META TAG (title):
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1 Chelating Agents and Treatment of Poisoning
11.1 Chelating Agents & Treatment of Poisoning
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2 Dental Pharmacology
12.1 Antiseptics & Disinfectants
12.2 Astringent and Obtundents
12.3 Mummifying and Bleaching Agents
12.4 Styptics (Local Haemostatics) and Disclosing Agents
12.5 Dentifrices and Mouth Washes
12.6 Caries and Fluorides
12.7 Pharmacotherapy of Common Oral Conditions & Dental Emergencies
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3 Miscellaneous
13.1 Vaccines, Sera and Other Immunological Agents
0/ Vitamins and Trace Elements388seborrhoea like lesions, mental confusionand growth retardation.It is indicated to prevent and treatisoniazid, hydralazine, penicillamineand cycloserine induced neurological dis-turbances, mental symptoms in womenon oral contraceptives, pyridoxine re-sponsive anaemia and homocystinuria,morning sickness and hyperemesisgravidarum, convulsions in infants andchildren.Dosage: Adults: 100 mg daily. Insuppression of lactation: 2 tablets thricedaily followed by one tablet daily.CYANOCOBALAMIN(METHYLCOBALAMIN)Methylcobalamin is the coenzymeform of vitamin B12. It is neurologicallyactive, most bioavailable and best uti-lized. Unlike cyanocobalamin, it doesnot require any conversion after ab-sorption by the body and is better re-tained by the liver and other tissues. Ithas exhibited beneficial effects againstbrain aging, irregular sleep patterns. Itsupports immune function and pro-mote normal cell growth. It representsone of the best values in nutritionalproducts, given its comparably lowcost and its wide range of potentialbenefits.Methyl B12 is the superior form ofvitamin B12.Deficiency symptoms are glossitis, GITdisturbances, megaloblastic anaemia,subacute combined degeneration of spinalcord, peripheral neuritis, poor memory,mood changes and hallucinations.Clinical ApplicationsBell’s palsy: It increases the recoverytime for facial nerve function in Bell’s palsy.Cancer: Experimental studies indicatethat it inhibits the proliferation of malignantcells.Diabetic neuropathy: Oral administra-tion of methylcobalamin (500 mcg threetimes daily for four months) resulted insubjective improvement in burning sensa-tion, numbness, loss of sensation andmuscle cramps.Immune system regulation: It has beensuggested that vitamin B12 plays animportant role in immune systemregulation, but the details are still obscure.Rheumatoid arthritis: Vitamin B12 is apotential agent in management of RA. Itmainly acts by correcting abnormalities inRACD8+ T cells in autologous mixedlymphocyte reaction (AMLR).Eye function: It protects retinal neuronsagainst N-methyl-D-aspartate receptormediated glutamate neurotoxicity.Deterioration of accommodation followingvisual work has also been shown to improvein individuals receiving methylcobalamin.Heart rate variability: Methylcobalaminproduces improvement in several componentsof heart rate variability, suggesting a balancingeffect on the nervous system.HIV: Under experimental conditions,methylcobalamin inhibited HIV-1 infectionof normal human blood monocytes andlymphocytes.Homocysteinemia: Elevated levels ofhomocysteine can be a metabolic indicationof decreased levels of the methylcobalaminform of vitamin B12.
Vitamins and Trace Elements389Male impotence: It is known toincrease sperm count in male patients withimpotence.Sleep disturbances: The use ofmethylcobalamin in the treatment of avariety of sleep-wake disorders is verypromising.Vitamin B complex preparations areindicated in vitamin deficiency states.Specific vitamin B preparations can be usedas per indications mentioned above in thepharmacological write up; as an adjuvantto antibiotic therapy; combination withlactobacillus are indicated in aphthousstomatitis, thrush.Preparations of vitamin B1 + B6 + B12are indicated to prevent and treat isoniazid,hydralazine and cycloserine induced neu-rological disturbances, mental symptoms inwomen on oral contraceptives, pyridoxineresponsive anaemia and homocystinuria,neuropathies, subacute combined degenera-tion, beriberi, anaemia, hepatitis, debility.FOLIC ACIDIt plays a vital role in variousintracellular reactions e.g. conversion ofserine to glycine, synthesis of thymidylate,synthesis of purines, histidine metabolismetc. Due to folic acid deficiency thesereactions are affected.Deficiency symptoms: The character-istic feature of folic acid deficiency is mega-loblastic anaemia. Deficiency also leads toglossitis, enteritis, diarrhoea, general debil-ity, weight loss and sterility.It is indicated in folic acid deficiencystates e.g. megaloblastic anaemia, tropicaland nontropical sprue, alcoholism;adjunctive therapy in nutritional anaemiasand anaemias of pregnancy.Dosage:Adults: Therapeutic: 5 to 20 mg daily individed doses.Children: 5 to 10 mg daily in divideddoses.VITAMIN C (ASCORBIC ACID)It functions as a cofactor in number ofamidation and hydroxylation reactions.The active form of vitamin C is ascorbicacid itself. The main function of ascorbate isas a reducing agent in a number of differentreactions. Vitamin C has the potential to reducecytochrome a and c of the respiratory chainas well as molecular oxygen. The mostimportant reaction requiring ascorbate as acofactor is the hydroxylation of prolineresidues in collagen. Vitamin C is, therefore,required for the maintenance of normalconnective tissue as well as for wound healingsince synthesis of connective tissue is the firstevent in wound tissue remodeling. Vitamin Cis also necessary for bone remodeling due tothe presence of collagen in the organic matrixof bones. It is also required for conversion offolic acid to folinic acid, biosynthesis of adrenalsteroids, catecholamines, oxytocin and ADH;metabolism of cyclic nucleotides andprostaglandins.Deficiency symptoms: In vitamin Cdeficiency scurvy develops. It is character-ized by ecchymosis, petechiae, swollen andbleeding gums, subperiosteal haemorrhage,bones are painful to touch, impairedwound healing, anaemia, loosening of teethand gingivitis.
0/ Vitamins and Trace Elements390It is indicated for treatment of scurvy,for prophylaxis of vitamin C deficiency, toacidify urine, anaemia of vitamin Cdeficiency, as antioxidant to protect naturalcolour and flavour of many foods, dentalcaries and increased capillary fragility.Dosage:Adults: Prophylaxis : 50-500 mg daily.Pregnancy and lactation: 100-150 mgdaily.CALCIUMCalcium is the most abundant bodyconstituent (approx. 2% of body weight). Itcontrols excitability of nerves and musclesand regulates permeability of cellmembranes. It act as intracellular messengerfor hormones and autacoids and help incoagulation of blood.Plasma calcium level is precisely regu-lated by three hormones e.g. parathormone,calcitonin and calciferol (which is a activeform of vitamin D). They control its absorp-tion, exchange with bone and excretion.Calcium is present in three forms e.g.,as free calcium ion, bound to plasma proteinalbumin and in diffusable complexes. Theendocrine system, through parathyroidhormone and calcitonin, helps in keepingthe concentration of ionized plasmacalcium in normal level. Decrease in plasmalevels of ionized calcium leads to increasedparathyroid hormone secretion.Parathyroid hormone tends to increaseplasma calcium level by increasing boneresorption, increasing intestinal absorptionand increasing reabsorption of calcium inkidney. Vitamin D acts by stimulatingintestinal absorption of calcium anddecreasing the renal excretion.Calcium play vital role in excitation- contraction coupling in myocardium.Calcium mediates contraction invascular and other smooth muscles.Calcium is required for exocytosis andalso involved in neurotransmittersrelease. Calcium also help in maintain-ing integrity of mucosal membranes andmediating cell adhesions. Hypercalcemiamay occur in hyperthyroidism,vitamin D intoxication and renalinsufficiency, which can be treated byadministration of calcitonin, edetatesodium, oral phosphate etc. Hypocal-cemia may occur in hypothyroidism,malabsorption, osteomalacia second-ary to leak of vitamin D or vitamin Dresistance, pancreatitis and renalfailure. Hypocalcemia can be treatedby chloride, gluconate, gluceptate,lactate and carbonate salts of calcium.TRACE ELEMENTSNICKELIt is an essential trace element for mam-mals, but little is known about its role orrequirement in human metabolism. Inhumans, serum levels of nickel are about1.1 to 1.6 mcg/l. This level increases inconditions such as stroke and acute myo-cardial infarction. A dietary requirementfor adults is about 30 mcg/day.Nickel occurs mainly in plant foods,especially grains and vegetables with littlein animal food sources or fats.
Vitamins and Trace Elements391CHROMIUMLess than 6 mg of chromium is found inthe body, with the highest concentrationsoccurring in the adrenal glands, brain, skin,muscles and fat.The total body content of chromium isestimated to be 6 to 10 mg. The recommendedsafe limit for daily chromium intake by adultis 0.05 to 0.2 mg.MANGANESEThe body contains only 20 mg ofmanganese, found mostly in the bones andglands. The plasma level is low, about 2.5mcg/dl.The best sources of manganese arewheat bran, dried legumes, seeds, nuts andleafy green vegetables, other good sourcesare cereal grains, coffee and tea. Theadequate range in adult diet is 2.5 to 5.0mg/day.Manganese is a cofactor of enzymesinvolved in energy metabolism and is re-quired for hemoglobin synthesis, thiaminutilization and tendon and bone formation.Unlike nutrients that fulfil unique func-tions, other minerals sometimes can sub-stitute for manganese.MOLYBDENUMMolybdenum is found primarily in theliver, kidneys, bone, skin and adrenal glands.Organ meats, legumes and grains aregood sources. The adequate range ofmolybdenum intake for adults is 75 to 250mcg/day. It is equally excreted in the urineand the faeces.Because molybdenum is a copperantagonist, high levels of copper decreasethe absorption of molybdenum. It is equallyexcreted in the urine and the faeces.Molybdenum is a cofactor for enzymesinvolved in protein synthesis.SELENIUMSelenium is an essential trace elementin the human body. This nutrient is an im-portant part of antioxidant enzymes thatprotect cells against the effects of free radi-cals that are produced during normal oxy-gen metabolism. Selenium is also essentialfor normal functioning of immune systemand thyroid gland.
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Chelat ng Agents&Treatment of Po son ngChelating Agents andTreatment of Poisoning
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(Mode of Action of Drugs)PharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsChapter1. 4Chapter11.1Chelating Agents &Treatment ofPoisoningAntidotes are used in life threateningsituations and are administered for a shorttreatment course. They can be divided intothree main categories:• Antidotes that remove active poisonfrom its site of action e.g. hydroxylamineused in organophosphate anticholinest-erase poisoning.• Antidotes that act pharmacologicallye.g. naloxone used in opioid poisoning.• Antidotes that antagonised othermacromolecules e.g. carbon monoxideproduce poisonous condition bybinding the haemoglobin and othercellular components.The antidotes are classified into fourmain types.i. Mechanical antidotes: These sub-stances interfere with the absorption ofpoison. They act by forming a coat overmucous membrane of the stomach. e.g.fats, oils, albumin, activated charcoalis specifically used in adsorbing alka-loidal poisons.ii. Chemical antidotes: They react withpoison to form harmless insoluble forme.g. acids are neutralised by alkalis,KMnO4 used in opium poisoning.iii. Systemic antidotes: They produce theaction which are opposite to that ofpoison e.g. caffeine for morphine andatropine for pilocarpine.iv. Universal antidotes: These antidotescan be given in all such conditionswhere nature of poison is not knownor where more than one poison issuspected to be taken e.g. charcoal asadsorbent of toxins and alkaloids,tannic acid for precipitating alkaloids,glycoside and many metals.CHELATING AGENTSChelating agents are widely used as specificantidotes for heavy metals. They form stable,soluble, nontoxic complexes and in easilyexcreted form. They promote dissociation ofbound metal from tissue enzymes and otherfunctional macromolecules. These metalchelates are water soluble. e.g. EDTA, BAL,desferrioxamine etc.DIMERCAPROL (BRITISH ANTILEWISITE, BAL)It acts by forming chelation com-plexes between its sulphydryl groups andmetals. Its effectiveness is much more, ifChelating Agents &Treatment ofPoisoning
1/ Chelating Agents & Treatment of Poisoning396given immediately after exposure to themetal.It is given by parenteral route (deep IMinjection) and has short plasma half life.Adverse effects include increasedblood pressure, burning sensation in lips,mouth and throat; nausea, vomiting,sweating, pain in chest, throat or hands;painful sterile abscess at site of injection;haemolytic anaemia in patients with G-6-PD enzyme deficiency; hypertension,tachycardia, salivation, lacrimation andconjunctivitis.It is indicated in metallic intoxicationdue to arsenic, mercury, gold, bismuth,lead, nickel, thallium and antimony; inconjunction with sodium calcium edetatefor lead poisoning. It is also useful inhepatolenticular degeneration (Wilson’sdisease). It is contraindicated in iron andcadmium poisoning.Dose: BAL; 2.5 to 5.0 mg/kg QIDdepending upon the severity of thepoisoning.D-PENICILLAMINEIt is a monothiol, prepared by alkalinehydrolysis of benzyl penicillin andchemically it is beta-dimethylcysteine.It acts as a chelating agent which helpsin elimination of heavy metal ions byforming stable soluble complexes whichcan be easily excreted by the kidneys.It is used in poisoning due to copper,mercury and lead; Wilson’s disease,cystinuria, scleroderma and rheumatoidarthritis.Adverse effects include skin rash,proteinuria, bone marrow depression,nausea and loss of taste sensation.Dose: CILAMIN; 0.5-1 g/day individed dose.DESFERRIOXAMINEIt is a iron chelating agent, available forintramuscular, subcutaneous andintravenous administration.When injected, it forms a stable water-soluble iron complex (ferrioxamine) thatprevents the iron from entering intofurther chemical reactions and is readilyexcreted in the urine giving the urine acharacteristic reddish colour. Some of it isalso excreted in the faeces via the bile. Itcan also chelate aluminium and thus isuseful in aluminium overload. It isprimarily a chelator used in acute ironpoisoning and chronic iron overload as inthalassemia patients needing multipletransfusions.Adverse effects include flushing,urticaria, hypotension, shock, tachypnoea,hypoxaemia, tachycardia, cardiacarrhythmias, convulsions, erythema,swelling, GIT disturbances, dysuria, fever,allergic skin rashes. Leg cramps on long termtherapy and reversible ocular and auditorydisturbances have also been reported.DESFERALAcute iron intoxication: Initially 1 g IMfollowed by 500 mg every four hours fortwo doses. Subsequent doses of 500 mg aregiven 4 to 12 hourly depending on response,maximum 6 g in 24 hours.Patients with cardiovascular collapse: IVinfusion 50 mg/kg/hour up to a maximumof 80 mg/kg in 24 hours.
Chelating Agents & Treatment of Poisoning397Chronic iron overload: 0.5 to 1 g IMdaily. In addition 2 g IV infusion givenseparately with each unit of bloodtransfused.CALCIUM DISODIUM EDETATEIt is the calcium chelate of disodiumedetate having high affinity for metals likelead, zinc, cadmium, copper, manganeseand some radioactive metals. Given by IVroute, it is distributed extracellularly andexcreted unchanged in urine by glomerularfiltration carrying the toxic metal along.It is primarily indicated in leadpoisoning. It is also useful in iron, zinc,copper, manganese and radioactive metalbut not mercury poisoning.Adverse effects include nephrotoxic-ity, anaphylactoid reaction, chills, bodyacheand malaise.DEFERIPRONEIt is an orally active iron chelator. It isuseful in acute iron poisoning, ironoverload in cirrhosis, transfusion siderosisin thalassemia patients. Adverse effectsare anorexia, vomiting, altered taste, jointpain and neutropenia.DISULFIRAM (ESPERAL)It is relatively nontoxic, used as anadjunct in the treatment of chronicalcoholism.It exerts its action by inhibiting alde-hyde dehydrogenase enzyme. Disulfiramthus increases the concentration of acetal-dehyde in body when ethanol is ingestedby an individual pretreated with disul-firam. The symptoms and signs producedare flushing, pulsating headache, nausea,vomiting, thirst, marked uneasiness, ver-tigo, weakness, confusion, hypotension andcirculatory collapse.After oral administration it is rapidlyabsorbed from gastrointestinal tract.Adverse effects include urticaria,allergic dermatitis, restlessness, tremor,dizziness, metallic taste, fatigue, decreasein sexual potency and lassitude.It is indicated in chronic alcoholismin a dose range of 1 g on 1st day, 0.75 g on2nd day, 0.5 on 3rd day, decreasing to0.125-0.25 g/day. Sensitization to alcoholdevelops after two to three hours of firstdose and lasts for 7 to 14 days afterstopping it.LEUCOVORINIt is used as leucovorin calcium(calcium folinate). It is 5-formyl derivativeof tetrahydrofolic acid and it acts as anantidote to folic acid antagonists likemethotrexate or pyrimethamine whichinhibit the enzyme dihydrofolatereductase.Well absorbed by the oral or IM routeand is rapidly converted to biologicallyactive folate. Distribution occurs to all bodytissues and it is concentrated in the CSF. Itis excreted in the urine.Adverse effects include pyrexia whichoccurs rarely.It is indicated in overdose ofmethotrexate, folic acid antagonists and asadjuvant treatment of colorectal carcinoma.Dose: NYRIN; 120 mg per day by IMor IV infusion.
1/ Chelating Agents & Treatment of Poisoning398PRALIDOXIMEIt causes reactivation of thephosphorylated acetylcholinesteraseenzyme. After administration, it ismetabolised in liver.Adverse effects include blurred vision,dizziness, diplopia, headache, tachycardia,mild weakness and nausea. In high dose itcan cause neuromuscular blockage.It is indicated as antidote for organo-phosphorus poisoning like malathion,TEPP, parathion etc.NICOTINENicotine is a tertiary amine compoundcomposed of a pyridine and a pyrrolidinering. It binds selectively to acetylcholinereceptors at the autonomic ganglia in theadrenal medulla at neuro-muscularjunction and in the brain. It exerts astimulating effect in the cortex and a‘reward’ effect via the ‘pleasure system’ inthe limbic system.Adverse effects include erythema, pru-ritus or burning at the site of application,headache, somnolence, dizziness, arthral-gia, myalgia, dyspepsia, dry mouth, diar-rhoea, sweating, BP changes, angioneuroticedema, urticaria and dyspnea.It is used in the treatment of nicotinedependence and as an aid to stop smoking.BUPROPIONThe mechanism by which bupropionacts as an aid in smoking cessation is un-known. Bupropion weakly inhibits neu-ronal reuptake of noradrenaline and se-rotonin and inhibits the reuptake ofdopamine. In tissues from rat brain,bupropion produced greater inhibition ofdopamine reuptake than noradrenalinereuptake; however in, in vivo models,bupropion is a stronger inhibitor of no-radrenaline than dopamine reuptake. Themetabolites hydroxybupropion andthreohydrobupropion are pharmacologi-cally active in vitro and in animal modelsof depression and are expected to con-tribute to the therapeutic effects ofbupropion.Adverse effects include abdominalpain, chest pain, facial edema, nausea, drymouth, constipation, diarrhoea, anorexia,mouth ulcer, thirst, myalgia, arthralgia,anxiety, disturbed concentration, dizziness,nervousness, tremor, dysphoria, rhinitis,increased cough, pharyngitis, sinusitis,dyspnea, epistaxis, agitation, insomnia andheadache.It is indicated in smoking cessation inthe dose of 150 to 300 mg twice daily.TREATMENT OF POISONINGThe treatment of different drug poison-ing is discussed in individual chapters.In this section, general treatment isdiscussed.The general principles of treatment are:1. Support ventilation.2. Maintain cardiovascular function.3. Reverse hypothermia if present.4. Treat convulsions.5. Correct fluid, acid-base and electrolyteimbalance.6. Relieve pain.7. Good nursing care.
Chelating Agents & Treatment of Poisoning399Prevention of Poison AbsorptionThe aim is to reduce the absorption ofpoison.1. Gastric lavage may be useful for sixhours after ingestion of poison. Thelavage should be done as early aspossible but only if vital functions areadequate.2. It is inappropriate to employ gastriclavage unless the lungs can beprotected, either by virtue of patienthaving an adequate cough reflex or bymeans of a cuffed endotracheal tube.3. Gastric lavage is contraindicated ifcorrosive or caustic substances havebeen taken, because oesophageal andgastric erosion and perforation mayoccur.4. Activated charcoal is probably moreeffective than either emesis or lavage.Accelerating Poison EliminationAlkalinisation of urine (alkalinediuresis) is effective for salicylates andphenoxyacetate herbicides.Repeated dose of activated charcoaladministered by oral route have beenshown to enhance the non-renal elimi-nation of carbamazepine, salicylates,phenobarbitone, phenytoin, digoxin,theophylline and meprobamate. In se-vere cases activated charcoal is to be ad-ministered via a nasogastric tube.Haemoperfusion, using a cartridgecontaining charcoal or an uncharged resinis effective in enhancing drug excretion infew selected cases of poisoning e.g.theophylline, barbiturates, non-barbituratehypnotics, etc. (Also see Section I for themanagement of poisoning).Frequent administration of activatedcharcoal is effective for the followingsubstances:1. Substances which form masses: Aspirin,iron, lithium, enteric-coated tablets,meprobamate.2. Substance which remain in the stomachfor a long time: Barbital, aspirin, iron,alcohol, cholinergic blockers, narcoticdrugs, phenytoin, antidepressants.3. Substances which have a long half-lifewhen present in large amounts: Theo-phylline, aspirin, alcohol, phenytoin,chloral hydrate, acetaminophen.4. Substances which have active metabolites:Benzodiazepines, chloral hydrate,acetaminophen, antidepressants,procainamide.5. Substances whose poisonous metabolites areeliminated slowly: Ethylene glycol, metha-nol, primidone, isopropyl alcohol, car-bon tetrachloride, levothyroxine.6. Substances which are reabsorbed from theurinary tubules in a pH dependent manner😛henobarbital, aspirin, amphetamine.7. Substances with persistent tissue accumu-lation: Iron, lithium.8. Substances which enter the enterohepaticcirculation: Carbamazepine, digoxin,phenobarbital.The specific antidotes for variouspoisons are listed in table 11.1.1ORGANOPHOSPHORUS POISONINGThese compounds are mainly used asagricultural and household insecticides.The poisoning may be occupational (forthose who are involved professionally withthese agents), accidental (accidental con-sumption) or suicidal due to intentionalingestion of these compounds.
1/ Chelating Agents & Treatment of Poisoning400a. Local exposure produces miosis,spasm of accommodation, headache,irritation of eye, lacrimation andblurring of vision.b. On ingestion fall in blood pressure, ta-chycardia, cardiac arrhythmias, ataxia,convulsion, respiratory paralysis andvasomotor collapse occurs. The deathis generally due to respiratory failure.Treatment1. Gastric lavage, fresh air fortermination of further exposure tocompound.2. Maintenance of a patent airway. Useoropharyngeal or nasopharyngealairway or endotracheal intubation ifairway obstruction persists.3. Washing of skin, mucous membraneand eye.4. Supportive therapy: Maintenance ofblood pressure, artificial respiration,rehydration (fluid/electrolyte therapy)and control of convulsions.5. Antidote/Reactivators.a. Atropine is highly effective incounteracting the muscarinicPoison Antidote1. Arsenic Dimercaprol, BAL, D-penicillamine2. Cyanide Oxygen (100%), dicobalt edetate, Amyl nitrite, sod. nitrite3. Ethylene glycol, methanol Ethanol4. Opioids Naloxone5. Organophosphorus insecticides Atropine and pralidoxime mesylate6. Iron Desferrioxamine7. Beta-blockers Atropine for bradycardia, glucagon8. Digoxin Digoxin specific antibody fragments (DIGIBIND)9. Carbon monoxide Oxygen (100%)10. Oral anticoagulants Vitamin K (phytomenadione)11. Heparin Protamine sulfate12. Lead (inorganic) Sodium calcium edetate, D-penicillamine13. Mercury (inorganic) Dimercaprol, D-penicillamine, BAL14. Methanol Ethanol15. Paracetamol, gold N-acetylcysteine16. Benzodiazepines Flumazenil17. Atropine Physostigmine18. Isoniazid Pyridoxine19. Folic acid antagonists Folinic acid20. Acetaminophen (Paracetamol) N-acetylcysteine21. Copper BAL, EDTA D-penicillamine22. Methotrexate Folic acid, Leucovorin23. Snake bite Antisnake venom polyvalent24. Hydroxzines Pyridoxine25. Theophylline Esmolol26. Curare compounds Neostigmine27. Insulin GlucoseTable 11.1.1 List of specific antidotes for various poisons.
Chelating Agents & Treatment of Poisoning401symptoms. It is given in a dose of 2mg IV every 10 min till muscariniceffects are controlled.b. The cholinesterase reactivators are usedto restore neuromuscular transmission.Pralidoxime (pyridine-2-aldoximemethiodide; 2-PAM) is an antidote andcholinesterase reactivator. It breaks thebond between the organophosphatepoison and the molecular surface ofacetylcholinesterase and the enzyme isfreed and reactivated to hydrolyse theexcess of acetylcholine at the receptorsites. It is to be given in the dose of 1-2g IV infusion along with 100-200 mgof atropine.Other cholinesterase reactivators arediacetylmonoxime (DAM) which combineswith free organophosphate molecule in thebody fluids. It is administered 1-2 g IV slowly.CHRONIC ALCOHOLISMIt is associated with development ofpsychic dependence, tolerance and physicaldependence and sudden withdrawal ofalcohol may lead to withdrawal syndrome.In addition, the alcohol addicts are li-able to other neuropsychiatric syndrome(Korsakoff’s psychosis) which is associatedwith hallucination, suicidal tendencies andencephalopathy. They may also suffer fromhyperlipidemia, hyperuricemia, pancreati-tis and hepatitis.Drug Treatment of Chronic Alcoholism(Aldehyde Dehydrogenase Inhibitors)DISULFIRAMChemically it is tetraethyl thiuramdisulphide, commonly known as antabuseand available in 200 mg tablet. Thetreatment is initiated with 800 mg singledose which is gradually reduced over 5 daysto a maintenance dose of 100 to 200 mgdaily and treatment may be continued upto one year.After a week’s therapy, if a smallquantity of alcohol is consumed by thepatient, it produced unpleasant toxicreactions such as flushing, palpitation,nausea, vomiting throbbing headache,uneasiness, dizziness, visual disturbances,fall in blood pressure and even collapse.The patient thus realizes that during thetreatment he can not tolerate even a smallamount of alcohol and would abstain fromalcohol drinking.The drug disulfiram interferes with theoxidation of acetaldehyde formed duringthe metabolism of alcohol. This increasesthe blood level of acetaldehyde which actsdirectly on cardiovascular system andproduce these toxic reactions. Disulfiramalso inhibits dopamine beta oxidase andthus interferes with the synthesis ofnoradrenaline, which causes depletion ofcatecholamines.Disulfiram is slowly absorbed incom-pletely from the gut and is metabolisedslowly.METHYL ALCOHOL (METHANOL)Methyl alcohol is only used to denatureethyl alcohol in 5 percent concentration. Itis metabolised to formaldehyde and formicacid by alcohol and aldehyde dehydroge-nases. Its absorption and distribution aresimilar to ethyl alcohol.Ingestion of methyl alcohol producesthe following signs and symptoms:
1/ Chelating Agents & Treatment of Poisoning402• Nausea and vomiting.• Blurring of vision, hyperemia of opticdisc and blindness.• Pancreatitis.• Albuminuria.• Coma followed by death.Treatment of Methanol Poisoning• Gastric lavage, activated charcoal.• Hospitalization: Correction ofacidosis.• IV/oral ethyl alcohol.• Maintenance of nutrition.• Administration of folinic acid (1 mg/kg, IV) together with folic acid (1 mg/kg IV) to accelerate the metabolicdegradation of formate.• Administration of 4-methylpyrazole(inhibitor of alcohol dehydrogenase).• In severe case: Haemodialysis.TREATMENT OF SNAKE BITEVipers, Cobras and Kraits are the commonpoisonous snakes and in India 40,000 to50,000 deaths recorded per year due tosnake bite.Local Signs & Symptoms in the BittenPart• Fang marks.• Local pain & bleeding.• Bruising.• Lymphangitis.• Inflammation (swelling, redness,heat).• Blistering.• Lymph node enlargement.• Local infection, abscess formation &necrosis.Generalised (Systemic) Symptoms &Signs• Nausea, vomiting, malaise, abdominalpain weakness.• Visual disturbances, faintness, collapse,shock, hypotension, pulmonary edema& conjunctival edema.• Bleeding & clotting disorders.• Skeletal muscle breakdown.• Acute pituitary/adrenal insufficiency.First-aid Treatment• First aid treatment is carried outimmediately before hospitalisation.• Immobilise the bitten limb with a splintor sling.• Consider pressure-immobilisation forsome elapid bites.• Avoid any interference with the bitewound as this may introduce infec-tion, increase absorption of the venomand increase local bleeding.• Tight (arterial) tourniquets are notrecommended.Treatment in hospital• Rapid clinical assessment andresuscitation.• History (especially the snake identifi-cation).• Physical examination.• Investigation/laboratory tests:– 20 minute whole blood clotting test(20 WBCT).– Haemoglobin concentration/haematocrit.– Platelet count.– WBC count.– Biochemical abnormalities.– Urine examination etc.
Chelating Agents & Treatment of Poisoning403Supportive TherapyBlood pressure, ECG, blood gas analysis,urine output and respiration are to bemonitored. To correct coagulationparameters, blood transfusion may beneeded.ANTISNAKE VENOMAntivenom is the only specific antidoteto snake venom. Antivenom is immunoglo-bulin purified from the serum or plasma of ahorse or sheep that has been immunised withthe venoms of one or more species of snake.Antivenom should be given by the intrave-nous route. Freeze dried (lyophilised)antivenoms are reconstituted, usually with10 ml of sterile water for injection per am-poule. Adrenaline should always be drawnup in readiness before antivenom is adminis-tered for any possible anaphylactic reactions.
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