Carbamate poisoning & an case presentation

1. CARBAMATE POISONING
BY,
FAREED
1

2. Definition :
A class of compounds that reversibly inhibit the enzyme
acetylcholinesterase . Some are used as insecticides, others as
medicines.
Carbamates are as popular as organophosphates in their role as
insecticides (and fungicides) and share a number of similarities
2

3. 3
Common Carbamates are ;

4. Usual fatal dose :
Toxicity Rating*:
 The following are extremely toxic (LD50: 1 to 50 mg/kg), or highly
toxic (LD50: 51 to 500 mg/kg)— Aminocarb, Bendiocarb, Benfuracarb,
Carbaryl, Carbofuran, Dimetan, Dimetilan, Dioxacarb, Formetanate,
Methiocarb, Methomyl, Oxamyl, Propoxur.
 The following are moderately toxic (LD50: 501 to 5000 mg/kg), or
slightly toxic (LD50: more than 5000 mg/kg)— Aldicarb, Bufencarb,
Isoprocarb, MPMC, MTMC, Pirimicarb.
4

5. Mode of Action and Clinical Features :
 Carbamates (like organophosphates) are inhibitors of
acetylcholinesterase, but carbamylate the serine moiety at the active
site instead of phosphorylation. This is a reversible type of binding
and hence symptoms are less severe and of shorter duration. As a
result both morbidity and mortality are limited when compared to
organophosphate poisoning. Also, since carbamates do not penetrate
the CNS to the same extent as organophosphates, CNS toxicity is
likewise much less
 Carbamates are rapidly metabolised. They are rapidly hydrolysed by
liver enzymes to methyl carbamic acid and a variety of low toxicity
phenolic substances. These metabolites may sometimes be measured
in urine as long as 2 to 3 days after significant pesticide absorption.
5

6.  Miosis, a muscarinic effect, is characteristic of severe and moderately
severe poisonings, but may appear late. Pupil dilation may occur as a
nicotinic effect and may be present in up to 10% of patients.
 Sinus tachycardia with ST segment depression may occur early in the
course of poisoning. Repolarisation abnormalities may occur and are
generally transient. Dyspnoea is a common manifestation of
carbamate exposure
 Chest tightness, bronchospasm, increased pulmonary secretions, and
rales may develop secondary to muscarinic effects. Acute lung injury
(pulmonary oedema) is a potential clinical manifestation of severe
carbamate poisoning and is attributed to the muscarinic action of the
insecticide. Contributing factors to the development of pulmonary
oedema include bradycardia and weakened cardiac contraction from
an accumulation of acetylcholine on the cardiovascular system.
Hypoxia may develop due to increasing capillary permeability
6

7.  Children may be more likely to develop CNS depression, convulsions,
and hypotonia than the typical cholinergic syndrome.
 The presence of either a cardiac arrhythmia or respiratory failure is
associated with a higher incidence of fatal poisoning
 Various peripheral neuropathies have been reported after carbamate
use. The symptoms are similar to those seen with organophosphates.
Acute pancreatitis has been reported with propoxur.
7

8. Diagnosis :
 In the case of carbamate poisoning, measurement of cholinesterase
activity in blood may be misleading due to in vitro reactivation of
carbamylated enzyme. In vitro decarbamylation has been found to be
promoted by dilution of the sample. The carbamylated sample should
be stored undiluted and refrigerated or frozen. Carbamylated
cholinesterase activity follows a non-linear kinetic pattern over time,
whereas phosphorylated enzyme activity is linear. At inhibition of
greater than 40%, the non-linear pattern characteristic of carbamates
is easily mapped.
 One technique for assessing absorption of the principal N-methyl
carbamate compounds is measurement of specific phenolic
metabolites in urine, e.g. carbaryl (alpha-naphthol), carbofuran
(carbofuranphenol) propoxur (isopropoxyphenol).
 Chest X-ray should be obtained in all symptomatic patients. The major
cause of morbidity and mortality in carbamate insecticide poisonings
is respiratory failure and associated pulmonary oedema 8

9. Treatment :
 An important differentiating point from organophosphates is that
oximes are generally not recommended, while atropine can be given.
Especially in carbaryl poisoning, oxime therapy can lead to the
production of a carbamylated oxime which may be a more potent
acetylcholinesterase inhibitor than carbaryl itself. With other
carbamate insecticides (particularly aldicarb), oximes may be a useful
adjunct to atropine therapy. In 1986, a consensus of international
experts concluded that pralidoxime can be used in conjunction with
atropine for specific indications as follows:
 Life-threatening symptoms such as severe muscle weakness,
fasciculations, paralysis, or decreased respiratory effort.
 Continued excessive requirements of atropine.
 Concomitant organophosphate and carbamate exposure.
9

10.  In all cases, administer atropine in repeated doses intravenously until
atropinisation is achieved (indicated by drying of pulmonary
secretions). Adult dose—2 to 4 mg IV every 10 to 15 minutes.
Paediatric dose—0.05 mg/kg IV every 10 to 15 minutes.
 Convulsions can be controlled with a benzodiazepine (diazepam or
lorazepam). If they persist or recur, administer phenobarbitone.
10

11. Case study on Transdermal carbamate
poisoning :
SUBJECTIVE :
A 52 years male patient presented to emergency department with the
history of altered sensorium and vomiting for last three hours
He did not have any premorbid and psychiatric illness and was happy
with his family.
11

12. OBJECTIVE :
On examination his GCS was 11/15 ( E 4 V2 M5) and full of sweats all over
the body. His vitals were HR 110/min, RR 28 / min, Sp02 98% with six
litres of oxygen via face mask and BP 110/80 mmHg. Chest had bilateral
equal air entry with normal vesicular breath sounds except few
conducted sounds at the basal region. Pupils were two mm bilateral and
reacting to light. His hematological as well as biochemical laboratory
investigations were all unremarkable.
ABG showed respiratory alkalosis and chest X ray was normal. Random
blood sugar and electrolytes were normal.
12

13. On further evaluation of the history, his wife told that patient was fine
three hours ago when he applied a pesticide all over his body except his
face. He wanted to kill mites in his body with this pesticide and for this
he mixed approximately 5 gm of carbamate ( Carbofuran 3%) in 30 ml of
coconut oil and applied all over his body. After half an hour, he
developed dizziness, nausea and sweating.
DIAGNOSIS :
Acute carbamate poisoning
13

14. PLAN :
In our case we used normal soap water for cleaning the body as soon as
we confirmed the history. Rapid decontamination of the exposed part is
an essential step to stop further absorption.
The patient was initially resuscitated following ABC (airway, breathing
and circulation) protocol and was atropinized with 30 mg of atropine
once the diagnosis of carbamate poisoning was made
Patient was shifted to medical ICU and was managed with continuous
infusion of atropine starting with 12 mg of atropine per hour. Atropine
was gradually decreased and finally stopped on 9th day as the patient
clinically improved and was shifted to ward next day.
14

15. THANK YOU !
15

16. Reference ;
 VV-Pillay-Modern-Medical-Toxicology-4th-Edition
 Journal of College of Medical Sciences-Nepal, Vol-12, No 4, Oct-Dec 016
16