Symptoms of toxicity

Nurses must carefully monitor the patient s blood levels of drugs to ensure that they remain within the therapeutic range Any deviation should be reported to the primary health care provider. Because some dragp can cause toxic reactions even in recommended doses, the nurse should be aware of the signs and symptoms of toxicity of commonly prescribed drugs. 

The incidence of adverse reactions appears to be higher when larger doses of isoniazid are prescribed. Adverse reactions include hypersensitivity reactions, hematologic changes, jaundice, fever, skin eruptions, nausea, vomiting, and epigastric distress. Severe, and sometimes fatal, hepatitis has been associated witii isoniazid tiierapy and may appear after many months of treatment. Peripheral neuropathy (numbness and tingling of the extremities) is the most common symptom of toxicity. 

The nurse monitors the patient taking isoniazid for toxicity. The most common symptom of toxicity is... 

The nurse monitors the alcoholic patient taking acetaminophen for symptoms of toxicity, which include... 

The onset of symptoms of barbiturate toxicity may not occur until several hours after the drug is administered. Symptoms of acute toxicity include CNSand respiratory depression, constriction or paralytic dilation of the pupils tachycardia, hypotension, lowered body temperature, oliguria, circulatory collapse, and coma. The nurse should report any symptoms of toxicity to the primary health care provider immediately. 

Digitalis toxicity can occur even when normal doses are being administered or when the patient has been receiving a maintenance dose Many symptoms of toxicity are similar to tiie symptoms of the heart conditions for which tiie patient is receiving the cardiotonic. This makes careful assessment of the patient by the nurse a critical aspect of care... 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

Clinical signs and symptoms of toxicity are related to the overstimulation of muscarinic, nicotinic, and central nervous system receptors in the nervous system. Muscarinic receptors are those activated by the alkaloid drug muscarine. These receptors are under the control of the parasympathetic nervous system, and their hyperactivity results in respiratory and gastrointestinal dysfunction, incontinence, salivation, bradycardia, miosis, and sweating. Nicotinic receptors are those activated by nicotine. Hyperactivity of these receptors results in muscle fasciculations even greater stimulation results in blockade and muscle paralysis (Lefkowitz et al. 1996 Tafliri and Roberts 1987). Hyperactivity of central nervous system receptors results in the frank neurological signs of confusion, ataxia, dizziness, incoordination, and slurred speech, which are manifestations of acute intoxication. Muscarine and nicotine are not... 

TCDF is not very toxic to the mouse (acute oral LDjq < 6000 pg/kg) but is highly toxic to the guinea pig (acute oral LD50 5-10 pg/kg). Symptoms of toxicity in the gninea pig were similar to those fonnd with 2,3,7,8-TCDD. Thus, the selectivity pattern was similar to that for 2,3,7,8-TCDD, but toxicity was considerably less (see Environmental Health Criteria 88). 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

There is only a limited capacity to metabolize vitamin A, and excessive intakes lead to accumulation beyond the capacity of binding proteins, so that unbound vitamin A causes tissue damage. Symptoms of toxicity affect the central nervous system (headache, nausea. 

To determine the toxicity of parathion to warmblooded animals, tests were made with mice, rats, guinea pigs, rabbits, and dogs. Greatest hazards are associated with insecticidal use, but symptoms of toxicity may be detected well in advance of severe toxic actions. 

Based upon the available data, derivation of AEGL-1 values was considered inappropriate. The continuum of arsine-induced toxicity does not appear to include effects consistent with the AEGL-1 definition. The available human and animal data affirm that there is a very narrow margin between exposures that result in little or no signs or symptoms of toxicity and those that result in lethality. The mechanism of arsine toxicity (hemolysis that results in renal failure and death), and the fact that toxicity in humans and animals has been reported at concentrations at or below odor detection levels (-0.5 parts per million (ppm)) also support such a conclusion. The use of analytical detection limits (0.01 to 0.05 ppm) was considered as a basis for AEGL-1 values but was considered to be inconsistent with the AEGL-1 definition. 

Daily dose of 3 mg for 2 weeks may cause severe poisoning in infants, and symptoms of toxicity in adults... 

Increased plasma concentrations of TCAs and symptoms of toxicity may occur when fluoxetine and paroxetine are added to a TCA regimen. 

Deaths as the result of acute exposure by ingestion of endrin have been observed in humans in a variety of incidents. In 1967, in Doha, Qatar, and Hofuf in Saudi Arabia, 874 people were hospitalized after an acute exposure to endrin-contaminated flour which resulted in 26 known deaths (Weeks 1967). Deaths occurred within 12 hours of the onset of symptoms of toxicity (convulsions, loss of consciousness, headache, nausea, vomiting) however, recovery of survivors was rapid. Concentrations of endrin in bread eaten by victims ranged from 48 to 1,807 ppm (Curley et al. 1970). The contaminated flour used to make the bread contained 2,153-3,367 ppm endrin. 

With an approved IND, the drug company can place me in humans at lower doses, mainly to observe any overt symptoms of toxicity and to evaluate my PK characteristics, and the study may use 10 to 20 healthy subjects. These data are then resubmitted to FDA (Phase 1). After my Phase I is completed, drug testing begins for my clinical efficacy, with trials at different doses and given to different populations under strict supervision. A successful study may require a few thousand patients and the involvement of several study centers across the country (or perhaps across the world) to collect extensive data. It is not unusual to have 100,000 patients take me before the data are submitted to the FDA for drug approval — the so-called marketing approval. 

There has been only one report of industrial poisoning, a fatality caused by very high vapor inhalation in a small enclosure. The isomeric concentration of the vapor was not reported, nor were the level and duration of the exposure or symptoms of toxicity. In another early report, exposure to the trans isomer at 2200ppm caused nausea, drowsiness, fatigue, vertigo, and increased intracranial pressure in two human subjects. ... 

In a plant, 21 workers were exposed at different times to TEL and then to TML under similar conditions for similar periods of time. TML had three times the airborne level found during TEL production, yet the urinary lead levels were nearly the same in both cases this suggests that TML is absorbed more slowly then TEL. No signs or symptoms of toxicity were noted. 

In mice and male rats, the oral LD50 was approximately 4g/kg symptoms of toxicity were ataxia and hyperactivity followed by inactivity, loss of muscular tone, labored breathing, clonic convulsions, and death within 2-7 days. Daily administration of 132mg/kg body weight in the diet for 13 weeks decreased the fertility of CD rats 14 days at 96mg/kg altered the estrous cycle of females." In female rats 50 mg/kg injected intraperitoneally on the day of proestrus delayed ovulation and resulted in a lower fertility rate, a reduction of live fetuses, an increase in resorptions, and a slower rate of fetal development. Gavage doses in rats of... 

Obtain cultures Obtain cultures and determine susceptibility before treatment. Determine blood levels Determine blood levels weekly for patients having reduced renal function, for individuals receiving more than 500 mg/day, and for those with symptoms of toxicity. Adjust dosage to maintain blood level less than 30 mcg/mL. Anticonvulsant drugs or sedatives Anticonvulsant drugs or sedatives may be effective in controlling symptoms of CNS toxicity, such as convulsions, anxiety, and tremor. Closely observe patients receiving more than 500 mg/day for such symptoms. Pyridoxine may prevent CNS toxicity, but its efficacy has not been proven. 

Movsas B, Scott C, Sause W, et al. Age dramatically impacts on the quality-adjusted time without symptoms of toxicity (Q-Twist) in locally advanced non-small cell lung cancer - A Radiation Therapy Oncology Group (RTOG) analysis. Proc Am Soc Thera Rad Oncol (ASTRO). IJROBP 2000 48 92A (abstr). 

Health professionals may be asked to provide an opinion of the cause and effect relationship between exposure to a xenobiotic and an adverse health effect ranging from symptoms of toxicity to death. Certain principles, including an assessment of temporality, should be considered in such an evaluation. Do the... 

Toxicity Serum electrolytes (especially potassium), renal function tests, BP, ECG (hyperkalemia), signs and symptoms of toxicity... 

Lipid profile, LFTs, serum CPK, electrolytes, blood glucose, signs and symptoms of toxicity (GI symptoms, headache, rash) pattern of daily bowel activity and stool... 

Bone mass density (T-score, hip, spine), N-telopeptide serum calcium (adjusted forhypoalbuminemia), phosphorus, magnesium, renal function, liverfunction, serum electrolytes, signs and symptoms of toxicity (i.e., esophageal irritation)... 

Notify the physician if signs and symptoms of toxicity, including blurred vision, diarrhea, nausea, dizziness, flu-like symptoms, or headache... 

Other symptoms of toxicity that can be seen include sedation or paradoxical excitability, signs of anticholinergic blockade including delirium and tachycardia, dry skin, blurred vision, hyperpyrexia, and flushing of the skin, and seizures. 

It soon became evident that no available antidotes could block the pharmacologic activity of these chemicals, alleviate the signs and symptoms of toxicity, or restore normal bodily functions after exposure. Atropine readily antagonized the muscarinic actions, including those in the central nervous system (CNS), but elicited no reversal of the nicotinic effects. Better forms of therapy were sought, particularly to alleviate the nicotinic effects of anticholinesterase agents. 

The elimination of phenytoin is dose-dependent. At very low blood levels, phenytoin metabolism follows first-order kinetics. However, as blood levels rise within the therapeutic range, the maximum capacity of the liver to metabolize phenytoin is approached. Further increases in dosage, though relatively small, may produce very large changes in phenytoin concentrations (Figure 24-5). In such cases, the half-life of the drug increases markedly, steady state is not achieved in routine fashion (since the plasma level continues to rise), and patients quickly develop symptoms of toxicity. 

The therapeutic blood level is greater than 150 mg L-1 but symptoms of toxicity occur at blood levels of around 300 mg L-1. Therefore, knowledge of the blood level is important, particularly when aspirin is given in repeated doses. In children, therapeutic overdosage is responsible for the majority of fatalities from aspirin. When an overdose is suspected, measurement of the plasma level on two or more occasions will allow an estimate to be made of the severity of the overdose and whether the plasma level has reached its maximum. For interpretation of the blood level, the Done nomogram can be used. An overdose of 50 to 300 mg tablets in adults will give rise to moderate to severe toxicity and a blood level of 500 to 750 mg L-1 at 12 hours. The blood level must be interpreted with caution, however, because... 

Depending upon the type and concentration of the herbicides, a range of activity from little impact on plant growth to severe symptoms of toxicity were found [114] and these varied effects proved to be associated with marked changes in secondary metabolism. 

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