Overdoses

The various barbiturates differ m the time required for the onset of sleep and m the duration of their effects All the barbiturates must be used only m strict accordance with instructions to avoid potentially lethal overdoses Drug dependence m some mdi viduals IS also a problem... 

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. 

Sodium bicarbonate is a gastric antacid that may cause systemic alkalosis on overdose and may contribute to edema owing to sodium retention. It is useful for systemic acidosis because both deficient ions are present in the same molecule, and it can be used topically as a moist paste or in solution as an antipmritic. Sodium bicarbonate also is an ingredient of many effervescent mixtures, alkaline solutions, etc. One gram of NaHCO neutralizes 115 mL 0.1 NHCl. 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

The second-generation antidepressants, particularly RIMAs and SSRJs, are much less toxic ia overdose than the older TCAs and irreversible MAO inhibitors. However, similar to first-generation antidepressants, the therapeutic effect only becomes manifest after several weeks. Up to one-third of depressed patients are nonresponders. Ideally, an antidepressant would combine a more rapid onset of action with greater clinical efficacy and a higher responder rate, as well as even better tolerability. 

Health and Safety Factors. Clinical side effects and LD q values of most commercially available analeptics have been summarized (2). Overdoses produce symptoms of extreme CNS excitation, including resdessness, hyperexcitabiUty, skeletal muscle hyperactivity, and ia some cases convulsions. 

Overdose or extended treatment studies in the target species. 

A bacterial maltogenic amylase preparation has unique quaUties as an antistaling agent. Additionally, it cannot be overdosed, which means that there is no risk of obtaining sticky doughs and a gummy cmmb stmcture. 

Chemical Oxidation This process has not been widely utihzed because of its high cost. Onlv wEere the concentration of the target compound is very low will tlie quantity of oxidant required be low enough to justify treatment by chemical oxidation. The efficiency of this process is also low, as many side reactions can occur that will consume the oxidant. In addition, complete oxidation of organics to carbon dioxide and water often will not occur unless a significant overdose is used. However, renewed interest has recently occurred for two reasons. 

A thiazole derivative that incorporates a fragment of the amphetamine molecule shows some CNS stimulant activity more specifically, the compound antagonizes the depression caused by overdoses of barbiturates and narcotics. Reaction of benzalde-hyde with sodium cyanide and benzenesulfonyl chloride gives the toluenesulfony1 ester of the cyanohydrin (141). Reaction of this with thiourea leads directly to aminophenazole (143) It is probable the reaction proceeds by displacement of the tosylate by the thiourea sulfur to give 142 addition of the amino group to the nitrile followed by tautomerization affords the observed product. ... 

Duration and intensity of effect may be dissociated (i.e., duration can be prolonged though receptor compartment loading with no target overdose). 

Antidepressants are used in the treatment of neuropathic pain and headache. They include the classic tricyclic compounds and are divided into nonselective nor-adrenaline/5-HT reuptake inhibitors (e.g., amitriptyline, imipramine, clomipramine, venlafaxine), preferential noradrenaline reuptake inhibitors (e.g., desipramine, nortriptyline) and selective 5-HT reuptake inhibitors (e.g., citalopram, paroxetine, fluoxetine). The reuptake block leads to a stimulation of endogenous monoaminer-gic pain inhibition in the spinal cord and brain. In addition, tricyclics have NMDA receptor antagonist, endogenous opioid enhancing, Na+ channel blocking, and K+ channel opening effects which can suppress peripheral and central sensitization. Block of cardiac ion channels by tricyclics can lead to life-threatening arrhythmias. The selective 5-HT transporter inhibitors have a different side effect profile and are safer in cases of overdose [3]. 

Although flumazenil binds with high affinity to the benzodiazepine site of GABAa receptors, it has practically no action when given alone. However, flumazenil competitively blocks the action of benzodiazepine site agonists. Flumazenil can be used to terminate the action of benzodiazepines, e.g., after a benzodiazepine overdose. It may also serve as a diagnostic tool in this regard. 

Opiate overdose is a medical emergency that can result in respiratory and CNS depression. The opioid receptor antagonist naloxone immediately reverses cardiorespiratory depression. However, repeated naloxone administration is required, since the effects of naloxone last for 30 min, while opioid agonists can remain at potentially lethal blood levels for several hours. 

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