Transcript Poisoning

DRUG / TABLET
OVERDOSAGE
Drug Overdosage
What is it that is not a poison?
All things are poison and nothing is without
poison. Solely, the dose determines that a
thing is not a poison
Paracelsus (1493 – 1541)
Drug overdosage
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Poisoning – development of harmful
effects following exposure to chemicals
Overdosage – exposure to excessive
amounts of a substance normally intended
for consumption and does not necessarily
imply poisoning
Harrison
General approach
Poisoned patient
Treatment
Airway
Breathing
Circulation
“DONT”/Decontamination
Enhanced elimination
Focused therapy
Get Tox help
Diagnosis
History
Physical examination
Toxidrome recognition
Diagnostic tests
Vital signs
Bradycardia (PACED)
Propranolol, poppies, propoxyphene,
physostigmine
Anticholinesterase drugs, antiarrhythmics
Clonidine, CCBs
Ethanol or other alcohols
Digoxin, digitalis
Vital signs
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Tachycardia (FAST)
Free base or other forms of cocaine, freon
Anticholinergics, antihistamines,
antipsychotics, amphetamines, alcohol –
withdrawal
Sympathomimetics, solvent abuse,
strychnine
Theophylline, TCAs, thyroid hormones
Vital signs
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Hypothermia (COOLS)
Carbon monoxide
Opioids
Oral hypoglycemics, insulins
Liquor (alcohol)
Sedative-hypnotics
Vital signs
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Hyperthermia (NASA)
Neuroleptic malignant, nicotine
Antihistamines, alcohol withdrawal
Salicylates, sympathomimetics, serotonins
Anticholinergics, antidepressants,
antipsychotics
Vital signs
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Hypotension (CRASH)
Clonidine, CCBs
Rodenticides (arsenic, cyanide)
Antidepressants, aminophylline,
antihypertensives
Sedative- hypnotics
Heroin or other opiates
Vital signs
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Hypertension ( CT SCAN )
Cocaine
Thyroid supplements
Sympathomimetics
Caffeine
Anticholinergics, amphetamines
Nicotine
Vital signs
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Rapid respiration ( PANT )
PCP, paraquat, pneumonitis(chem.),
phosgene
ASA, and other salicylates
NCPE, nerve agents
Toxin-induced metabolic acidosis
Vital signs
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Slow respiration ( SLOW )
Sedative-hypnotics ( Barb’s & Benzodiaz)
Liquor ( alcohols )
Opioids
Weed ( marijuana )
Vital signs
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Coma ( LETHARGIC )
Lead, lithium
Ethanol, ethylene glycol, ethchlorvynol
TCAs, thallium, toluene
Heroin, hemlock, HE, heavy metals, hydrogen
sulphide, hypoglycemics
Arsenic, antidepressants, anticonvulsants,
antipsychotics, antihistamines
GHB – gamma hydroxybutyrate
Isoniazid, insulin
Carbon monoxide, cyanide, clonidine
Seizures ( OTIS CAMPBELL)
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OPCs, OHAs
TCAs
Isoniazid, insulin
Sympathomimetics, strychnine, salicylates
Camphor, cocaine, CO, cyanide, chlorine-HC
Amphetamines, anticholinergics
Methyl xanthines, methanol
Phencyclidine, propranolol
BNZ-withdrawal, botanicals(nicotine),
bupropion
Ethanol withdrawal, ethylene glycol
Lithium, lidocaine
Pupils/Eye
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Miosis ( COPS )
Cholinergics, clonidine, carbamates
Opiates, OPCs
Phenothiazines, pilocarpine, pontine HE
Sedative-hypnotics
Mydriasis ( SAW )
Sympathomimetics
Anticholinergics
Withdrawal
Nystagmus – phenytoin, barbiturates
EXAMINATION OF SKIN
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DRY SKIN -belladona, datura
HEAVY PRESPIRATION - organophosphates
PINK - carbon monoxide
BULLAE - barbiturates
VASCULITIS - propylthiouracil, hyadantoin
RAYNAUDS - betablockers, ergot
SERUM SICKNESS - betalactams,
betablockers
BASIC LAB WORK UP
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GLYCEMIC STATUS
ABG
SERUM ELECTROLYTES
RFT& LFT
HEMOGRAM
PREGNANCY TESTS – CHILD BEARING AGES
DRUG LEVELS IF POSSIBLE – BLOOD,
URINE
ANION GAP
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Normal anion gap [Na – (Cl – HCO3)] -12meq/l
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An increase>20mEq/l indicates organic acidosis
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Increased anion gap – lactic acidosis, uremia &
sepsis and Toxins like ethylene glycol,
methanol, paraldehyde & salicylate
Decreased AG — lithium, hyperkalemia
hypercalcemia ,hypermagnesemia
Hypoglycemia
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β – blockers
Ethanol
Insulin
Oral hypoglycemics
Quinine
Salicylates
Hyperglycemia
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Acetone
β – agonists
CCB’s
Iron
Theophylline
Vacor
ELECTROLYTE DISTURBANCES
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Hyperkalemia ---potassium sparing
diuretics
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Hypokalemia---amphoB, cyclosporine,
diuretics
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Hyponatremia---diuretics, naso gastric
losses
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Hypomagnesemia---cisplatin, cyclosporin,
diuretics
DRUGS CAUSING HIGH ANION
GAP or METABOLIC ACIDOSIS
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ACETAMINOPHEN>75gm
AMILORIDE
INH
DAPSONE
CYANIDE
IRON
KETAMINE
METFORMIN
NSAIDS
NITROPRUSSIDE
TERBUTALINE
OUT DATED TETRACYCLINE
ACUTE HEPATO TOXICITY
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ACUTE CYTOLYTIC HEPATITS—
acetaminophen
ACUTE CHOLESTATIC HEPATITS or
MIXED—macrolides, phenothiazines
ACUTE BLAND CHOLESTASIS—anabolic
steroids, estrogens.
Abdominal radiographs
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Agents visible on ABR’s ( COINS )
Chloral hydrate, cocaine packets, calcium
Opium packets
Iron, lead, arsenic, mercury (H.metals)
Neuroleptic agents
Sustained – release or EC agents
Chest Radiographs
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NCPE ( MOPS )
Meprobamate, methadone
Opioids
Phenobarbital, propoxyphene, paraquat,
phosgene
Salicylates
Toxidromes
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Cholinergics – OPCs, carbamates,
pilocarpine (DUMBELLS)
Diarrhoea, diaphoresis
Urination
Miosis
Bradycardia, bronchorrhoea
Emesis
Lacrimation
Lethargic
Salivation
Toxidromes
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Nicotinic – days of the week
Monday – mydriasis
Tuesday – tachycardia
Wednesday – weakness
Thursday – tremors
Friday – fasciculations
Saturday – seizures
Sunday - somnolence
Toxidromes
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Anticholinergic –
antihistamines, TCAs,
atropine, benztropine,
phenothiazines
Hyperthermia
Flushing
Dry skin
Dilated pupils
Delirium, hallucinations
Tachycardia
Urinary urgency and retention
Traditional description
Hot as a hare
Dry as a bone
Red as a beet
Blind as a bat
Mad as a hatter
Toxidromes
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Sympathomimetics – cocaine,
amphetamines, ephedrine, phencyclidine
Mydriasis
Tachycardia
Hypertension
Hyperthermia
Seizures
Toxidromes
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Opioid – heroin, morphine, codeine,
methadone, fentanyl, oxycodone
Miosis
Hypotension
Hypoventilation
Coma
Toxidromes
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Drug Withdrawal
Diarrhoea
Mydriasis
Goose flesh
Tachycardia
Lacrimation
Hypertension
Yawning
Cramps
Hallucinations
Seizures
CRITERIA FOR ICU ADMISSION
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Respiratory depression - PaCO2>45mmHg
Emergency intubation
Seizure
Cardiac arrhythmia
Systolic BP<80mmHg
Glasgow score <12
Need for emergency HD,HP.
Hypothermia, Hyperthermia & neuroleptic
malignant syndrome
TCA toxicity with QRS>0.12secs/QT>0.5secs
Pulmonary edema
Goals of Therapy
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Support of vital signs
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Prevention of further absorption
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Enhancement of elimination
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Administration of specific antidotes
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Prevention of re-exposure
Multi-dose Activated Charcoal
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1g/kg; 4th hourly, for drugs with enteral
circulation
Carbamazepine
Dapsone, Diazepam, Digoxin
Glutethimide
Meprobamate, Methotrexate
Phenobarbitol, phenytoin
Salicylate
Theophylline
Valproic acid
Scenario
An under graduate student of our college
with ingestion of 20 pills and admitted in our
toxicology with vomiting and deranged LFT
later….
Acetaminophen Metabolism
~ 50%
~ 45%
P450
Glucuronidation
(non toxic)
~ 5%
NAPQI
Glutathione + NAPQI
= nontoxic product
Sulfation
(non toxic)
N-acetylcysteine (NAC)
Liver cell damage
Paracetamol Toxicity
90% Conjugation
NAPQI
Glutathione
NAPQI
PARACETAMOL
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Hepatic toxicity – depletion of hepatic
glutathione and accumulation of toxic
metabolite – N-acetyl-p-benzo quinonimine
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Toxic dose – >140mg/kg or >7.5g
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Toxicity increased with alcohol intake, INH
intake
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Acetaminophen levels >10 mcg/ml
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Hepatic enzymes – rise in 24hrs and peak at
72-96hrs and recovery follows
Time to N-acetylcysteine (hours)
and hepatotoxicity (%)
30
25
20
15
10
5
0
0 to 4
4 to 8
8 to 12
12 to 16
16 to 20
20 - 24
Smilkstein MJ et al. Efficacy of oral N-acetylcysteine in the treatment of
acetaminophen overdose: Analysis of the national multicenter study
(1976 to 1985). N Engl J Med 1988; 319:1557-1562
PARACETAMOL
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Activated charcoal – hepatoprotective
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N-acetylcysteine – specific antidote
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140mg/kg stat and 70mg/kg for 17 doses every 4hrs
– orally
IV-Acetadote 150mg/kg in 1hr in 200ml D5 and 50
mg/kg in 500ml in 4hrs followed by 100mg/kg in
500ml over 16hrs
Alternate medication: oral methionine
Paracetamol - summary
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Ingestion < 140mg/kg is probably not toxic
If no serum level available treat based on
dose
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IV acetylcysteine or oral methionine
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Start antidote within 8 hours
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Liver or kidney damage delayed 24-48 hrs
Scenario
A 45 year old man, known RHD patient on
treatment presented to our emergency
department with unconsciousness. He
developed VT and was stabilized at
cardiology with defibrillation. He was later
shifted to our toxicology???
Cyclic Antidepressants
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Amitryptilline, imipramine, desipramine,
nortriptyline, doxepin and protriptyline
Central and peripheral anticholinergic activity,
block reuptake of norepinephrine & serotonin,
alpha blocking (depression of myocardial
contractility), quinidine like (conduction
defects), and CNS effects
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>50mg/kg is lethal
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Anti-Cholinergic, Cardiovascular and CNS
Cyclic Antidepressants
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Gastric lavage regardless of time of
presentation and repetitive activated charcoal
Continuous cardiac monitoring
Maintain alkaline pH 7.45-7.55 – NaHCo3 /
pCO2
Arrhythmia management –
lidocaine/phenytoin, magnesium, atrial
overdrive pacing / V. pacing
CNS – Physostigmine – 2mg IV over 1min or
barbiturates, diazepam
Respiratory - ventilation
Newer antidepressants
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SSRIs (specific serotonin reuptake
inhibitors)
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citalopram
escitalopram
fluoxetine
fluvoxamine
paroxetine
sertraline
RIMA (reversible inhibitor of monoamine
oxidase A)
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moclobemide
Newest antidepressants
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SNRI (serotonin noradrenergic reuptake
inhibitors)
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NaSSA (noradrenergic and specific
serotonergic antidepressant)
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venlafaxine
mirtazapine
NaRI (selective noradrenaline reuptake
inhibitor )
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reboxetine
NAselective
Nonselective
5-HTselective
Ratio NA: 5-HT uptake inhibition
Selectivity of antidepressants
1000
Nisoxetine
100
Nomifensine
Maprotiline (approx)
10
1
0.1
0.01
0.001
Desipramine
Imipramine
Nortriptyline
Amitriptyline
Clomipramine
Trazodone
Zimelidine
Fluoxetine
Citalopram (approx)
RIMA
NaSSA
NaRI
SSRI
NaSSA
Serotonin excess
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Primary neuroexcitation (5–HT2A)
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mental status
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agitation/delirium
motor system
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clonus/myoclonus
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tremor/shivering
hyperreflexia/hypertonia
autonomic system
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inducible/spontaneous/ocular
diaphoresis/tachycardia/mydriasis
Other responses to neuroexcitation
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fever
rhabdomyolysis
Severe serotonin toxicity
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Combination therapy
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Rapidly rising temperature
Respiratory failure
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multiple different mechanisms of serotonin
elevation
hypertonia/rigidity
Spontaneous clonus
Seizures – fluoxetine, citalopram
Tachycardia, QT - citalopram
Therapy
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Oral therapy
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q 4–6h PO (5–HT1A & 5-HT2A antagonist)
Oral therapy unsuitable or fails
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cyproheptadine 12 mg stat then 4–8 mg
chlorpromazine 25–50 mg IV stat then up to 50 mg orally or IV q6h
Ventilation impaired and/or fever > 39oC
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anaesthesia, muscle relaxation ± active cooling
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chlorpromazine 100–400 mg IM/IV over first two hours
Conclusions
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Serotonin toxicity is a spectrum disorder
not a discrete syndrome
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Newer agents with little or no risk of
serotonin toxicity
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Reboxetine and mirtazapine
First line of treatment is to remove the
offending agent(s)
Specific inhibitors of 5–HT2 have a role
but paralysis and ventilation may be
needed
Scenario
An young girl was admitted to our
toxicology after ingestion of 100 pills of
AMLONG-AT
Beta-blockers
Clinical features:
CVS – bradycardia & hypotension,
Respiratory – bronchospasm & pulmonary
edema
CNS depression
Hypoglycemia
Renal Failure
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ECG, blood sugar, electrolytes
Beta-blockers
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Brady – atropine 2mg IV
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Hypotension – IVF
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Glucagon- 50 to 150mcg/kg IV in 1min and
1-5mg/hr in 5D, (stimulate adenyl cyclase)
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Isoproterenol, Norepinephrine and Calcium
chloride 10%(0.2ml/kg).
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Beta agonists - theophylline
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IV glucose, ventilation, dialysis for some,
diazepam/phenytoin for seizures
Calcium channel Antagonists
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Bradycardia, AVblock, asystole, hypotension,
pulmonary edema, hypocalcemia,
hyperglycemia
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Gastric lavage and activated charcoal
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For SR tabs. - Gastroscopy/WB irrigation
Calcium channel Antagonists
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IV saline, dopamine
10% Cacl 10-20ml IV or Ca. gluconate
drip(0.6ml/kg bolus & 0.6-1.5ml/kg IV
infusion)
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Glucagon for Heart Block or hypotension
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Atropine/pacemaker
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Seizure control
Scenario
1)
2)
An young girl ingested 30 tablets of
DAPSONE and presenting in a stuporous
state
An young man presented after ingesting
CELL OIL ( anti-termite liquid) developed
cyanosis
Methemoglobinemia
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Caused by – nitrites, nitroprusside, NTG, chlorates, sulfonamides,
aniline dyes, nitrobenzene, antimalarials and dapsone ---- Cell oil?
(oxidation of ferrous hemoglobin to ferric form)
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Headache, fatigue, dyspnoea, cyanosis, hypotension
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>50% - CNS depression, arrhythmias. >70% - fatal
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Normal PaO2 & cyanosis not responding to O2, “chocolate brown”
blood
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100% O2 , Lavage and charcoal
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Methylene blue 1-2mg/kg IV over 5min repeat in 1hr and 4th hrly.
To max. of 7mg/kg (contraindicated G6PD deficiency patients)
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Hyperbaric O2 and exchange transfusion
Scenario
A famous personality was found
unconscious after inhaling opioid compound
with his friends. Two of them died at the
spot. He was saved after shifting him to a
famous private hospital.
Opioids
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From poppy – morphine, codeine
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Semi-synthetic – Heroin (diacetyl morphine)
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Purely synthetic – meperidine,
propoxyphene, diphnoxylate, fentanyl,
buprenorphine, tramadol, methadone,
pentazocine
Opioids
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Resp. depression, miosis, CNS ,
hypotension, brady., pulmonary edema.
No emesis, give lavage and charcoal, WBI
Naloxone HCl – 2 mg IV initially or SL / IN
/ ET
Ventilatory support
Scenario
A recently married young girl was admitted
in our toxicology after ingesting OIL OF
WINTERGREEN 15ml in an obtunded state
with respiratory distress
Salicylates
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Toxicity – severe if >300-500mg/kg
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Nausea, vomiting, tinnitus, fits, coma and NCPE
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PT prolongation, hypoglycemia
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ABGs – early respiratory alkalosis and later
metabolic acidosis.
Fever and acidosis – poor prognosis
Salicylates
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Multidose charcoal / WBI
FAD – watch for fluid overload
Cerebral edema – hyperventilation and
osmotic diuresis
Seizures – diazepam, phenobarbital
HD – refractory acidosis, CNS, PE, RF
Mechanical ventilation – high FiO2 and
PEEP
Scenario
A young boy was admitted after ingesting
40 tablets of GARDENAL which he was
taking for his seizure control
ANTICONVULSANT
POISONING
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Carbamazepine
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Phenytoin
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Barbiturates
Carbamazepine - Toxicokinetics
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Absorption
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Slow absorption
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Pharmacobezoar formation is common
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Carbamazepine decreases gastrointestinal motility
Metabolised by inducible P450 enzymes
Enterohepatic circulation
Half life - 20-65 hours normal adults
5-17 hours epileptics
Carbamazepine - Clinical effects
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CNS
disorientation, confusion
 ataxia
 dystonia
 athetosis
 drowsiness, stupor
 coma
 hyperreflexia
 hyporeflexia
 tremor
 seizures
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Carbamazepine - Clinical effects
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Cardiovascular
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bradycardia
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hypotension
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heart block
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QRS prolongation (quinidine like)
Nausea, vomiting
Decreased bowel sounds
Hypothermia
Carbamazepine - Treatment
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Supportive
Lavage and charcoal
Repeat doses of activated charcoal
ECG monitoring (if ECG abnormal)
Serial levels until falling level
demonstrated
No antidotes
No effective elimination enhancement
Phenytoin - Toxicokinetics
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Delayed absorption
Peak concentrations as late as 24 hours
Protein binding 90%
Ph dependent protein binding
Metabolism zero autokinetics
Saturable metabolism by P450 enzymes
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Therapeutic half life 20-30 hours
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Overdose half life 24-230 hours
Phenytoin - Drug interactions
that increase half life
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ethanol
disulfiram
imipramine
diazepam
cimetidine
thioridazine
valproate
proproxyphene
chlorpromazine
ethosuximide
Phenytoin - Clinical effects
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CNS
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dilated pupils
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nystagmus - horizontal and vertical
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ataxia
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drowsiness
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coarse tremor
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clonus
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myoclonus
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hyperreflexia
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seizures (paradoxical intoxication)
Phenytoin - Clinical effects
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Cardiovascular
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bradycardia
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AV block
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direct myocardial depression
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VF
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asystole
Nausea & vomiting
Hyperglycaemia
Hepatitis
Phenytoin - Treatment
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Respiratory support (avoid acidosis)
Hypotension - IV fluids
Seizures - diazepam
Heart block - atropine + pacemaker
GI decontamination up to 12 hours post
ingestion
Elimination enhancement not usually
helpful
Serial levels required until falling
Barbiturates
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primidone
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phenobarbitone
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pentobarbitone
Barbiturates - toxicokinetics
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Rapid absorption
Rapid onset of action
Hepatic metabolism is predominant though
phenobarbitone has significant renal
elimination
Many drug interactions
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Induces p450 enzymes
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Synergistic CNS depression
Barbiturates - Clinical effects
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CNS
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ataxia
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nystagmus
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dysarthria
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lethargy, confusion
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Areflexia (except pupillary)
respiratory & cardiac depression
Vasodilation, hypothermia
Skin – ‘Barb bullae’
EEG may be iso-electric
Barbiturates - Treatment
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Respiratory support
Intravenous fluids
GI decontamination
Serial doses of activated charcoal
Forced Alkaline Diuresis (FAD)
Haemodialysis
Haemoperfusion
Beware barbiturate withdrawal syndrome
Scenario
An young male was working in a
rehabilitation centre as a drug dispenser. He
was found unconscious inside the pharmacy
with diazepam tablets strewn around. He
was suspected to have consumed >100
tablets.
Benzodiazepines
Drug
Flurazepam
Temazepam
Flunitrazepam
Alprazolam
Triazolam
Nitrazepam
Diazepam
Bromazepam
Chlordiazepoxide
Lorazepam
Oxazepam
Clobazam
Clorazepate
Deaths per million
prescriptions
15.0
11.9
8.1
5.9
5.1
4.4
4.0
3.0
2.8
2.3
2.3
1.6
1.4
Benzodiazepines







Fatalities rare
Drowsy, dysarthrytic, ataxic, miosis, coma,
resp.
Lavage, activated charcoal
Intubation – resp. depression
Hypotension, bradycardia
Flumazenil – reverse toxicity without Resp.
depression, use with caution (during coingestion)
0.2mg(2ml) IV in 30secs, 0.3mg in 1 min
interval for total dose of 3mg or 0.1-
Scenario
A 30 year old man presented after
ingesting 40 tabs of chlorpromazine with
severe hypotension, seizures and EPS
Antipsychotic
Phenothiazines
Chlorpromazine, fluphenazine, flupenthixol, Pimozide, thioridazine, trifluoperazine, zuclopenthixol
Butyrophenones
droperidol
haloperidol
Newer Antipsychotics

Atypical agents

aripiprazole

clozapine

risperidone

quetiapine

amisulpride

olanzapine
Antipsychotics
Modes of action
 All anti-psychotic drugs have inhibitory
effects on the D2 receptor
 Some have actions against the D4 receptor
 All have other effects - to varying degrees



Serotonin 5HT2 blockade (may improve
negative symptoms)
Histamine H1 blockade (drowsiness)
Alpha adrenoceptor blockade (postural
hypotension)
Antipsychotics

Control the ‘positive’ features of the disease,
but little effect on the ‘negative’ features


clozapine may be superior in this regard
The main side-effects are on the extrapyramidal
motor system



Akathisia (hours)
Dystonias (hours to days)
Parkinsonism (weeks to months)


rigidity, tremor, and loss of mobility
Tardive dyskinesia (months to years)


Repetitive abnormal movements of face and upper limbs
Thought to be due to proliferation of D2 receptors in the
striatum
Clinical effects - antipsychotics
Clinical effects - differences




All effective antipsychotic drugs block D2
receptors
Chlorpromazine and thioridazine
 block α1 adrenoceptors more potently than D2
receptors
 block serotonin 5-HT2 receptors relatively
strongly
 affinity for D1 receptors is relatively weak
Haloperidol
 acts mainly on D2 receptors
 some effect on 5-HT2 and α1 receptors
 negligible effects on D1 receptors
Pimozide and amisulpride
Toxic effects
Atypical antipsychotics





Atypical antipsychotics have serotonin
blocking effects as well as dopamine
blockade
As a group have less chance of
extrapyramidal side effects
Most have weight gain and insulin
resistance as a side effect (except perhaps
aripiprazole and maybe amisulpride)
May be associated with stroke when used
for behavioural control in dementia
Many have idiosyncratic toxicities
Antipsychotics
Pill concretions in stomach by radiographs
Lavage, WBI.
Lidocaine, phenytoin, noradrenaline, seizure
control, dystonias – benztropine, benadryl –
diphenhydramine
Neuroleptic malignant syndrome
Acidosis correction
Neuroleptic malignant syndrome








Adverse, idiosyncratic drug reaction
Mortality – 4 to 30%
“akinetic hypertonic syndrome”
Hyperthermia, tachycardia, muscle rigidity,
altered mental status, akinesia
Tachypnoea, diaphoresis, incontinence,
sialorrhea, flushing
Disruption of central dopamine neurotransmitter
in nigrostriatal & hypothalamic thermoregulation
Lab: leukocytosis, elevated creatine kinase
Rx: heparin, dantrolene, bromocriptine, IV
levodopa, benzodiazepines
Scenario
A nursing student of our college was
admitted after ingesting 45 tablets of
deriphylline to our toxicology
Theophylline




PDI’s, degradation of cyclicAMP, enhance
endogenous catecholeamine actions
Nausea, vomiting, tachycardia, arrhythmias,
tremors and agitation
>90mg/ml – severe intoxication cause
hallucination, seizures and hypotension, rarely
rhabdomyolysis-ARF
ABGs, ECG, hypokalemia, hypophosphatemia,
hypocalcemia, hyperglycemia
Theophylline




Multidose charcoal, WBI – for SR
preparations.
Perinorm/ondansetron, dopamine/IVF
Phenobarbital, diazepam is for seizures(No
phenytoin)
IV esmolal / propranolol – arrhythmias
ROLE OF NEPHROLOGIST IN
POISIONING

Drug removal

Fluid & Electrolyte balance

Acid - base disturbance

Rx of ARF due to nephrotoxins
NEPHROLOGIC INTERVENTIONS

Forced Alkaline diuresis

Forced acid diuresis

Peritoneal dialysis

Hemodialysis

Hemoperfusion

Exchange transfusion
FORCED ALKALINE DIURESIS


PRINCIPLE
Urine PH modulation causes ion trapping
and decreases the renal reabsorbtion
GOAL
Maintain the urine PH around 7.5 to8.5
urine flow rate of 300 to 500 ml
INDICATIONS FOR FAD

Copper sulphate poisoning

Phenobarbital >10mg/dl

Salicylate >50mg/dl

Chloropropamide

Sulphonamides
FAD



Administer 100meq (2 amps) of NaHCo3 in
1000ml D5/0.45 saline at 10-15ml/kg/hr
Maintain alkalinization – 2-3 ml/kg/hr
Monitor urine output(3-6ml/kg/hr), urine
pH(7-8), K+

20 meq of KCl is simultaneously administered

Avoid vigorous correction in elderly
COMPLICATIONS of FAD

Hyponatremia

Water intoxication

Pulmonary edema

Alkalosis

SECOND HOURLY MONITORING OF URINE
pH IS A MUST
ROLE OF DIALYSIS


Clinical deterioration despite supportive care
Severe intoxication presenting in the form of
severe hypotension, hypothermia,
hypoventilation

Development of unconsciousness

Development of cardiac,renal,hepatic
dysfunction

Toxins above critical blood levels
Haemodialysis



Blood is pumped (150-300ml/min) across a semipermeable membrane (MW 500D)
 performed for 4-8hrs at a time (intermittent)
Dialysis fluid infused countercurrent on the other
side of the membrane establishing a
concentration gradient
Solutes diffuse across the membrane into the
dialysate


corrects uraemia and electrolyte / acid-base
disturbances
Anticoagulation is required (either systemic or of
the circuit)
COMMON POISONS AMENABLE
TO DIALYSIS













Barbiturates
Theophylline >40mg/dl
Paraqat 0.1mg/dl
Trichloroethyelene >500mg/dl
Carbamazepine, valproic acid
Primidone, ethosuximide
Amphetamines, MAOI s
Ethanol, ethyleneglycol, methanol
Salicylates, paracetamol
Amikacin, gentamicin, streptomycin
INH, ethambutal, cycloserine
Ranitidine
Lithium
COMMON NON DIALYSABLE
POISON










Secobarbital
Diazepam, Heroin
TCAs, Amitryptylline
Vancomycin
Erythromycin, Chloramphenicol
Chloroquine
Azathioprine, Methotrexate
Digoxin, Quinidine
Organophosphates
CCL4, Eucalyptus oil
COMPLICATIONS OF HD
Hypophosphatemia
Alkalosis
Dialysis disequilibrium syndrome
Haemoperfusion: Technique

Blood is pumped (150 - 250 mL/min)
through a column containing an
adsorbent, usually activated charcoal,
coated with a biocompatible ultrathin®
membrane
POISONS AMENABLE TO
HEMOPERFUSON
Carbamazepine
Phenobarbitone
Theophylline
Meprobomate
Phenytoin
Sodium Valproate
Salicylates
COMPLICATIONS OF
HEMOPERFUSION







Thrombocytopenia
Hypocalcaemia
Leucopenia
Hypoglycemia
Hypothermia
Hypotension
Bleeding
Hemoperfusion

The limited data available suggests that:
-

there is a continuing role for cHPF in severe theophylline & carbamazepine poisoning particularly in patients who are deteriorating despite MDAC or in those in whom MDAC use is limited by ileus
Future developments in carbon technologies
may allow an expansion in the indications for
cHPF in toxicology & increased efficacy
ROLE OF HEMOFILTRATION

AV—pressure difference induces
convective transport of solutes through
hollow fiber / flat sheet

Removes molecules </= to 40,000

Blood is pumped through the filter

Can be done intermittently at 6L/hr OR
continuously at 100ml/hr
Haemofiltration & haemodiafiltration
(CVVHF)

Haemodiafiltration can be achieved by infusing dialysis
fluid countercurrent to the membrane allowing diffusive
solute removal by dialysis in addition to the convective
removal by filtration
CVVHF

(CVVHDF)
CVVHDF
HDF allows greater removal of smaller molecules
(<500D) and also better control of
hyperkalaemia and other metabolic disturbances
(CUPID = combination of CVVHF and intermittent
DRUGS AMENABLE TO
HEMOFILTRATION


AMINOGLYCOSIDE antibiotics
METAL CHELATE complexes of ALUMINUM
or IRON DESFEROXAMINE
ADVANTAGES OF HF






Consistent homeostasis
No hypotension---no disequilibrium
No need to restrict fluid administration
Less amount of extracorporeal blood
No effect on complement or leukocytes
USEFUL in clearance of mid –molecular
weight substances
DISVANTAGES OF
HEMOFILTRATION

Anticoagulation is needed

Vascular access complication

LOWER clearance of LOW MOLECULAR Wt.
solutes
PLASMAPHERESIS



SEPERATES CELLULAR BLOOD
COMPONENTS FROM PLASMA
EFFICACY DEPENDS ON NUMBER OF
CYCLES
SACRIFICES PATIENTS OWN PLASMA
DRUGS AMENABLE TO
PLASMAPHERESIS









Vincristine
Inorganic mercury
Amanita
Theophylline
ATG
Digoxin antibody complexes
Phenytoin
Dapsone
Carbmazepine
PLASMA EXCHANGE &
EXCHANGE TRANSFUSION



Highly protein bound drugs
Exchange transfusion is useful in poisons
with intense hemolysis
HD+HP +Chelation is useful in metal
poison like mercury, thallium
ROLE PERITONEAL DIALYSIS

Not an acceptable substitute to HD

Peritoneal dialysis—slow removal poisons

NEVER USED IN DRUG OVERDOSE &
POISONING
Conclusions

For most severely poisoned patients supportive care is all
that is necessary and extracorporeal techniques are
indicated in only a limited number of poisonings
Haemoperfusion
- Carbamazepine, theophylline, phenobarbitone
Haemodialysis
- Salicylates, alcohols, (theophylline), lithium
Haemofiltration
- ?Lithium, alcohols
- Correction of electrolyte disturbances or lactic
acidosis and for renal support
- Aminoglycosides, removal of iron-DFO in patients
Antidotes
Antidote
N-acetyl cysteine
Ethanol/Fomepizole
Oxygen/hyperbarics
Naloxone/nalmefene
Physostigmine
Nitrates
Glucagon
Sodium Bicarbonate
Calcium/insulin/dextrose
Dextrose/glucagon
Indication
Acetaminophen
Methanol/Ethylene glycol
Carbon monoxide
Opioids
Anticholinergics
Cyanide
Beta-blockers
TCA’s
CCB’s
Oral hypoglycemics