Toxkso.pptx

Clinical Toxicology Cardiovascular Lec=6 Drugs: Antiarrhythmics agents Household Toxins: Iodine Hydrogen Peroxide Hypochlorites Antiarrhythmics agents classification of antiarrhy-thmic drugs 1. Class I: Sodium Channel Blockers • Class I a:disopyramide, procainamide, quinidine. • Cla...

Clinical Toxicology Cardiovascular Lec=6 Drugs: Antiarrhythmics agents Household Toxins: Iodine Hydrogen Peroxide Hypochlorites Antiarrhythmics agents classification of antiarrhy-thmic drugs 1. Class I: Sodium Channel Blockers • Class I a:disopyramide, procainamide, quinidine. • Class I b lignocaine, phenytoin, mexiletine, • Class I c flecainide, propafenone. 2. Class II: Beta Adrenergic Blockers: atenolol, esmolol, ect. 3. Class III: Potassium Channel Blockers: amiodarone, bretylium, sotalol. 4. Class IV: Calcium Channel Blockers: diltiazem,, verapamil. 5. Unclassified: adenosine Class IA Drugs  These drugs have a low toxic-to-therapeutic ratio.  In severe overdosage, almost any type of cardiac arrhythmia can occur, including increased Q-T and QRS intervals,, polymorphic ventricular tachycardia (torsade de pointes) and the fatal ventricular fibrillation.  Hypotension in severe cases caused by depressed myocardial contractility via the Na+ channel blockage and peripheral vasodilation. Vasodilation results primarily from the K+ channel blocking activity of these drugs.  CNS symptoms, such as lethargy, confusion, coma, respiratory .depression, and seizure .  Quinidine : Cinchonism, a syndrome characterized by GI symptoms (abdominal cramping, nausea, vomiting, and diarrhea), tinnitus, and altered mental status may occur in both chronic and acute toxicity , quinidine syncope .  Disopyramide:It has negative inotropic and anticholinergic properties, The anticholinergic property leads to symptoms of urinary retention, constipation, dry mouth, and blurred vision. Procainamide: anticholinergic mental effects, status respiratory depression, depression, seizures, nausea, vomiting and diarrhoea. Long-term therapy with procainamide may also cause a lupus syndrome (arthralgias, myalgias, rash, and fever.) Treatment .Decontamination : stomach wash and activated charcoal-1 Resin haemoperfusion or haemodialysis are the methods of choice for .3 . removal of these drugs Continuous ECG monitoring, airway and circulatory support, and IV .4 .access Sodium bicarbonate or sodium lactate may help in reversing the sodium .5 . blockade. Cardiac toxicity often responds to intravenous sodium bicarbonate Lignocaine is1st line agents for stable monomorphic ventricular tachycardia, Sotalol is an alternative. Atropine may be used when severe bradycardia Class IB Drugs  In severe intoxication with class IB drugs, the cardiac manifestations are similar to those of class IA drugs.  CNS toxicity is more common and may be manifest as confusion, coma, or seizure. Lidocaine :Nystagmus is an early sign of lidocaine toxicity. Vertigo, drowsiness, confusion and pareshesia , Massive overdose can produce rapid onset of hypotonia ,apnoea, and asystole. Even after recovery, symptoms can persist for a prolonged period because of persistent metabolites (active metabolite). Tremor and nausea are the major dose-related adverse effects of . mexiletine and tocainide Tocainide is rarely used due to its potential to cause fatal bone marrow aplasia and severe pulmonary . interstitial fibrosis Treatment 1.Stomach wash, activated charcoal ( for Mexiletine). 2.Atropine (1 mg intravenously and repeat in 3 to 5 minutes if asystolic cardiac arrest persists) for bradycardia 3.Diazepam for convulsions. 4. Fluids, dopamine, adrenaline, and cardiac pacing as necessary . Class IC Drugs Drugs in this class have much in common with agents in class IA. The prominent clinical presentations in severe overdoses include coma, respiratory depression, and seizure. Propafenone: has beta and Ca blocking activities gastrointestinal upset, blurred vision, hypotension, drowsiness, prolongation of the QRS interval. Neurologic disturbances are relatively common with propafenone overdose, and several types of convulsions have been described including minor motor and tonic-clonic seizures. Dizziness, amnesia, disorientation, neuropathy, paraesthesias . Treatment 1-Decontamination : stomach wash and activated charcoal. 2- Continuous ECG monitoring, airway and circulatory support, and IV access. 3-Sodium loading : molar sodium lactate, sodium bicarbonate, or hypertonic saline may be administered. Serum alkalinisation with sodium bicarbonate may be useful in treating arrhythmias. 4-Atropine may be used when severe bradycardia 5-Diazepam for convulsions. 6-Class IB agents (lignocaine, phenytoin, mexiletine, tocainide) may be the best alternative based on electrophysiologic properties, but could also exacerbate toxicity. Class III: Potassium Channel Blockers Bretylium is only available in intravenous form the drug reduces the release of norepinephrine, causing hypotension and bradycardia. In fact, hypotension is a common problem during bretylium therapy Amiodarone is a class III antiarrhythmic agent that primarily prolongs cardiac action potential duration, and non-competitive blocker for alpha and beta sympathetic receptor resulting in vasodilation. Toxicokinetics Amiodarone can be given orally or intravenously. Oral bioavailability is low. Absorption is slow and variable (22 to 86%). First pass metabolism in the gut wall or liver may be the cause. Amiodarone is extensively distributed, with concentrations in the skin, skeletal muscle, adipose tissue, lung, liver, and myocardium. Tissue concentrations generally exceed that of plasma. where it may get concentrated upto 50 times that of the serum. The volume of distribution is large ,protein binding is to the extent of 98%, and the elimination half-life varies from 3 to 21 hours. the principal route of elimination is by hepatic excretion into the bile Clinical (Toxic) Features Amiodarone toxicity following acute overdose is rare, because poor bioavailability and a large volume of distribution limit the peak serum concentration. Acute toxicity may include hypotension due to vasodilation and depression of myocardial performance. The most severe toxic effect during chronic therapy is pulmonary fibrosis exact mechanism unknown. Other toxic effects during long-term use of amiodarone include Q-Tc prolongation, disturbances bradycardia, such as corneal blurred microdeposits, Visual vision, coloured halos or photophobia, hepatitis, thyroid abnormalities, neuromuscular symptoms, and photosensitivity Treatment 1-Decontamination measures may be effective upto several hours postingestion. Oral cholestyramine may help in reducing the half-life of amiodarone. 3-Pulmonary toxicity responds to corticosteroids, but rapid withdrawal may lead to recurrence 4-Bradycardia responds to beta-adrenergic agonists or pacemaker. With chronic therapy, bradycardia has been unresponsive to atropine, presumably due to the noncompetitive nature of amiodarone’s antiadrenergic effects. 5-Intravenous magnesium sulfate for torsade de point Hypotension responds to vasopressors 6-Haemodialysis and haemoperfusion do not appear to be beneficial. Unclassified: Adenosine Adenosine, a nucleoside found in all cells, is released from myocardial cells under physiologic and pathophysiologic conditions. It is administered as a rapid IV bolus to terminate reentrant supraventricular tachycardia. The resultant hyperpolarization of adenosine reduces the rate of cellular firing. Cutaneous flushing, dyspnoea, chest pain, nausea, vomiting, vertigo, headache, hypotension. Infusion of adenosine causes angina-like chest pain in susceptible persons without ECG signs of ischaemia The duration of electrophysiologic and clinical effects with adenosine is extremely short, usually less than 10 seconds, due to rapid cellular uptake and metabolism. Laboratory measures are not likely to be useful in an intoxication. Symptomatic and supportive measures Household toxins Antiseptics are applied to living tissue to kill or prevent the growth of .microorganisms Disinfectants are applied to inanimate objects to destroy pathogenic .microorganisms Despite the lack of rigorous evidence that they prevent infection, they are used widely in households, the food industry, and hospitals. These agents are often used as dilute solutions that usually cause little or no toxicity Iodine The most common iodine-containing antiseptic is povidone-iodine, is described as an iodophor, which is a complex of iodine and polyvinylpyrrolidone, a solubilizing agent. It is intended to liberate free iodine in solution for its effect. This compound is very poorly absorbed from the gastrointestinal tract, because of the rapid conversion of free iodine to iodide in the stomach. Though highly concentrated iodine solutions or iodine salts are corrosive to the .gastrointestinal tract. It is likewise poorly absorbed from intact skin All symptomatic poisonings reported have occurred either after repeated .exposure to burned skin or following irrigation of wounds, joints Initial manifestations of iodine poisoning include rhinorrhoea, conjunctivitis, and cough (especially if fumes have been inhaled). There is burning pain extending from the mouth to the abdomen, salivation, metallic taste, vomiting, and diarrhoea. skin and mucous membranes are stained yellowish brown. pulmonary oedema, delirium, hallucinations, convulsions, tachycardia, hypotension, metabolic acidosis, and renal failure. Hypothyroidism, hyperthyroidism, and thyrotoxicosis But chronic poisoning can result from long-term therapeutic intake of iodide salts leading to iodism which is characterised by metallic taste, anorexia, insomnia, lymphadenopathy, parotid swelling (“iodide mumps”), stomatitis, pharyngitis, conjunctivitis, rhinorrhoea, and skin manifestations (erythema, .urticaria, acne, etc. together referred to as “ioderma”) Treatment of Iodine Toxicosis 1.Decontamination: a. Skin: Wash thoroughly with soap and water. b. Eyes: Irrigate with water for 15 minutes. c. GIT: If oesophageal injury is not present or suspected, gastric lavage can be attempted with starch solution, or 5% solution of sodium thiosulfate, or even plain milk.Activated charcoal binds iodine and can be administered. 2. Sodium bicarbonate IV for metabolic acidosis. 3. Supportive treatment for renal failure, tachycardia, hypotension, and circulatory collapse. 4. Osmotic diuresis and salt loading may enhance elimination. 5. Iodism is treated by ceasing iodide intake while enhancing the intake of sodium chloride which promotes excretion of iodides. Chloride competes with iodide at the level of the renal tubules Hydrogen Peroxide Hydrogen peroxide decomposes to water and oxygen. When used in closed spaces or under pressure, liberated oxygen cannot escape. Systemic oxygen embolisation and surgical emphysema can occur. Household hydrogen peroxide (3 to 9%) is mildly irritating to mucus membranes. In general, ingestion, ocular, or dermal exposure to small amounts of dilute hydrogen peroxide will cause no serious problems • 1 ml of a 3% solution liberates 10 ml of oxygen. Therefore ingestion of a large amount of hydrogen peroxide solution even if it is very dilute can result in gastric distension. Irritation of gastrointestinal tract often results in vomiting. .Oral contact with dilute (3%) solutions may induce oral gingival ulceration or enhance prior injuries of the mucous membranes of the mouth. Hypertrophy of the papillae of the tongue may occur from chronic use of hydrogen peroxide mouthwash. • Ingestion of industrial strength hydrogen peroxide (35 to 90%) can cause severe burns of GI mucosa with a tendency to gastric perforation (due to oxygen liberation). Oxygen emboli can also be produced which can be life-threatening. Foam formation can result in respiratory tract obstruction and respiratory failure. Metabolic acidosis and convulsions. • Dermal exposure to concentrated solutions has resulted in burns and gangrene Treament 1.Aggressive airway management comprising endotracheal intubation, oxygen administration and mechanical ventilation. 2. Following ingestion, administer water immediately to dilute the peroxide. Spontaneous vomiting is common.. 3. After endotracheal intubation, cautious gastric lavage may be attempted with iced saline. 4. Supportive measures with particular reference to control of metabolic acidosis and convulsions. 5. Laparotomy may be required if there is evidence of air in the GI tract. 6. Hyperbaric oxygen therapy may help alleviate life threatening gas embolisation. Hypochlorites  Sodium and calcium hypochlorite solutions are of relatively low toxicity. They are mildly corrosive to eyes, and mucous membrane burns have been reported. Despite the large number of reports to poison control, significant poisonings are very infrequent with these agents in solution.  When hypochlorite solutions are mixed with acids or ammonia solutions, chlorine or chloramine gas is produced, resulting in an irritant with pulmonary toxicity. Many brief exposures have led to transient symptoms requiring limited emergency department management abdominal and retrosternal pain and diarrhoea. Aspiration of liquid may lead to pulmonary complications such as acute respiratory distress syndrome (ARDS).Prolonged exposure or exposure to high concentrations carries the potential of severe toxic pneumonitis. Ocular exposure to household bleach can cause mild irritation and temporary discomfort if eyes are washed immediately. Treatment of Hypochlorite Toxicosis 1. After oral exposures, do not use gastric emptying. If a granular material is ingested and the patient has symptomatic mucosal burns, refer patient to a surgeon or gastroenterologist for consideration of endoscopy and management. 2. If vomiting has not occurred, give patient water or milk for dilution, not to exceed approximately 15 mL/kg in a child or 120-240 mL in an adult. Administration of acids is contraindicated, because of the risk or increasing generation of chlorine gas. 3. If a high concentration solution is in contact with the eyes, wash eyes profusely and examine corneas carefully. If burns have occurred, obtain ophthalmologic care. 4. Manage skin exposure with copious water dilutions. 5. If exposure to vapors or chlorine or chloramine gas has occurred, move patient immediately to fresh air. If symptoms occur or persist, oxygenation should be assessed and oxygen administered as needed. If persistent symptoms occur, obtain a chest film and consider hospitalization. Intensive care may be appropriate in severe inhalations.