Excretion overdose

Reported cases of vitamin toxicity owing to overdose are usually associated with increased over-the-counter availabiHty of supplemental vitamins and indiscriminate supplementation. The misconception that if a Httle is good a lot is better has compounded toxicological problems with the vitamins. Eat-soluble vitamins tend to accumulate in the body with relatively inactive mechanism for excretion and cause greater toxicological difficulties than do water-soluble vitamins. 

Lithium toxicity can occur as a result of intentional overdose therefore, care must be taken when administering lithium to potentially suicidal patients with BPAD. Inadvertent lithium toxicity may also occur. For example, diuretics and nonsteroidal anti-inflammatory drugs such as ibuprofen (Advil, Motrin) slow the excretion of lithium and can lead to accidental toxicity. Consequently, the patient should be advised not to take such commonly available medications while treated with lithium. In addition, dehydration resulting from varied causes such as diarrhea, vomiting, and profuse sweating can lead to accidental lithium toxicity. One should advise the patient who takes lithium to be careful to remain well hydrated at all times and to contact his/her physician if any medical condition arises that may cause rapid fluid losses (e.g., stomach virus, high fevers). 

Since only a few vitamins can be stored (A, D, E, Bi2), a lack of vitamins quickly leads to deficiency diseases. These often affect the skin, blood cells, and nervous system. The causes of vitamin deficiencies can be treated by improving nutrition and by administering vitamins in tablet form. An overdose of vitamins only leads to hypervita mi noses, with toxic symptoms, in the case of vitamins A and D. Normally, excess vitamins are rapidly excreted with the urine. 

In foods vitamin B2 occurs free or combined both as FAD and FMN and complexed with proteins. Riboflavin is widely distributed in foodstnffs, but there are very few rich sources. Only yeast and liver contain more than 2mg/100g. Other good sources are milk, the white of eggs, fish roe, kidney, and leafy vegetables. Since riboflavin is continuously excreted in the urine, deficiency is qnite common when dietary intake is insufficient. The symptoms of deficiency are cracked and red lips, inflammation of the lining of the month and tongue, mouth ulcers, cracks at the comer of the mouth, and sore throat. Overdose of oral intake present low toxicity, probably explained by the limited capacity of the intestinal absorption mechanism [417]. 

What the body does to the drugs which enter the system may be referred to as pharmacokinetics. During a drug overdose and subsequent intoxication, the various parameters for pharmacokinetics are altered, and these will include changes in elimination half-lives, protein binding, saturation kinetics and excretion. These deviations from the normal pharmacokinetics may be referred to as toxicokinetics. 

Effects of pH on urinary drug elimination may have important applications in medical practice, especially in cases of overdose. For example, one can enhance the elimination of a barbiturate (a weak acid) by administering bicarbonate to the patient. This procedure alka-linizes the urine and thus promotes the excretion of the now more completely ionized drug. The excretion of bases can be increased by making the urine more acidic through the use of an acidifying salt, such as ammonium chloride. 

Mechanism of Action An intratracheal respiratory inhalant that splits the linkage of mucoproteins, reducingtheviscosityof pulmonary secretions.Tiierapeutic Effect Facilitates the removal of pulmonary secretions by coughing, postural drainage, mechanical means. Protects against acetaminophen overdose-induced hepatotoxicity. Pharmacokinetics Protein binding 83% (injection). Rapidly and extensively metabolized in liver. Deacetylated by the liver to cysteine and subsequently metabolized. Excreted in urine. Half-life 5.6 hr (injection). 

Pharmacokinetics Onset of action is about 10 min and duration of action is 7 hr or more. Absorption occurs from the nasal mucosa and can produce systemic effects, primarily following overdose or excessive use. Excreted mostly in the urine as well as the feces. Half-life 5-8 hr. 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

Na/K/2CI transporter in the ascending limb of Henle s loop excretion, some wasting, hypokalemic metabolic alkalosis, increased urine Ca and Mg peripheral edema, hypertension, acute hypercalcemia or hyperkalemia, acute renal failure, anion overdose duration of action 2-4 h Toxicitiy Ototoxicity, hypovolemia, wasting, hyperuricemia, hypomagnesemia... 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

The half-life will be independent of the dose, provided that the elimination is first order and therefore should remain constant. Changes in the half-life, therefore, may indicate alteration of elimination processes due to toxic effects because the half-life of a compound reflects the ability of the animal to metabolize and excrete that compound. When this ability is impaired, for example, by saturation of enzymic or active transport processes, or if the liver or kidneys are damaged, the half-life may be prolonged. For example, after overdoses of paracetamol, the plasma half-life increases severalfold as the liver damage reduces the metabolic capacity, and in some cases, kidney damage may reduce excretion (see chap. 7). 

The blood pH may return to normal in adults with mild overdoses. However, the blood pH can drop too far in children or more severely poisoned adults, resulting in metabolic acidosis. A lower buffering capacity or plasma protein-binding capacity may underlie the increased susceptibility to acidosis in children. Excretion of bicarbonate also means the bicarbonate in the blood is lower, and hence, there is an increased likelihood of metabolic acidosis. 

Figure 7.59 The effect of pH on the dissociation, distribution, and excretion of salicylic acid. The numbers represent the proportions of ionized and nonionized salicylic acid. The small horizontal arrows indicate the situation after overdose and the lower pH.

Urine pH is an important determinant of renal elimination of PCP. In a study in which urine pH was uncontrolled (6.0 to 7.5), the average total clearance of PCP was 22.8 4.8 L/h after intravenous administration.4 In the same study, renal clearance was 1.98 0.48 L/h. When the urine was made alkaline, the renal clearance of PCP was found to decrease to 0.3 0.18 L/h. If the urine was acidified (pH 6.1) in the same subjects, renal clearance increased to 2.4 0.78 L/h.13 Aronow et al.14 determined that if the urine pH was decreased to <5.0, renal clearance increased significantly to 8.04 1.56 L/h. There is disagreement about the utility of urine acidification in the treatment of PCP overdose, even though excretion may be increased by as much as 100-fold.15 It should be noted that acidification may increase the risk of metabolic complications.16... 

Cocaine is metabolized very quickly by the body. Within minutes, enzymes in the blood and in the liver split the cocaine molecule into two halves, rendering it inactive. Cocaine and its metabolites are excreted in the urine. The body s efficient metabolism of cocaine causes the high to be relatively short-lived. This often causes cocaine users to take several doses of cocaine in a short time, which can increase the chances of an overdose. 

When overdosing occurs, gastric lavage is advised and an alkaline, high urine output state should be maintained (see Chapter 59 Management of the Poisoned Patient). Hyperthermia and electrolyte abnormalities should be treated. In severe toxic reactions, ventilatory assistance may be required. Sodium bicarbonate infusions may be employed to alkalinize the urine, which will increase the amount of salicylate excreted. 

Methotrexate is administered by the intravenous, intrathecal, or oral route. Up to 90% of an oral dose is excreted in the urine within 12 hours. The drug is not subject to metabolism, and serum levels are therefore proportionate to dose as long as renal function and hydration status are adequate. Dosages and toxic effects are listed in Table 55-3. The effects of methotrexate can be reversed by administration of leucovorin (citrovorum factor). Leucovorin rescue has been used with accidental overdose or experimentally along with high-dose methotrexate therapy in a protocol intended to rescue normal cells while still leaving the tumor cells subject to its cytotoxic action. 

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