Benzodiazepine respiratory effects

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

Other adverse cardiovascular and respiratory effects Orthostatic hypotension, with or without syncope, can occur with clozapine treatment. Rarely, collapse can be profound and accompanied by respiratory and/or cardiac arrest. Orthostatic hypotension is more likely to occur during initial titration in association with rapid dose escalation. In patients who have had even a brief interval off clozapine, start treatment with 12.5 mg once or twice daily (see Warnings). Because collapse, respiratory arrest, and cardiac arrest during initial treatment have occurred in patients receiving benzodiazepines or other psychotropic drugs, caution is advised when clozapine is initiated in patients taking a benzodiazepine or any other psychotropic drug. 

Benzodiazepines, especially lorazepam, are used to prevent and treat CINV.5,10 Lorazepam is thought to prevent input from the cerebral cortex and limbic system from reaching the central vomiting center in the brain stem.10 Sedation and amnesia are common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are combined with benzodiazepines. 

These differences may become particularly germane if co-prescribing with some antipsychotics is undertaken. For example, in certain individuals, combinations of clozapine with benzodiazepines may lead to unexpected adverse events, including delirium and augmented respiratory depression (Jackson, Markowitz Brewer-ton, 1995 Grohmann et al, 1989). Presumably if there are additive or synergistic effects of ethnicity on clearance of one or both substances, adverse events may be enhanced. Similar interactions are theoretically possible with olanzapine, as adverse interactions have been described between olanzapine and benzodiazepines, at least in the elderly (Kryzhanovskaya etal, 2006). 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

Side effects of benzodiazepines include sedation, dizziness, poor coordination, and, at higher doses, amnesia. Benzodiazepines also increase the effects of alcohol therefore, alcohol use should be avoided or markedly curtailed. Benzodiazepines can also exacerbate the breathing problems of patients with sleep apnea and other respiratory disorders such as emphysema. Like the barbiturates, long-term use of benzodiazepines can lead to physical dependence, and abrupt discontinuation can produce an unpleasant, or even dangerous, withdrawal syndrome. 

Side effects of benzodiazepines include drowsiness and reduced respiratory function. In patients who are severely medically ill, especially those with lung disease, this side effect can be problematic. However, benzodiazepines are much safer in this regard than their predecessors, the barbiturates, and untreated delirium tremens, the most severe form of alcohol withdrawal, can be fatal. 

Hypoventilation Monitor patients who have received flumazenil for the reversal of benzodiazepine effects (after conscious sedation or general anesthesia) for resedation, respiratory depression or other residual benzodiazepine effects for an appropriate period (120 minutes or less) based on the dose and duration of effect of the benzodiazepine employed, because flumazenil has not been established as an effective treatment for hypoventilation due to benzodiazepine administration. Flumazenil may not fully reverse postoperative airway problems or ventilatory insufficiency induced by benzodiazepines. In addition, even if flumazenil is initially effective, such problems may recur because the effects of flumazenil wear off before the effects of many benzodiazepines. 

However, adverse effects also include dependence and thus drug abuse. Tolerance develops within 3 months for anxiety. However considerable interindividual variability exists for the development of this tolerance. Benzodiazepines have very little effect on respiration which is not seen with sedative doses. In cases involving benzodiazepine intoxication, respiratory assistance has only been needed in patients who had also taken another CNS depressants. 

Patients in whom haloperidol is contraindicated can be treated by intramuscular injection of benzodiazepines, but these can cause respiratory depression or respiratory arrest if given in too high a dose, are contra-indicated in patients with preexisting respiratory depression, and have no specific anti-psychotic effect. 

Flumazenil Romazicon) is a benzodiazepine antagonist that specifically reverses the respiratory depression and hypnosis produced by the benzodiazepine receptor agonists. Its block of the amnesic effect of the agonists is less reliable. Flumazenil is particularly useful when an overdose of benzodiazepines has occurred. It is also employed when a benzodiazepine has been used to produce conscious sedation and rapid recovery of psychomotor competency is desirable. To avoid resedation, flumazenil may require administration by intravenous infusion. 

The acute effects of depressants can include euphoria, anxiety reduction, anticonvulsant activity, sedation, ataxia, motor incoordination, impaired judgment, anesthesia, coma, and respiratory depression resulting in death. The benzodiazepines are rarely involved in lethality, but all CNS depressants enhance the effects of other depressant drugs. The physiological effects of high-dose depressants include miosis, shallow respiration, and reduction in reflex responses. 

Monitor for seizures, sedation, respiratory depression, or other residual benzodiazepine effects for an appropriate period (up to 120 min) based on dose and duration of effect of the benzodiazepine employed pharmacokinetics of benzodiazepines are not altered in the presence of flumazenil... 

Monitor and maintain a patent airway and prepare to assist with ventilation if flumazenil does not fully reverse the respiratory depressant effects of the benzodiazepine... 

For the treatment of panic disorder, the starting adult dose is 0.25 mg twice a day, which may be increased by one mg daily after three days. Clonazepam s safety and effectiveness has not been determined for individuals under the age of 18. Side effects in the treatment of panic disorders are similar to many of the benzodiazepines, and include allergic reaction, inflamed sinuses or nasal passages, flu, menstrual problems, respiratory infection, speech problems, and vaginal inflammation. 

Drugs that stimulate respiration (analeptics) have a place in anaesthetic practice but are not a substitute for mechanical ventilation. They have a direct effect on respiratory drive they do not share a common molecular structure. Respiratory stimulation is generally better achieved by antagonising the depressant effects of the depressant drug, e.g. flumazenil for benzodiazepines naloxone for opioids. 

The benzodiazepine antagonist flumazenil can be used to accelerate recovery when excessive doses of intravenous benzodiazepines are administered (especially in elderly patients). However, reversal of benzodiazepine-induced respiratory depression is less predictable. The short duration of action (< 90 minutes) of flumazenil may necessitate multiple doses to prevent recurrence of the CNS depressant effects of the longer-acting benzodiazepines (eg, lorazepam, diazepam). 

These medications are only safe to use with other substances under a physician s supervision. Typically, they should not be used with alcohol, antihistamines, barbiturates, or benzodiazepines. Because these other substances slow breathing, their effects in combination with opioids could lead to life-threatening respiratory depression. 

The respiratory depression induced by morphine can add to that of alcohol, barbiturates, benzodiazepines (such as Valium), and even with antihistamines taken for allergies. Combined effects of these drugs with morphine can dangerously compromise breathing. Tricyclic antidepressants can hamper the metabolism of morphine. 

Although the BZDs have minimal depressant effects on respiration, when combined with other CNS depressants (alcohol, opioids), BZDs can cause fatal respiratory suppression. However, most non-BZD sedatives may also cause death by suppression of breathing and heart failure if taken in sufficient quantity. Benzodiazepines can also cause some degree of memory loss called anterograde amnesia—a form of amnesia that involves the formation of memories after a specific event a person with anterograde amnesia cannot remember information presented to them after ingesting the BZD, a process similar to an alcohol black-out. 

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