PeterWenaweser, MD

• Attending Physician
• Department of Cardiology
• University Hospital Bern
• Bern, Switzerland

The most recent epidemic occurred in 1998 in Delhi useless id symptoms generic 250 mg cordarone with visa, claiming 65 lives out of a total number of 2552 cases reported from all across the state 97110 treatment code order cordarone without prescription. Almost all the outbreaks have been due to consumption of mustard oil or other vegetable oils contaminated with argemone oil (except the South African epidemic which occurred due to adulteration of wheat flour with argemone seeds) symptoms xanax abuse buy cordarone 100mg. South Indian states have been largely spared because mustard oil is not very popular here treatment vertigo purchase cordarone cheap online. Toxin Scombroid poisoning is a form of ichthyosarcotoxicosis (the toxin is contained within the flesh of the fish) medications emts can administer order online cordarone. Poisoning occurs from consumption of improperly preserved fish in which the endogenous histidine has been broken down by bacteria into high levels of histamine and saurine symptoms yeast infection purchase 250 mg cordarone free shipping. To add insult to injury, even if such contaminated fish is subsequently cooked well or smoked, the toxins are not destroyed. Immediately after being caught the fish is generally non-toxic, but toxicity increases as the bacterial count rises. Poisonous fish are subdivided into: Ichthyosarcotoxic fish, which contain a toxin within their flesh, Ichthyohaemotoxic fish, which have poisonous blood, and Ichthyo-otoxic fish, which contain a toxin mainly in their gonads. Based on the nature of toxin, there are 5 types of seafood poisoning-scombroid, ciguatera, tetrodotoxic, paralytic shellfish, neurotoxic shellfish, and amnesic shellfish poisoning. Chapter 33 Incubation Period Few minutes to few hours: Symptoms may develop as early as 5 to 10 minutes after eating the fish, or be delayed up to 1 to 2 hours. Although most cases are mild and self-limiting, resolving in 3 to 36 hours, potentially life-threatening effects have occurred. Manifestations are mostly histamine-mediated, and comprise erythema of face, urticaria, pruritis, dermal flushing, diaphoresis, burning sensation of the mouth, dizziness, throbbing headache, vomiting, diarrhoea, and abdominal cramps. Detection and quantitation of histamine in implicated fish flesh is more important. Illness is usually associated with more than 100 mg of histamine per 100 gm of flesh (though illness can result from much less concentrations). Occasionally, the skin may have a "honeycombed" appearance, or the taste may turn pungent or peppery. Diagnosis can be confirmed by measuring the histamine level in the fish which may exceed 100 mg%. The recommended method of estimating histamine level in fish is capillary electrophoretic assay. Cimetidine has been successful in patients refractory to conventional antihistamines. Barracuda, sea bass, parrot fish, red snapper, grouper, amberjack, kingfish, sturgeon, and many other large-sized fish are the main culprits. The latter are in turn consumed by larger carnivorous fish, and the ciguatoxin Table 33. Ciguatera poisoning is said to be endemic in the Caribbean, South Pacific, and Australia. A few cases of poisoning have been reported from some areas of the Indian Ocean also, as well as from East Asia, and South Asia. The toxins are mainly contained in the muscle, skin and mucosa of the fish, with the highest concentration present in the viscera (liver, intestines, gonads). Sudden onset of sweating, abdominal cramps, nausea, vomiting, profuse watery diarrhoea, dysuria, tingling and numbness of lips, tongue, and throat, metallic taste, paraesthesias, dysaesthesias, chills, headache, myalgia, arthralgia, tremor, ataxia, vertigo, blurred vision, and convulsions. Paraesthesias are the hallmark of ciguatera poisoning, and may also persist for weeks. But this is not a true sensory switch; it can be described as the sensation one gets when gripping something very cold. This phenomenon is said to be due to abnormal bursts of discharges occurring specifically in the peripheral C-polymodal nociceptor fibres (cutaneous afferent unmyelinated fibres). Other sensory effects include a metallic taste, and a "carbonated" sensation when food or drink is consumed. Extrasystoles may occur, probably because of noradrenergic myocardial stimulation. Neurological manifestations tend to linger for a long time even in patients who have fully recovered. Ocular effects include blurred vision, photophobia, visual loss (usually temporary), mydriasis and lacrimation. Painful ejaculation and dyspareunia in the unaffected partner have been reported occasionally. Symptoms of ciguatera poisoning are exacerbated by ethanol and stress (physical and/or emotional). Foetal distress has occurred after ingestion of ciguateracontaminated fish by the pregnant mother. Infants exposed to ciguatoxin in late pregnancy have been noted to have abnormal prenatal movement and temporary cranial nerve deficits. Several cases of ciguatera poisoning in breastfeeding infants whose mothers were poisoned have also been reported. A rapid test (dipstick immunobead assay) is being developed to test suspect fish for the presence of toxin. Other marine poisonings (scombroid poisoning, neurotoxic shellfish poisoning) Organophosphate poisoning Monosodium glutamate (in susceptible individuals) Botulism Other bacterial food poisoning. Decontamination (activated charcoal, catharsis) may be of benefit if the patient is seen within 2 hours of ingestion. The primary treatment is the use of antihistamines; cold showers can also be helpful. Some investigators are of the opinion that mannitol is not effective in the management of neurological manifestations of ciguatera poisoning. Chronic neurologic symptoms may resolve with tocainide, mexiletine, or amitryptiline. Avoidance of alcohol and exercise (which can exacerbate symptoms), is recommended. Snails: In a study of several outbreaks of tetrodotoxinassociated snail poisoning in Zhoushan city, China, the following snail species were identified as culprits: Zeuxis samiplicutus, Zeuxis siguinjorensis, Zeuxis variciterus, and Z. Its action is thought to interfere with the increase in sodium permeability associated with nerve excitation, with changing potassium permeability. The highest concentration is found in the ovaries, and hence the female is most poisonous, especially if eaten during the spawning season. Clinical Features Mode of action Tetrodotoxin affects myelinated nerve fibres throughout the entire length of the axon by lowering the conduction of sodium currents at nodes of Ranvier. Main features of poisoning include headache, sweating, dysaesthesias, and paraesthesias of lips, tongue, mouth, face, fingers, and toes. Circumoral tingling may include the tongue and inner surface of the mouth, and generally occurs within 10 to 45 minutes of ingestion. Later, the following are seen: salivation, dysphagia, dysarthria, nausea, vomiting, abdominal pain, ataxia, weakness, fasciculations, and ascending paralysis in 4 to 24 hours. Blurred vision, aphonia, and dysphagia may be seen as muscle paralysis progresses. The main toxin is saxitoxin which is produced by the following dinoflagellates (unicellular algae): Pyrodinium, Gymnodinium and Alexandrium. Because dinoflagellates can occur in tropical and moderate climate zones, shellfish can accumulate these toxins worldwide. These toxins affect the central nervous system and can produce muscular nerve block and paralysis. These are natural phenomena triggered by a series of events, which can include human pollution. Over 300 phytoplankton species can produce red tides*, but only 60 to 70 species are actually harmful. There are 3 grades of severity: Y Mild: Tingling and numbness of the tongue and lips, that soon spreads to the face, neck, arms, fingers and toes; headache and nausea. Y Moderate: Limb weakness, ataxia, incoherent speech, difficulty breathing, hypersalivation, and sweating. Y Severe: Muscle paralysis, "choking" sensation, severe respiratory difficulty, and respiratory failure. Assisted ventilation may be necessary for 4 to 6 hours, and in some cases up to 12 hours. Haemodialysis may be effective in the treatment of tetrodotoxin poisoning, because the toxin has low molecular weight, is water soluble, and is not significantly bound to protein. Shellfish Poisoning Source Shellfish (especially oysters, clams, mussels, and scallops) contaminated by dinoflagellates. Other sources include univalve mollusks, starfish, limpets, sand crabs, whelks, turban shells, top shells, xanthid crabs and various fish. Since saxitoxin is excreted mainly via urine, diuresis can enhance renal excretion Supportive measures: Most patients recover with supportive care alone. Patients with significant neurotoxicity may need endotracheal intubation and mechanical ventilation. Because saxitoxin acts by blocking sodium channels, sodium bicarbonate may be effective in reversing ventricular conduction delays and arrhythmias, though this has not been proved: administer 1 to 2 mEq/kg sodium bicarbonate as a bolus, and repeat as necessary. Neurotoxic Shellfish Poisoning Neurotoxic shellfish poisoning results from eating shellfish (cockles, oysters, whelks, and clams) that have consumed the dinoflagellates containing brevetoxins. The main dinoflagellate involved is Ptychodiscus brevis (formerly called Gymnodinium breve). Besides causing major fish kills, these toxins produce various ill effects in man and other shore animals. Unlike saxitoxin, they produce a stimulatory rather than a depressant nervous effect, and open the sodium channels in nerves, while saxitoxin closes them. Main features include nausea, vomiting, diarrhoea, abdominal pain, rectal burning, paraesthesias of the face, throat, fingers, and toes, burning sensation of the mucous membranes, reversal of hot and cold temperature sensation, myalgia, vertigo, ataxia, headache, dysphagia, bradycardia, decreased reflexes, and mydriasis. Treatment involves decontamination, administration of beta2 adrenergic agonists and corticosteroids. Amnestic Shellfish Poisoning the main toxin involved is domoic acid, produced by the diatom Nitzschia pungens. The main features include nausea, vomiting, diarrhoea, abdominal pain, amnesia, hemiparesis, grimacing, purposeless chewing, ophthalmoplegia, convulsions, and coma. The last mentioned will be discussed in this section, while the other two entities are discussed elsewhere. Food additives may be antioxidants, flavouring agents, colouring agents, sweetening agents, thickening agents, or preservatives (Table 33. Uses Flavouring agent in foods, especially Chinese food, sausages, canned soup, etc. Y Eat only freshly prepared, broiled, or sauteed meats or fish (without sauces or seasoning). In the second group, individuals with severe and poorly controlled asthma may, in addition, experience difficulty in breathing. Chapter 33 Not specified for any of these agents Food Poisoning Source Glutamate, a major building block of proteins, is released during breakdown of a protein molecule, and occurs naturally in many foods (meat, milk, mushrooms, cheese, tomatoes, etc. It is produced by the following processes: Y Fermentation of carbohydrate sources such as sugar beet molasses. Y By action of Micrococcus glutamicus upon a carbohydrate, and subsequent partial neutralisation. Features include burning or tingling sensation and numbness of face, trunk, and upper limbs, weakness, dizziness, syncope, flushing, lacrimation, sweating, chest pain, headache, nausea, gastric distress, and rarely bronchospasm and angioedema. An outbreak of Yersinia enterocolitica O: 8 infections associated with pasteurized milk. Outbreak of aflatoxin poisoning - eastern and central provinces, Kenya, January - July 2004. Gastrointestinal decontamination is generally not indicated after an acute ingestion. An outbreak of foodborne botulism associated with food sold at a salvage store in Texas. A botulism case of a 12-year-old girl caused by intestinal colonization of Clostridium botulinum type Ab. Frozen chicken nuggets and strips - a newly identified risk factor for Salmonella heidelberg infection in British Columbia, Canada. An outbreak of food poisoning due to egg yolk reaction-negative Staphylococcus aureus. Neurotoxic shellfish poisoning and brevetoxin metabolites: a case study from Florida. Shiga toxin-producing Escherichia coli infections associated with hemolytic uremic syndrome Italy, 1988-2000. An outbreak of Escherichia coli O157 infection following exposure to a contaminated building. The criteria for substance abuse do not include tolerance, withdrawal, or a pattern of compulsive use, and instead include only the harmful consequences of repeated use. It is to be noted that the term "abuse" when used by itself, merely refers to the use of an illicit drug, or the use of a licit drug outside of legitimate medical practice. Use of psychoactive substances to experience pleasurable effects is not a recent phenomenon, but has been indulged in by human kind for hundreds, even thousands of years. Terminology in the field of substance abuse has changed frequently leading to a great deal of confusion.

While it is a fact that many individuals experiment with drugs especially in their youth symptoms 4dp3dt cheap cordarone 100 mg online, not all become dependant on them symptoms you need glasses buy cordarone 250mg cheap. In fact treatment wax purchase cordarone 250 mg without prescription, it is only a small proportion of susceptible individuals who go on to become addicts medications ending in pam order 200mg cordarone with visa. Medical professionals should be familiar with these risk factors which can help them to identify potential abusers and take pre-emptive action whenever possible treatment of ringworm order 250 mg cordarone with visa. It is also important to be able to recognise signs and symptoms of drug abuse as well as identify clues in the form of behavioural changes which point to surreptitious abuse (Table 34 symptoms 6 year molars cheap 200 mg cordarone with visa. Tranquillisers and Sedatives Barbiturates, benzodiazepines, chloral hydrate, chlormethiazole, ethchlorvynol, glutethimide, hexapropymate, meprobamate, methyprylon, methaqualone, zolpidem, zopiclone 4. Inhalants Fluorinated hydrocarbons (freons), ethers, ketones, aromatic and aliphatic hydrocarbons 10. Miscellaneous Substances Caffeine, datura seeds, analgesics, anabolic steroids, cough syrups, laxatives Several of these compounds have been discussed in detail elsewhere, and the reader is advised to consult the Index for locating them. Every part of the plant (except the seed) contains nicotine, the maximum concentration of which is in the leaves. Nicotine is a colourless to pale yellow, very hygroscopic, oily liquid with an unpleasant pungent odour, and sharp, burning, persistent taste. Substances of Dependence and Abuse Mode of Action By far the commonest source of nicotine poisoning (acute or chronic) results from smoking tobacco in the form of cigarettes. When a cigarette is lit and inhaled, the smoker is exposed to both gaseous and particulate matter. The usual nicotine content of a "regular" cigarette varies between 13 and 20 mg, while certain European and Turkish cigarettes can contain higher amounts. When a cigarette is smoked, more than half the nicotine escapes in the sidestream smoke, while a large fraction remains in the butt and filter, and it is only 0. Turkish tobacco is prepared from the leaves of Nicotiana rustica, and is more potent. They are more harmful than cigarettes and produce higher levels of carbon monoxide, nicotine, and tar. Also, because of low combustibility of tendu leaf, bidi smokers tend to inhale more often and more deeply, breathing in greater quantities of tar and other toxins than cigarette smokers. There has been a resurgence of popularity in the use of snuff in recent times, paralleling the decline in cigarette smoking in most parts of the world. Because smoking is not involved, people generally believe that snuff is more socially acceptable and less harmful. Snuff is usually available as finely cut tobacco powder which is packaged dry or moist. The nicotine dissolves in the saliva and is absorbed through the mucous membrane of the mouth, as well as through the intestinal mucosa after the saliva is swallowed. A portion of the tobacco that is placed in the mouth each time for chewing is referred to as a "quid". Ultimately, the tobacco chewer gets approximately the same dose of nicotine (or slightly more) than the tobacco snuffer. The smokeless tobacco user who takes 8 to 10 quids per day gets a nicotine equivalent of 30 to 40 cigarettes per day. Several cases of severe nicotine poisoning due to exposure (dermal and oral) to these pesticides have been reported, some of which have ended in death. Nicotine binds stereo-specifically to select acetylcholine receptors (nicotine receptors). These receptors are present throughout the body, particularly in the autonomic ganglia, adrenal medulla, central nervous system, spinal cord, neuromuscular junctions, and chemoreceptors of carotid and aortic bodies. Nicotine stimulation of vagal centres in the medulla induces nausea and vomiting, while the gastro-oesophagal reflux is provoked due to a lowering of sphincter pressure and increased acid secretion. Nicotine suppresses appetite while increasing basal energy expenditure, resulting in weight loss. Habitual use of nicotine by women results in decreased oestrogen levels (due to enhanced hydroxylation of oestradiol), thereby increasing the risk of osteoporosis. This alteration of drug metabolism is due to induction of microsomal enzyme systems, not by nicotine itself, but most probably by polynuclear aromatic hydrocarbons. While smoking has no effect on the clearance of alcohol, concomitant use exaggerates the cardiovascular response of nicotine, as a result of which the heart rate and blood pressure go up. This is thought to be catecholamine mediated, and it has been suggested that smokers may have increased tendency to suffer from arrhythmias and sudden death during alcohol use. A primary position upbeat nystagmus is seen following cigarette smoking, chewing of nicotine gum, and ingestion of nicotiana glauca leaves, and is the direct result of nicotine. Death may occur, especially in the case of ingestion of cigarettes (inadvertently) by children, or exposure to insecticidal nicotine. Ingestion of large amount can cause weakness, paralysis, coma, and rarely respiratory failure resulting in death. Occupational dermal exposure to wet, uncured tobacco may produce "green tobacco sickness" among workers, characterised by nausea, vomiting, headache, vertigo, pallor, and sweating. Chronic Poisoning (Addiction): Nicotine dependence is the most widely prevalent and deadly of all substance dependencies. The dependence-producing effects of nicotine appear to be modulated by dopamine which is increased in smokers. Section 11 Drug Interactions Smoking alters the metabolism of some commonly used drugs. Metabolism is enhanced in the case of benzodiazepines, caffeine, H2 antagonists, imipramine, nicotine, opiates, phenacetin, propranolol, and theophylline. As a result of such interference, the therapeutic efficacy of opiates, benzodiazepines, beta-adrenergic antagonists, nifedipine, H2 antagonists, and Table 34. With repeated exposure, many youngsters find the physiological effects of nicotine well suited to help them with the difficult periods during adolescence. In addition, physical dependence begins so that cessation of nicotine use becomes uncomfortable. Children more likely to start smoking are those who have a high need to conform, display low academic performance, rebelliousness, depressive symptoms, and have poor self-esteem. Nicotine withdrawal: Manifestations of nicotine withdrawal can occur within 4 to 8 hours of the last cigarette. In fact most chronic smokers experience some withdrawal symptoms on waking up each morning. Manifestations include changes in mood, insomnia, difficulty concentrating, restlessness, decreased heart rate (average decline is 8 beats per minute), and weight gain (average is 2 to 3 kg). Craving is common, and increased coughing, poor performance on vigilance tasks, etc. Nicotine withdrawal is worst in cigarette smokers, intermediate in users of smokeless tobacco, and mild in users of nicotine replacement products. In some, it may last for several months, especially features such as craving and weight gain. Acute poisoning can be confirmed by estimating plasma nicotine level; but the short half-life of nicotine necessitates early withdrawal of blood. High pressure liquid chromatography is generally utilised to assay nicotine levels. Polymorphonuclear leucocytosis and glycosuria are often encountered in nicotine overdose. Passive tobacco smoke exposure is usually determined by estimating cotinine levels in plasma, urine, or saliva. Urine cotinine is also used as an index to nicotine exposure in tobacco workers (especially harvesters). Acute Poisoning Mild overdose (with spontaneous vomiting) requires only observation for 4 to 6 hours, after which the patient can be discharged. But it is not recommended by most investigators since it can aggravate the condition of a convulsing patient in whom there is rhabdomyolysis. Animal experiments indicate that drugs such as pempidine and mecamylamine may have antidotal effects against nicotine. Hexamethonium (a ganglionic blocking agent) has prevented nicotine-induced convulsions in animals. Chronic Poisoning (Addiction) Nicotine withdrawal must be treated by a combination of therapies including psychosocial, psychopharmacological, and nicotine replacement. Nicotine replacement therapy- the rationale behind nicotine replacement is to prevent or relieve nicotine withdrawal symptoms while stopping smoking behaviour by replacing it with another behaviour. Approximately 50 to 70% of the nicotine is absorbed through the buccal mucosa, while additional amounts are absorbed through swallowed saliva. Peak plasma concentration is reached 15 to 30 minutes after starting to chew the gum, as compared with 1 to 2 minutes after initiating smoking. Chewing the gum too rapidly and vigorously can raise nicotine concentrations to uncomfortable levels producing adverse effects (especially if the patient is also smoking at the same time). If the gum is inadvertently swallowed, there is no cause for undue concern since the nicotine is released and absorbed slowly producing only low blood concentrations. The actual efficacy of nicotine gum, and the dose and duration of therapy are highly variable. The nicotine patch is generally available in 3 sizes, 30 cm2, 20 cm2, and 10 cm2, which deliver 21 mg, 14 mg, and 7 mg of nicotine respectively, over 16 or 24 hours. The nicotine is released either directly through the skin or through a membrane system in contact with the skin. Side effects are mild and include doserelated sleep disturbances, dyspepsias, myalgias, and increased cough. It is available as a metered dose inhaler containing 100 mg of nicotine at 10 mg/ml, designed to deliver 200 equivalent puffs each releasing 0. Absorption occurs through the nasal mucosa which may be affected to some extent in the presence of rhinitis. While initial reports have been favourable, use of the spray is relatively unpleasant and unsightly. Absorption occurs through the buccal and pharyngeal mucosa, and respiratory tree (on slow deep inhalation). Subsequent studies on its utility in nicotine withdrawal have shown that it could be effective in promoting abstinence from cigarettes also. Although the exact mechanism is not clear, it is postulated that clonidine is effective for most withdrawal syndromes because it inhibits noradrenergic neurons in the locus ceruleus. However, clonidine use is associated with a high incidence of adverse effects including tachycardia, hypotension, headache, vertigo, sedation, and visual disturbances. These are minimised by substituting oral therapy with transdermal patches in much the same way as nicotine patches. There are recent reports of very satisfactory results by combining both transdermal nicotine and clonidine, since the former reduces behavioural withdrawal symptoms, while the latter reduces craving. Antidepressants: Since it is well known that smokers who stop smoking have a high incidence of depression, antidepressants such as doxepin and sertraline have been tried with varying degrees of success in combating nicotine withdrawal. Nicotine agonists and antagonists: these drugs have the potential to block the effect of nicotine, i. Lobeline, the first of these drugs to be studied in this regard, is a partial agonist that binds weakly and competitively to nicotine receptor sites. However, it has not been found to be very effective in practice, though it continues to be sold abroad as a smoking cessation aid under the brand name CigArrest. Mecamylamine is a nicotine receptor antagonist that is said to reduce the craving for cigarettes if administered for more than 6 weeks, though it can produce unpleasant side effects including abdominal cramps, constipation, and urinary retention. Adverse effects can be minimised by combining mecamylamine with nicotine skin patch. Section 11 Substance Abuse Forensic Issues Tobacco abuse has been described as being the most widespread cause of death and disability worldwide than any single disease entity. Apart from the health problems brought on by smoking and other forms of tobacco use on the user himself (detailed in earlier sections of this chapter), environmental tobacco smoke inhalation can have deleterious effects on other individuals as well. The * Adrenergic hyperactivity in the locus ceruleus (a dark-coloured depression in the floor of 4th ventricle of brain) is common in many withdrawal syndromes. Government of India is making attempts at prohibiting tobacco smoking in public, and a few states have begun to implement this with varying success rates. Passive smoking can cause the following health problems: Y Adults: Lung cancer, small airway damage, worsening of angina, hypertension. Y Children: Bronchitis, pneumonia, worsening of asthma, middle ear effusions, decreased height, sudden infant death syndrome. The term "foetal tobacco syndrome" is applied in those cases where the mother had smoked 5 or more cigarettes per day throughout the pregnancy, had no evidence of hypertension during pregnancy, and the newborn baby showed symmetrical growth retardation as manifested by low birth weight (less than 2. As far as acute nicotine poisoning is concerned, the circumstances could be accidental, suicidal, or even homicidal. Y Accidental poisoning could occur in children who play with old tobacco pipes, or who ingest cigarettes out of curiosity. Accidental poisoning in horticulture due to the use of nicotine as a pesticide was not uncommon in the past. Apart from occupational exposure to nicotine spray, even fruits contaminated with nicotine used to reach the general public. Careless storage of nicotine in containers which could be mistaken for some other product also sometimes caused accidental poisoning. Y Similarly, suicidal ingestion of nicotine pesticides used to be reported occasionally in the past, until such preparations were withdrawn from use.

Total dose should not exceed 3 mg/kg or more than 200 to 300 mg during a one hour period medications zanaflex buy cordarone with amex. For a child: 1 mg/kg initial bolus intravenously; followed by a continuous infusion of 20 to 50 mcg/kg/min medicines360 buy cordarone 250 mg line. Even after recovery medicine 5e order cordarone online now, symptoms can persist for a prolonged period because of persistent metabolites symptoms thyroid problems cheap 200 mg cordarone overnight delivery. Chapter 22 mexiletine and Tocainide Mexiletine (mexiletene) and tocainide are analogues of lignocaine with modified structures (to enable them to be administered orally for long periods) medicine world buy cheap cordarone 250mg line. Both drugs have been used for ventricular arrhythmias with varying degree of success 5 medications post mi buy cordarone 250 mg low price. Its primary use is as a Class 1B antiarrhythmic drug with electrophysiologic properties in man similar to lignocaine, but dissimilar from quinidine, procainamide, and disopyramide. Tocainide is rarely employed in practice because of the potential risk of bone marrow aplasia and pulmonary fibrosis. Mexiletine was originally introduced as an anorectic agent but is no more used for that purpose today. Mexiletine is rapidly and well absorbed (greater than 90%) when administered orally. Mexiletine is highly protein-bound (70%), and also has a high volume of distribution (5. Diuretics, Antihypertensives and Antiarrhythmics Lignocaine (Lidocaine)* Lignocaine is an aminoacyl amide, and is a synthetic derivative of cocaine. Rare cases of severe hepatic necrosis have been reported during therapeutic use of mexiletine. Acute overdose: a Vertigo, paraesthesias, hypotension, nausea, drowsiness, disorientation, bradycardia, heart block, torsades de pointes, asystole, convulsions, hypokalaemia. Toxicokinetics Lignocaine is generally given intravenously, and is 50% bound to protein with an apparent volume of distribution of 1. Blood levels of more than 5 mcg/ml are associated with serious toxicity, and more than 15 mcg/ml with death. Vertigo, drowsiness, confusion, ataxia, dysarthria, hearing loss, visual disturbances, agitation, fasciculations, convulsions, cardiovascular collapse, and coma. Atropine (1 mg intravenously and repeat in 3 to 5 minutes if asystolic cardiac arrest persists) for bradycardia. Insertion of a temporary pacemaker is the treatment of choice for bradyarrhythmias induced by drugs of this class. Although urinary acidification will enhance the renal clearance of mexiletine, it is unlikely to be of clinical significance, and risks aggravating acidaemia and other adverse renal effects in convulsing patients outweigh theoretical benefit. 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, coma and mania have also been reported. Lignocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Sodium loading: molar sodium lactate, sodium bicarbonate, or hypertonic saline may be administered. Serum alkalinisation with sodium bicarbonate may be useful in treating arrhythmias. A reasonable starting dose is 1 to 2 mEq/kg as an intravenous bolus, repeated as needed to maintain arterial pH 7. There are a few cases reported of beneficial effects following the use of infused adrenaline and temporary internal pacemaker. Propafenone is structurally related to propranolol and is administered orally for the treatment of life-threatening ventricular arrhythmias. It can have proarrhythmic effects and its use is not recommended in lesser ventricular arrhythmias. It is 95% absorbed, peaks in 2 to 3 hours, has a plasma halflife varying from 2 to 32 hours, and less than 1% is excreted unchanged in the urine. Propafenone is metabolised by the cytochrome P-450 pathway which produces the major metabolites 5-hydroxy propafenone and N-desalkyl propafenone. Constipation and nausea have been commonly reported side effects with propafenone therapy. Amiodarone Amiodarone (3,5-Diiodophenyl ketone hydrochloride) is an iodinated benzofuran derivative with a structural similarity to thyroxine. Bioavailability on oral administration is low (28 to 50%), with peak plasma levels achieved 3 to 8 (range 2 to 12) hours after therapeutic doses. Amiodarone is extensively distributed, with concentrations in the skin, skeletal muscle, adipose tissue, lung, liver, and myocardium. Its major metabolite is desethylamiodarone, and the principal route of elimination is by hepatic excretion into the bile where it may get concentrated upto 50 times that of the serum. Mode of Action Prolongs the action potential duration of myocardial cells without altering the resting membrane potential. Non-competitive alpha and beta sympathetic receptor blockade resulting in vasodilation. Adverse Effects and Clinical (Toxic) Features Rapidly progressive adult respiratory distress syndrome. Symptoms develop either acutely, resembling an infectious pneumonitis, or slowly with cough, dyspnoea, and weight loss. Pulmonary toxicity (interstitial pneumonitis or pulmonary fibrosis) may manifest as dyspnoea, cough, fever, chest pain, malaise, weakness, anorexia, weight loss, and abnormal pulmonary function tests following amiodarone therapy. Haemoptysis, an unusual adverse effect of amiodarone therapy, is associated with amiodarone-induced pulmonary toxicity. Hypo- or hyperthyroidism: Both hypo-and hyperthyroidism have been reported during chronic therapy. Amiodarone has been demonstrated to cause congenital myxoedema in infants born of amiodarone-treated women. Hepatotoxicity: Transient liver enzyme elevations may occur with chronic use, but are often asymptomatic. Signs and symptoms may include hepatomegaly, ascites, abdominal pain, nausea, vomiting, anorexia, and weight loss. Prolonged exposure to sunlight after 6 to 39 months of chronic amiodarone therapy may result in blue or purple skin discolouration (pseudocyanosis). Cutaneous hyperpigmentation occurs in 1 to 5% of patients taking therapeutic doses of amiodarone. Photosensitivity reactions consisting of burning, flushing, urticaria, maculopapular eruptions, alopecia, erythema and skin blisters have been reported after brief exposure to sunlight in patients receiving amiodarone for as little as one week. Peripheral neuropathy: Proximal muscle weakness, myopathy, and myalgias have been noted in conjunction with neuropathies. Malaise, fatigue, tremors, lack of co-ordination, abnormal gait, ataxia, dizziness, and/or paraesthesia can occur in up to 4 to 9% of patients receiving amiodarone. Corneal microdeposits: Benign pigmented corneal micro-deposits occur in 76 to 100% of patients receiving chronic therapy. Visual disturbances such as blurred vision, coloured halos or photophobia may accompany these changes. A typical symptom is described as blue-green coloured rings or halos around surrounding light sources. Blue-white opacities can occur in the anterior subcapsular region of the lens following amiodarone therapy. These changes may develop in 50 to 60% of the patients receiving therapy and are not reversible with drug cessation. In substantial overdose, bradycardia and/ or heart block, torsades de pointes and hypotension should be anticipated. Amiodarone administration in pregnancy may result in neonatal hypothyroidism and prematurity. Perform stomach wash only while cardiac monitoring is done, since profound bradycardia can occur. Oral cholestyramine (4 grams every hour for 4 hours) may help in reducing the half-life of amiodarone. Pulmonary toxicity responds to corticosteroids, but rapid withdrawal may lead to recurrence. Chest X-ray findings in patients with amiodarone-induced pulmonary toxicity are nonspecific, including areas of consolidation, infiltrates, and interstitial disease. Beta-adrenergic agonists such as isoproterenol or ephedrine may be helpful in cases of sinus arrest. Adenosine (9-beta-D-ribofuranosyladenine) is a nucleotide found in all cells, and is released from myocardial cells under various physiological and pathological conditions. As an intermediate metabolite in several biochemical pathways, adenosine contributes to the regulation of numerous physiologic processes, including platelet Section 6 function, coronary and systemic vascular tone, and lipolysis in adipocytes. Adenosine, an endogenous coronary vasodilator, is used in a continuous infusion (0. Adenosine causes more vasodilation in normal coronary arteries, leading to increased thallium uptake in normal myocardium versus ischaemic areas. Adenosine acts by decreasing spontaneous depolarisation in the sinus node and conduction velocity in the A-V node. Its direct negative chronotropic and dromotropic properties are the basis for its wide therapeutic application in patients with supraventricular tachycardia. Total clearance from plasma occurs in less than 30 seconds following intravenous administration. Adenosine is rapidly cleared from the plasma by cellular uptakes, particularly by erythrocytes, vascular endothelial cells, and cardiomyocytes. Within cells, adenosine is rapidly degraded to inosine by adenosine deaminase and subsequently to hypoxanthine. Cutaneous flushing, dyspnoea, chest pain, nausea, vomiting, vertigo, headache, hypotension, and proarrhythmias. Occasionally there may be minimal cardiac adverse effects including atrial fibrillation, atrial flutter, bradycardia, and angina-like chest pain at doses as high as 23 milligrams. It is thought that adenosine can produce bronchoconstriction by enhancing IgE-dependant release of pre-formed mediators from mast cells. Until further data are available, adenosine should be used with caution in asthmatic patients. Adenosine triphosphate: May be associated with a higher incidence of adverse effects than adenosine. Noncardiac adverse effects include flushing, malaise, hyperpnoea, headaches, retching, vomiting, seizures (rare), and coughing. Significantly lower doses of adenosine should be administered to patients receiving dipyridamole. Adenosine may not be effective in patients receiving methylxanthines; methylxanthines are competitive antagonists of adenosine and can completely block the electrophysiologic effects of the drug. If adenosine is used to treat patients with toxic concentrations of calcium channel blockers, prolonged bradycardia may occur. Mechanisms of adenosine-mediated actions on cellular and clinical cardiac electrophysiology. The duration of electrophysiologic and clinical effects with adenosine is extremely short, usually less than 10 seconds, due to rapid cellular uptake and metabolism. The incidence of adverse effects with adenosine triphosphate can be reduced with the use of smaller initial doses (10 mg). The common name of this plant is foxglove, and it grows well in the hilly regions of Darjeeling, Nilgiris, and Kashmir. It is a biennial or perennial herb belonging to family Scrophulariaceae, growing upto 1 to 1. There is a related species, Digitalis lanata, which is also rich in cardiac glycosides. The following discussion will be mainly with reference to the digitalis glycosides digoxin and digitoxin, which are the most widely used cardiac glycosides. Cardiac Glycosides Diuretics Vasodilators Beta Adrenergic Receptor and Dopaminergic Receptor Agonists 6. The following discussion is restricted only to those drugs which have not been dealt with so far. Uses Treatment of mild to moderate heart failure Control of ventricular response rate in patients with chronic atrial fibrillation. Digoxin increases left ventricular ejection fraction resulting in improvement of heart failure symptoms. Digoxin is often used in conjunction with a diuretic and an angiotensinconverting enzyme inhibitor for the treatment of heart failure. Massive acute cardiac glycoside overdose differs significantly from chronic toxicity. In acute overdose, the sodium-potassium pump is poisoned, producing a fall in intracellular potassium and a rise in extracellular potassium, which may be marked. The normal membrane resting potential is reduced, and electrical conduction is slowed, with eventual complete loss of myocardial electrical function. Clinically this results in high grade heart block, and eventually in asystole, which may not respond to electrical pacing. The most serious arrhythmias are ventricular tachycardia and ventricular fibrillation. Eye: Transient amblyopia, blurred vision, scotomata, photophobia, and chromatopsia. Toxicity is increased by diuretics (except potassiumsparing) and corticosteroids, because of hypokalaemia.

Monitor fluid and electrolyte status in patients with significant nausea and vomiting medicine daughter lyrics cheap cordarone 250mg on-line. Significant toxicity is not anticipated after ingestion because of limited bioavailability medicine 3604 order cordarone 250 mg fast delivery. Classification Metoclopramide Metoclopramide is a benzamide analogue symptoms miscarriage buy generic cordarone from india, and is structurally related to procainamide medicinenetcom 200 mg cordarone with mastercard, but lacks local anaesthetic and antiarrhythmic actions treatment ringworm discount cordarone online. Metoclopramide enhances the motility of smooth muscle of oesophagus medications listed alphabetically purchase cordarone with american express, stomach, and upper small intestine, leading to an acceleration of gastric emptying and intestinal transit. Metoclopramide is used in the treatment of gastroesophageal reflux, gastric stasis, vascular headache (adjunct treatment) and persistent hiccups. It is also useful for managing diabetic gastroparesis, oesophageal reflux, and vomiting, including that due to postoperative- and cancer chemotherapy-related. Bromopride is used as an antiemetic, and for the treatment of various gastrointestinal disorders, similar to metoclopramide. Adverse effects include drowsiness, vertigo, anxiety, extrapyramidal effects (tremors, agitation, parkinsonian syndrome). Overdose results in increased muscle tone, opisthotonus, torticollis, trismus, cog-wheel rigidity, grimacing, extrapyramidal reactions, confusion, irritability, panic-like reactions, agitation, nystagmus, strabismus, conjugate deviation of eyes, and convulsions. Methaemoglobinaemia has also been reported, as well as rare reports of sulfhaemoglobinaemia. Acute dystonic reactions are more common in children and young adults, whereas prolonged reactions such as tardive dyskinesia, and parkinsonism are more common in elderly patients. Bile Acids and Pancreatic Enzymes Bile Acids Bile acids are constituents of bile and are synthesised from cholesterol. After being secreted, they are largely reabsorbed in the ileum and recycled via an enterohepatic cycle. Examples include cholic acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid. Adverse effects include diarrhoea, pruritis, dry skin, sweating, hair thinning, nausea, dyspepsia, myalgia, rhinitis, insomnia. They are used in cases of pancreatic enzyme insufficiency, such as that found in cystic fibrosis. Examples include pancreatin and pancrelipase, which contain amylase, lipase, and protease. They are used in the treatment of chronic pancreatitis and pancreatic insufficiency. Perianal irritation, particularly in infants, has been reported with therapeutic use. Many of these products are made from hog pancrease, and hence, individuals sensitive to pork protein may experience allergic reactions. Pancreatic alpha amylase and trypsin have been determined to be two of the causative allergens. Toxicity is uncommon, but there have been cases of hypersensitivity after inhalation, anal irritation, and oral irritation when the tablets are held in the mouth. Asthma, bronchial hypersensitivity, and pulmonary hypersensitivity have been reported after exposure to the powder in both home and occupational settings. Fibrosing colonopathy have been reported in children with cystic fibrosis following long-term pancreatin therapy, with the majority of patients receiving high-dose preparations. It has been theorised that delayed gastrointestinal transit time and prolonged exposure of the colon to high-strength pancreatic enzymes in cystic fibrosis patients may be associated with the development of fibrosing colonopathy in these patients. In general, pancreatic enzyme tablets are low in toxicity and are not expected to produce serious overdose effects. Patients should be monitored for irritation of the gastrointestinal tract, possible hypersensitivity reactions, and increased uric acid in the blood and urine. Dilution may be indicated following ingestion of large amounts in order to reduce irritation. Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion. Symptoms of gigantism and/or acromegaly may be observed following long-term overdosage. Prolactin Prolactin is synthesised and secreted not only by the pituitary, but also by decidual cells in the terminal luteal phase of the menstrual cycle. On the other hand, excessive secretion of prolactin (hyperprolactinaemia) can cause problems such as galactorrhoea, amenorrhoea, and infertility in women, and impotence, gynaecomastia, and infertility in men. Causes of hyperprolactinaemia include disorders of hypothalamus or pituitary, renal failure, primary hypothyroidism, and the use of dopaminergic antagonists. Treatment is accomplished by administering dopaminergic drugs such as bromocriptine. The usual mode of administration is subcutaneous injection, though it can also be given intramuscularly. Somatropin is a biosynthetic polypeptide hormone with an amino acid sequence identical to that of human growth hormone. It has the identical sequence of 191 amino acids constituting pituitary-derived human growth hormone and an additional amino acid, methionine, on the N-terminus of the molecule. The commercial preparation is administered after reconstitution with bacteriostatic water for injection, containing benzyl alcohol as an antimicrobial preservative. Section 9 Thyroid and Antithyroid Drugs Thyroid Hormone Major therapeutic use of thyroxine is as hormone replacement therapy for hypothyroidism and cretinism. Natural (desiccated thyroid and thyroglobulin) thyroid hormone is available to treat hypothyroid disease states and thyroid cancer. Synthetic preparations of thyroid hormone include Levothyroxine sodium (T4) and Liothyronine sodium (T3). Liotrix is a mixture of thyroxine and tri-iodothyronine (4 parts T4 to 1 part T3). Both hormones (T3 and T4) are metabolised primarily by deiodination with only 20% of the hormone excreted in the faeces intact or conjugated. Adverse effects include exacerbation of angina, arrhythmias, and provocation of myocardial infarction. Tremor, sweating, headache, flushing, tachycardia, and palpitations have been reported. Toxicity following massive overdosage may occur within 12 to 24 hours if a tri-iodothyronine (T3) containing product has been ingested. Acute ingestions of levothyroxine result in Adverse Effects Pain at the injection site. Intracranial hypertension: Benign intracranial hypertension with papilloedema (visual changes, headache, nausea and vomiting) has been reported in several patients treated with growth hormone products. Symptoms usually occurred within the first 8 weeks of therapy and resolved upon discontinuation of the therapy, or a reduction of the growth hormone dose. Local reactions at injection site including pain, numbness, * Adrenocorticotropic hormone is discussed in a subsequent section (page no 481). Adults rarely experience symptoms with one-time ingestions of at least 6 grains desiccated thyroid (usual adult dose is 1. The following signs and symptoms have occurred in overdose cases: vomiting, diarrhoea, abdominal pain, fever, tachycardia, palpitations, hypertension, increased sweating, congestive heart failure, and cardiac arrhythmias. Pulmonary oedema, presenting as sudden dyspnoea several days after overdose, requiring endotracheal intubation, has been reported after tri-iodothyronine overdose. Symptoms may be delayed up to 10 to 15 days, and hence keeping the patient under observation is important. Mild hypertension may occur due to adrenergic discharge resulting in hyperthyroidism. Chronic intake causes weight loss, myocarditis, angina, and ventricular arrhythmias. Thyrotoxicosis is fairly common after chronic overdoses of T3 and T4, but is generally unusual following acute ingestions. Thyroid compounds may induce myocarditis in chronic overdoses and can be associated with sudden death in the presence of coronary artery disease. Other examples include methimazole and carbimazole, which are organic thiourea antithyroid drugs included in the chemical class of mercaptoimidazolines. Carbimazole is rapidly and completely metabolised to methimazole in the body, with the antithyroid activity of carbimazole dependant upon this conversion to methimazole. Antithyroid drugs inhibit the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. They also inhibit the coupling of these iodotyrosyl residues to form iodothyronines by inhibiting the peroxidase enzyme. In addition to blocking hormone synthesis, propylthiouracil (unlike other antithyroid drugs) inhibits the peripheral deiodination of thyroxine to tri-iodothyronine. However, consider administration of activated charcoal after a potentially toxic ingestion. Cholestyramine (4 grams orally every 6 to 8 hours) to block the enterohepatic circulation of thyroid hormone. Sodium ipodate and iopanoic acid have been advocated as effective and safe alternatives for the treatment of hyperthyroidism. Arthralgia: Arthritis syndrome, which is rare, is generally transient, occurring within 2 months of initiation of therapy and resolving within 4 weeks of stopping therapy. Following therapeutic use of carbimazole or methimazole, dizziness, paresthesias, and headache have been described occasionally. Methimazole therapy has uncommonly been reported to be related to the occurrence of T-lymphotropic virus type I-associated uveitis, with vitreous opacities and retinal vasculitis. Reversible nephrotic syndrome has been observed in a very few patients during therapy with methimazole or carbimazole. It is likely that this is the result of a direct toxic effect on the glomerular basement membrane and epithelial podocytes. Carbimazole hypersensitivity resulting in the development of antibodies to connective tissue or neural antigens in the cochlea has been reported. Clinical signs/symptoms of overdose with carbimazole or methimazole may include manifestations of hypothyroidism, including nausea and vomiting, constipation, headache, drowsiness, coldness, dry and puffy skin, muscle aches, and goitre. Very little data are available on the effects of acute overdose with propylthiouracil. Decreased T3 and elevated alkaline phosphatase levels were the only effects seen after a massive overdose in a young girl. Chronic overdose may result in clinical hypothyroidism (nausea and vomiting, constipation, headache, drowsiness, coldness, dry and puffy skin, muscle aches). Propylthiouracil is transferred across the placenta and can induce goitre and hypothyroidism in the unborn. The administration of propylthiouracil to the mother from the 14th week of pregnancy or later has been of concern because of the possible development of goitre and mental retardation in the infant. Incidence of birth defects was not significantly higher in children of women who had been treated with propylthiouracil during pregnancy. Methimazole crosses the placental membrane readily and can induce goitre and cretinism in the developing foetus. Congenital defects such as aplasia cutis (manifested by scalp defects), oesophageal atresia with tracheoesophageal fistula, and choanal atresia with absent/hypoplastic nipples have occurred rarely in infants exposed to methimazole in utero. Most adverse effects are dose-related and occur within the first 4 to 8 weeks of therapy. Chronic propylthiouracil use has been linked with acute myeloblastic leukaemia in isolated cases. Administration of recombinant human granulocyte colony-stimulating factor may hasten recovery. Treatment with these drugs has been shown to significantly shorten recovery time in patients with methimazole-induced agranulocytosis. Infection or fever in neutropenic patients should be treated aggressively with antibiotics. Appropriate broad-spectrum antibiotics should probably be initiated before culture results are known. Haemodialysis, peritoneal dialysis, forced diuresis, or charcoal haemoperfusion have not been shown to be beneficial in overdose with these agents. Oestrogens, Progestins, and their Antagonists Oestrogens Oestrogens are hormones secreted primarily by the ovarian follicles and also by the adrenals, corpus luteum, placenta and testes, or they are synthetic steroidal and non-steroidal compounds. Following intramuscular administration of aqueous suspensions or oil solutions, absorption begins promptly and continues for several days. Natural, unconjugated oestrogens are inactivated in the gastrointestinal tract and liver following oral administration. Conjugated oestrogens, some synthetic derivatives and the non-steroidal oestrogens can be administered orally. Oestrogens are widely distributed throughout most body tissues with the greatest concentrations in fat deposits. Endogenous oestrogens appear in the urine as glucuronides and sulfates of oestradiol, oestrone, and oestriol. The steroids and their metabolites are conjugated which increases their water solubility and facilitates excretion into the urine, which is the primary route of excretion. Elevations in alkaline phosphatase do not necessarily reflect liver toxicity and may be related to increased bone or bile isoenzyme. Total and differential leukocyte counts should be performed in patients with suspected haematologic reactions. Steroidal oestrogens-oestradiol, ethinyl oestradiol, polyestradiol mestranol, quinestrol, estrone, equilin, equilenin. Adverse Effects Carcinogenicity: Oral contraceptives can increase the risk of breast cancer, (controversial). Post-menopausal women taking unopposed oestrogen or taking oestrogen combined with progestin have an increased risk of breast cancer compared with post-menopausal women taking no hormone replacement therapy.

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