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06/01/09

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ABC in drug Poisoning
) for education purposes only(

By Dr. Ahmed Shaker Ali Please send any comments regarding this lecture AhmedShaker21@yahoo.com 06/01/09

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Objectives

General Principles in the Management of Poisoning e.g charcoal √√ Specific management options with certain substances e.g
   

Paracetamol√√ Opiates )Heroin, Methadone, Morphine( NSAIDs )ibuprofen ( Tricyclic Antidepressants )

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Topics
 

Introduction General guidelines
regarding the exam (

) most slides are optional

  

ABC, toxidromes, decontamination, antidote Acetaminophen toxicity Heroin toxicity Optional ) Tricyclic antidepressant toxicity (

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Introduction
Types of Intoxication

Acute
Subacute Chronic

A sudden and severe exposure to a toxic agent
Repeated exposures over a period of hours or days Repeated exposure over weeks or even years

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Assessment & management
History & Evaluation, diagnosis life saving measures ) ABC .. ( General measures :
o Stop Exposure: o Limit GI Absorption o Hasten Elimination
Many steps may be performed simultaneously

o Specific antidote Further Investigations & follow up

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General Management -1
   

A )Airway( B )Breathing( C )Circulation( D )Disability-AVPU/ Glasgow Coma Scale( DEFG ) Don’t ever forget the Glucose( GET A SET OF BASIC

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History
 

Who – pt’s age, weight, relation to others What – name and dose of medication, coingestants and how much amount ingested When – time of ingestion, single vs. multiple ingestions Where – route of ingestion, geographical location Why – intentional vs. unintentional,

Also consider : Psychiatric history & other Circumstances Drug history, I identify, keep any drugs came with the patients , or empty containers

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Toxidromes =symptoms of
toxicity


 

Physical Examination
eye { pupil size, nystagmus CNS – level of arousal, GCS, mental status, neurologic exam CVS – Blood pressure, Pulse rater, rhythm Respiration – pattern, depth, wheezing GI – bowel sounds, distention Vomiting Skin – color, temp, sweating, signs of trauma Other observations Odors
:

    

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Essential Clinical laboratory tests
U & Es, LFTs , glucose, ABG, clotting,



Drug monitoring & Toxicology screening
E.g Acetaminophen , salicylate , Antiepileptic , digoxin , selective screen ) e.g drugs of abuse ( NB : Toxicology screening need urine samples+ blood samples. Other may be considered : urine analysis Serum osmolality and osmolar gap Osmolar gap = measure - calculated = 0 ± 5 ?? Calculated Os = 2 Na+ glucose + BUN ??

    

Summery of ABC Management 11 plan

Supportive monitoring and management of serious life threatening problems

Correct hypoxia, hypotension, dehydration, hypo- hyperthermia, and acidosis Control seizures

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General measures
2- Decontamination Surface Decontamination Skin : protect yourself,

 

remove contaminated clothes , washing, soap and shampoos for oily substances etc EYE : place the victim in supine position under tap water or use IV tubing to direct a stream of water across the nasal bridge into the medial aspect of the eye ) use at least 1L /eye ( Inhalation : remove the patient from exposure, subliminal humidified oxygen, Assist vent. If necessary , Observe closely for URT edema , and late onset pulmonary edema etc

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√GIT decontamination-3
Methods
     

activated charcoal Gastric Lavage ? Whole bowel irrigation ? Emesis ???? Cathartics???? Surgery ????????

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√√√Activated Charcoal

Indications
 

Within 1 hour of ingestion Nearly all suspected toxic ingestions except ) inorganic salts, acids, alkali, heavy metals, Iron, alcohols , ethylene glycol (

Contraindications : no absolute
contraindications

Complications
 

Intestinal impaction if multiple doses Distension of the stomach with potential of pulmonary aspiration.

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√√√Activated Charcoal

1g/kg PO or NG at least 10 times the ingested dose. One or two additional doses may be used at 1-2 hr intervals

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Whole bowel irrigation

PEG in a balanced electrolyte soln. via NG at 1-2 L/h )500cc/h in peds( until effluent clear

  

+ activated charcoal 25-50 g / 2-3 hr Indications Large doses of SR or EC prep of dangerous drugs e.g Theophylline , carbamazepine, aspirin etc
  

Ingested packets of illicit drug )stuffers, packers( Substances not adsorbed by AC Iron ingestions Ileus , Bowel perforation or obstruction, Intractable vomiting GI bleeding Unprotected airway Hemodynamic instability ?? Nausea, vomiting, cramps Aspiration Reduce effectiveness of charcoal

Contraindications
   

Complications
  

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‫ربما ضرر التقيىء ) من نفعه‬ Emesis Ipecac –syrup ????‫اكثر‬not used in hospitals (
Emetic – both peripherally and central acting >90% effective Dose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 mo


Indications

Early pre-hospital management when activated charcoal is not available , prolonged transport time to hospital Unprotected or anticipated unprotected airway Hydrocarbons, crossover agent Substance likely to cause CNS depression or seizure in short time Obtunded, comatose or convulsive patients Cardiac and pulmonary patients < 6 month Diarrhea, lethargy/drowsiness, prolonged vomiting, hemorrhagic gastritis s

Contraindications
     

Complications ) many (

A soapy water) dishwashing liquid or lotion , 2 teaspoonful in a glass of water ( solution may be used as alternate emetic

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Gastric Lavage

Overview : Occasionally used in ER,, not necessary for small to moderate ingestion of most substances if activated charcoal can be given promptly

Indications
  

Recent ingestion )<1-2 hr( Massive overdose or a particularly toxic subsetance Agents not adsorbed by AC Obtunded, comatose or convulsive patients SR or enteric coated tab. Corrosives ?? Hydrocarbons Risk of GI bleed or perforation mostly from bad manipulation mechanical injury, Aspiration pneumonia , laryngospasm, hypoxia,, fluid/electrolyte imbalances

Contraindications
    

Adverse effects :
 

Technique : protect airway, proper position, administer activated charcoal before
starting lavage

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)Enhancing elimination) EE
Overview : Application of toxic kinetics is necessary for appropriate use # 3 Q ?  Q1: Does the patient need EE?  Q2 : Is the drug accessible to the procedure ?

this depends on PK ) vd, protein binding ( this depends on Total CL & t-half.

Q3: Will the method work ?

Methods avialble  Urinary manipulation ) Alkalinization of urine for acidic
drugs or diuretics(
   

Hemodialysis Hemoperfusion Hemofilteration Repeated dose activated charcoal

Details are optional ) Annex 2 (

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POISON

Antidotes ANTAGONISING THE EFFECTS OF THE
)

Antidote

N-acetylcysteine
atropine Ca gluconate or Ca chloride kit Cyanide

Poison acetaminophen
organophosphate Calcium channel blockers cyanide

Deferoxamine Fab digoxin
Dimercaprol )BAL(

Iron Digoxin
Arsenic, mercury, lead

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Antidotes
Antidote
ethanol
flumazenil Fomepizole glucagon Methylene blue

poison MeOH, et glycol
Benzodiazepine MeOH Β-blocker, CCB methemoglobin

naloxone
physostigmine pralidoxime pyridoxine

opioids
anticholinergic organophosphate isoniazid

Sodium bicarbonate

TCA, cocaine, salicylates

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Paracetamol toxicity

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Toxicity
Little to no toxicity in therapeutic dosing With overdose:

Hepatic toxicity progressing to fulminant hepatic failure, encephalopathy and death within days Other systemic effects

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Pharmacological basis of √√√√√ Acetaminophen toxicity
Acetaminophen
O ll HN-C-CH3

Glucuronidation

Sulfation

OH

P450

N-Acetyl-p-benzoquinonamine

NAPQI Oxidant tissue damage
Glutathione

Non-toxic metabolites

Oxidant tissue damage

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Overdose
Normal conjugation metabolism routes are saturated More NAPQI is produced Glutathione reserves fall below 30% Unable to detoxify all NAPQI formed Cellular injury results

   

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Management
NB in initial phases no clear symptoms. Drug monitoring is very valuable if done properly N-actylcystine is the anti-dote Use the Rumack-Matthew Nomogram to identify the potential toxicity

 

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Rumack-Matthew Nomogram for Acute Acetaminophen Toxicity

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Opiate Poisoning- Features
   

Heroin ) addiction ( Methadone, analgesics in Elderly General toxidromes.
  

‫بئس المصير‬

1. PINPOINT PUPILS 2. RESPIRATORY DEPRESSION 3.COMA

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Opiate OverdoseManagement
    

INITIAL MANAGEMENT A B C D

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Opiate OverdoseManagement 2

NALOXONE
    

Opioid antagonist High Affinity for the opiate receptors Little other effects Rapid onset Effects last 2-4 hrs, may need repeated doses Give I-M or I-V

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References
You may visit these sites  http://www.clintox.org  http://www.aapcc.org  TOXNET database http://toxnet.nlm.nih.gov/index.htm/  Text book : Poisoning and & drug overdose  Kent R OLSON 4th ed . LANGE P. 66-69 , 286-289

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) Optional section ) SDL

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A irway

 

Assessment :
Patients awake )monitor closely ( lethargic or obtunded ) consider management (

 

Management : Optimize the airway position
o o o

)practical skill (

Sniffing position Jaw thrust Head down, left sided position


Remove any obstruction or secretions
Perform endotrachial intubations if indicated
o o

Nasotrachial orotracheal

or

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B reathing
1-Ventilatory failure
cause : CNS depression by opiates, barbiturates alcohol, Tricylic antidepressants, etc ) R.O other causes ( Assessment : Arterial blood gases ) PCO2 > normal values( indicate the need for assisted ventilation Treatment : Assisted ventilation : optimal programming of the ventilator

2- Hypoxia
cause : sedative hypnotic , opiates ,salicylates,) R.O other causes ( Treatment : Correct hypoxia : Administer oxygen as indicated based on arterial PO2

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Breathing cont
3- Cellular hypoxia
cause : CO , Cyanide & hydrogen sulfide Treatment : CO ) 100 % oxygen , consider hyperbaric oxygen ( refer to the specific guide

4- Bronchospasm

Cause : Direct irritant ) gases, aspiration of petroleum distillates ( Pharmc effects of poisons or drugs ; e.g Organophosporous , carbamates insecticides, B-blockers . Hypersensitivity : many drugs & poisons Treatment : o Administer oxygen, assist ventilation, endotrachial intubations if needed , o Administer bronchodilators o e.g albutrol 2.5-5 mg in nebulizer o ibratroprium bromide 0.5 mg 4-6 h o consider iV theophylline in case of B-blockers poisoning

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C irculation

I-General

Check BP , pulse rate & rhythm. CRP ) cardiopulmonary resuscitation( if no pulse ACLS [ Advanced cardiac life support ] for severe arrhythmia and shock Begin cont EEG monitoring Begin IV infusion of appropriate fluids Secure venous access  II: Bradicardia & AV block
no treatment unless the pt is symptomatic Treatment include : maintain airway and assists ventilation if necessary Atropine 0.01-0.03 mg/kg IV or isopreternol 1-10 mcg/min, ER pacemaker Specific antidote if appropriate o Glucogon for bet-blockers over dose o Fab digoxin for digoxin toxicity

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Circulation cont

III-QRS INTERVAL PROLONGATION
>0.12S INDICATE POSIONING BY TCA OR OTHER MEMBRANE DEPRESSANT DRUGS eg digitalis , b-blockers


o o o

Treatment :
maintain airway and assists ventilation if necessary Treat hyperkalimia and hypothermia if present Treat AV block by atropine , isoppteternol and pacemaker if necessary for TCA or other sodium channel blockers give 1-2 mEq sod bicarc IV bolus, repeat as needed Other antidote if appropriate

o

o

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Circulation

theophylline , cocaine Treatment observation and sedation if no chest pain or hypotension sympathomimetic induced : propranolol or esmolol If tachycardia is anticholinergic induced ; consider use of neostigmine these drugs should be avoided in case of TCA ) A systole additive depression of
conduction (

III-Tachycardia causes : many e.g sympathomimetic agents : Amphetamine ,

V-Ventricular arrhythmia  Causes : many drugse.g exissive Sympathetic stimulation ) cocaine ,
amphetamine (

Treatment :

follow the standard guidelines for management of arrhythmia with exception : Procanimide and bretylium should not be used esp if TCA or B-blockers over dose is suspected.

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Circulation cont
VI-Hypotension
 

 

Causes : many drugs. Opiates , sedative hypnotics , theophylline , TCA Treatment :usually respond to simple measures Fluid therapy and low dose of pressor drugs IF not resolved use systematic approach Which consider management of Airway, Arrhythmia, hypothermia, dopamine ) nor-epinephrine in case of TCA Specific antidote

VII-Hypertension
Causes : With Tachycardia : LSD, Cocaine, Amphetamine, TCA  Treatment : it depends on other symptoms: No Tachycardia : phentolamine or nitroprusside Presence of Tachycardia : As above + propranolol or esmolol or labetolol NB : not use These drugs alone for treatment of hypertensive crisis

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Mental Status

 
   

Coma and stupor
Cause: many Treatment :
:Generalized CNS depressants & sympatholytic 1-Maintain airway , assists ventilation, administer oxygen if necessary 2-DRUGS : Dextrose, Thiamine, Naloxone ) if respiratory depression, Flumazenil ) If Benzodiazepine alone is suspected

(

 

Hypothermia : follow the guidelines Hyperthermia : follow the guidelines

Key words :,, Treatment : immediate rapid cooling  1- as above, 2- Fluids, 3- Control of seizure 4-External cooling with tepid sponging and fanning 5- specific drugs , neuromuscular paralysis by vecuronium Malignant hyperthermia : Give dantrolene neuroleptic malignant syndrome : Consider bromocriptine serotonin syndrome : cryptoheptadine or methylsergide my helpful

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Mental Status cont
Seizure :

Causes :

many drugs including adrenergic sympathomimetic agents

Antidepressants and antipsychotic

Treatment :
1- 1-Maintain airway , assists ventilation, administer oxygen if
necessary 2- Nalxone : if seizure is due to narcotic 3-correct hypoglycemia : dextrose and thiamine as for coma 4- Appropriate anticonvulsant drug ) Diazepam, Lorazepam, Midazolam, phenobarbital, pentoparbital, propofol , phenytoin } 5-Specific antidote : Pralidoxime or atropine or both for organophosphate or carbamate insectside

  

Agitation, delirium or Psychosis follow the
guideline

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Other complications
     

Dystonic reactions Dyskinesia Rigidity Rhabdomylosis Anaphylaxis Anaphylactoid reactions

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Details of Enhanced elimination

44

Hemodialysis
  

Blood passed across membrane with countercurrent dialysate flow Toxins removed by diffusion Patient must be anticoagulated
    

Properties required:
Molecular weight < 500 daltons High water solubility Low or saturable plasma protein binding Low Vd )<1L/kg( Low endogenous clearance)<4ml/min/kg(

Complications
     

Bleeding at venous puncture site hypotension DVT Bleeding due to systemic anticoagulation Infection Air embolus

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Hemoperfusion
Overview : Blood passed through cartridge containing AC  Toxins removed by adsorption Advantages : Drug characteristics are less important  Usually greater clearance rate Disadvantages Systemic anticoagulant is required  Thrombocytopenia is a common complication

Properties required:
 

Low Vd <1L/kg Low endogenous clearance <4cc/min/kg Adsorbable to AC

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Peritoneal dialysis

  

Easer to perform than other dialysis tech. Only 10-15 % as effective , slow Cl. rate Can be performed continuously 24 hr Pr. D = 4 hr of Hemo. D.

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Alkalinization
 

Enhances elimination of weak bases by ion trapping Useful for:

Salicylates, phenobarbital, chlorpropamide, methotrexate, myoglobin

  

NaHCO3 1-2 mEq/kg IV Q3-4H Aim for Urine pH 7-8 Must replace K

48

Multiple Dose Activated Charcoal

Consider only if life-threatening amount of:
    

Carbamazepine Phenobarbital Dapsone Quinine Theophylline amitriptyline, propoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, sotalol

May also increase elimination of :

49

Details of Toxicity of Acetaminophen

50

Phase I
 

0 to 24 hours Usually asymptomatic

“silent overdose”:

Importance of obtaining level

Nausea, vomiting, abdominal pain

51

Phase II
 

24-72 hours Resolution of initial physical symptoms

May develop right upper quadrant pain Elevation of LFT, PT, Bilirubin

Evolving liver injury

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Phase III
 

3 to 4 days Nausea, vomiting, and abdominal pain reoccur Maximal manifestation of hepatic injury-AST/ALT in 10,000s Coagulopathy, hepatic necrosis, acidosis, encephalopathy Coma and anuria precede death

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Phase IV
  

Beyond 4 days Recovery phase LFTs will decrease, but bilirubin may remain elevated for some time May take several weeks for LFTs to normalize

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Other Overdose Sequelae

Renal toxicity

Occasionally renal failure can occur from massive overdoses

Possibly 2° to P450 activity in the kidney

 

Pancreatitis Pneumonitis

55

The Nomogram

Is a guideline for determining who should be treated for a single acute ingestion Is not a representation of the elimination kinetics

Serial levels not useful ↑ sensitivity – no missed cases ↓ specificity

In US, line positioned 25% lower
 

Important to use a 4-hour level whenever possible

56

Ingestion of single dose

Treatment indicated if:
   

Level above 150mg/dL at 4 hours Ingestion of 150 mg/kg in children Ingestion of 7.5 g in adults Patient is unreliable or unconscious

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N-acetylcysteine

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Mechanism of N-acetylcysteine

Restores glutathione:

Allows NAPQI detoxification

 

Augments sulfation reaction Direct anti-oxidant:
 

Directly detoxifies NAPQI Improves organ function and limits hepatocyte injury

59

Unknown ingestion time

Treat if any sign of liver injury even without history of APAP ingestion Detectable APAP level in altered patient If AST/ALT are normal

And APAP is less than 10 µg/ml
 

Do not treat Narrow window of risk

60

Laboratory Assessment

If patient is sick, one should obtain LFTs, PT, electrolytes, BUN/Cr, amylase, lipase and glucose

 

Late presenting sick patients will not have detectable acetaminophen levels Diagnosis can be more difficult They will require treatment

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Repeat or Chronic ingestion
 

Nomogram does not apply Suggested threshold:
 

150 mg/kg per 24 hours in children 7.5 g per 24 hour period in adults

Obtain acetaminophen level, AST, ALT, PT, BUN/Cr and electrolytes

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Repeat or chronic ingestion

Patients who should be treated )similar to unknown ingestion time(:
  

Signs of hepatotoxicity )elevated AST( APAP level of ≈25 mcg/ml or greater Symptomatic

“Gray area”: APAP 11-25 mcg/ml and normal AST in asymptomatic patient

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Ethanol And Acetaminophen

Ethanol is metabolized to some extent by P450 system Chronic ethanol ingestion causes increase in 2E1 P450 activity

Acute acetaminophen ingestion is treated the same in patients who consume alcohol chronically

64

N-acetylcysteine

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N-acetylcysteine

Greatest benefit if administered within 8 hours:
 

No clinical difference within the first 8 hours All patients that have a normal AST at time of NAC initiation survive Treatment within 8 hours of single ingestion completely prevents liver failure Improved mortality even in patients with hepatic failure when initiated 2-3 days after ingestion

“Too Late” does not exist

66

Oral N-acetylcysteine

Oral loading dose is 140 mg/kg
 

Dilute 4:1 with palatable liquid Repeat doses are 70mg/kg every 4 hours Total of 17 doses for total of 72 hours

Antiemetic treatment may be required

NAC is very foul “rotten egg” liquid

67

IV N-acetylcysteine

Can cause anaphylactoid reaction
 

Rash, hypotension, bronchospasm and death Rate related; rare when given slowly

Higher, continuous blood levels obtained then oral NAC Bolus administered first, then constant infusion rate may be given

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IV vs. Oral

 

Both have their advantages and disadvantages Each may be more appropriate in certain settings No side by side studies to date Conclusions of relative benefits are speculative

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