drug overdose poisoning
TRANSCRIPT
DRUG OVERDOSE POISONING
Dr Ranjita Santra (Dhali)Assistant ProfessorDepartment of Clinical & Experimental PharmacologySchool of Tropical MedicineKolkata
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
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
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 Statistics Query 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. 2012 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 30th annual report. Clin Tox 2013;51:9491229.
Centers for Disease Control and Prevention. National Vital Statistics System mortality data. (2015) Available from URL: http://www.cdc.gov/nchs/deaths.html
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 Indian Academy of Medical Sciences. 2013;5:142-7
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.
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
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
Uptake and Elimination
BiologicalSystemUptake EliminationK1 K2
K1 > K2 : Accumulation & Toxic effect
Toxicokinetics1. Uptake2. Transport3. Metabolism &
Transformation4. Sequestration5. Excretion
Uptake of Toxicants
1. Passive diffusion2. Facilitated transport3. Active transport4. Pinocytosis
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
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
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
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
softtissue bone
Gastrointestinal tract
Lung
feces
InhalationIngestion
distribution
Important principles of toxicokinetics The effect which a drug produces is
dependent on:1. The dose2. 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
Toxicokinetics and toxicityToxicity 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.
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
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
Digoxin
Extracardiac adverse effects
Cardiac adverse effects VT Nodal & Ventricular extrasystoles Pulsus bigeminus VF AFL, AF, severe bradycardia
Antiarrythmic drugs
Qunidine, Procainamide – torsades de pointes
Sotalol – intraventricular conduction defect results into VT AND VF
Adenosine - bronchospasm
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
Common Toxidromes
Acute drug overdoses
Specific therapies
Specific therapies
Specific therapies
Substance Abuse and Overdose
Addiction Habituation Physiological dependence Psychological dependence Tolerance
Withdrawal Drug Overdose
Common Drugs of Abuse
Common Drugs of Abuse
Common Drugs of Abuse
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)
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.
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
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 or TICTAC (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