• call pusat racun websiteToxicology Laboratory Services
    Office hours

    Tel: +604 653 2171 / +604 653 2191
    Monday - Friday: 8:10am - 5:10pm
    E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. 

prn8099 - Number 37, February 2003

Total War Against “DADAH” 

Introduction

In the year 2002, a total of 31,893 drug addicts were detected in the country compared to 31,556 in 2001 and 30,593 in 2000. Out of the 31,893, 53.5 percent of them are new cases aged between 15 and 40. These increasing numbers indicate the need to increase the efforts in curbing the problem. On 21st January 2003 the Government had announced year 2003 as “Tahun Memerangi Dadah Habis-Habisan” (Total War Against Drugs) to curb illegal production, trafficking, addiction, and smuggling of drugs. During the announcement, the Deputy Prime Minister, Datuk Seri Abdullah Ahmad Badawi said that new approach is important to be implemented in order to achieve Malaysia and ASEAN drug free vision by the year 2015.  He added that these new approaches to curb drug abuse include maximizing power, engendering situation slightly like a war and getting all sector in the society to involve in these efforts. Currently, the main ministries involved in curbing drug abuse are the Ministry of Home Affairs, Ministry of Education, Ministry of Youth and Sport, and Ministry of Information but with the new approach this year, everyone is encourage to contribute.

What are the efforts that the health related sectors could contribute?

Proactive health professionals are always at the front line to help and contribute in the efforts to curb drug abuse. There are few areas of contribution that health professionals can benefit their professionalism, where other people might not be able to do it.

Health professionals, who are involved in education activities, should use various effective approaches to deliver information and educate any target groups especially the youngsters to prevent them from abusing drugs. Their specialize knowledge in medical/pharmaceutical field is an advantage for them to elaborate each information and convince the audience on the information delivered.

Pharmacists or doctors may be able to identify and monitor possible or potential drug abuser. This group of people tends to abuse common drug to treat common illness. The best effort is to educate them, counsel and help them to stop the habit.  Refuse to dispense or prescribe certain drugs may be a good decision if there are high tendency of abuse by the patient. Better communication between pharmacists or doctors in a neighbourhood is also important to curb abusers who used a number of premises to get their drugs. Pharmacists or doctors should not let themselves to be misused with regards to the prevention, counselling and treating of their patients. They are perceived to be knowledgeable and have to use their specialized knowledge and other skills to curb drug abuse.

There are still many research areas related to drug problems that remain to be discovered. New discovery or innovation is something that may be beneficial as this problem is becoming worse year by year although many actions have been taken. For example, health professionals in research and development field could contribute by conducting research to design and develop products that will be more effective in rehabilitation programme of drug addicts and may prevent them from repeating the habit after recovery.

Health professionals in the enforcement sector should create effective rules and regulation to control drug related activities and at the same time helping in the prevention of drug abuse. The current rules and regulation may also need to be reviewed from time to time depending on the problems related to drug activities.

Co-operation among health professionals is essential to contribute their professionalism towards Malaysia free from “Dadah”.  


PESTICIDES - RODENTICIDES

Types of Common Rodenticide

Active Ingredients

Toxicity Profile

General Management

Anticoagulant

(Short-Acting)

Warfarin

- Household use:

  0.05-1% w/w

- Technical grade :

   99% w/w  

Ingestion

  • Single ingestion of a few mouthfuls of the household grade may not be harmful

  • Large ingestion may cause bleeding

Ingestion

In large ingestion

  • Activated Charcoal

  • Gastric Lavage

  • Monitor PT and INR. Give Inj Vit K and  blood transfusion if necessary

Anticoagulant

(Long-Acting)

Superwarfarin, examples are :

Brodifacoum

Bromadiolone

Chlorophacinone

Coumatetralyl

Difethialone

Diphacinone

Fluocomafen

Ingestion

  • May cause anticoagulation lasting several weeks or even months

Ingestion

  • Gastric lavage

  • Obtain PT or INR at 24 and 48 hours post-ingestion. Repeat, if prolonged.

  • Give Inj Vit K1 if indicated.

  • Immediate transfusion with fresh frozen plasma or whole blood if bleeding has occurred.

  • Follow-up patient for several months.

Phosphides

Zinc Phosphide- in powder form for household use.

Aluminium Phosphide - produces phosphine gas for fumigation purpose.

Ingestion/Inhalation

  • Toxicity is mainly due to the Phosphine Gas released when zinc phosphide becomes wet.

  • Early symptoms are : mucosal irritation, nausea, vomiting, abdominal pain, headache, thirst, and dypsnea.

  • In severe cases, renal and hepatic dysfunctions, metabolic acidosis, seizures, dysrrhythmias, and shock may occur.

Ingestion

  • Gastric lavage.

  • Symptomatic and supportive.

  • Monitor vital signs, serum electrolytes, fluid balance, and renal and hepatic functions.

Sources :

  1. Registered Pesticide List (2000-2003), Pesticide Board Malaysia

  2. PoisindexÒ System, Micromedex Healthcare Series, Volume 113, 3/2003


Review on

Carbon Monoxide Poisoning (Part11)

By Dr Syed Azhar Syed Sulaiman, PharmD, Clinical Pharmacy Discipline, School of Pharmaceutical Sciences, Universiti Sains Malaysia.

How do we manage carbon monoxide poisoning ?

Prehospital Care:

  • Promptly remove from continued exposure and immediately institute oxygen therapy with a nonrebreather mask.
  • Perform intubation for the comatose patient or, if necessary, for airway protection.
  • Institute cardiac monitoring. Pulse oximetry, although not useful in detecting HbCO, is still important because a low saturation causes an even greater apprehension in this setting.
  • Give notification for comatose or unstable patients, because rapid or direct transfer to a hyperbaric center may be indicated.
  • If possible, obtain ambient CO measurements from fire department or utility company personnel, when present.
  • Early blood samples may provide much more accurate correlation between HbCO and clinical status; however, do not delay oxygen administration to acquire them.
  • Obtain an estimate of exposure time, if possible.
  • Avoid exertion to limit tissue oxygen demand.

Emergency Department Care:

  • Cardiac monitor: Sudden death has occurred in patients with severe arteriosclerotic disease at HbCO levels of only 20%.
  • Pulse oximetry: HbCO absorbs light almost identically to that of oxyhemoglobin. Although a linear drop in oxyhemoglobin occurs as HbCO rises, pulse oximetry will not reflect it. Pulse oximetry gap, the difference between the saturation as measured by pulse oximetry and one measured directly, is equal to the HbCO level.
  • Continue 100% oxygen therapy until patient is asymptomatic and HbCO levels are below 10%. In patients with cardiovascular or pulmonary compromise, lower thresholds of 2% have been suggested.
  • Calculate a gross estimate of the necessary duration of therapy using the initial level and half-life of 30-90 minutes at 100% oxygen.
  • In uncomplicated intoxications, venous HbCO levels and oxygen therapy are likely sufficient. Evaluate patients with significant cardiovascular disease and initial HbCO levels above 15% for myocardial ischemia and infarction.
    • Consider immediate transfer of patients with levels above 40% or cardiovascular or neurologic impairment to a hyperbaric facility, if feasible. Persistent impairment after 4 hours of normobaric oxygen therapy necessitates transfer to a hyperbaric center.
  • Serial neurologic examinations, including funduscopy, CT scans, and, possibly, MRI, are important in detecting the development of cerebral edema. Cerebral edema requires intracranial pressure (ICP) and invasive blood pressure monitoring to further guide therapy. Head elevation, mannitol, and moderate hyperventilation to 28-30 mm Hg PCO2 are indicated in the initial absence of ICP monitoring. Glucocorticoids have not been proven efficacious, yet the negative aspects of their use in severe cases are limited.
    • Do not aggressively treat acidosis with a pH above 7.15 because it results in a rightward shift in the oxyhemoglobin dissociation curve, increasing tissue oxygen availability. Acidosis generally improves with oxygen therapy.
    • In patients who fail to improve clinically, consider other toxic inhalants or thermal inhalation injury. Be aware that the nitrites used in cyanide kits cause methemoglobinemia, shifting the dissociation curve leftward and further inhibiting oxygen delivery at the tissue level. Combined intoxications of cyanide and CO may be treated with sodium thiosulfate 12.5 g intravenously to prevent the leftward shift.
    • Admit patient to a monitored setting and evaluate acid-base status if HbCO levels are 30-40% or above 25% with associated symptoms.

Consultations:

  • Hyperbaric oxygen therapy
    • Hyperbaric oxygen therapy (HBO) currently rests at the center of controversy surrounding management of CO poisoning. Increased elimination of HbCO clearly occurs. Certain studies proclaim major reductions in delayed neurologic sequelae, cerebral edema, pathologic central nervous system (CNS) changes, and reduced cytochrome oxidase impairment.
    • Presently, universal treatment criteria do not exist. The most common selection criteria (regardless of HbCO level) include the following: coma (98%), transient loss of consciousness (77%), ischemic ECG changes (91%), focal neurologic deficits (94%), and abnormal neuropsychiatric testing (91%). Ninety-two percent of HBO facility directors use HBO for headache, nausea, and HbCO levels above 40%; yet only 62% have a specific minimum HbCO level in asymptomatic patients. One half of the centers place a time limit on delay of treatment in patients with transient loss of consciousness alone.
    • HBO at 3 atm raises the amount of oxygen dissolved in the serum to 6.8%, enough to sustain cerebral metabolism. Elimination half-life is reduced to 15-23 minutes. Elimination half-life of CO from methylene chloride intoxication of 13 hours at room air temperature is reduced to 5.8 hours. Chambers are either small monoplace hulls, allowing space for a single supine patient who can be viewed through a window at the head, or they are acrylic walled and allow full visualization. Many of these monoplace chambers allow for care of the critically ill, including IV lines, arterial lines, and ventilator. Others are large multiplace chambers that permit ventilation equipment and allow medical teams to accompany the patient.
    • Treatment regimens usually involve 100% oxygen at 2.4-3 atm for 90-120 minutes. Re-treatment, although controversial, may be performed for acutely and chronically persistent symptoms. One recent study suggests that degree of acidosis can predict the need for re-treatment.
    • Complications of therapy include decompression sickness, sinus and middle ear barotrauma, seizure, progression of pneumothorax to tension pneumothorax, gas embolism, reversible visual refractive changes, and complications related to transport of unstable patients.
    • For treatment of complications from therapy, decongestants are useful, prophylactic myringotomy is common and a requirement for intubated patients, and chest tube placement is mandatory with pneumothorax. Exercise caution in patients who have experienced chest compressions, central venous catheterization, intubation, and positive pressure ventilation. Seizures are most often secondary to oxygen toxicity and do not mandate anticonvulsant therapy or discontinuation of HBO therapy.
    • In multiplace chambers, seizure therapy consists of removing the oxygen mask. In monoplace chambers, decompression lowers oxygen concentration. It is crucial not to do this during the tonic phase of the seizure because it may cause pulmonary barotrauma secondary to gas expansion in the lungs.

Admitted patients generally require monitored settings, telemetry beds, or cardiac care unit/medical intensive care unit (CCU/MICU) beds for more severe cases. Patients with cerebral edema may be most appropriately treated in a neurosurgical ICU setting; this may dictate transfer to another facility. Admission to a toxicology service is helpful in these cases.

Further Outpatient Care:

  • Asymptomatic patients with HbCO levels below 10% may be discharged.
  • Arrange early follow-up care with a medical toxicologist or hyperbaricist experienced in CO poisoning.

Prognosis:

  • Variability of clinical severity, laboratory values, and outcome limits prognostic accuracy.
  • Cardiac arrest, coma, metabolic acidosis, and high HbCO levels are associated with poor outcome.
  • Abnormal findings on CT scan are associated with persistent neurologic impairment.
  • Neuropsychiatric testing may have prognostic efficacy in determining delayed sequelae.

Patient Education:

  • Discuss the possibility of delayed neurologic complications, although they are much more common in admitted patients.
  • Suggest minimizing physical activity for 2-4 weeks.
  • Advise patient to stop smoking.

Special concerns in pregnant mothers:

A pregnant CO-poisoned patient represents a particular quandary for the emergency physician. Although the mother may appear well with seemingly nontoxic levels, the developing fetus is at increased risk.

With a relatively small amount of scientific data support, conservative thought dictates treatment for any pregnant patient with evidence of CO exposure. CO displaces the oxygen-hemoglobin dissociation curve to the left. Fetal oxyhemoglobin dissociation curve lies further to the left than normal adult hemoglobin.

In the pregnant patient, a significant lag time exists for uptake and elimination of CO between the mother and fetus.

Fetal HbCO levels indicate little change during the first hour of maternal intoxication, yet they increase slowly over the first 24 hours. The peak actually may exceed maternal HbCO levels.

The fetus is particularly vulnerable with increased accumulation in fetal blood 10-15% higher than maternal blood and lower PaO2 levels (20-30 mm Hg compared with 100 mm Hg in adults). It is important to realize that acute nonlethal maternal intoxication may result in fetal demise. After intoxication, during the washout phase at room air temperature, fetal HbCO half-life is 7-9 hours.

Fetal HbCO half-life with pure hyperbaric oxygen treatment is not accurately known; however, with maternal normobaric oxygen therapy, the fetal HbCO half-life can be reduced to 3-4 hours.

Because fetal hemoglobin constitutes 20­-30% of the total at 3 months, neonates are at particularly greater risk than their infant and toddler counterparts.

 What can we do to avoid carbon monoxide poisoning?

Prevention is always the key to avoid from carbon monoxide poisoning. Table III listed some of the ways to properly avoid the situation.

Table III: The Key to Avoid Carbon Monoxide Poisoning

P

DO have your fuel-burning appliances -- including oil and gas furnaces, gas water heaters, gas ranges and ovens, gas dryers, gas or kerosene space heaters, fireplaces, and wood stoves -- inspected by a trained professional at the beginning of every heating season. Make certain that the flues and chimneys are connected, in good condition, and not blocked.

P

DO choose appliances that vent their fumes to the outside whenever possible, have them properly installed, and maintain them according to manufacturers’ instructions.

P

DO read and follow all of the instructions that accompany any fuel-burning device. If you cannot avoid using an unvented gas or kerosene space heater, carefully follow the cautions that come with the device. Use the proper fuel and keep doors to the rest of the house open. Crack a window to ensure enough air for ventilation and proper fuel-burning.

P

DON’T idle the car in a garage -- even if the garage door to the outside is open. Fumes can build up very quickly in the garage and living area of your home.

P

DON’T use a gas oven to heat your home, even for a short time.

P

DON’T ever use a charcoal grill indoors -- even in a fireplace.

P

DON'T sleep in any room with an unvented gas or kerosene space heater.

P

DON’T use any gasoline-powered engines (mowers, weed trimmers, snow blowers, chain saws, small engines or generators) in enclosed spaces.

P

DON’T ignore symptoms, particularly if more than one person is feeling them. You could lose consciousness and die if you do nothing.

Conclusions:

Carbon monoxide poisoning can be fatal if precaution is not taken promptly. Proper education on risks of poisoning is crucial to avoid any unwanted consequences. Oxygen therapy, proper cardiac monitoring and other supportive therapy are warranted to overcome any other complications.


Update in Clinical Toxicology

The Recognition and Management of Serotonin Syndrome

Each year, new agents are being added to the pharmacopoeia, expanding the list of possible toxicologic reactions. In response, new antidotes are introduced, uses of more established antidotes evolve, and new therapeutic approaches to well-established toxicologic syndromes are developed. This brief update on critical care toxicology focuses on a few of the important developments.

In this issue of PRN8099, a summary of ‘The recognition and management of the serotonin syndrome’ are discussed as an example of a toxicologic syndrome that is occurring more frequently as a consequence of the introduction of new pharmacotherapies.

What is Serotonin Syndrome?

  • a complication of the use or misuse of medications for treating psychiatric disorders such as depression and bipolar affective disorders which include agents that increase central nervous system (CNS) serotonin transmission and activity.
  • characterized by confusion, autonomic instability, and neuromuscular abnormalities. (Table 1)

Table 1. SUGGESTED DIAGNOSTIC CRITERIA FOR SEROTONIN SYNDROME *

Coincident with the addition of or increase in a  known serotonergic agent to an established medical regimen, at least 3 of the following clinical features should be present:

Mental status changes (confusion, hypomania)             Shivering

Agitation                                                                           Tremor

Myoclonus                                                                        Diarrhea

Hyperreflexia                                                                    Incoordination

Diaphoresis                                                                       Fever

Other etiologies (e.g., infectious, metabolic, substance abuse, or withdrawal) must be excluded.

A neuroleptic must not have been started or increased in dosage before the onset of the signs and symptoms listed above.

* Adapted from Sternbach (1991)

What is the Pathophysiology of Serotonin Syndrome?

  • not entirely clear but animal studies implicates 5-hydroxytryptamine 1A receptor activation in the brainstem and spinal cord as playing an important role in the genesis of the syndrome.

When is Serotonin Syndrome Often Seen?

  • In patients taking two or more medications that increase CNS serotonergic activity by different mechanisms (Table 2).
  • Most commonly reported combinations are monoamine oxidase inhibitors with :      - tryptophan,      - tricyclic antidepressants.
  •  
  •       - selective reuptake inhibitors, or
  •       - pethidine,
  • Single agents may also precipitate the syndrome, sometimes at therapeutic doses, but mainly in overdoses. Examples are, Clomipramine and 3,4-Methylenedioxymethamphetamine (Ecstasy).
     

Table 2. PHARMACOLOGIC AGENTS THAT ENHANCE CNS SEROTONIN ACTIVITY : LISTED BY MECHANISMS OF ENHANCEMENT

Serotonin agonists

Inhibit serotonin reuptake

Buspirone

Amphetamines

Ergot Alkaloids

Cocaine

Lithium

Pethidine

LSD

Nefazadone, Trazadone

MCPP

SSRI

Metoclopramide

Tramadol

Triptans

TCA

   

Increase serononin release

Inhibit serotonin sysnthesis

Amphetamines

MAOI

Codeine and derivatives

 

Dexfenfluramine

Enhance serotonin synthesis

Dextromethorphan

l-Tryptophan

Fenfluramine

 

MDMA

 

Definiton of abbreviations: CNS – central nervous system; LSD – Lysergic acid diethylamide; mCPP – meta-chlorophenylpiperazine; SSRI – selective serotonin reuptake inhibitors; TCA – tricyclic antidepressants; MAOI – monoamine oxidase inhibitor; MDMA – methylenedioxymethamphetamine.

How to Manage Serotonin Syndrome?

 A.   Recognizing symptoms

  1. Sternbach Criteria for diagnosing the Serotonin Syndrome may be used as a guide (Table 1).
  2. Onset of symptoms – within minutes to hours post-ingestion, usually resolve within 12 – 24 hours.
  3. Mild cases – present with limited symptoms.
  4. Severe cases – altered sensorium, and muscular hyperactivity manifested by myoclonus, shivering, rigidity, and hyperthermia.
  5. Complications, if untreated – risks include rhabdomyolysis, renal failure, hepatic dysfunction, disseminated intravascular coagulation.
  6. In massive overdoses – may result in cardiovascular collapse and death.

B. Treatment-symptomatic

 If possible, avoid all serotonergic medications, such as pethidine or dextromethorphan.

  1. Benzodiazepines – to decrease muscular hyperactivity. If benzodiazepines failed, cyproheptadine or neuromuscular blockade may be necessary.
  2. Rapid external cooling – to reduce body temperature in hyperthermia.

With good supportive care applied promptly, patients may recover quickly.

Bibliography : Update in Non-Pulmonary Critical Care by Jason Chu, Richard Y. Yang, and Nicholas S.Hill as published in the American Journal of  Respiratory and Critical Care Medicine, Vol 166, pg 9-10, 2002.

Request for a copy of the original article can be made to the National Poison Centre, Universiti Sains Malaysia, 11800 Minden, Penang.

 


s utube s fb