Carbamate ppt

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