NTA Level 5 • Semester 1 • PST05104

Management of Acute Poisoning

Pharmacology and Therapeutics • Source Session/Topic 27

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Session 27: Management of Acute Poisoning

Total Session Time: 120 minutes

Prerequisites

None

Learning Tasks

By the end of this session students are expected to be able to:

Describe approaches/measures in management of acute poisoning

Describe management of specific drug overdoses/poisoning of clinical importance

Describe management of overdoses/poisoning of other chemicals of clinical importance

Resources Needed:

Flip charts, marker pens, and masking tape

Black/white board and chalk/whiteboard markers

Computer and LCD projector

Handout 27.1: Management of Specific Drug Overdoses/Poisoning of Clinical Importance

SESSION OVERVIEW

Step

Time

Activity/

Content

Step

Time

Activity/

Content

Step

Time

Method

Content

Method

05 minutes

Presentation

Introduction, Learning Tasks

60 minutes

Presentation/

Approaches/Measures in Management of

60 minutes

Buzzing

Acute Poisoning

Buzzing

Acute Poisoning

25 minutes

Presentation/

Management of Specific Drug

25 minutes

brainstorming

Overdoses/Poisoning of Clinical Importance

brainstorming

Overdoses/Poisoning of Clinical Importance

20 minutes

Presentation

Management of Overdoses/Poisoning of Other

20 minutes

Presentation

Chemicals of Clinical Importance

05 minutes

Presentation

Key Points

05 minutes

Presentation

Evaluation

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SESSION CONTENTS

STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)

READ or ASK students to read the learning objectives and clarify

ASK students if they have any questions before continuing.

STEP 2: Approaches/Measures in Management of Acute Poisoning (60minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

What are approaches in management of poisoned/overdosed patients?

ALLOW few pairs to respond and let other pairs add on points not mentioned

WRITE their response on the flip chart/board

CLARIFY and SUMMARIZE by using the content below Supportive Therapy

In general involves maintaining of the airways flow, proper breathing, adequate circulation.

After an initial assessment of vital signs and instigation of appropriate resuscitation, repeated observations are necessary, as drugs may continue to be absorbed with a subsequent increase in plasma concentration.

In the unconscious patient, repeated measurements of cardiovascular function, including blood pressure, urine output and (if possible) continuous electrocardiographic (ECG) monitoring should be performed.

Plasma electrolytes and acid-base balance should be measured.

Hypotension is the most common cardiovascular complication of poisoning. o Hypotension can usually be managed with intravenous colloid.

o If this is inadequate, positive inotropic agents (e.g. dobutamine) may be considered. o If dysrhythmias occur any hypoxia or hypokalaemia should be corrected, but anti-

dysrhythmic drugs should only be administered in life-threatening situations.

Prevention of Further Absorption

Emesis:

o Replaced by lavage/charcoal

o Syrup of ipecacuanha is no longer recommended in the management of poisoning. o Contraindicated in corrosive poisonings/aspiration risk.

PST 05104 Pharmacology & Therapeutics 209 NTA Level 5 Semester 1 Facilitator Guide

Gastric Lavage:

o Technique involves placing of patient in left lateral head down position if not intubated.

o Then Insertion of a soft lubricated tube through mouth or nose into stomach.

o Aspirate and save contents and then lavage repeatedly with 50-100ml of fluid until returns are clear .

o Use luke warm water or saline.

o Gastric aspiration and lavage should only be performed if the patient presents within one hour of ingestion of a potentially fatal overdose.

o If there is any suppression of the gag reflex, a cuffed endotracheal tube is mandatory.

o Gastric lavage is unpleasant and is potentially hazardous.

o Indications: Removal of gastric contents (within the first hour). Examination of gastric contents is important.

o Contraindications: Do not do if patient comatose unless intubated. Also do not use if corrosives are ingested

Activated Charcoal:

o Adsorbs almost all drugs and poisons. Poorly adsorbed substances are Lithium, Potassium, alcohol, iron, cyanide. Metal salts, alcohols and solvents are not adsorbed by activated charcoal.

o To be effective, large amounts of charcoal are required, typically ten times the amount of poison ingested, and again timing is critical, with maximum effectiveness being obtained soon after ingestion. Its effectiveness is due to its large surface area (1000m2/g). Binding of charcoal to the drug is by non-specific adsorption.

o The use of repeated doses of activated charcoal may be indicated after ingestion of sustained-release medications or drugs with a relatively small volume of distribution, and prolonged elimination half-life (e.g. salicylates, quinine, dapsone, carbamazepine, barbiturates or theophylline).

o The rationale is that these drugs will diffuse passively from the bloodstream if charcoal is present in sufficient amounts in the gut or to trap drug that has been eliminated in bile from being re-absorbed.

o Whole bowel irrigation using non-absorbable polyethylene

o Contraindications: Comatose or obtunded unless given by gastric tube or intubated as drinking charcoal can cause emesis. Ileus or intestinal obstruction (delays expulsion of charcoal). Corrosive poisonings where endoscopy is planned. Oral charcoal may also inactivate any oral antidote (e.g. methionine).

Whole Bowel Irrigation : o Cleanses the GI tract

o Indications: Whole bowel irrigation using non-absorbable polyethylene glycol solution may be useful when large amounts of sustained-release preparations, iron or lithium tablets or packets of smuggled narcotics have been taken by ―body stuffers/packers‖ (People who swallow packets of drugs for smuggling.)

PST 05104 Pharmacology & Therapeutics 210 NTA Level 5 Semester 1 Facilitator Guide

Contraindication: Paralytic ileus

Decontamination

Sometimes it may be necessary to wash the skin or remove clothes and other coverings to minimize contact with the source of allergy /poison.

Enhanced Elimination

Urine manipulation:

o Alkaline diuresis (urinary alkalinization) should be considered in cases of salicylate, chlorpropramide, phenoxyacetate herbicides and phenobarbital poisoning, and may be combined with repeated doses of oral activated charcoal.

o Acid diuresis may theoretically accelerate drug elimination in phencyclidine and amphetamine/ ‘ecstasy‘ poisoning.

Haemodialysis and charcoal haemoperfusion:

o Not all drugs or poisons can be cleared by this method.

o Hepatic or renal failure where excretion of the drug may be compromised.

Administration of Antidote

Antidotes are available for a small number of poisons and the most important of these, including chelating agents have been discussed in the previous sessions.

Table 27.1 Drugs and their Antidotes

Drug

Antidote

Acetaminophen

N-Acetylcysteine i.v. ,Methionine

Organophosphates

Atropine/Pralidoxime

Opioids

Naloxone

Benzodiazepines

Flumazanil

Ethylene Glycol

Fomepizol

Methanol

Fomepizol

Beta-blockers

Atropine, Glucagon, Isoprenaline

Carbon monoxide

Oxygen,Hyperbaric oxygen

Iron

Desferrioxamine

Cyanide

Oxygen, dicobalt edetate i.v. or sodium nitrite i.v. followed

by sodium thiosulphate i.v.

Lead (inorganic)

Sodium EDTA i.v., Penicillamine p.o., Dimercaptosuccinic

acid (DMSA)

Mercury

Dimercaptopropane sulphonate(DMPS),

Dimercaptosuccinic acid (DMSA),

Dimercaprol,

Penicillamine

Organophosphorus

Atropine, pralidoxime

insecticide

Digoxin

Digoxin-specific fab antibody fragments

Calcium-channel blockers

Calcium chloride or gluconate i.v.

Insulin

20% dextrose i.v., Glucagon i.v. or i.m.

PST 05104 Pharmacology & Therapeutics

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STEP 3: Management of Specific Drug Overdoses/Poisoning of Clinical Importance (25 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What is the management of poisoned/overdosed patients?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

Paracetamol poisoning/overdose

Treatment

o Acetaminophen is metabolized by the cytochrome P450 pathway to a toxic intermediate that is detoxified by glutathione.

o With acute acetaminophen overdose hepatocellular glutathione is depleted allowing the toxic intermediate (NAPQI) N-acetyl-p-benzoquinoneimine) to attack cell proteins and cause cell necrosis.

o Patients with enhanced cytochrome P450 activity like alcoholics and anticonvulsant users are at greater risk of hepatotoxicity.

o If a potentially toxic overdose is suspected, the stomach should be emptied if within one hour of ingestion. The antidote should be administered and blood taken for determination of paracetamol concentration, prothrombin time (INR), creatinine and liver enzymes.

o Rumack-Matthew Nomogram utilized to decide whether treatment with N-acetylcysteine is required.

o Intravenous acetylcysteine and/or oral methionine are potentially life-saving antidotes and are most effective if given within eight hours of ingestion; benefit is obtained up to 24 hours after ingestion.

o For serious paracetamol overdoses seen greater than 24 hours after ingestion, advice should be sought from poisons or liver specialists.

o Acetylcysteine is administered as an intravenous infusion.

o Methionine is an effective oral antidote in paracetamol poisoning. It may be useful in remote areas where there will be a delay in reaching hospital or when acetylcysteine is contraindicated.

PST 05104 Pharmacology & Therapeutics 212 NTA Level 5 Semester 1 Facilitator Guide

Salicylate poisoning/overdose

Treatment

o Respiratory alkalosis frequently predominates and is due to direct stimulation of the respiratory centre.

o The metabolic acidosis is due to uncoupling of oxidative phosphorylation and consequent lactic acidosis.

o If acidosis predominates, the prognosis is poor.

o The typical presentation includes nausea, tinnitus and hyperventilation and the patient is hot and sweating.

o Immediate management includes estimation of arterial blood gases, electrolytes, renal function, blood glucose (hypoglycaemia is particularly common in children) and plasma salicylate concentration.

o The patient is usually dehydrated and requires intravenous fluids. o A stomach washout is performed, if within one hour of ingestion.

o Activated charcoal should be administered. Multiple dose activated charcoal is advised until the salicylate level has peaked.

o Depending on the salicylate concentration and the patient‘s clinical condition,

o An alkaline diuresis should be commenced using intravenous sodium bicarbonate.

However, this is potentially hazardous, especially in the elderly.

Children metabolize aspirin less effectively than adults and are more likely to develop a metabolic acidosis and consequently are at higher risk of death.

Plasma electrolytes, salicylate and arterial blood gases and pH must be measured

regularly.Frequent monitoring of serum electrolytes is essential.

If the salicylate concentration reaches 800–1000 mg/L, haemodialysis is likely to be necessary.

Haemodialysis may also be life-saving at lower salicylate concentrations if the patient‘s metabolic and clinical condition deteriorates.

REFER Students to Handout 27.1: Management of Specific Drug Overdoses/Poisoning of Clinical Importance

STEP 4: Management of Overdoses/Poisoning of other Chemicals of Clinical Importance (20 minutes)

Ethylene Glycol/Methanol

Treatment

o Ethanol loading dose: Traditionally been used as antidote for Methanol and Ethylene Glycol

o Mechanism: Preferred substrate of alcohol dehydrogenase therefore inhibits formation of NEW toxic substrate. Systemic alcohol is used in poisoning by methanol or ethylene glycol, since it competes with these for oxidation by alcohol dehydrogenase, slowing the production of toxic metabolites (e.g. formaldehyde, oxalic acid).

PST 05104 Pharmacology & Therapeutics 213 NTA Level 5 Semester 1 Facilitator Guide

Fomepizole (4-methypyrazole): Competitive Inhibitor of Alcohol dehydrogenase (in vitro: 80,000 times affinity for ADH than methanol).

Ethanol

Treatment

o Disulfiram and other Alcohol-sensitizing drugs: These produce an unpleasant reaction when taken with alcohol.

The only drug of this type used to treat alcoholics is disulfiram, which inhibits aldehyde dehydrogenase, leading to acetaldehyde accumulation if alcohol is taken, causing flushing, sweating, nausea, headache, tachycardia and hypotension.

Cardiac dysrhythmias may occur if large amounts of alcohol are consumed.

Disulfiram also inhibits phenytoin metabolism and can lead to phenytoin intoxication.

Unfortunately, there is only weak evidence that disulfiram has any benefit in the treatment of alcoholism.

Its use should be limited to highly selected individuals in specialist clinics.

Acamprosate: The structure of acamprosate resembles that of GABA and glutamate.

It appears to reduce the effects of excitatory amino acids and, combined with counselling, it may help to maintain abstinence after alcohol withdrawal.

Acamprosate-inhibt NMDA receptor prolongs abstinence.

STEP 6: Key Points (5 minutes)

Management of poisoned patients involve different approaches

There are specific antidotes for some chemicals/drugs poisoning

STEP 7: Evaluation (5 minutes)

What are approaches in management of poisoned patients?

What are antidotes for ethanol poisoning?

What is the treatment for isoniazid poisoning?

PST 05104 Pharmacology & Therapeutics 214 NTA Level 5 Semester 1 Facilitator Guide

References

Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.

Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.

Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:

Jaypee Brothers Medical P.

Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.

Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael. (2014). Pharmacotherapy: A Pathophysiologic Approach (9th ed.). New York, McGraw-Hill Education.

Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.

School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).

Dar es Salaam, ARDHI University press.

The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.

The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.

PST 05104 Pharmacology & Therapeutics 215 NTA Level 5 Semester 1 Facilitator Guide

Handout 27.1 Management of Specific Drug Overdoses/Poisoning of Clinical Importance

Tricyclic Antidepressants poisoning/overdose

Treatment

o Tricyclic antidepressants cause death by dysrhythmias, myocardial depression, convulsions or asphyxia.

If the patient reaches hospital alive they may be conscious, confused, aggressive or, in deep coma.

Clinical signs include dilated pupils, hyperreflexia and tachycardia

Gastric lavage may be performed up to one hour after ingestion if the patient is fully conscious.

Occasionally, assisted ventilation is necessary.

o The most common dysrhythmia is sinus tachycardia, predominantly due to anticholinergic effects and does not require any intervention. Broadening of the QRS complex can result from a quinidine-like (sodium ion blocking) effect and is associated with a poor prognosis.

Anti-dysrhythmic prophylaxis should be limited to correction of any metabolic abnormalities, especially hypokalaemia, hypoxia and acidosis. Intravenous sodium bicarbonate (1–2 mmol/kg body weight) is the most effective treatment for the severely ill

patient and its mode action may involve a redistribution of the drug within the tissues.

If resistant ventricular tachycardia occurs, intravenous magnesium or overdrive pacing have been advocated.

Convulsions should be treated with intravenous benzodiazepines. Oral benzodiazepines may be used to control agitation.

Selective Serotonin Reuptake Inhibitors (SSRIs) poisoning/overdose

Treatment

SSRIs do not have anticholinergic actions and are much less cardiotoxic unlike TCAs o Nausea and diarrhoea are common.

Seizures may occur and are associated with venlafaxine (which blocks noradrenaline, as well as serotonin reuptake).

Supportive and symptomatic measures are usually sufficient.

Oral activated charcoal is recommended following the ingestion of more than ten tablets within one hour.

PST 05104 Pharmacology & Therapeutics 216 NTA Level 5 Semester 1 Facilitator Guide

Ca Channel Blockers poisoning/overdose

Treatment

o Symptoms of the poisoning include bradycardia, conduction delays, impaired contractility and hypotension.

o Gastric lavage and activated charcoal are usually employed o Patients may respond to atropine and isoproterenol.

o If no response IV calcium chloride or calcium gluconate are used to treat hypotension and conduction defects.

o Glucagon is occasionally beneficial in severe toxicity Atropine & Anticholinergics poisoning/overdose

Treatment

o Symptoms: Dry mouth, thirst, blurring of vision, constipation.

o Signs: Psychosis, dilated pupils, fever, ileus, urinary retention. o Activated charcoal is beneficial as there is delayed gut emptying o Physostigmine is administered (with ECG monitoring).

Beta Blockers poisoning/overdose

Treatment

o Management of Bradycardia: Breathing and circulatory support is necessary.

o Management of hypotension: fluids administration and dopamine are preferred

o Bradycardia management: atropine, pacers, dopamine are employed

o Catecholamines (epi, dobutamine, dopamine) often are ineffective in treating beta – blocker effect because they act on the same beta receptor which is blocked therefore action requires free receptors or replacement of the drug (beta blocker at the receptor).

Affinity to the receptor could be a major determinant. Dopamine is only 25% Effective while Epinephrine is 67% effective.

o Glucagon: Drug of choice for beta –blockers & calcium channel blockers poisoning/overdose. Glucagon is secreted by pancreas secondary to hypoglycaemia.

Glucagon Receptors are found in heart muscle. The drug acts by stimulating adenylate cyclase independent of beta –receptor resulting to positive chronotropic and inotropic effects despite beta –adrenergic receptor blockade.

Isoniazid (INH) poisoning/overdose

Treatment

o Isoniazid enhances elimination of pyridoxine leading to pyridoxine deficiency. Isoniazid also inactivates the conversion of pyridoxine to pyridoxal 5 phosphate resulting to GABA deficiency hence seizures develop due to lack of inhibitory activity of GABA.

o As with all seizing patients, ABC‘s (airway protection, IV fluids) is important.

o Benzodiazepines (Valium, 5-10 mg iv) are used in initial approach. However Benzodiazepines may not be effective because their action requires the presence of GABA which is depleted by Isoniazid.

o Pyridoxine (Vit B6) is the only antidote available for INH toxicity

PST 05104 Pharmacology & Therapeutics 217 NTA Level 5 Semester 1 Facilitator Guide

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