1. PRINCIPLES OF MANAGEMENT OF ACUTE POISONING

2. IMPORTANT RULE
All poisoned patients should be managed as if they have a potentially life-threatening intoxication, although they appear normal

3. Initial assessment & stabilization of VFs
Definitive care of poisoning cases:
Measures to identify the toxic agent.
PreventioHistory and circumstantial evidence
Symptoms and signs (including toxidromes)
Investigations
Postmortem picture
Decrease further absorption.
Antidote therapy (if available).
Enhance elimination (excretion) of the toxic substance.
Treatment of systemic complications resulting from poisoning
A secondary survey for: INFECTION, TRAUMA, METABOLIC DISTURBANCE

4. STABILIZATION OF THE PATIENT
The initial approach to the poisoned patient should be essentially similar in every case, irrespective of the toxin ingested.
Similar to the initial approach to the trauma patient
Applied as initial approach to all patients in ED irrespective of the mechanism of injury.
This approach can be termed as routine poison management

5. INITIAL ASSESSMENT & STABILIZATION
The Basic Life Support including ABCDE should be applied before all other considerations.
Many toxic substances can lead to potentially life-threatening changes that should be identified and treated quickly.
Many poisoned patients require only supportive therapy alone.

6. A= Airway Patency Airways should be kept patent and any suspicion for obstructing material must be removed
The most common factor contributing to death from poisoning is loss of airway-protective reflexes with subsequent airway obstruction caused by:
Flaccid tongue
Pulmonary aspiration of gastric contents
Respiratory arrest
All poisoning patients should be suspected of having a potentially compromised airway.

7. The most common cause of airway obstruction in an unconscious patient is passive obstruction by the tongue.
The neck lift with jaw thrust may be the first maneuver performed by the physician on the unconscious poisoned patient followed by endotracheal intubation

8. Loss of consciousness is often accompanied by loss of muscle tone (A)Occlusion of the airway by the tongue can be relieved by a head-tilt chin-lift (B) or a jaw thrust (C). In patients with possible cervical spine injury, the angles of the jaw should be lifted anteriorly without hyperextending the neck.

9. Indications for endotracheal intubation
in the poisoned patient include:
Protection of the airway in the obtunded or comatose patient with a depressed or absent gag reflex to prevent aspiration during gastric lavage
Controlled ventilation in patients who demonstrate respiratory depression or failure
Removal of secretions in patients who develop pulmonary edema secondary to a toxic substance
Institution of positive end-expiratory pressure (PEEP) therapy for those patients who are at risk for developing adult respiratory distress syndrome (ARDS).

10. Aspiration of secretions and regurgitated food and stomach contents.
The other issues to keep airways patent:
Aspiration of secretions and regurgitated food and stomach contents.
Removal of foreign bodies, dentures, or mucous from mouth.
Prevent falling back of the tongue in comatose patient by oropharyngeal tube.

11. B= Breathing assisted ventilation is done according to the situation:
Monitoring of RR is important. Patients may have one or more of the following complications: bradyapnea, ventilatory failure, hypoxia, or bronchospasm.

12. Normal Respiratory Rates
AGE
BREATHS/MIN
Newborn to 6 weeks
Infant (6 weeks to 6 months)
Toddler ( 1 to 3 years)
Young Children ( 3 to 6 years)
Older Children (10 to 14 years)
Adults

13. C= Circulation Check blood pressure and pulse rate and rhythm.
Begin continuous ECG monitoring
Secure venous access
Draw blood for routine studies.
E. Begin intravenous infusion If the patient is hypotensive, normal saline or another isotonic crystalloid solution is preferred

14. Disability (Neurological):
A decreased level of consciousness is the most common serious complication of drug overdose or poisoning.
Coma
C.N.S depressant: barbiturate, benzodiazepine and opiate
Hypoglycemic agent and alcohol.
Hypoxic agent (CO).
Metabolic agent (Salicylate, methanol).
Other as organophosphate.
For patients with altered consciousness or respiratory depression of unknown cause give "coma cocktail“:
Dextrose (Hypoglycemia)
Thiamine (Alcohol-related Amnestic Syndromes)
Naloxone (Opiates)
O2 (Hypoxia)
Disability (Neurological):

15. Coma Cocktail According to the age of the patient:
loss of consciousness of unknown cause or persistence of symptoms, try coma cocktail:
100% oxygen
Glucose (Important)
Naloxone
Thiamine
Coma cocktail is administered for a diagnostic and therapeutic reasons.

16. Seizures
seizures caused by specific toxins can exhibit certain specific properties.
Strychnine is unique in that it can cause generalized seizures while the patient is alert. ‘‘spinal seizure.’’
Other drug-induced seizures will respond only to specific antidotal therapies and not to conventional antiseizure medication.
anticholinergic-induced seizures may respond to physostigmine
isoniazid-induced seizures, which respond to pyridoxine.
theophylline-induced seizures rarely respond to phenytoin alone and often only to multidrug therapy

17. DEFINITIVE CARE WITH POISONING

18. Try to identify the poison
Accurate and complete history
History from sources other than patient (family, friends, pharmacist, & pill bottles at the scene).
Attempt to establish the time and amount of the ingestion

19. CAREFUL PHYSICAL EXAM
Based on knowledge of drug pharmacology & effects on ANS
The vital signs should be monitored accurately.
Level of consciousness (AVPU), pupillary size and reaction to light.
Skin examination and breath odors
Recognizing toxidromes.
Exam should include evaluation for head trauma, focal neurological findings, needle track marks.

20. Breath odors & Skin Findings
Bitter almonds: cyanide
Fruity: DKA, isopropranolol
Oil of wintergreen: methylsalicylate
Rotten eggs: sulfur dioxide, hydrogen sulfide
Pears: chloral hydrate
Garlic: organophosphate, arsenic
Mothballs: camphor
SKIN
Diaphoretic Skin
Sympathomimetics
Organophosphates
Salicylates
Red Skin
CO, boric acid
Blue Skin
Cyanosis
methemoglobinemia

21. EXAMPLES OF TOXIC VITAL SIGNS
Bradycardia (PACED)
P propranolol
A anticholinesterase
C clonidine, Ca ch. blocker
E ethanol + alcohols
D digoxin, dravon (opiates)
Tachycardia (FAST)
F free base (cocaine)
A anticholinergic, antihistamin
S sympathomimetic
T theophylline
Hypothermia (COOLS)
C CO
O opiates
O oral hypoglycemics, insulin
L liquor (Alcohols)
S sedative hypnotics
Hyperthermia (NASA)
N neuroleptic malignant syndome
A antihistamines
S salicylates, sympathomimetics
A anticholinergics, antidepressant
Hypotension (CRASH)
C clonidine
R reserpine
A antidepressants
S sedative hypnotics
H heroin (opiates)
Hypertension (CTSCAN)
C cocaine
T theophylline
S sympathomimetics
C caffeine
A anticholinergics, amphetmine
N nicotine

22. Toxic Physical Findings
Miosis (COPS
C cholinergics, clonidine
O opiates, organophosphates
P phenothiazines, pilocarpine, pontine hemorrage
S sedative hypnotics
Midriasis (AAAS)
A antihistamines
A antidepressants
A anticholinergics, atropine
S sympathomimetics (amphetamine)
Seizures
Organophosphates
TCA
Insulin
Sympathomimetics
Camphor
Cocaine
Amphetamine
Theophylline
Beta blockers
Lithium
Lead
Lidocaine

23. TOXIDROMES Opioids Cholinergics: carbamate and organophosphate
Triad: respiratory depression, PPP, decreased level of consc
Bradycardia, hypotension, hypothermia
Cholinergics: carbamate and organophosphate
SLUDGE
Seizures, coma
Muscle fasciculations
Miosis
Serotonin Syndrome: fluoxetine, trazadone, meperidine
Irritability, agitation, altered mental status
Hyperreflexia, tremor, myoclonus, trismus
Ataxia, incoordination
Flushing, diaphoresis, fever
Diarrhea
Extrapyramidal: haloperidol, phenothiazines
Rigidity, tremor
Opisthotonus, trismus
Choreoathetosis
Hyperreflexia

24. EXAMPLE 1 Acute Phenothiazine Toxicity
Blocking dopamine, alpha-adrenergic, serotonin receptors
In cases of hypotension unresponsive to fluids, alpha-adrenergic (norepinephrine) can be given but……
Dopamine (α & β adrenergic stimulator) if given will exaggerate hypotension because of stimulation of β receptors while α-receptors are blocked by phenothiazines

25. selective alpha-blocker (prazocin)
EXAMPLE 2
Scorpion Sting
Scorpion Venom Epinephrine & NE & Angiotensin II
α- receptor stimulation
Hypertension
selective alpha-blocker (prazocin)

26. INVESTIGATIONS Toxicology Screening
Essential clinical laboratory tests

27. Toxicology Screening
Quantitative serum levels of Acetaminophen, Salicylates, Digoxin, Iron, Lithium, Methanol, Theophylline, Phenobarb, Ethylene glycol may influence therapy.
Toxico screening provides direct evidence of ingestion, but must not affect initial management (first 6-8 hrs) and should not await results.
The management must depend mainly on the clinical status and available lab studies

28. TOXICOLOGY SCREENING
Comprehensive blood and urine screening is of little practical value in the initial care of the poisoned patient.
On the other hand, specific toxicologic analyses and quantitative levels of certain drugs may be extremely helpful.
Urine and gastric specimens are the best samples for broad qualitative screening.
Blood samples should be saved for possible quantitative testing, but blood is not a good specimen for screening for many common drugs, including psychotropic agents, opiates, and stimulants.

29. Limitations of toxicology screens
Comprehensive toxicology screens may look specifically for only 40–50 drugs out of more than 10,000 possible drugs or toxins (or 6 million chemicals).
However, these 40–50 drugs account for more than 80% of overdoses.
The time factor for reading toxicology screening is very long .
If the initial urine screen is done too soon after ingestion. The drugs found on the screen may not be responsible for the symptoms seen, especially if the drugs are not quantitated.

30. DRUGS COMMONLY INCLUDED IN A COMPREHENSIVE URINE SCREEN
Alcohols
Acetone
Ethanol
Isopropyl alcohol
Methanol
Analgesics
Acetaminophen
Salicylates
Anticonvulsants
Carbamazepine
Phenobarbital
Phenytoin
Primidone
Antihistamines
Benztropine
Chlorpheniramine
Diphenhydramine
Pyrilamine
Trihexylphenidyl
Opiates
Codeine
Dextromethorphan
Hydrocodone
Meperidine (Pethidine)
Methadone
Morphine
Oxycodone
Pentazocine
Propoxyphene

31. DRUGS COMMONLY INCLUDED IN A COMPREHENSIVE URINE SCREEN
Phenothiazines
Chlorpromazine
Promethazine
Thioridazine
Trifluoperazine
Sedative-hypnotic drugs
Barbiturates
Benzodiazepines
Chloral hydrate
Glutethimide
Meprobamate
Methaqualone
Stimulants
Amphetamines
Caffeine
Cocaine and benzoylecgonine
Phencyclidine (PCP)
Strychnine
Tricyclic antidepressants
Amitriptyline
Desipramine
Doxepin
Imipramine
Nortriptyline
Protriptyline
Other drugs
Diltiazem
Lidocaine
Procainamide
Propranolol
Quinidine and quinine
verapamil

32. DRUGS COMMONLY INCLUDED IN A COMPREHENSIVE BLOOD SCREEN
Alcohols
Acetone
Ethanol
Isopropyl alcohol
Methanol
Analgesics
Acetaminophen
Salicylates
Anticonvulsants
Ethosuximide
Carbamazepine
Phenobarbital
Sedative-hypnotic drugs
Barbiturates
Diazepam
Ethchlorvynol
Glutethimide
Meprobamate

33. Investigations CBC LFT RFT Electrolytes, CPK Blood Sugar
Arterial Blood Gas
CO, MetHgb, Cyanide toxicity
Respiratory or metabolic acidosis Example (Salicylates)
7. Urinalysis
Ferric chloride test for salicylates
Ketones ( salicylates, ketoacidosis )
Calcium oxalate crystals (ethylene glycol and oxalic acid )

34. EXAMPLE: Potassium Changes
Hypokalemia
Barium
Beta-adrenergic drugs
Caffeine
Diuretics (chronic)
Epinephrine
Theophylline
Toluene (chronic)
Salicylates
Hyperkalemia
Alpha-adrenergic agents
Digitalis glycosides
Fluoride
Lithium
Potassium
Renal failure

35. OG = (measured serum osmolality) – (calculated osmlality)
Osmolal Gap
OG = (measured serum osmolality) – (calculated osmlality)
Calculated osmolality: [2(Na+) + (Glucose/18) + (BUN/2.8)].
Normal Serum osmolality is mOsm/kg.
Normal osmolal gap is 8-12 mOsm/kg.
Elevation due to presence of unmeasured, low-molecular weight molecules that are osmotically active:
Methanol
Ethylene glycol
Diuretics, such as glycerol, manitol, sorbitol
Isopropanol
Ethanol

36. Anion Gap
AG is an indirect measure of phosphates, sulfates, & organic acids.
Na + unmeasured cations = (Cl + HCO3) + unmeasured anions
Na – (Cl + HCO3) = unmeasured anions – unmeasured cations
Anion gap = (Na ) – (Cl + HCO3)
Normal anion gap is mEq/L.

37. a. An elevated anion-gap acidosis is usually caused by an accumulation of lactic acid but may also be caused by other unmeasured acid anions such as formate (eg, methanol poisoning) or oxalate (eg, ethylene glycol poisoning).
Note: Combined osmolar- and anion gap elevation may also be seen with severe alcoholic ketoacidosis and diabetic ketoacidosis.
b. In any patient with an elevated anion gap, also check the osmolar gap; a combination of elevated anion and osmolar gaps suggests poisoning by methanol or ethylene glycol.
c. A narrow anion gap may occur with an overdose by lithium, bromide, or nitrate, all of which can increase the serum chloride level measured by some laboratory instruments.

38. Causes of high anion gap metabolic acidosis:
excessive acid production or with addition of exogenous acids:
Carbon monoxide, Cyanide.
Alcoholic ketoacidosis
Toluene
Methanol
Uremia
Diabetic ketoacidosis
Paraldehyde, Phenformin
Iron, Isoniazid
Lactic acidosis
Ethylene glycol
Salicylates

39. Causes of low anion gap with acidosis
Acetazolamide
Amiloride
Ammonium chloride
Amphotericin B
Bromide
Iodide
Lithium
Polymyxin B
Spironolactone
Toluene

40. Oxygen Saturation Gap
The difference between the oxygen saturation calculated from routine blood gas analysis and the oxygen saturation measured by pulse oximetry.
Others use this term for the difference between the calculated oxygen saturation from a standard blood gas machine and the measured value from a co-oximeter.
An oxygen saturation gap is present when there is more than a 5% difference.
Causes of elevated oxygen saturation gap include
carbon monoxide
Methemoglobinemia
hydrogen sulfide
Cyanohemoglobin does not result in this finding. Although cyanide poisoning may result from smoke inhalation, it is not associated with an oxygen saturation gap, but rather with an elevated serum lactate and a severe metabolic acidosis.

41. PREVENTION OF FURTHER ABSORPTION
A- Dermal Exposure
Remove all clothing.
Washing skin gently with soap and water for at least 30 minutes.
Forceful washing may damage skin and promotes further absorption.
Protection of medical staff
B- Eye Exposure
Washing conjunctiva with running water or normal saline for 20 minutes. Solid corrosives should be removed by forceps.
C- GIT Exposure
Gastrointestinal Decontamination
Intestinal Decontamination
Induction of emesis
Gastric lavage
Activated Charcoal
Activated charcoal
Cathartics
Whole bowel irrigation

42. INDUCTION OF EMESIS Syrup Ipecac
The only safe method for induction of vomiting. Poison Treatment in the Home. Pediatrics 2003;112;1182
From the root of Cephalus Ipecachuana: emetine & cephaline
Early phase: within 30 minutes by direct GIT stimulation.
Late phase: after 30 minutes through action on CTZ.
Dose: Adults: 30 ml; 15 ml for children more than 2 Yrs, 5-10 ml for children 6 months to 2 yrs. Not more than 2 doses
If emesis does not occur within 30 minutes, move around the patient, if no emesis a second dose can be given.
Syrup of ipecac should no longer be used routinely as a poison treatment intervention in the home.

43. INDUCTION OF EMESIS Contraindications Convulsions. Corrosives.
Hydrocarbons.
Sharp objects (e.g. needles).
Coma or impending coma
Decreased gag reflex.
Severe CVS disease or respiratory distress or emphysema.
Recent surgical intervention.
Hemorrhagic tendencies (varices, active peptic ulcer, thrombocytopenia).
Previous significant vomiting (spontaneously).
Less than 6m of age (not well developed gag reflex).

44. GASTRIC LAVAGE Technique:
used in hospitals when emesis was failed or there was contraindication for it.
Gastric lavage is effective in the first 4-6 hrs after ingestion.
Technique:
An assistant with suction machine should be available.
Dentures, mucous, vomitus should be removed from patient's mouth.
Proper tube size to be selected according to the patient age.

46. Absolute contraindications:
Complications:
Bradycardia, especially, in cases of organophosphate or digitalis toxicity.
Laryngospasm and cyanosis.
Vomiting & Aspiration pneumonia.
Stress reaction that may cause hypertension, and or tachycardia.
Hyponatremia, if tape water is used in children.
Mechanical gut injury.
Faulty introduction of the tube in the trachea
Contraindications:
Absolute contraindications:
Corrosives
Froth producing substances as shampoo or liquid soap.
Oesophageal varices or peptic ulcer
Relative contraindications
coma.
Convulsions.
Petroleum distillates.

47. ACTIVATED CHARCOAL
Adsorption of a wide variety of drugs and chemicals.
It is not digested; it stays inside the GI tract and eliminates the toxin when the person has a bowel movement.
Adult dose is 1 gm/kg.

48. Substances not adsosorbed by AC
Corrosives
Alcohols
Cyanide
Oils
Glycols
Metals (Iron, Lithium, Lead, Mercury,..)
Petroleum distillates
Sodium chloride
Sodium hypochlorite bleach

49. Contraindications 1) Coma 2) Intestinal obstruction. 3) Corrosives
ACTIVATED CHARCOAL
Contraindications
1) Coma
2) Intestinal obstruction.
3) Corrosives
4) If an oral antidote is given
5) Hydrocarbons

50. Multiple-dose Activated Charcoal
Multiple-dose activated charcoal is defined as the administration of more than 2 doses of activated charcoal in the treatment of a given poisoning
The recommended indications for the use MDAC are:
(1) the patient has ingested a potentially life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline
(2) in the clinical judgment of the clinician the benefits outweigh the risks
(3) alternative methods of treatment are not effective.

51. CATHARTICS (laxatives)
These are substances that enhance the passage of material through GIT and decrease the time of contact between the poison and the absorptive surfaces of the stomach and intestine.
a) Osmotic cathartics: increase osmotic pressure in the lumen, as Mg sulfate.
b) Irritant cathartics: act by increasing motility, such as caster oil.
Contraindications:
GIT hemorrhage.
Recent bowel surgery.
Intestinal obstruction.
Renal failure for magnesium salts.

52. WHOLE BOWEL IRRIGATION
The goal of WBI is to clean GIT from nonabsorbed ingested toxins. Polyethylene glycol electrolyte solutions are used, should be administered by gravity.
Indications
Ingestion of a toxin that is known to be poorly adsorbed by A charcoal.
Ingestion of massive amounts of drugs / impractical AC
Ingestion of sustained-release or enteric-coated preparations (e.g. aspirin)
Removal of ingested packets of illegal drugs (body packers).
Ingestion of large amount of drugs that may form concretions or bezoars
Treatment of suspected drug concretion
Continual rise in measurable toxin concentrations despite charcoal administration).
Drugs that may form concretions: Salicylates, Barbiturates, Carbamazepine, Enteric coated or sustained release tablets, Meprobamate.

53. ANTIDOTES

54. DEFINITION according to
International Programme on Chemical Safety
United Nations Environmental Programme
WHO
A THERAPEUTIC SUBSTANCE USED TO COUNTERACT THE TOXIC ACTION(S) OF A SPECIFIED XENOBIOTIC

55. ANTIDOTES Classification
According to mechanism of action
1- Interacts with the poison to form a nontoxic complex that can be excreted e.g. chelators
2- Accelerate the detoxification of the poison: N-acetylcysteine, thiosulfate.
3- Decrease the rate of conversion of the poison into its toxic metabolites: Ethanol, Fomepizole.
4- Compete the poison for certain receptors: Naloxone.
5- Block the receptors through which the toxic effects of the poison are mediated: atropine
6- Bypass the effect of the poison: O2 treatment in CO and cyanide toxicity.
7- Antibodies to the poison: digiband, antivenoms.
According to mode of action
1- Physical
2- Chemical
3- physiological

56. 1- Physical Antidotes
Agents used to interfere with poisons through physical properties, not change their nature
a) Adsorbing: the main example is activated charcoal.
b) Coating: a mixture of egg & milk makes a coat over the mucosa. It can be effective in corrosives, but not in cases of organophosphate. It decreases efficacy of AC.
c) Dissolving: 10% alcohol or glycerine for carbolic acid.

57. 2- Chemical Antidotes
a) Oxidizing: Amyl Nitrite is used in cyanide toxicity.
b) Reducing:
Methylene Blue: it is used with MetHb producers: nitrates, nitrites, phenacetin, chlorates, sulfonamides.
Vitamin C: used for drugs causing Met-Hb.
c) Precipitating:
Starch: it makes blue precipitate with iodine. 50 gm in glass water.
Egg albumin, gelatin, skimmed milk: in mercury but should be rapidly washed as the precipitate dissolves in excess albumin.

58. 3- Physiological (Pharmacological) Antidotes a) Antagonism
1- Competitive Antagonists
Naloxone:
Naltrexone: Opiate dependence; longer action with affinity for mu receptors.
Flumazenil: antagonist for benzodiazepines
Atropine: organophosphate, carbamate, and other parasympathomimetic (pilocarpine, muscarine). It is used as antidote to correct bradycardia caused by morphine, digitalis, aconitine, β-blockers, and calcium channel blockers. .

59. 2) Non-Competitive Antagonism
Anticonvulsants: for treatment of convulsants.
Calcium gluconate: used for:
a) Calcium channel blockers especially verapamil.
b) Black widow spider bite.
c) Lead colic
d) Oxalic acid.
Pralidoxime (2-PAM): ChE activator by breaking the alkylphosphate-ChE bond. It is used in organophosphate toxicity to form an oxime-phosphate complex and leaves the ChE enzyme activated. Contraindicated in carbamate toxicity because of short duration of action.
Diacetyl Monoxime (DAM): same action as PAM with more BBB penetration and reactivation of ChE in CNS.
Physostigmine: counteract the anticholinergic effects such as in severe atropine or TCA toxicities.

60. b) Chelating Agents: 1- Dimercaprol (BAL)
Unite metallic poisons to form soluble, nonionizable, less toxic, and easily excreted chelates.
1- Dimercaprol (BAL)
prototype chelator (bisulfide molecule)
removes intracellular and extracellular lead
lipid-soluble drug and must be administered IM only
It has the typical sulfide odor and patients often complain of the taste
It is the first chelator used in encephalopathic individuals. Rapidly crosses the BBB.
Adverse effects
fever, pain at the injection site, nausea, vomiting, headache, and sterile abscess formation. It is recommended to alkalinize urine as the chelate may dissociate in acidic urine.
Indications:
Lead, Arsenic, inorganic Mercury, Copper, Gold.
Contraindications:
a) Liver failure as metallic chelate is excreted mainly through the bile.
b) G6PD deficiency.
c) Transtoxicity or concurrent iron supply.
d) Organic Mercury; risk of neurotoxicity.

61. 2- Calcium disodium edentate (Ca Na2 EDTA)
Unites with the metal which takes place of its calcium.
It is water soluble and may be used IM or IV
It allows extracellular lead to be renally eliminated
In cases of lead encephalopathy, BAL should be given first to avoid redistribution of lead mobilized by CaNa2EDTA to CNS.
3- D-Penicillamine: Hydrolysis product of penicillin approved for the treatment of Wilson disease and cystinosis. Effective orally and has few adverse effects.
a) It can chelate lead even in low blood levels.
b) It is effective in children with blood levels µg/100ml.

62. 4- Succimer (Di-Mercapto Succinic Acid; DMSA) The best for lead chelation in children with a lead level higher than 45 µg/dL. An effective oral chelator that approaches the effect of both CaNa2EDTA and BAL. 5- Dimerval (DMPS) Has become antidote for most heavy metal intoxications. In the oral form and in a water-based parenteral form. 6- Cobalt edetate (Kelocyanor) Cobalt compounds directly chelate cyanide, thus reducing its toxicity, bypassing the formation of a toxic (methemoglobin) intermediate. Kelocyanor is thought to work faster than any of the MetHb-formers.

63. N-Acetyl Cysteine (NAC):
Antidote in acetaminiophen toxicity:
1-Precursor for glutathione. NAC is converted to cysteine, which can replenish glutathione stores.
2- NAC also directly detoxifies acetaminophen toxic metabolite to nontoxic metabolites.
3-NAC can provide a substrate for sulfation
a) Oral NAC: It is effective in preventing hepatotoxicity regardless of the initial acetaminophen level if it is started within 8 hrs of ingestion.
b) Intravenous NAC: IV administration of NAC is recommended for selected patients, including those with GIT bleeding or obstruction, potential fetal toxicity, or an inability to tolerate oral NAC.

64. d) Antibodies (Immunology-based Antidotes) 1- Digoxin Specific Antibody Fragment (FAB fragments, Digiband): Life-threatening arrhythmias Initial potassium level >5 mEq/l. Digoxin SL >10 ng/mL at 6-8 h postingestion Digoxin SL >15 ng/mL in an acute ingestion Ingestion >10 mg in healthy adults or > 4 mg in children. 2- Polyvalent Snake Antivenom: 3- Scorpion Antivenom: Indications include: a) All children and old patients presenting with any of systemic manifestations. b) Patients with CV disease. 4- Antibotulism Serum:

65. Vitamin B12 (Hydroxycobalamin):
4) Other Antidotes
a) Vitamins
Vitamin K:
a) Agents causing hypoprothrombonemia: organic arsenic, salicylates, coumarin.
b) Vitamin A toxicity: inhibits flora, antagonism of hepatic action of vit K.
Vitamin B12 (Hydroxycobalamin):
contains cobalt ion, able to bind to cyanide with greater affinity than cytochrome oxidase to form nontoxic cyanocobalamin that is excreted in urine.
Glucagon:
is used in β-blocker poisoning to stimulate the β-adrenergic nerves on a receptor different from that occupied by the β-blocker.

66. Cyanide Antidote Kit Step I
Amyl nitrite & Sodium nitrite: induce methemoglobinemia so that cyanide, with high affinity for ferric iron (Fe3+), may attach to it to form cyanomethemoglobin, rather than to the iron of the cytochrome, thus restoring or allowing cellular respiration
Step II
Sodium Thiosulfate: detoxification of the formed cyanomethemoglobin compound so that it can be excreted. The presence of thiosulfate in the blood allows rhodanese to detoxify Cyano-MetHb by catalyzing the formation of thiocyanate, which is nontoxic and rapidly excreted in the urine.

67. ENHANCEMENT OF EXCRETION OF ABSORBED POISONS

68. Forced Diuresis It is a simple method for some poisons.
It is effect is increase with manipulation of urine pH.
It is efficient only in poisons with the following properties:
Substances excreted mainly by kidneys.
Substances with low volume distribution.
Substances with low protein binding.
Types:
1- Fluid Diuresis
2- Osmotic Diuresis: mannitol 10%, which is excreted by renal tubules leading to increases in its osmotic pressure

69. Manipulation of Urine pH
This method acts depending on the extent of ionization (pKa)
Forced alkaline diuresis
b) Acid diuresis
It is uncommonly used method for certain substances such as amphetamine. It is a dangerous method because of the risk of myoglobin precipitation in renal tubules.

70. Dialysis
by allowing toxic substances to pass through semi-permeable membrane depending on the concentration gradient. It is beneficial when renal function is impaired. Dialyzable substances for good results must have:
Low volume distribution.
Low molecular weight.
Low protein binding.
Examples for dialyzable substances: alcohols, barbiturates, salicylates.
Examples for nondialyzable substances: opiates, atropine, antidpressants.

71. a) Peritoneal dialysis Acts by considering peritoneum as semipermeable membrane. Complications: intra-abdominal bleeding, perforation of abdominal organs, peritonitis, dehydration or overhydration. Contraindications: pregnancy, abdominal hernia, or respiratory distress.

72. b) Hemodialysis
The semipermeable membrane is a cellulose bag (artificial kidney).
Indicated when the condition is deteriorating despite proper treatment, or in toxicities with potentially lethal blood levels.
Complications:
Hypotension.
Bleeding tendency (due to heparin).
Electrolyte imbalance.
Cross infections.
Muscle cramps.
Air embolism.

73. Hemoperfusion Using equipment and vascular access similar to that for hemodialysis, the blood is pumped directly through a column containing an adsorbent material (either charcoal or Amberlite resin). Systemic anticoagulation is required, often in higher doses than for hemodialysis, and thrombocytopenia is a common complication. 1. Because the drug or toxin is in direct contact with the adsorbent material, drug size, water solubility, and protein binding are less important limiting factors. 2. For most drugs, hemoperfusion can achieve greater clearance rates than hemodialysis. For example, the hemodialysis clearance for phenobarbital is 60–80 mL/min, whereas the hemoperfusion clearance is 200–300 mL/min.

74. Contraindications: Patients with coagulopathy
Contraindications: Patients with coagulopathy. Patients with uncorrected hypotension. Complications: Thrombocytopenia. Hypocalcemia. Hypoglycemia. Hypotension. Adsorption of therapeutic drugs.