1. DRUG OVERDOSE POISONING
Dr Ranjita Santra (Dhali)
Assistant Professor
Department of Clinical & Experimental Pharmacology
School ofTropical Medicine
Kolkata

2. Drug Overdose
 When a drug is eaten, inhaled, injected, or
absorbed through the skin in excessive
amounts and injures the body
 Overdoses are either intentional or
unintentional
 If the person taking or giving a substance did
not mean to cause harm, then it is
unintentional
 Drug poisoning is the toxic effect resulting due
to drug overdose

3. The Problem
 Drug overdose was the leading cause of injury
death in 2012
 Among people 25 to 64 years old, drug overdose
caused more deaths than motor vehicle traffic
crashes
 The drug overdose death rate has more than
doubled from 1999 through 2013
 In 2013, 35,663 (81.1%) of the 43,982 drug
overdose deaths in the United States were
unintentional, 5,432 (12.4%) were of suicidal
intent, and 2,801 (0.06%) were of undetermined
intent

4. The Problem
 Among children under age 6,
pharmaceuticals account for about 40% of all
exposures reported to poison centres
 Centers for Disease Control and Prevention. Webbased Injury StatisticsQuery and Reporting System
(WISQARS) [online]. (2014) Available from URL:http://www.cdc.gov/injury/wisqars/fatal.html
 Mowry JB, Spyker DA, Cantilena LR, Bailey JEFord M. 2012Annual report of theAmerican
Association of Poison Control Centers’ National Poison Data System (NPDS): 30th annual report.
ClinTox 2013;51:9491229.
 Centers for Disease Control and Prevention. NationalVital Statistics System mortality data. (2015)
Available from URL: http://www.cdc.gov/nchs/deaths.html

5. The Problem
 The exact incidence of this problem in our
country remains uncertain but it is estimated
that about 10-15 million cases of drug
overdose poisoning are reported every year,
of which, more than 50,000 die
Aggarwal et al.Acute poisoning-Management Guidelines. Journal of IndianAcademy of Medical Sciences. 2013;5:142-7

8. Most Common Drugs Involved in
Overdoses
 Of the 22,767 deaths relating to pharmaceutical overdose in
2013, 16,235 (71.3%) involved opioid analgesics (also called
opioid pain relievers or prescription painkillers), and 6,973
(30.6%) involved benzodiazepines
 Benzodiazepines are frequently found among people
treated in EDs for misusing or abusing
Drugs
 People who died of drug overdoses often had a
combination of benzodiazepines and opioid analgesics in
their bodies
Substance Abuse and Mental Health Services Administration. Highlights of the 2011 Drug Abuse
Warning Network (DAWN) findings on drugrelated emergency department visits. The DAWN
Report. Rockville, MD: US Department of Health and Human Services, Substance Abuse and
Mental Health Services Administration; 2013. Available from URL:
http://www.samhsa.gov/data/2k13/DAWN127/sr127DAWNhighlights.

9. Risk Factors for Drug
Overdose
 Men were 59% more likely than women to die
 Whites had the highest death rate, followed by
American Indians/Alaska Natives and then
blacks
 Highest death rate was among people 45-49
years of age
 lowest death rates were among children less
than 15 years old
Source : htttp://www.cdc.gov/homeandrecreationalsafety/overdose/facts 2012.html

14. Toxicokinetics & Toxicodynamics
 Toxicokinetics (Determines the no. molecules that
can reach the receptors)
 Uptake
 Transport
 Metabolism & transformation
 Sequestration
 Excretion
 Toxicodynamics (Determines the no. of receptors
that can interact with toxicants)
 Binding
 Interaction
 Induction of toxic effects

15. Uptake and Elimination
Biological
System
Uptake Elimination
K1 K2
K1 > K2 : Accumulation &Toxic effect

16. Toxicokinetics
1. Uptake
2. Transport
3. Metabolism &Transformation
4. Sequestration
5. Excretion

17. Uptake of Toxicants
1. Passive diffusion
2. Facilitated transport
3. Active transport
4. Pinocytosis

18. Diffusion governed by
Flicks law
D/dt = KA (Co - Ci) / X
 Where:
 dD/dt = rate of transport accross the membrane
 K= constant
 A= Cross sectional area of membrane exposed to the
compound
 Co = Concentration of the toxicant outside the membrane
 Ci= Concentration of the toxicant inside the membrane
 X=Thickness of the membrane

19.  Toxicokinetic data is best derived using radio labeled
dose of the drug. This allows for following the fate of
the drug, metabolic products, distribution in the tissue,
storage sites, as well as its elimination
 Unfortunately, these methods do not provide
knowledge about proportion of the drug left intact to its
metabolites

20. Toxicodynamics
 Toxicodynamics is the study of toxic actions
of xenobiotic substances on living systems.
 Toxicodynamics is concerned with processes
and changes that occur to the drug at the
target tissue, including metabolism and
binding that results in an adverse effect.
 Simply,TD is concerned with what the
toxicant do to the body

22. Blood and lymph
Liver
Intravenous Intraperitoneal
Subcutaneous
Intramuscular
Dermal
extracellular
fluid
fat
Secretory
Structures
Bile
Kidney Lung
Bladder Alveoli
Urine Expired Air Secretions
body
organs
soft
tissue bone
Gastrointestinal
tract
Lung
feces
InhalationIngestion
distribution

23. Important principles of
toxicokinetics
 The effect which a drug produces is
dependent on:
1. The dose
2. The concentration in the target organ
 The kinetics of a drug may differ from
therapeutic dose to its toxic dose
 Toxicokinetics is important in predicting the
plasma concentration of a drug

24. Toxicokinetics and toxicity
Toxicity depends on:
 Duration and concentration of drug at the portal of entry
 The rate and amount (extent) of drug absorbed; toxicity will
be low at slow absorption rates.
 A highly toxic drug that is poorly absorbed may have same
hazard as another with low toxicity but is highly absorbed.
 The distribution of drug within the body; where most drugs
are distributed in highly perfused organs like brain, liver and
kidneys
 In some cases, the organ in which the drug is concentrated
may not necessarily suffer the damage
 An example is organochlorine compounds concentrated in
adipose tissue while the target organ is the brain.

25.  The efficiency of biotransformation and nature of
metabolites; where, in some cases, a drug may be
transformed to a more toxic metabolite or a more
lipid soluble or water soluble metabolite, which
affects absorption and distribution e.g.
paracetamol, INH, dapsone, hydralazine
 The ability of the drug to pass through cell
membranes and interact with cell constituents.
Example, some organochlorines affect the DNA
 The amount and storage duration of the drug or
its metabolites in the tissue e.g. Lead in bones is
an example
 The rate and site of excretion; where the more
rapid the excretion, the less toxicity it will produce

26. Cumulative toxicity
 The state at which repeated administration of a drug may
produce effects that are more pronounced than those
produced by the first dose is known as cumulative effect
 Results into cumulative toxicity
 Anticancer drugs -induced cardiotoxicity
 Non-cardiac pulmonary edema – Mtx, Cocaine, tocolytics,
hydrochlorothiazide, iodinated contrast agents, opiates
(hydrocodone, morphine etc.)
 Bronchiolitis obliterans-organizing pneumonia – Acebutolol
Amiodarone, Amphotericin B, Bleomycin, Carbamazepine
 Bronchospasm – Amp B, Aspirin, Amiodarone, ACEIs, inhaled
pentamidine, beta-blockers
 Iron, lead, mercury, aluminium, arsenic – developmental
disorders, degenerative disorders, haematological disorders

27. Digoxin
 Extracardiac adverse effects
 Cardiac adverse effects
 VT
 Nodal &Ventricular extrasystoles
 Pulsus bigeminus
 VF
 AFL, AF, severe bradycardia

28. Antiarrythmic drugs
 Qunidine, Procainamide – torsades de pointes
 Sotalol – intraventricular conduction defect
results intoVT ANDVF
 Adenosine - bronchospasm

29. Toxidromes
 Toxidromes are constellations of symptoms
commonly encountered with certain drug
classes, including anticholinergics,
cholinergics, opioids, and sympathomimetics
 Evaluation of possible medication poisonings
should include basic laboratory studies, such
as a complete metabolic profile, to determine
electrolyte imbalances and liver and renal
function

30. Common Toxidromes

31. Acute drug overdoses

32. Specific therapies

33. Specific therapies

34. Specific therapies

35. Substance Abuse and Overdose
 Addiction
 Habituation
 Physiological dependence
 Psychological dependence
 Tolerance
 Withdrawal
 Drug Overdose

36. Common Drugs of Abuse

37. Common Drugs of Abuse

38. Common Drugs of Abuse

39. General survey
 Directed cardiovascular, respiratory, abdominal and neurological
examination.
 Vital signs, pupils, etc. mentioned in 'Resuscitation' section, above.
 Temperature - hypothermia (phenothiazines, barbiturates, or tricyclics) or
hyperthermia (amfetamines,
 ecstasy, MAOIs, cocaine, antimuscarinics, theophylline, serotonin
syndrome).
 Muscle rigidity (ecstasy, amfetamines).
 Skin - cyanosis (methaemoglobinaemia), very pink
(carboxyhaemoglobinaemia, cyanide, hydrogen
 sulphide), blisters (barbiturates, tricyclic antidepressants (TCAs),
benzodiazepines), needle tracks,
 hot/flushed (anticholinergics).
 Breath - ketones (diabetic/alcoholic ketoacidosis), "bitter almonds"
(cyanide), "garlic-like"
 (organophosphates, arsenic), "rotten eggs" (hydrogen sulphide), organic
solvents.
 Mouth - perioral acneiform lesions (solvent abuse), dry mouth
(anticholinergics), hypersalivation (parasympathomimetics)

40. Investigations
 12-lead electrocardiogram.
 Blood glucose, anion gap ± lactate and osmolal gap.
 LFTs and coagulation profile
 Arterial blood gases analysis
 Comprehensive toxicology screens not normally indicated in the
emergency treatment unless in suspected cases
 Carboxyhaemoglobin levels if carbon monoxide poisoning is
suspected.
 Urinalysis - query rhabdomyolysis; save sample for possible
toxicological analysis.
 CXR if pulmonary oedema/aspiration suspected.
 CT scan of the brain may be needed to exclude other causes of
alterations in conscious level.

41. Differential diagnosis
 Head trauma (especially, in the ethanol-
intoxicated patient).
 Stroke/subarachnoid haemorrhage (SAH).
 Meningitis.
 Metabolic abnormalities (such as
hypoglycaemia, hyponatraemia, or
hypoxaemia).
 Liver disease.
 Post-ictal state

42. Poisoning reporting centres
 UK National Poisons Information Centres
 Toxbase®: NHS intranet and internet-based
information from the National Poisons
Information Centre (registration free to NHS GPs
and hospitals)
 Mims Colour index orTICTAC (a computer-aided
tablet and capsule identification system
available to authorised users, including Regional
Drug Information Centres and Poisons
 Information Centres.: to aid pill identification.
 British National Formulary (BNF)/Data Sheet
Compendium