Advisor:Y.Bhg.Tan Sri Dato' Musa Mohamad
Consulting Editor:Dr Zaki Morad Mohd Zaher
Editor:Assoc.Prof Dzulkifli Abdul Razak
Co-Editor:Dr Rahmat Awang,Dr Mohd Isa Abdul Majid, Rosman Ahmad

NICOTINE POISONING
by Abu Bakar Abdul Majeed PhD

Introduction
Come May 31, 1995 residents of Planet Earth will once again observe the World NO-TOBACCO Day, courtesy of the World Health Organisation. In conjunction with this auspicious ocassion, perhaps it is time to take another har d look at that notorious alkaloid closely associated with tobacco especially in matters pertaining to its excessive consumption, either by choice or by chance.

Nicotine is the most readily available and commonly abused substance in modern Malaysian society. Exposure to nicotine may occur during smoking. Although nicotine is one of 3,800 chemical substances found in cigarette smoke, it is the main source of addiction. The fatal dose of pure nicotine is approximately 40-60 mg (0.6-1.0 mg/kg, 1-2 drops) i.e. the quantity contained in 2 g of tobacco (equivalent to 2 common blend cigarettes; 15-25 mg of nicotine per cigarette). However, the smoke contains less than 3 mg per cigarette, with smoke of most nonfiltered brands containing 1.2 to 2.4 mg and filtered brands between 0.2 and 1.0 mg. Up to 90 percent of the nicotine in mainstream smoke will be absorbed by the smoker. Because of diminished bioavailability, tobacco is much less poisonous than expected on the basis of its nicotine content. Furthermore, the dose may be spread throughout the day and this is not unusual for a cigarette smoker.

When tobacco is smoked, most of the nicotine is burned but a number of carcinogens are produced. Nicotine is well absorbed via inhalation, dermal and rectal exposure, but poorly from the gastrointestinal tract. Polacrilex, nicotine-containing chewing gum (Nicorette), is less toxic than nicotine and is used as a tobacco substitute.

Nicotine Poisoning

Nicotine is one of the most lethal poisons known. At present, virtually all toxicities involving nicotine are being reported from cigarettes. More than 90% of toxic exposures from cigarettes in the United States are reported in children less than 5 years of age. A recent report from Germany states that most of the cases are within the 7 month to 2 year old age range. In Nigeria, a herbal drug containing nicotine increases morbidity and mortality in this paediatric group. Ingestion of 1 cigarette (or 3 but ts) or drinking saliva expectorated by tobacco chewer (which is often collected in a can) should be considered potentially toxic for children. In adults, suicidal ingestion of nicotine-containing pesticides, and occasionally after cutaneous exposure to ni cotine, such as tobacco harvesters can cause poisoning. Green tobacco sickness (GTS) is an illness resulting from dermal exposure to dissolved nicotine from wet tobacco leaves. GTS is characterised by nausea, vomitting, weakness, dizziness and sometimes f luctuations in blood pressure or heart rate. Nicorette intoxication is uncommon.

More than 95% of the reported cigarette toxicity is either asymptomatic (70%) or mild (25%). Most of the recently reported serious toxic states from nicotine have been from accidental exposure to animal control agents by their handlers.

No specific histological changes occur after nicotine poisoning. The mouth, pharynx, oesophagus and stomach may show evidence of the caustic effect following the ingestion of nicotine.

Symptoms

Respiratory stimulation and gastrointestinal hyperactivity are two main symptoms of nicotine poisoning.

Acute poisoning can result from skin contamination or inhalation of tobacco smoke, depending on the doses.

Small doses: Respiratory stimulation, nausea and vomitting, dizziness, headache, diarrhoea, tachycardia, elevation of blood pressure, sweating and salivation. Patient will gradually recover, after a period of weakness.
Large doses: Burning sensation of the mouth, throat, stomach, followed immediately by the above symptoms. Patient may progress to prostration, convulsions, bradycardia, arrhythmia and finall y coma. Death may occur within 5 min to 4 hours.

Among others, tobacco smoking increases the incidence of coronary heart disease and respiratory tract cancer. The chart below esimates the number of smoking-related deaths in the United States in 1990.

Pharmacokinetics

Peak serum levels: Peak serum levels are attained 30 minutes after chewing nicotine gum, compared to 5 to 10 minutes after smoking cigarettes. For example, mean steady-state levels of 11.8ng/ml are achieved after 2 mg of gum. Protein binding is 20% . Nicotine has an apparent volume of distribution in adults of about 1 L/kg. Smokers appear to have a decreased volume of distribution compared to non-smokers. Between 80-90% of the absorbed compound is detoxified in the liver, while 10-20% is excreted un changed by the kidneys. The principle metabolites are cotinine and nicotine-1'-N-oxide. The elimination half-lives of nicotine is approximately 0.8 hour in smokers and 1.3 hours in non-smokers.

Treatment
Acute Poisoning

Emergency Procedure
  • In case of contamination, wash skin by flooding with water and scrubbing vigorously with soap.
  • Emesis - patient may already be vomitting. Emesis is not advisable because it may be dangerous. If possible, give activated charcoal orally to adsorb any remaining nicotine. Administer charcoal slurry, aqueous or mixed with saline cathartic or sorbitol. The FDA suggests 240 ml of diluent/30 g of charcoal. Usual charcoal dose is 30 to 100 g in adults and 15-30 g in children (1-2 g/kg in infants).
  • Administer one dose of a cathartic, mixed with charcoal or given separately.
  • Gastric lavage - may be indicated if performed soon after ingestion, or in patients who are comatose or at risk of convulsing. Protect airway by placement in Trendelenburg and left lateral decubitus position or by cuffed endotracheal intuba tion. Use tap water containing activated charcoal, if available.
  • After control of any seizures present, perform gastric lavage. Volume of lavage return should approximate fluid given.
  • Initiate artificial respiration using oxygen, is available.

Specific Drugs and Antidotes
  • Mecamylamine is a specific antagonist of nicotine actions; however since it is only available in tablets, therefore it is not suitable for a patient who is vomitting, convulsive or hypotensive.
  • either give atropine sulphate, (adult 0.4-2 mg; child 0.01 mg/kg, not to exceed 0.4 mg per dose) i.m. or i.v. and repeat every 3-8 min. until signs of parasympathetic toxicity are controlled. Repeat atropine frequently to maintain control o f symptoms. As much as 12 mg of atropine has been given safely in the first 2 hours in adult. Ensure proper oxygenation to avoid arrythmias associated with hypoxia. Interruption of atropine therapy may be rapidly followed by fatal pulmonary oedema or resp iratory failure.
  • or give phentolamine 1-5 mg i.m. or i.v. to control signs of sympathetic hyperactivity, such as hypertension.

General Measures
  • Control convulsions: Administer diazepam i.v. bolus (adult, 5-10 mg initially which may be repeated every 15 minutes PRN up to 30 mg; child, 0.25-0.4 mg/kg dose up to 10 mg/dose) or lorazepam i.v. bolus (adult, 4-8 mg; child, 0.05-0.1 mg/kg).
  • Do not administer antacids since nicotine is better absorbed in an alkaline media.
  • Monitor ECG and vital signs carefully.

Chronic Poisoning

Remove from further exposure to dust or smoke.

Prognosis

Survival for more than 4 hours is usually followed by complete recovery.

CASE REPORT:
Suicidal poisoning due to nicotine
An Autopsy Case of Fatal Nicotine Poisoning Takayasu, T. et al. Nippon Hoigaku Zasshi, 46: 327-32 (1992)

A fatal case of nicotine poisoning is reported in which a 44-year-old female committed suicide in a short time by taking orally the eluate from tobacco. External examination showed no abnormal findings except for markedly dark red-purple postmortem lividi ty, and internal examination demonstrated no pathological changes but the signs of sudden death. Through the toxicological investigation by GC and GC-MS, however, nicotine was detected in the solution which she had taken orally and in the blood, urine and the contents of the stomach and small intestine. The nicotine concentrations of the blood, urine and contents of stomach and small intestine were 6.3 micrograms/ml, 1.5 micrograms/ml, 30 micrograms/ml and 71 micrograms/g respectively, and enough to be le thal.


PRN CONSULT

Review of Organophosphate and Carbamate Poisonings:
Mohd Isa Abdul Majid, Ph.D

Organophosphate and carbamate are widely used pesticides that may cause acute or chronic poisoning after accidental or suicide exposure. Untreated patients usually die within 24 hours while treated patients who died do so within 10 days.

Death occurs secondary to respiratory arrest caused by respiratory muscular weakness, central nervous system depression and excessive bronchial secretions.

For this issue, PRN Consult reviews some of the salient points in organophosphate and carbamate poisonings. This review assumes that basic life support measures such as seizure control have been instituted.

Of SLUD, DUMBELS AND MATCH

Organophosphate and carbamate usually contain solvents such as petroleum distillates that may be listed as inert ingredients but can produce toxic effects in an overdose.

When such poisonings occur, there may be persistent effects to the central and peripheral nervous systems lasting from several weeks to months. These include peripheral neuropathies, memory impairment, personality changes, depression, confusion and though t disorders.

What substances are classified as organo-phosphate and carbamate?

Both organophosphate and carbamate are classified as insecticides, use to eradicate insects and undesirable pests. Organophosphates are esters, amides or thiol derivatives of phosphoric, phosphonic, phosphorothionic or phosphonothioic acids. They can be c lassified into two groups; aryl phosphates which must be activated by liver microsomal enzymes before becoming toxic and alkyl phosphates which do not require activation for toxicity. Most organophosphates are polar, water-soluble chemicals but a few lipo philic compounds exist and thus formulated in petroleum distillate vehicles. On the other hand, carbamates are mainly esters of carbamic acid and therefore are commonly formulated in petroleum distillates. Among the organophosphates approved to be used in Malaysia are as tabulated below:

ORGANOPHOSPHATES CARBAMATES
High toxicity (LD50 < 50 mg/kg - based on oral LD50 in rats)
Azinphosethyl Fenamiphos Methamidophos Methidathion
Monocrotophos Coumaphos

Moderate toxicity (LD50 > 500 mg/kg)
Chlorpyrifos Fenitrothion Chlorpyrifosmethyl Diazinon
Dichlorovos Dimethoate Fenthion Phenthoate
Formothion Phosmet Profenofos Quinalphos
Thiometon Trichlorfon Isazofos Propetamphos

Low toxicity (LD50 > 1000 mg/kg)
Acephate Etrimfos Malathion Phoxim
Pirimiphosmethyl Prothiophos Azamethipos
High toxicity (LD50 < 50 mg/kg - based on oral LD50 in rats)
Carbaryl Carbofuran Buprofezin MIPC
Mercaptodimethur

Moderate toxicity (LD50 = 300-500 mg/kg)
Isoprocarb Cartap Bendiocarb Propoxur
MTMC; Metacrate BPMC; Fenobucarb

How do organophosphate and carbamate exert their toxic effects?

Organophosphates are rapidly absorbed by inhalation, ingestion and through the skin. The absorbed chemical as well as the active metabolite formed then bind to and phosphorylate the carboxylic esterase enzymes, including RBC acetylcholinesterase (true cho linesterase) and plasma cholinesterase (pseudocholinesterase). The binding to these enzymes will lead to their inactivation and hence renders them incapable of degrading the neurotransmitter acetylcholine. The excessive acetylcholine then accumulates at n euroeffector junctions in the skeletal muscle system and in the autonomic and central nervous systems. This inactivation becomes progressively irreversible after 24-36 hours. For carbamates, the toxic effects are typically short-lived. Spontaneous hydroly sis of the carbamylated acetylcholinesterase enzyme will regenerate the enzymatic activity usually within 24 hours.

It is also important to take note that the hydrocarbon diluents and/or impurities in formulated pesticides can enhance or contribute to toxicity.

What are the signs and symptoms of organophosphate and carbamate poisoning?

There are differences between the signs and symptoms produced by organophosphate and carbamate. In carbamate poisoning, the signs and symptoms are transient in nature and the chemicals classified under this group do not penetrate the CNS. Thus CNS toxicit y is limited. With respect to all other clinical manifestations, there is little difference between organophosphate and carbamate. In organophosphate poisoning, the signs and symptoms may be classified into:

  1. Stimulation of muscarinic receptors - affecting the bronchial tree, gastrointestinal system, sweat and lacrimal systems, heart, pupil, ciliary body and bladder. The major symptoms may be best remembered by DUMBELS.
    Defecation
    Urination
    Miosis (a common sign of toxicity)
    Bradycardia, bronchospasm
    Emesis
    Lacrimation
    Salivation

    In other instances, the major symptoms may also be remembered by SLUD.

    Salivation
    Lacrimation
    Urination
    Defecation

  2. Stimulation of nicotinic receptors - affecting striated muscle and symphatetic ganglia. The major symptoms may be best remembered by MATCH.
    Muscle weakness and fasciculations
    Adrenal medulla activity increase
    Tachycardia
    Cramping of skeletal muscle
    Hypertension

    SLUD or DUMBELS and MATCH are mnemonics to be remembered for signs and symptoms associated with organophosphate and carbamate poisonings.

  3. CNS manifestation - resulting in restlessness, anxiety, lethargy, confusion, coma, seizures and depression of respiratory and cardiovascular centres.

The toxic signs and symptoms of organophosphate and carbamate poisonings in children (n=37) include:

Muscarinic
Miosis 73% Excessive salivation 70%
Nausea/vomitting 32% Diarrhoea/defecation 27%
Bradycardia 19% Wheezing 19%
Diaphoresis 13%

Nicotinic
Muscle weakness 68% Hypotonia 35%
Tachycardia 49% Fasciculations 22%
Hyporeflexia 41% Hypoglycemia 22%

CNS
Lethargy 54% Seizures 22%
Ataxia 24% Coma 22%
Depressed mental status 19% Anxiety/Restlessness 13%

Miscellaneous or combined
Respiratory distress 59% Respiratory insufficiency 38%

These symptoms may appear within a few minutes or up to 12 hours after exposure. In a study it was noticed that patients developed paralysis and/or respiratory distress 24 to 96 hours after organophosphate poisoning. This clinical feature is termed as intermediate syndrome and frequently occurs in patients with minimal to no therapy of pralidoxime (2-PAM). In some organophosphates, delayed polyneuropathy may develop 6 to 21 days following exposure.

When should one suspect organophosphate or carbamate poisonings and how to confirm for these poisonings?

The diagnosis can be made using four criteria:

  • appropriate history of exposure to an insecticide or pesticide.
  • sign and symptom of excessive muscarinic and nicotinic stimulations.
  • depressed plasma and RBC cholinesterase levels.
  • response to atropine and pralidoxime therapy.

Laboratory confirmation of organophosphate exposure can be determined by measuring the activity of true cholinesterase in RBC or plasma pseudocholinesterase. The depression in the activity of true cholinesterase provides a more accurate assessment of expo sure than the depressed pseudocholinesterase level. Levels 30-50% of the normal indicate exposure and symptoms usually appear when the level falls to 20%. In some reports, a gradual increase in cholinesterase levels generally parallels clinical improvemen t.

In the recovery from organophosphate poisoining, usually in a few days or weeks, plasma cholinesterase (plasma ChE) activity recovers slowly due to the irreversible nature of organophosphate inhibition. Red blood cell (RBC) acetylcholinesterase (AChE) rec overs in several days to 4 months depending on severity of depression.

Other conditions may also exhibit the signs and symptoms of organophosphate and carbamate poisonings. These include nicotinic poisoning, gastroenteritis, drugs and clinical conditions associated with miosis such as opioids, clonidine, phencylidine, phenot hiazines and sedative-hypnotics, asthma, poisoning from other cholinesterase inhibitors such as neostigmine and pyridostigmine, mushrooms' poisoning which may exhibit muscarinic (without nicotinic) stimulation and Guillain-Barre's syndrome.

What are the general management and treatment for organophosphate and carbamate poisonings?

Organophosphate Poisoning

In inhalational exposure, the patient should be brought to fresh air and any respiratory distress should be monitored. If any difficulty of breathing develops, evaluate for respiratory tract irritation, pneumonitis or bronchitis by performing arter ial blood gases, chest x-ray and pulmonary function test. If possible, supplemental 100% humidified oxygen be given to the patient.

In dermal exposure, remove contaminated clothing from the patient. The skin should be decontaminated by washing with copious amount of tap water and soap. Emergency care personnel should wear gloves and avoid contamination.

In eye exposure, decontamination can be carried out by irrigating the exposed eye with copious amount of tepid water for at least 15 minutes. If irritation, pain, swelling, lacrimation or photophobia persist, the patient should be seen in a health care facility.

In oral exposure, inducing emesis is contraindicated due to the rapid onset of seizures and respiratory depression as the poisoning progresses. Gastric lavage may be performed with extra care to prevent aspiration as many organophosphate for mulations contain hydrocarbon diluents. Activated charcoal and a cathartic may be indicated unless contraindicated for the poisoned patient. As a general measure, an airway should be established as the first priority for the patient. Frequent suction of o ral secretions should be maintained throughout until atropine, which is one the recommended antidote for organophosphate poisoning, exerts its maximum effect.

Atropine is a competitive antagonist of acetylcholine at the muscarinic receptor sites. However, it will not reverse the nicotinic effects such as muscular and diaphragmatic weakness, fasciculations, muscle cramps etc. It is a tertiary amine that crosses the blood-brain barrier and thus can be used to treat the muscarinic effects and possibly the CNS toxicity. It should be administered to patients with proper oxygenation procedure so as to avoid the increased risk of arrhythmias associated with hy poxia. The dosage for atropine should be individualized in each case. The amount of dose depends on the dose of the organophosphate consumed and the response of the patient to atropine. A preliminary diagnostic dose can be initiated to assess the sever ity of the poisoning. If the toxic effects of atropine (dry mouth, rapid pulse, dilated pupils etc) occur following a diagnostic atropine dose, the patient is probably not seriously poisoned. The diagnostic dose for adult is 1 mg IV or IM ; for child 0.25 mg (or 0.01 mg/kg) IV or IM. The recommended dose for atropine is 2 to 4 mg IV every 10 to 15 minutes as needed until atropinization is achieved (drying of pulmonary secretions can be used as an indicator for complete atropinization). This atropiniza tion may be required for hours or days. For children, the recommended dose is 0.05 mg/kg every 10 to 15 minutes as needed. In severe poisoning where atropinization may be required for a period of several days, continous atropine infusion may be preferable . Initial undiluted atropine infusion rates of 0.02 to 0.08 mg/kg/hour have been recommended.

Severe organophosphate poisoning with nicotinic and/or central manifestations should be treated with pralidoxime in addition to atropine. Pralidoxime, a quaternary amine oxime, specifically regenerates acetylcholinesterase by attacking the phosphat e moiety of the organophosphate-acetylcholinesterase complex to form an oxime-phosphonate. This new complex then will be dissociated from the acetylcholinesterase-organophosphate complex and thus releasing the acetylcholinesterase for its normal activity. Through this, 2-PAM reverses both nicotinic and muscarinic effects of organophosphate toxicity.

2-PAM should be administered in all cases of known or suspected organophosphate poisoning. It is most effective if given in the first 48 hours and may have some beneficial effect even when given more than 48 hours after the exposure. When given, it is reported to be efficacious for up to 6 days. The recommended dose for adult is 1 to 2 g IV at 0.5 g/min. For children, the dose is 25 - 50 mg/kg over 5 to 30 minutes infusion. The same dose can be repeated in 1 hour and then every 6 to 12 hours if mus cle weakness or coma has not been resolved. The onset of action of 2-PAM occurs in 10-40 minutes after the initial dose with improvement in symptoms and a decrease in atropine dosage. A rather controversial method of administering 2-PAM is through a conti nous infusion at a rate of 500mg/hour for adult or 25-50 mg/kg followed by 9-19 mg/kg/hour. Among the adverse effects for 2-PAM include: pain at injection site, transient elevations of CPK, SGOT, SGPT, dizziness, tachycardia, hyperventilation and muscu lar weakness, blurred vision, diplopia, drowsiness and nausea.

In known cases of organophosphate poisoning from the dimethoxy or diethoxy groups (such as dimethoate), obidoxime dichloride (ToxogoninŽ), may be less toxic and more efficacious alternative to pralidoxime. In some countries, obidoxime is fav oured over pralidoxime in clinical practice. The recommended initial dosing for adult is 250mg to be given as an IV or IM injection. For subsequent dosing, 250 mg repeated once or twice at 2 hour intervals, up to a total of 750 mg/day. It can also be give n as continous infusion with a dosage of 35 mg per hour for a 75 kg person or a loading dose of 5 mg/kg/hour followed by 0.5 mg/kg/hour maintenance infusion. For children, single doses of 4 to 8 mg/kg , not to exceed 250 mg in older children may be given.

Carbamate Poisoning

Carbamates form a reversible complex with the acetylcholinesterase and dissociate more readily than the organophosphate complex. Pseudocholinesterase and true cholinesterase are not useful in the diagnosis of carbamate poisoning as the enzyme activity ret urns to normal value within a few hours even though the symptoms of poisoning still remain.

The treatment and management of carbamate poisoning is similar to organophosphate poisoning with the exception of the use of 2-PAM in releasing the acetylcholinesterase from the poison-enzyme complex. These include establishment of airway, stabilisation o f vital signs; removal of the poison by gastric lavage with extra precautions and the use of atropine as an antidote for identified cases of carbamate poisoning.

The use of 2-PAM for carbamate toxicity is rather controversial. 2-PAM is not recommended in patients with known carbamate poisoning as the cholinesterase-carbamate complex is subjected to spontaneous hydrolysis to regenerate the enzymatic activity in within 24 hours. Animal studies showed that 2-PAM, when given together with atropine in carbaryl poisoning, can decrease the effectiveness of atropine due to the formation of carbamylated oximes. It can be considered when a patient suffers from concom itant organophosphate and carbamate toxicity or showing symptoms typical of cholinesterase inhibition.


CHEMICAL WARFARE AGENTS
SARIN, TABUN, SOMAN and VX

The recent incident of a nerve gas attack, sarin, in a Japanese subway station represents the lethal action of a chemical warfare agent. The compound, sarin, or also chemically known as isopropyl methylphosphonofluoridate, is a volatile liquid that when absorbed into the human body will react irreversibly with carboxylic esterase enzymes including the RBC acetylcholinesterase and plasma cholinesterase. The binding to these enzymes will lead to the inactivation of these enzymes and hence accumulatio n of acetylcholine (Ach) at nerve endings leading to a condition known as cholinergic overdrive. The signs and symptoms of such poisoning are similar to the organophosphate and carbamate toxicity (please refer to previous article - Of SLUD, DUMBELS and MATCH).

Other chemicals that belong to the same group as this nervous system altering agent include tabun or ethyl phosphorodimethylamidocyanidate, soman or pinacolyl methylphosphonefluoridate and VX or ethyl S-2-diisopropyl aminoethyl methyl phosphorothioate.

The characteristics and relative toxicity of these compounds are as follows:

 

Nerve Gases Characteristics
1. TABUN Dark amber liquid.
No odour in pure state.
Emits rotting fruit odor as it oxidises.
Mean lethal dose : 14 mcg/kg
2. SARIN Colourless liquid.
No odour in pure state.
Evaporates at the same rate as water.
Mean lethal dose : 0.01 mg/kg
3. SOMAN Colourless liquid.
Emits rotting fruit as it oxidises.
Impurities may impart a camphor-like odour.
Mean lethal dose : 1500 ng/kg
4. VX Pale amber liquid.
Colourless vapour.
Odourless
Mean lethal dose: 1500 ng/kg

What are the general management and treatment for these nervous system altering agents?

Decontamination

If a confined space has been contaminated with these agents, emergency personnel should wear protective clothings to prevent absorption of these compounds. The protective assembly includes protective mask and hood, charcoal impregnated suit and butyl rubb er gloves and boots. For decontamination of these agents from any surfaces, caustic soda or bleaches are recommended to break down these compounds.

Systemic Effects

In cases of exposure, the emergency medical team should also be well protected to prevent absorption. A pretreament of 30 mg pyridostigmine, a reversible acetylcholinesterase inhibitor, every 8 hourly provides protection by preventing the attachment of th e nerve gas agent to the receptor sites.

  • Atropine
    In the presence of symptoms, atropine is given to block the muscarinic receptors on the nerve endings from the continual increase of acetylcholine which tend to cause the excessive discharge of electrical impulse along the body's nervous system. The recom mended dose for atropine is 2-4 mg IV every 10-15 minutes until atropinization is achieved.
  • Pralidoxime Chloride (2-PAM)
    2-PAM will specifically regenerate the acetylcholineseterase (AChE) and thus allowing the enzyme to breakdown the circulating acetylcholine. It should be given in cases of nerve gas poisoning provided there is no irreversible binding between the chemical warfare agent to the acetylcholinesterase has occured. The irreversible binding of the chemical warfare agent to AChE is also known as aging. If aging has occured, then 2-PAM will be ineffective in reversing both the nicotinic and muscarinic effects of ne rve gas toxicity. The onset time taken life for aging among the nerve gases are as follows: soman (2 minutes), tabun (5minutes), sarin (5 hours ) and VX (longer than 5 hours). Please refer to the recommended dose of 2-PAM as outlined in the previous artic le.

Technical Report on Organophosphate and Carbamate Poisonings will be available from PRN soon.
Dr Mohd Isa is an Associate of PRN and has a special research interest on Pesticides. He heads the Research and Documentation Services.

CECT - Review of Paracetamol Poisoning


A Bimonthly Bulletin Published Pusat Racun Negara, Universiti Sains Malaysia, 11800 Pulau Pinang
Tollfree: 800-8099, Fax: 04-6568417, E-mail: prn8099@cs.usm.my
Printed by: Unit Percetakan Pusat, Universiti Sains Malaysia