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Number 40, August 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

Living With The Enemy

On  7 - 10 August 2003, the Science and Technology Expo 2003 was held at the Putra World Trade Centre, Kuala Lumpur. The exposition had successfully gathered together experts and information from various niches in the science field, focusing on updates and the latest findings in the world of science and technology. The National Poison Centre participated in the four-day exhibition with the theme “Living with the Enemy”. The theme was chosen with the aim of creating awareness among the public, especially parents, regarding the dangers and hazards caused by substances commonly found in the house. In this article, we share some of the ‘enemies’ found in our ‘Poison House’.

Starting from the garden, the most common chemical found there are plant fertilisers. They   contain nitrogen, phosphorus and potassium. These substances, if ingested in a significant amount, may burn up the skin as well as cause gastrointestinal problems, renal impairment, fatigue, muscle cramps and hypotension. The effects will either appear to be severe or mild, depending on the amount ingested. Other types of ‘enemies’ include garden plants like Kemunting Cina (Katharanthus roseus), Keladi Daun Batik (Dieffenbachia sp), Keladi Bintik (Caladium sp) and Keladi Gajah (Alocasia macrorrhiza). The ingestion of certain parts of these plants may give rise to shortness of breath, gastrointestinal problems, inflammations, seizures, hallucinations, comas and even death.   

When you step into the living room, cigarette smoke is waiting to destroy your lungs by causing infections, inflammations, cell necrosis and breeding cancer cells. This is what second hand smoke is all about. The ingestion of nicotine present in cigarette butts, frequently by toddlers, may cause nausea, vomiting, salivation; ingestion of a large amount can result in confusion, seizures and several cardiovascular complications.

In the bedroom, there are mosquito coils or mats, air fresheners, cosmetic products and a great deal more. Mosquito coils and mats mainly contain pyrethroids, a widely used insecticide. The poisoning caused may not be that alarming, but in severe cases, it may alter various body functions. Chronic exposure to aerosolised or non-aerosolised air fresheners may cause irritation of the eyes and skin, and if ingested, seizures and death may result. Many cosmetic products contain alcohol in a range of 60-95%. In significant quantities, the main complications of alcohol are suppression of the central nervous system, hypoglycemia and liver problems.

The kitchen also harbours ‘enemies’ including moth balls, dishwashing detergents and medicines. Some moth balls contain naphtalene which may enhance the breakdown of red blood cells and serious exposure may lead to anemia, seizures and comas. Dishwashing detergents also contain numerous toxic ingredients. Sodium hypochlorite, which is the main ingredient in many bleaching liquids, may cause corrosive damage to the oropharynx, esophagus or stomach.

In the toilet and bathroom, we often use toilet bowl cleaners, floor cleaners, disinfectants, laundry liquids, detergents (liquid or powder) and hard surface cleaners (for mosaics, marbles, parquet and others). Generally, the contents of these cleaners may be irritating and corrosive especially if ingested, or splashed into the eyes or on the skin.

Finally, the last but not the least part of our ‘poison house’ is the garage. This is where all sorts of tools, car liquids and corrosive oils are kept. The most common one is the wet cell battery. It contains sulfuric acid, a corrosive chemical which may cause burning of the contact area and also blindness following eye exposure. The presence of lead, besides being a potential cancer agent, may also cause renal and nerve impairments. Car polish contains petroleum naphta, a flammable type of chemical. It can cause headaches and irritation through any route of exposure. With prolonged, chronic exposure, our skin may become more photosensitive.

There is, therefore, little doubt that our house is like a poison house which is full of enemies. However, with proper handling, usage, and storage, these ‘enemies’ will definitely become our good friends, helping us significantly in our daily activities.N  

 HERBICIDE : PARAQUAT POISONING

 References:

1. Micromedex Healthcare Series, Volume  117, 2003.
2. Poisoning & Drug Overdose, 3^rd Edition, California Poison Control System
3. Goldfrank’s Toxicologic Emergencies, 7^th Edition.
4. Registered Pesticides List, 2000-2003, Pesticide Board of Malaysia.

    

Review on

Sedative-hypnotic (Part 1)

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

Introduction:

CNS depression is usually caused by a group of drug known as sedative-hypnotics. Some of the most commonly used agents in this class are benzodiazepines and barbiturates. Other agents include the non-barbiturate, non-benzodiazepine sedative-hypnotics, such as buspirone, zolpidem, ethchlorvynol, glutethimide, chloral hydrate, meprobamate, methaqualone, methyprylon, carisoprodol, and gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL). Usually toxicity with this group of drugs is deliberate attempts of suicide and used commonly abused recreational drugs.

Barbiturates

Barbiturates were introduced in 1903, and by early 1970’s barbiturate overdose and abuse potential were significantly increased in hospital setting.  The basic information regarding this drug is listed below:

Table 1. Type of barbiturates and its duration of action

Non-barbiturates

Some of the other non-barbiturate that has the same sedative-hypnotic properties is listed in table 2. 

Table 2: Non-barbiturates hypnotic-sedative agents

How sedative-hypnotic toxicity does occur?

All the sedative-hypnotics are general CNS depressants. Most agents stimulate the activity of GABA, the principal inhibitory neurotransmitter in the CNS. GHB is a sedative-hypnotic recently banned for sale to the public in the USA because of frequent abuse and serious toxic adverse effects. GHB is a neuroinhibitory neurotransmitter or neuromodulator in the CNS. It also appears to increase GABA B receptor activity and dopamine levels in the CNS. Benzodiazepines are one of the most frequently prescribed medications in the world. Most of the serious ingestions are suicide-related. These drugs also are used with other drugs of abuse (e.g., amphetamines, hallucinogens) to offset stimulatory effects. Barbiturates have the highest morbidity and mortality of the sedative-hypnotics. Pure benzodiazepine ingestion usually causes little more than sedation and ataxia; it very rarely results in death. Death from sedative-hypnotics is caused by respiratory arrest. 

What information is required to review sedative-hypnotic toxicity?

In order to evaluate sedative-hypnotic toxicity cases carefully few information is required. This included full patient history and complete physical examination to rule out other potential diagnosis.

The history should include the following information:

• Agents ingested

• Amount of ingestion

• Time of ingestion

• Cause and/or reason for ingestion (e.g., accidental, intentional, suicide attempt, recreational)

• Whether ingestion is acute or chronic

• Past medical history and history of drug abuse

• Circumstances surrounding the overdose

Physical examination plays an important role in detailing the information regarding the toxicity. Focus the physical examination on vital signs and neurological and cardiopulmonary status. Mild toxicity resembles ethanol intoxication. Severe respiratory depression is more likely to occur when the sedative-hypnotic is ingested with other CNS depressants.  Some of the characteristics for sedative-hypnotic agents are listed in table 3.

Table 3: Characteristics of poisoning for various agents

 In order to further evaluate the poisoning condition, lab results may be done to support the diagnosis.  Those lab studies and other evaluation should include:

• Obtain a complete blood count (CBC), arterial blood gas (ABG), glucose, chemistry, and toxicology screen. Screen for alcohol, salicylate, and acetaminophen with all intentional exposures.

• Quantitative serum drug concentrations are recommended for patients with serious toxicity

• Barbiturates: For short-acting drugs, the lethal dose is 3 g or a serum concentration higher than 3.5 mg/dL. For long-acting drugs, the lethal dose is 5-10 g or a concentration higher than 8 mg/dL.

• Methaqualone: A serum concentration higher than 8 mg/L is life threatening.

• Glutethimide: Consider hemodialysis if the serum concentration is higher than 3 mg/dL.

• Methyprylon: A serum concentration higher than 3 mg/dL is associated with severe toxicity and concentration higher than 6 mg/dL is typically fatal.

• Ethchlorvynol: Perform charcoal hemoperfusion for ingestion more than 100 mg/kg or a serum concentration higher than 10 mg/dL.

• Chloral hydrate: The lethal dose is 10 g and a concentration higher than 100 mcg/mL is toxic.

• Meprobamate: Coma occurs at 6-20 mg/dL. The drug is fatal at serum concentrations higher than 20 mg/dL.

Imaging Studies:

• Obtain an abdominal x-ray. Chloral hydrate is radiopaque.

Other Tests:

• Obtain an electrocardiogram (ECG); Co-ingested drugs may have direct cardiac effects (eg, tricyclic antidepressants).N

 Clinical Updates

Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution

Author(s): McKinney P E; Rasmussen R

Source: Ann Emerg Med, Vol 42, Iss 1, Pg 20-24, Yr 2003

Abstract: A 29-year-old woman ingested 8 g of nortriptyline and presented to the emergency department with coma, hypotension, and widened QRS interval. After intubation, gastric lavage, hyperventilation, and therapy with intravenous normal saline solution, sodium bicarbonate boluses (rapid intravenous push), and high doses of norepinephrine and dopamine, she transiently improved, only to deteriorate on arrival to the ICU. Because her arterial pH was alkalemic at this point, she was given additional sodium in the form of 200 mL of 7.5% NaCl by means of rapid intravenous push to treat hypotension and widening QRS interval with ventricular ectopy. A continuous 12-lead ECG documented narrowing of her QRS interval with concomitant improvement of hypotension within 3 minutes of hypertonic saline solution infusion. Hypertonic saline solution should be considered for wide complex QRS and hypotension caused by tricyclic antidepressant-induced cardiotoxicity that is unresponsive to standard therapies.  

Treatment of hyperkalemia in a patient with unrecognized digitalis toxicity

Author(s): Van Deusen S K; Birkhahn R H; Gaeta T J

Source: J Toxicol Clin Toxicol, Vol 41, Iss 4, Pg 373-376, Yr 2003

Abstract : Cardiac glycoside toxicity is frequently associated with hyperkalemia and dysrhythmias in patients with renal insufficiency. Two common therapeutic options for these complications (calcium and transvenous cardiac pacing) are considered contraindicated in the setting of cardiac glycoside toxicity.

We present the case of a patient presenting with a pronounced bradydysrhythmia and hyperkalemia who was treated with intravenous calcium and transvenous cardiac pacing and later found to have digitalis toxicity and acute renal failure. There were no adverse events associated with the therapies. The patient received digoxin-specific Fab fragments and hemodialysis as definitive therapeutic modalities. The case and the relevant literature evaluating the interaction of calcium salts and cardiac pacing in the setting of cardiac glycoside toxicity are discussed.  

Acute lithium intoxication and neuroleptic malignant syndrome

Author(s): Gill J; Singh H; Nu Gent K

Source: Pharmacotherapy, Vol 23, Iss 6, Pg 811-815,Yr 2003

Abstract : A 45-year-old man was admitted to a hospital after taking an intentional overdose of 90 sustained-released lithium tablets (450 mg each). The patient was stabilized with three sessions of hemodialysis. On day 7 of his hospital stay, his serum lithium level was 0.5 mEq/L. On day 10, he developed high fever, tachypnea, muscle rigidity, rhabdomyolysis, acute renal insufficiency, mental confusion, and obtundation. His creatine kinase level was 698 IU/L, serum creatinine 3.5 mg/dl. Late-onset neuroleptic malignant syndrome (NMS) was diagnosed. The patient died after developing acute renal failure and acute respiratory distress syndrome. Clinicians should be aware that lithium may cause NMS independent of other neuroleptic agents.N