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Number 38, April 2003

The Professional Bulletin of  The National Poison Centre, USM

ISSN 1394-5246 

prn lat. pro-re-nata, which translates as ocassionally when required or as needed is a universal abbreviation used in the practice of medicine and pharmacy. It is the official abbreviation for The National Poison Centre of Malaysia, which stands for Pusat Racun Negara (PRN) in the Malay Language.

prn-8099 the professional bulletin of the National Poison Centre aims at providing the link between PRN and professionals as well as scientific communities as home and abroad, 1-800-88-8099 being the toll-free number to call as needed.

A bimonthly with an annual index, published by Pusat Racun Negara, Universiti Sains Malaysia.

Advisor

Dzulkifli Abdul Razak

Consulting Editor

Zaki Morad Mohd Zaher

Editor

Rahmat Awang

Co-editors

Mohd Isa Abdul Majid

Mohamed Izham Mohamed Ibrahim

Abd. Fatah Hj Abd. Rahman

Syed Azhar Syed Sulaiman

Razak Hj Lajis

Coordinator

Haslina Hashim

DTP Editor

Rosman Ahmad

www Editor

Wan Zainal Azman Abdullah

Codeine Abuse: Problem and Solution

The February issue of PRN8099 has highlighted the importance of “Total War Against Dadah’. According to the statistical reports from the National Drug Agency, among the ‘dadah’ commonly consumed by addicts is cough preparations containing codeine.

Codeine is chemically classified as an opiate. Both physical and psychological dependence can develop with chronic use of codeine, however potential for dependence is much less than that with morphine.

Tolerance to opiates develops very quickly and after a few weeks of regular use, doses must be increased to produce the same effect. Drug addicts will do anything to get more supply and this can lead to other social problems. When they enjoy the effects, they will continue using it and this leads to chronic use.

Upon discontinuation of codeine, addicts may experience withdrawal symptoms including anxiety, tremors, muscle spasms, sweating, rhinorrhea, and paranoid delusions. Most symptoms fade fairly quickly but sleeplessness and feelings of weakness may continue for some months.

Cough preparations containing codeine have long been used as a substitute for heroin since it is relatively cheaper and more readily available. Despite actions taken by the Drug Control Authority (DCA) to curb misuse and abuse of codeine, this problem still persist and addiction towards this drug is becoming rampant. At its 137th meeting held on 20^th June 2002, the DCA decided to take the following steps for all liquid cough preparations containing codeine:

1. The registration of all these products will be cancelled with effect from 31^st December 2002 (As at 20 June 2002, 46 such products have been registered with the DCA).

2. The manufacture and sales of these products will be terminated on 1^st January 2003.

3. Registration holders are given until the end of 2002 to finish off their existing stocks (At its 141^st meeting on 18 November 2002, the DCA allowed an extended 6 months grace period until 30 June 2003)

There are other opiates alternatives for cough such as Pholcodine and Dextromethorphan. The DCA has already registered 6 products containing Pholcodine in the form of syrup and linctus. However, being opiates, there is still a potential for them being abused.

Dextromethorphan was initially thought to lack addictive properties and the potential for abuse. However, psychological dependence (not physical) has been demonstrated, and the drug has been abused for its euphoric effects. Cases of overdose of dextromethorphan among teenagers already have been detected.

After withdrawing codeine-containing cough preparations, is there a possibility of illegal sales of these products? We have to ensure that this problem will not occur and we also have to get ready to overcome the problem if it happens. There is also a possibility of increase of abuse of other kind of substitute drugs like tablet containing codeine or other antitussive similar to it.  Health professionals and other enforcement authorities have to cooperate to ensure this enforcement effort is effective.N  

 INSECTICIDE : ORGANOPHOSPHATE POISONING

References :

1.       Micromedex Healthcare Series, Volume 115, 2003.

2.       Algorithms of Common Poisonings : Part 1, National Poison Control and Information Service, Philippines.

3.       Goldfrank’s Toxicologic Emergencies, 7th Edition.

4.       Poisoning & Drug Overdose, 3rd Edition, California Poison Control System.

Review on

Hydrocarbon Toxicity (Part I)

By Dr Syed Azhar Syed Sulaiman, Pharm. D., Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, USM, Penang.

Introduction

Hydrocarbon (HC) is widely used in our community where they are found in homes, they provide power for vehicles, and are widely used in every industrial process.  In developing nations, kerosene is implicated in more than 33% of pediatric poisonings. Proportionately more fatalities are associated with children younger than 5 years, who often accidentally ingest hydrocarbons (HCs) and adolescents, who are more likely to abuse volatile HCs than any other age group.

HCs are organic compounds that are made primarily of carbon and hydrogen molecules.  HCs are formed by distilling petroleum or wood and consist of aliphatic (carbon chain) or aromatic (carbon ring) molecules. Toxicity results from the volatility and viscosity of an HC product and the chemical characteristics of the HC and any additives.

 HC toxicity is divided readily into clinical syndromes based on the organ system most severely affected. The lungs are affected most commonly, but instances of neurologic, cardiac, gastrointestinal, renal, hematologic, and skin pathology are well documented. The dose and route of exposure affect which systems are impacted and the severity of toxicity.

How does it cause toxicity?

 The toxicity of HCs is a function of the individual compound's viscosity, volatility, surface tension, and the chemical activity of any side chains. Less viscous compounds spread more easily and, thus, are more toxic. A patient who ingests turpentine or gasoline is more likely to aspirate than a patient who has ingested grease or petroleum jelly. Similarly, a compound with low surface tension readily disperses itself, increasing the risk of aspiration. The substances with the highest volatility are readily inhaled and can displace oxygen. Side chains may include halogens, aromatic HCs, or heavy metals (e.g., arsenic).

Pulmonary toxicity usually results from aspiration or diffusion of ingested HC. Even small amounts of HC may cause a chemical pneumonitis; because many HCs have poor water solubility, they penetrate deep into the bronchopulmonary tree, causing bronchospasm followed by an inflammatory response. In the alveoli, volatile HCs may displace oxygen and surfactant, leading to hypoxia and a diffuse hemorrhagic exudative alveolitis. Alveolar dysfunction, in turn, leads to ventilation-perfusion ratio (V/Q) mismatch, hypoxemia, and, possibly, resultant respiratory failure.

Most HCs cause direct mucosal irritation and are absorbed quickly across tissue layers. Some can cause chemical burns. Ingestion causes burning pain in the mouth and throat, abdominal pain, nausea, and vomiting. Emesis increases the risk of aspiration. In animal studies, very large volumes of HC were required for significant absorption from the GI tract.

HCs are lipophilic and, thus, are attracted to lipid-rich neural tissue. Systemic absorption of HCs can cause acute and chronic central nervous system (CNS) and peripheral nervous system (PNS) toxicity. Demyelinating peripheral polyneuropathy is associated with exposure to certain 6-carbon aliphatic HCs (e.g., n-hexane, methyl n-butyl ketone) that are metabolized into a compound that interferes with axonal transport. Long-term workplace exposure to other HCs or volatile HC abuse may result in chronic headaches, cerebellar ataxia, and encephalopathic findings of cognitive and psychopathic impairment.

Certain volatile agents, such as butane, benzene, toluene, and xylene, are acute CNS depressants and have a disinhibiting euphoric effect. They often are agents of abuse. Patients present with symptoms of CNS disinhibition, such as dizziness, slurred speech, ataxia, and even obtundation. Ventilatory drive may be compromised. The initial presentation may mimic alcohol intoxication. In some patients, an initial component of CNS stimulation may present as agitation, tremor, or seizure. High concentrations of HC sensitize the myocardium to catecholamines, which predisposes the patient to ventricular tachycardia or fibrillation. This is the cause of "sudden sniffing death," which may occur when abusers suddenly exert themselves following HC intoxication.

HCs are abused through "sniffing" (directly inhaling vapors), "huffing" (placing a saturated rag over the mouth and nose and inhaling), or "bagging" (placing the HC in a plastic bag and repeatedly inhaling the vapors). Volatile HCs also are associated with atrioventricular block and bradycardia. Some agents may decrease cardiac contractility and peripheral vascular resistance.  

What are the common signs and symptoms associated with hydrocarbon toxicity?

The information regarding the toxicity is very important. This information should include:

• the specific agent and amount,

• co-ingestion,

• the time of exposure,

• and the symptoms of toxicity

      Some of the most commonly occurring symptoms are respiratory distress, CNS abnormalities, cardiovascular complaints, GI distress, and local skin reactions.

1.  Respiratory distress

• The lung is the primary site of life-threatening toxicity in HC exposures. Pulmonary toxicity most often occurs following ingestion and aspiration of an HC. Respiratory symptoms generally, but not always, develop within 30 minutes of a significant ingestion. Coughing, choking, gasping, dyspnea, vomiting, tachypnea, grunting respirations, cyanosis, or coma suggests a history consistent with aspiration.

• Transient coughing is common in HC ingestion because of volatilization. Prolonged cough usually indicates aspiration; however, the absence of cough does not rule out aspiration.

2.  CNS symptoms

• Lethargy and depressed sensorium are the most common CNS symptoms. They may be associated with significant aspiration pneumonitis or caused by toxic additives from large intestinal ingestions.

• Solvent abuse (deliberate concentration and inhalation of vapors) causes a transient euphoria because of CNS effects.

3.  Cardiovascular complaints

• Dyspnea, syncope, and sudden cardiac death may result from arrhythmias. This is believed to be caused by HCs sensitizing the myocardium to catecholamines.

• A relatively young healthy patient may present in full arrest after engaging in strenuous athletic events following solvent abuse.

4.  Gastrointestinal complaints

• Nausea, vomiting, and sore throat are frequent with large ingestions but are relatively mild. GI complaints are more common with furniture polish than with other HC ingestions.

• Diarrhea, melena, and hematemesis are rare.

5.  Local reactions such as burning of the mouth, pruritus, or rash are common and generally mild.

Physical examination is crucial and should focus on the patient’s airway, breathing, and circulation (ABCs). Urgently triage patients with signs of respiratory distress and place them in a room where airway management equipment is readily available.

• Odor on breath or clothes from HCs is a common finding.

• Fever often is present but does not correlate with clinical symptoms.

• Tachypnea, grunting respirations, accessory muscle use, riles, wheezing indicates pulmonary toxicity. Hypoxia is observed with severe aspiration pneumonia and may lead to cardiac and CNS dysfunction.

• Cardiac toxicity is rare with acute ingestion. Evidence of cardiac toxicity includes tachycardia, cardiac dysrhythmias, and hypotension.

• Coma is uncommon. It is present in fewer than 3% of hospitalized patients. Depressed sensorium and lethargy are observed with serious aspiration pneumonias.

• Skin lesions, such as erythema, blistering, and pain, are common after dermal exposures. Chronic solvent abusers may have perioral and nasal irritant dermatitis or conjunctivitis from repeated contact with HCs. Patients may present with dermal irritation and destruction following injection of HC either subcutaneously or intravenously from suicide attempts or for recreational purposes.

What are the main reasons for hydrocarbon toxicity?

 Causes of HC exposure can be divided into 4 main categories, as follows:

• Accidental ingestion is the most common cause of HC exposure.

• Typically observed in children younger than 5 years who have access to HCs without supervision

• Also observed in adults and older individuals when HCs are placed in unlabeled containers (e.g., beverage cans)

• Intentional abuse for recreational purposes is observed most commonly in adolescents and young adults. It is common in minority populations and adolescents with a history of polysubstance abuse, adjustment disorders, and rebellion.

• Accidental exposures in the household or workplace are generally limited and involve dermal and inhalational exposure.

• Massive oral ingestions are associated with suicide attempts.

What are the laboratory studies that should be done for hydrocarbon toxicity?

Laboratory evaluation should be done in order to rule out some of the other possibilities. These studies are:

• Arterial blood gases

• Abnormalities include hypoxemia and hypocarbia caused by V/Q mismatch.

• Methemoglobinemia may be observed following exposure to nitrite-containing HCs (e.g., aniline, nitrobenzene).

• Complete blood count

• Leukocytosis is common within the first 48 hours.

• Anemia and thrombocytopenia from intravascular hemolysis and consumptive coagulopathy is rare.

• Chronic exposure to benzene is linked to aplastic anemia and acute myelogenous leukemia.

• Electrolytes, blood urea nitrogen, creatinine

• Hypomagnesemia, hypophosphatemia potassium abnormalities, and anion gap acidosis are observed with toluene exposure.

• Acute renal failure in massive HC exposure is rare.

• Hepatic function: Elevated aminotransferases may be observed with HC ingestions. The halogenated HCs are particularly hepatotoxic.

• Urinalysis: Urinalysis usually is normal; however, renal failure is documented with HC exposure and a baseline urinalysis may be helpful for substantial exposures.

• Creatine kinase: Acute rhabdomyolysis reported in association with isolated HC exposure, particularly toluene exposures, is rare.

Imaging Studies:

• Chest x-ray: Radiographic abnormalities generally occur within 30 minutes of significant aspiration but may be delayed for up to 12 hours. Approximately 75% of patients hospitalized for suspected HC aspiration have radiographic abnormalities. Radiographic abnormalities may lag behind clinical evaluation and often do not correlate with clinical presentation. A right lower lobe infiltrate is classic for aspiration pneumonia, but consider any evidence of an alveolar infiltrate as evidence of aspiration in an HC exposure. Radiographic abnormalities progressively worsen for the first 72 hours and then resolve over several days.

Other Tests:

• Obtain an ECG on all substantial HC ingestions. Individuals with solvent abuse are particularly prone to arrhythmias. Observe patients on cardiac monitors.N

 Clinical Updates

Rhabdomyolysis and Acute Renal Failure Following an Ethanol and Diphenhydramine Overdose

Author(s): Haas C E; Magram Y; Mishra A

Source: Ann Pharmacotherapy, Vol 37, Iss 4, Pg 538-542, Yr 2003

Abstract:

A 21-year-old white man was admitted through the emergency department following an intentional overdose of ethanol and diphenhydramine. The patient subsequently developed acute renal failure, and a diagnosis of nontraumatic rhabdomyolysis was made. With the absence of other common causes in this case, the rhabdomyolysis was believed to be due to the combined ethanol and diphenhydramine overdose.

Due to the potential severity of the complications of this syndrome and the importance of early recognition and treatment to prevent renal failure, clinicians should have a high index of suspicion for rhabdomyolysis following overdoses that involve alcohol or antihistamines.

What are the Adverse Effects of Ethanol used as an Antidote in the Treatment of Suspected Methanol Poisoning in Children?

Author(s): Roy M; Bailey B; Chalut D; Senecal P E; Gaudreault P

Source: J Toxicol Clin Toxicol, Vol 41, Iss 2, Pg 155-161, Yr 2003

Abstract:

This is a twenty-one-year retrospective chart review (1980-2000) from suspected methanol poisoning patients treated with ethanol in two large pediatric tertiary care centers.

A total of 60 children received ethanol for suspected methanol poisoning: orally and  intravenously. Median initial methanol level was 4.16 mmol/L (13.3 mg/dL). Median duration of ethanol treatment was 16 hours. None of the 60 patients developed symptomatic hypoglycemia. Six out of the 60 patients were described as more drowsy after ethanol but none was comatose or needed intubation. No child showed signs of hypothermia, hepatotoxicity or even thrombophlebitis. None of the 22 patients with toxic levels of methanol died or had ethanol-induced morbidity despite wide variation in ethanol levels.

Amphetamine-Related Acute Myocardial Infarction due to Coronary Artery Spasm

Author(s): Hung M J; Kuo L T; Cherng W J

Source: Int J Clin Pract, Vol 57, Iss 1, Pg 62-64, Yr 2003

Abstract:

A 27-year-old man developed acute myocardial infarction after intravenous amphetamine use. A coronary angiogram showed plaques in the mid-portion of the left anterior descending artery which developed coronary artery spasm after administration of intracoronary ergonovine. The findings in this case suggest that these coronary artery plaques played a role in the endothelial dysfunction resulting from amphetamine use, and that induction of coronary arterial spasm was the likely mechanism of amphetamine-related acute myocardial infarction.