamine and
preventing its recapture in the limbic system, cerebellum and
hippocampus
Cannabinoids act on all other systems of
neurotransmission including GABA-ergic, cholinergic,
serotoninergic and opioid system (interact with endorphins)
Acute Cannabis Intoxication:
Smoking Cannabis produces fairly instant intoxication
within 15 - 20 minutes, the effects lasting from 1 to 4 hours
depending on the amount used.
1. The most common and most desired effects are
talkativeness, cheerfulness, relaxation and greater
appreciation of sound and color.
2. High doses can cause mild euphoria and disinhibition.
 185
3. Apathy and sedation Very poor memory and lack of
concentration and attention Slurred speech and Increased
appetite.
4. Impaired judgment and disorientation to distance and
time.
5. Drowsiness, Decreased level of consciousness.
6. Conjunctival congestion.
7. Dry mouth.
8. Tachycardia.
9. Worsening of anxiety and panic reaction could be the first
experience of a new user. Fear of death is a common
complaint.
10.Nausea and vomiting.
Cannabis Dependence
Picture of Cannabis Abuse:
Repeated use of cannabis on daily basis expose the user,
in addition, to the following:
1. Cannabis psychosis; of short duration and relapse on re-
use of cannabis. Hallucinations and delusions are
reversible using neuroleptic drugs.
2. Lack of motivation
3. Mood swings, isolation, neglect of social and family life
obligations
4. Impaired immunity and increased tendency to chest
infections.
5. High mutagenic and carcinogenic potential.
Symptoms of withdrawal:
Characteristically, withdrawal symptoms and signs do
not start before 5 to 10 days as cannabis supply continue
during this time from the adipose tissue. In the mean time, the
user acquire the false experience that he may stop cannabis
without being affected and that he is not dependent.
Symptoms include:
1. Anxiety
2. Depression and mood changes
 186
3. Irritability
4. Insomnia.
5. Muscle pains and chills
6. Anorexia
Treatment:
No hospitalization is required unless the user has been
dependent to other drugs
A. Medications:
1. Anti-anxiety drugs: They share greatly to maintenance of
abstinence
2. Neuroleptics:
3. Anti-depressants. Mood stabilizers, however, may
worsen psychomotor tasks performance, cognitive and
mood performance
B. Psychotherapy.
 187
NICOTINE
Sources:
Present in the leaves of "Nicotiana Tabacum" plant.
Uses:
 The main source of exposure to nicotine nowadays is

 It was formerly used as an insecticide.

tobacco smoking.

Acute poisoning:

 Accidental due to exposure to nicotine containing

Mode of toxicity:

insecticides or ingestion of cigarettes by children.

Clinical Picture:
1. CNS: headache, tremors, irritability and convulsions,
followed by confusion and coma.
2. Skeletal muscles: twitches, fasciculations, then
paralysis and if it affects the respiratory muscles
cause dyspnea, cyanosis and respiratory failure.
3. Vomiting, colic and increased salivation, constricted
pupils, sweating, increased pulmonary secretions.
4. Tachycardia, arrhythmias and hypertension due to
stimulation of sympathetic ganglia and adrenal
medulla (catecholamines release).

 Respiratory failure (central or peripheral).

Causes of death:

Treatment:
I- Emergency measures (ABCD).

 Wash the skin if contaminated

II- Elimination:

 Emesis or gastric lavage and activated charcoal.

 Atropine for bradycardia,

III- Symptomatic treatment:

VOLATILE ABUSE
Some persons resort to sniffing (smelling and inhalation
through the nose) of volatile substances to reach a narcotic
state. They may sniff organic solvents as chloroform, acetone,
 188
thinner, ether and benzene. They also may sniff glue, nail
polish for the volatile organic solvent they contain.
Manifestations:
It is a state of chronic intoxication leading to:
1- Euphoria, irritability, excitement, hallucinations,
dementia, memory loss and in severe cases CNS
depression.
2- Peripheral neuropathy: weakness, wasting of muscles,
tingling, numbness, paresthesia, loss of sensations. Cranial
nerves affection occurs with toluene (optic neuritis).
3- Bone marrow depression: anemia, leucopenia,
thrombocytopenia, especially with benzene and toluene.
4- Ventricular arrhythmia, renal and hepatic damage.
5- Dermatitis and inflammation of the nose and upper lip,
nasal mucosa is ulcerated and inflamed.
6- Chronic inflammation of the respiratory tract.
Treatment:
1- Hospitalization.
2- Stop the habit.
3- Health and psychological care.
4- Symptomatic treatment.
Cocaine
(E-learning)
Performance enhancing drugs
(E-learning)
Summary:
Drug dependence is one of the major problems that affect
health and society. This chapter discussed the general aspects
of dependence describing the clinical presentation and
management of some substances of abuse.
Questions:
1. Which of the following would not be an illicit drug
a. Aspirin
b. Cocaine
 189
c. Heroin
d. Tylenol with codeine

2. A drug with high addiction potential and medical use

would be put in schedule
a. I
b. II
c. III
d. IV
e. V
3. Heroin is classified as
a. Stimulant
b. Narcotic
c. Steroid
d. Hallucinogen
4. Dronabinol
b. Is a plant
c. Comes from plant
d. Is totally synthetic
e. Is made from another drug
5. State if this statement is true or false:
Gas Chromatography is a confirmatory test for drugs ( ).
6. In what schedule is marijuana?
7. In what schedule is dronabinol?
8. Describe the treatment of chronic alcoholism.
9. Discuss the clinical presentation of acute amphetamine
toxicity.
10. Explain the pathophysiology and clinical presentation of
acute cannabis toxicity.
11. Give an account on cocainism.
12. Describe the clinical picture of benzodiazepines
dependence.
13. Discuss the clinical presentation and treatment of acute
nicotine toxicity.
14. Discuss management of acute opiate toxicity.
 190
15. Describe the clinical picture of opiate dependence.
16. Discuss the manifestations of volatile abuse.
 191

CHAPTER 16
Role of Laboratory in Clinical Toxicology
ILOs:
By the end of this chapter the student should be able to:
K1: Enumerate the role of lab in clinical toxicology.
K2: List the different types of samples and the advantages of
each.
K3: Discuss the timing of samples, their labeling and other
data needed by the laboratory.
K4: Discuss bedside tests.
A1: Realize the importance of the role of the laboratory in
diagnosing and directing the treatment of different
toxicities.
A2: Realize the importance of time factor in collecting
samples and the importance of their accurate labeling.
The role of the laboratory in the clinical toxicology
includes the following:
1- Diagnosis of poisoning whether acute or chronic poisoning.
2- Diagnosis and treatment of drug abuse.
3- Mass testing of employees for drugs of abuse.
4- In work places for health care, frequent random testing is
done for those working dangerous jobs.
5- In sports, winners are routinely tested for performance
enhancing drugs.
6- During therapy of some drugs to adjust the therapeutic level as
in digoxin, lithium, and theophylline.
7- Measurement of biological effect of drug as plasma ChE in
case of organophosphorous compounds, also CO-Hb level in
case of carbon monoxide poisoning.
8- Assessment for treatment by doing serial estimations of
plasma levels before, during and after treatment.
9- In addition to drug detection in body fluids, routine
laboratory studies include: CBC, electrolytes, BUN, glucose,
blood gases, prothrombin time, liver enzymes, etc...
 192
N.B.: Emergency management must not be delayed till
laboratory results, treat the patient instead.

SAMPLING
Sample should be o When the patient first arrives.
taken o After several hours to establish
"peak level".
o Serial sampling to evaluate the
efficacy of therapy.

Sample should be o Name.

labeled with the o Age.
patient's o Sex.
information (needed o Nationality.
by the lab) o Job.
o Place of performance of sampling.
o Name of the doctor in charge.
o Date and time of sampling.
o Present history.

Present history o Suspected time of ingestion of

poison
o Suspected poison
o Suspected dose
o Last meal in case of food poisoning
o Medical treatment given
o Level of consciousness of the
patient
o number of individuals involved in
same illness

N.B.: for medicolegal purposes, the first gastric aspiration,

blood or urine sample should be preserved and labeled as
above for further investigations by legal authorities.
 193

Types of sample:

Gastric Blood Urine

aspirate
Volume 30-50 ml 10 ml 30-50 ml
Form Vomitus
Gastric
aspirate
Stomach
wash
Advantage - First - Essential for - Large
sample of detection of quantities
washing is drugs with long available with a
the most 1/2 life or very non invasive
useful for recent ingestion technique.
quantitative so not yet - contains high
analysis excreted in urine concentration
- If drug e.g. long acting of drugs and
absorption benzodiazepines poisons.
is not yet & barbiturates. - Drugs with
occurred, - But, it is an large volume of
gastric fluid invasive distribution in
is the only technique. blood can be
positive. detected easily
in urine e.g.
phenothiazine
&
amphetamine.
 194
Bedside Tests:
These are simple tests done by the emergency
department personnel for rapid detection of the drug used or
its metabolites.
Color test done in urine: Specific colors given by specific
drugs with suitable reagents.

Examples of color tests:

1 Salicylates(1 Trinder's Violet color(lf

 salicylate in
ml urine) reagent(ferric + ve,
+ chloride) 5 drops
therapeutic
doses)

2 Phenothiazine FPN reagent (ferric Pink -

(1 ml urine) chloride, redorange

perchloric acid, color
+
nitric acid) 1 ml (+ve in
therapeutic
doses)


3 TCA Forrest reagent 1 Blue - green
+
(0.5 ml urine) ml color

Summary:
The role of laboratory in Clinical Toxicology is discussed,
enlightening its importance and the importance of accurate
sampling. Some examples of bedside tests are also discussed.

Questions:
1- Discuss the role of laboratory in Clinical Toxicology.
2- Describe the timing and labeling of samples taken to the
toxicology laboratory.
 195

References
Aygun, D.; Erenler, A.; Karatas, A.; et al. (2007): Intermediate syndrome following
acute organophosphate poisoning. Correlation with initial serum levels of muscle
enzymes. Basic Clin Pharmacol Toxicol 100: 201-4.
Barceloux, D. G.; Bond, G. R.; Krenzelok, E. P. et al (2002): American Academy of
Clinical Toxicology practice guidelines on the treatment of methanol
poisoning. J Toxicol Clin Toxicol. 35: 82-86.
Bosse, G. M. (1996): Benzodiazepines. In: Emergency Medicine: A Comprehensive
th
Study Guide. 4 ed. McGraw-Hill. p. 759-761.
Bronstein, A. C.; Spyker, D. A.; Cantilena, L. R.; Green, J. L.; Rumack, B. H.; Giffin, S.
L.( 2008): Annual Report of the American Association of Poison Control
Centers' National Poison Data System (NPDS): 26th Annual Report. Clin
Toxicol (Phila). 47: 911-1084.
Buckley, N. A.; Dawson, A. H.; Whyte, I. M.; O'Connell, D. L. (1995): Relative
toxicity of benzodiazepines in overdose. BMJ. 310: 219-21.
Chyka, P. A; Erdman, A. R; Christianson, G; Wax, P. M. Et al. (2007): Salicylate
poisoning: an evidence-based consensus guideline for out-of-hospital
management. Clin Toxicol. 45: 95-131.
Clark, R. F. (1999): Specific Poisons and Drugs: Diagnosis and Treatment. In:
Poisoning and Drug Overdose. Olson, K. R. (Ed.). Appleton & Lange, Stamford,
Connecticut. p. 286-298.
Crabb, D. W.; Matsumoto, M.; Chang, D. et al (2004): Overview of the role of
alcohol dehydrogenase and aldehyde dehydrogenase and their variants in
the genesis of alcohol-related pathology. Proc Nutr Soc. 28: 43-47.
de Ketttenis, P. (2005): The historic and current use of glycol ethers: A picture of
change. Toxicol Lett. 25: 32-38.
Ellenhorn, M. J.; Schonwald, S.; Ordog, G.; Wasserberger, J. (1997):
Envenomations, bites and stings. In: Ellenhorn's Medical Toxicology:
Diagnosis and Treatment of Human Poisoning. Williams & Wilkins, Baltimore.
p. 1737-1798.
Eyer, P.; Sziniez, L.; Thiermann, H. et al. (2006): Testing of antidotes for
organosphosphorus compounds; Experimental procedures and clinical reality.
Toxicity 233: 108-19.
Fulton, J. A. (2007): Caustics and batteries. In: Goldfrank's manual of toxicologic
emergencies. Hoffman, R. S.; Nelson, L. S. and Goldfrank, L. R. (Eds.).
McGraw-Hill, New York. p. 868-876.
Goel, A. & Aggarwal, P. (2007): Pesticide poisoning. NaH Med J India; 20: 182-91.
Goldfrank, L. R & Flomenbaum, N. E. (2002): Botulism. In: Goldfrank's toxicological
emergencies. Seventh edition. Hoffman, R. S.; Goldfrank, L. R. & Lewin, N. A.
(Eds.). McGraw-Hill, New York. p. 1100-1111.
Goldfrank, L. R. & Flomenbau, N. E. (2007): Sedative-hypnotic agents. In:
th
Goldfrank's Toxicologic Emergencies. 8 ed. Prentice Hall. p. 615-625.
Halavaara J, Valanne L, Setala –K (2002): Neuroimaging supports the clinical
diagnosis of methanol poisoning. Neuroradiology. 15: 32-37.
Harding, K. A. & Welch, K. R. E. (1980): Venomous snakes of the world-A checklist.
Pergamon Press, Oxford. p. 121-147.
 196
Hoffman, R. S.; Nelson, L. S.; Howland, M. A.; Lewin, N. A.; Flomenbaum, N. E.; and
Goldfrank, L. R. (2006): Analgesics and anti-inflammatory medications. In
th
Goldfra k’s a ual of to i ologi al e erge ies, 8 edition. McGraw Hill
Medical, USA. p. 654-670.
Hoyda, K. E.; Hunderi, O. H.; Rudberg, N. Et al. (2004): Anion and osmolal gaps in the
diagnosis of methanol poisoning: Clinical study in 28 patients. Intensive Care
Med. 21: 15-19.
Kim, S. (1999): Specific Poisons and Drugs: Diagnosis and Treatment. In: Poisoning
and Drug Overdose. Olson, K. R. (Ed.). Appleton & Lange, Stamford,
Connecticut. p. 173-176.
Kleber, H. D.; Weiss, R. D.; Anton, R. F. et al (2006): Treatment of patients with
substance use disorders, second edition. American Psychiatric
Association. Am J Psychiatry.163:5-82.
Marsha, F. (1993): Insecticides and pesticides: In: Handbook of medical toxicology,
ed., Peter Viccellio, Little, Brown and Company. Boston/Toronto/ London, p. 303-
13.
Miner, J. R.; Danahy, M.; Moch, A. et al. (2007): Randomized clinical trial of
etomidate versus propofol for procedural sedation in the emergency
department. Ann Emerg Med. 49: 15-22.
Mullen, W. H. (2007): Specific Poisons and Drugs: Diagnosis and Treatment. In:
Poisoning and Drug Overdose. Olson, K. R. (Ed.). Appleton & Lange, Stamford,
Connecticut. p. 157-159.
Murphy, M. (2002): Rodenticides. Vet Clin North Am Small Anim Pract 32: 469-484.
National Collaborating Centre for Mental Health (2004): Self-harm: the short-term
physical and psychological management and secondary prevention of self-
harm in primary and secondary care. London (UK): National Institute for
Clinical Excellence (NICE). p. 199.
Olson, K. R. (2007): Specific Poisons and Drugs: Diagnosis and Treatment. In:
Poisoning and Drug Overdose. Olson, K. R. (Ed.). Appleton & Lange, Stamford,
Connecticut. p. 296-297.
Otten, E. J. (2007): Snakes and other reptiles. In: Goldfrank's manual of toxicologic
emergencies. Hoffman, R. S.; Nelson, L. S. and Goldfrank, L. R. (Eds.).
McGraw-Hill, New York. p. 923-934.
Perry, H. (2007): Rodenticides. In: Clinical management of poisoning and drug
th
overdose, 4 edition, Shannon M, Borron S and Burns M, Saunders Company,
Philadelphia. p. 1213-1223.
Principles of Clinical Toxicology (2006): Forensic medicine and clinical toxicology
department. Faculty of Medicine Ain Shams University.
Rao, B. R & Hoffman, R. S. (2002): In: Goldfrank's toxicological emergencies.
Seventh edition. Hoffman, R. S.; Goldfrank, L. R. & Lewin, N. A. (Eds.).
McGraw-Hill, New York. p. 1323-1345.
Russel, F. F. (2001): Toxic Effects of Terrestrial Animal Venoms and Poisons. In:
Casarett a d Doull’s To i olog : The Basi “ ie e of Poisons. Klassern, C. D.
(Ed.). McGraw-Hill, New York. p. 945-964.
Serfaty, M. & Masterton, G. (1993): Fatal poisonings attributed to benzodiazepines
in Britain during the 1980s. Br J Psychiatry. 163: 386-93.
Tunik, M. G. (2007): Food poisoning. In: Goldfrank's manual of toxicologic
emergencies. Hoffman, R. S.; Nelson, L. S. and Goldfrank, L. R. (Eds.).
McGraw-Hill, New York. p. 386-393.
 197
Warrell, D. A. (1995): Clinical Toxicology of Snakebite in Africa and the Middle
East/Arabian Peninsula. In: Handbook of Clinical Toxicology of Animal
Venoms and Poisons. Meier, J. & White, J. (Eds.). CRC Press, New York,
London Tokyo. p. 433-474.
Woo, O. F. (1999): Specific Poisons and Drugs: Diagnosis and Treatment. In:
Poisoning and Drug Overdose. Olson, K. R. (Ed.). Appleton & Lange, Stamford,
Connecticut. p. 112-114.