POISONS management in pharmacology in nursing.

Pharmacology management of poisons

1. DR MARY ONYANGO
POISONS

2. General Info
All chemicals have potential to be poisons if given in a
large enough dose
Poisoning occurs when exposure to a substance adversely
affects function of any organ system

3. General Approach poison management
ABC’s
History
Physical examination
Labs, imaging
Diagnosis, antidotes
Disposition

4. ABC’s

5. Airway
Airway obstruction can cause death after poisoning
Look out for
Flaccid tongue
Aspiration
Respiratory arrest
Evaluate mental status and gag/cough reflex
Institute airway interventions to clear airways e.g.
Clear secretions
Left-sided position
Examine the oropharynx
Intubation

6. Breathing
Determine if respirations are adequate
Give supplemental oxygen if needed
Assist with bag-valve-mask
Check oxygen saturation, ABG
Auscultate lung fields
Bronchospasm: Albuterol nebulizer
Bronchorrhea/rales: Atropine
Stridor: Determine need for immediate intubation

7. Circulation
IV access
Obtain blood work
Measure blood pressure, pulse
Hypotension treatment:
Normal saline fluid challenge, 20 mL/kg
Vasopressors if still hypotensive
PRBC’s if bleeding or anemic
Hypertension treatment:
Nitroprusside, beta blocker, or nitroglycerin
Continuous ECG monitoring
Assess for arrhythmias, treat accordingly

8. Decontamination

9. Principles of Decontamination
External
Protect yourself and others
Remove exposure
Irrigate copiously with water or normal saline
Don’t forget your ABC’s
Internal
Patient must be fully awake or intubated
Most common complication is aspiration
Very little evidence for their use

10. Decontamination
Skin
Protect yourself and other HC workers
Remove clothing
Flush with water or normal saline
Use soap and water if oily substance
Chemical neutralization can potentiate
injury
Corrosive agents injure skin and can have
systemic effects

11. Decontamination
Eyes
remove contact lens
Flush copiously with water or normal saline
Use local anesthetic drops
Continue irrigation until pH is normal
Slit lamp and fluorescein exam

12. Decontamination
Inhalation
Give supplemental humidified oxygen
Observe for airway obstruction
Intubate as necessary

13. GI Decontamination
Syrup of ipecac
Within minutes of ingestion
Aspiration, gastritis, Mallory-Weiss tear, drowsiness
Rarely, if ever, given in ED
Gastric lavage
Does not reliably remove pills and pill fragments
Used 30-60 minutes after ingestion
Useful after caustic liquid ingestion prior to endoscopy
Not used for sustained release/enteric coated ingestions
Perforation, nosebleed, vomiting, aspiration

14. GI Decontamination
Activated charcoal
Limits drug absorption in the GI tract
Within 60 minutes of ingestion
Patient must be awake or intubated
Vomiting, aspiration, bezoar formation
Contraindication: bowel obstruction or ileus with distention
1 gram/kg PO or GT

15. Activated Charcoal
Not good for:
Lithium
Iron
Alcohols
Lead
Hydrocarbons
Caustics

16. GI Decontamination
Cathartics
Hasten passage of ingestions or AC
Contraindications: obstruction or ileus
Severe fluid loss, hypernatremia, hyperosmolarity
10% magnesium citrate 3ml/kg or 70% sorbitol 1-2 …./kg
Whole bowel irrigation
Large ingestions, SR or EC tablets, packers (ex. cocaine)
Contraindications: obstruction or ileus
Aspiration, nausea, may decrease effectiveness of charcoal

17. Enhanced Elimination
Urinary manipulation
Forced diuresis
Alkalinization
Repeat-dose activated charcoal
Very large ingestions of toxic substance
Sustained release and enteric coated preparations
Carbamazepine, phenobarbital, phenytoin
Salicylate, theophylline, digitoxin
Hemodialysis, Hemoperfusion
Peritoneal dialysis, Hemofiltration

18. Enhanced Elimination
Does the patient need it?
Severe intoxication with a deteriorating condition despite
maximal supportive care
Usual route of elimination is impaired
A known lethal dose or lethal blood level
Underlying medical conditions that can increase complications

19. Toxidromes

20. Toxidromes
Physiologically based abnormalities that are known to
occur with specific classes of substances and typically are
helpful in diagnosis

21. Cholinergic Toxidrome
Diarrhea Salivation
Urination Lacrimation
Miosis Urination
Bradycardia Defecation
Bronchospasm GI upset
Emesis Emesis
Lacrimation
Limp
Salivation, sweating

22. Cholinergics
Organophosphates
Irreversibly bind cholinesterases
Carbamate
Reversibly bind cholinesterases, poor CNS penetration
Muscarinic and nicotinic effects
Pesticides, nerve agents
Military personnel
Field workers, crop dusters
Truckers
Pest control, custodial workers
Antidote
Atropine for muscarinic effects
Pralidoxime reverses phosphorylation of cholinesterase

23. Anticholinergic Toxidrome
Dry mucus membranes
Mental status changes
Flushed skin
Mydriasis
Fever
Tachycardia
Hypertension
Decreased bowel sounds
Urinary retention
Seizures
Ataxia

24. Anticholinergics
Atropine
Scopolamine
Glycopyrrolate
Benztropine
Antispasmotics
Dicyclomine
Hyoscyamine
Oxybutynin
clidinium
TCAs
Mydriatics


Antihistamines
Chlorpheniramine
Cyproheptadine
Hydroxyzine
Diphenhydramine
Meclizine
promethazine
Antipsychotics
Clozapine
Olanzapine
Thioridazine
Jimson weed

25. Other Toxidromes
Opioids
Respiratory depression
Miosis
Hypoactive bowel sounds
Sympathomimetics
Hypertension
Tachycardia
Hyperpyrexia
Mydriasis
Anxiety, delirium

Sweating differentiates sympathomimetic
and anticholinergic toxidromes

26. Examination
Physiologic excitation –
anticholinergic, sympathomimetic, or central hallucinogenic
agents, drug withdrawal
Physiologic depression –
cholinergic (parasympathomimetic), sympatholytic, opiate, or
sedative-hypnotic agents, or alcohols
Mixed state –
polydrugs, hypoglycemic agents, tricyclic antidepressants,
salicylates, cyanide

27. Specific overdoses

28. Opiates
Antidote – naloxone
MOA: Pure opioid antagonist competes and displaces narcotics
at opioid receptor sites
I.V. (preferred), I.M., intratracheal, SubQ: 0.4-2 mg every 2-3
minutes as needed
Lower doses in opiate dependence
Elimination half-life of naloxone is only 60 to 90 minutes
Repeated administration/infusion may be necessary
S/E BP changes; arrhythmias; seizures; withdrawal

29. Benzodiazepines
Antidote – flumazenil
MOA: Benzodiazepine antagonist
IV administration 0.2 mg over 15 sec to max 3mg
S/E N&V; arrhythmias; convulsions
C/I concomitant TCAD; status epilepticus

30. Tricyclic antidepressants
PHARMACOLOGY —
TCAs have several important cellular effects, including inhibition of:

Presynaptic neurotransmitter reuptake

Cardiac fast sodium channels

Central and peripheral muscarinic acetylcholine receptors

Peripheral alpha-1 adrenergic receptors

Histamine (H1) receptors

CNS GABA-A receptors

31. TCAD overdose
clinical features
Arrhythmias
- widening of PR, QRS, and QT intervals;
heart block; VF/VT
Hypotension
Anticholinergic toxicity
- hyperthermia, flushing, dilated pupils,
intestinal ileus, urinary retention, sinus tachycardia
Confusion, delirium, hallucinations
Seizures

32. Diagnosis
History
Blood/urine toxicology screen
Levels not clinically useful

33. TCAD overdose -Treatment
ABC – many require intubation
Consider gastric lavage if taken < 2hrs
Activated charcoal
Treatment of hypotension with isotonic saline
Sodium bicarbonate for cardiovascular toxicity
Alpha adrenergic vasopressors (norepinephrine) for
hypotension refractory to aggressive fluid resuscitation and
bicarbonate infusion
Benzodiazepines for seizures

34. Salicylate overdose
Aspirin (acetylsalicylic acid)
Methyl salicylate
5 ml = 7g salicylic acid
Herbal remedies
Fatal intoxication can occur after the ingestion of 10 to
30 g by adults and as little as 3 g by children

35. Salicylate levels
Plasma salicylate concentration
Rapidly absorbed; peak blood levels usually occur within one hour
but delayed in overdose 6-35 hrs
Measure @ 4 hrs post ingestion & every 2 hrs until they are
clearly falling
Most patients show signs of intoxication when the plasma level
exceeds 40 to 50 mg/dL (2.9 to 3.6 mmol/L)

36. Salicylate overdose
Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins,
prostacyclin, and thromboxanes
Stimulation of the chemoreceptor trigger zone in the medulla causes nausea and
vomiting
Direct toxicity of salicylate species in the CNS, cerebral edema, and
neuroglycopenia
Activation of the respiratory center of the medulla results in tachypnea,
hyperventilation, respiratory alkalosis
Uncoupled oxidative phosphorylation in the mitochondria generates heat and
may increase body temperature
Interference with cellular metabolism leads to metabolic acidosis

37. Clinical features
Early symptoms of aspirin toxicity include tinnitus, fever, vertigo,
nausea, hyperventilation, vomiting, diarrhoea

More severe intoxication can cause altered mental status, coma,
non-cardiac pulmonary oedema and death

38. Metabolic abnormalities
Stimulate the respiratory center directly, early fall in the PCO2 and respiratory
alkalosis

An anion-gap metabolic acidosis then follows, due to the accumulation of
organic acids, including lactic acid and ketoacids

Mixed respiratory alkalosis and metabolic acidosis with ↑ anion gap

Arterial Ph variable depending on severity

39. Metabolic abnormalities
Metabolic acidosis increases the plasma concentration of
protonated salicylate

thus worsening toxicity by allowing easy diffusion of the drug
across cell membranes

40. Salicylate overdose - treatment
directed toward increasing systemic pH by the administration of sodium
bicarbonate

IV fluids +/- vasopressors

Avoid intubation if at all possible (↑ acidosis)

Supplemental glucose (100 mL of 50 percent dextrose in adults) to patients
with altered mental status regardless of serum glucose concentration to
overcome neuroglycopaenia

Hemodialysis

41. Alkalinization of plasma and urine
Alkalemia from a respiratory alkalosis is not a contraindication to sodium
bicarbonate therapy

A urine pH of 7.5 to 8.0 is desirable

Blood gas analysis every two hours

Avoid severe alkalemia (arterial pH >7.60)

42. Haemodialysis - indications
Altered mental status

Pulmonary or cerebral edema

Renal insufficiency that interferes with salicylate excretion

Fluid overload that prevents the administration of sodium bicarbonate

A plasma salicylate concentration >100 mg/dL (7.2 mmol/L)

Clinical deterioration despite aggressive and appropriate supportive care

43. Paracetamol
Widely available
Potential toxicity underestimated
Toxicity unlikely to result from a single dose of less than 150 mg/kg in child or
7.5 to 10 g for adult
Toxicity is likely with single ingestions greater than 250 mg/kg or those greater
than 12 g over a 24-hour period
Virtually all patients who ingest doses in excess of 350 mg/kg develop severe
liver toxicity unless appropriately treated

45. Factors influencing toxicity
Dose ingested
Excessive cytochrome P450 activity due to induction by chronic alcohol or
other drug use eg carbamazepine, phenytoin, isoniazid, rifampin
Decreased capacity for glucuronidation or sulfation
Depletion of glutathione stores due to malnutrition or chronic alcohol
ingestion
Acute alcohol ingestion is not a risk factor for hepatotoxicity and may even
be protective by competing with acetaminophen for CYP2E1

46. Clinical features
Stage I (0.5 to 24 hours)
No symptoms; N&V Malaise
Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
right upper quadrant pain, with liver enlargement and tenderness. Elevations of
prothrombin time (PT), total bilirubin, and oliguria and renal function abnormalities may
become evident
Stage III (72 to 96 hours)
Jaundice, confusion (hepatic encephalopathy), a marked elevation in hepatic enzymes,
hyperammonemia, and a bleeding diathesis hypoglycemia, lactic acidosis, renal failure
25%, death
Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4 and is complete by 7 days after overdose

47. Paracetamol overdose
The risk of toxicity is best predicted by relating the time of ingestion to the
serum paracetamol concentration
The dose history should not be used as studies have found no correlation
Peak serum concentrations reached within 4 hrs following overdose of
immediate-release preparations
May be delayed with extended releases preparations or drugs that delay gastric
emptying (eg, opiates, anticholinergic agents) are coingested
Check level at >= 4 hrs

48. Paracetamol overdose treatment
Activated charcoal within four hours of ingestion
May reduce absorption by 50 to 90 percent
Single oral dose of one gram per kilogram
Inhibits absorption of oral methionine

49. N-acetylcysteine
Antidote – MOA: a glutathione precursor
Limits the formation and accumulation of NAPQI
Powerful anti-inflammatory and antioxidant effects
IV infusion or oral tablets (also oral methionine)
150mg/Kg over 15 min; 50mg/Kg over next 4 hrs; 100mg/kg over next 16 hrs up
to 36hrs
Beyond 8 hours, NAC efficacy progressively decreases
S/Es nausea, flushing, urticaria, bronchospasm, angioedema, fever, chills,
hypotension, hemolysis and rarely, cardiovascular collapse

50. Paracetamol overdose treatment
At the end of NAC infusion, a blood sample should be taken for determination
of the INR, plasma creatinine and ALT. If any is abnormal or the patient is
symptomatic, further monitoring is required and advice sought from the NPIS

Patients with normal INR, plasma creatinine and ALT and who are
asymptomatic may be discharged from medical care. They should be advised to
return to hospital if vomiting or abdominal pain develop or recur

51. .
Indications for liver transplantation

Liver transplantation is life-saving for fulminant hepatic necrosis
The indications for liver transplantation are:
1 - Acidosis (pH < 7.3), or
2 - PT > 100 sec
3 - Creatinine > 300 mcg/l
4 - Grade 3 encephalopathy (or worse)
It is better to contact the local liver transplant centre earlier than this.
Grossly abnormal prothrombin times should trigger referral:
PT > 20 sec at 24 hr
PT > 40 sec at 48 hr

52. .
Alcohol poisoning

Clinical features of acute alcohol poisoning include:
Ataxia and anaesthesia leading to accidental injury
Dysarthria and nystagmus
Drowsiness which may progress to coma
Inhalation of vomit which can be fatal & should be prevented
Hypoglycaemia in children and some adults
Check BM stix and give 50% glucose i.v. if required

53. .
Coma (alcohol induced)

In cases of alcohol induced coma exclude:
1.Coincident head injury
2.Hepatic failure
3.Meningitis
4.Wernicke’s encephalopathy
5.Other associated drug ingestion
A blood test will confirm substantial levels of alcohol
Rule out alcoholic hypoglycaemia
The airway and circulation must be maintained
But glucose- containing fluids may precipitate Wernicke's encephalopathy
Thiamine should given to all
Intravenous naloxone has reversed coma in a proportion of cases

54. Methanol poisoning
Metabolizes are toxic
The metabolic pathways for ethanol in the liver:
1. NAD
+
+ Ethanol  NADH + Acetaldehyde
Enzyme: Alcohol Dehydrogenase
2. NAD
+
+ Acetaldehyde  NADH + Acetic acid
Enzyme: Aldehyde Dehydrogenase
3. Acetic acid  Water + CO
2
Methanol is metabolized by the same system first to
formaldehyde then to formic acid

55. management
Ethanol- competitive inhibition of methanol metabolism
4-methylpyrazole is ADH inhibitor

56. Antidotes
Acetaminophen/ paracetamol N-acetylcysteine
Organophosphates Atropine, pralidoxime
Anticholinergic physostigmine
Arsenic, mercury, gold dimercaprol
Benzodiazepines flumazenil
Beta blockers glucagon
Calcium channel block calcium
Carboxyhemoglobin 100% O2
Cyanide nitrite, Na thiosulfate
Digoxin digoxin antibodies (Digibind)

57. Antidotes
Ethylene glycol fomepizole, ethanol
Heparin protamine sulphate
Iron deferoxamine
Isoniazid pyridoxime
Methanol fomepizole, ethanol, HD
Methemoglobin methylene blue
Opioids naloxone
Salicylate alkalinization, HD
TCA’s sodium bicarbonate
Warfarin FFP, vitamin K