Benzodiazepines cardiovascular

A number of medications have been associated with an increased risk of falling, including drugs affecting mental status such as antipsychotics, benzodiazepines, tricyclic antidepressants, sedative-hypnotics, anticholinergics, and corticosteroids. Some cardiovascular and antihypertensive drugs also can contribute to falls, especially those causing orthostatic hypotension.9... 

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. 

Contraindications Anticholinergic signs (such as mydriasis, dry mucosa, and hypo-peristalsis), arrhythmias, cardiovascular collapse, history of hypersensitivity to benzodiazepines, patients with signs of serious cyclic antidepressant overdose (such as motor abnormalities), patients who have been given a benzodiazepine for control of a potentially life-threatening condition (such as control of status epilepticus or increased intracranial pressure ICP )... 

Bupropion overdose (n = 58) and combined overdoses of bupropion and benzodiazepines (n = 9) have been associated with symptoms of neurological toxicity, including lethargy, tremors, and seizures, and an absence of cardiovascular toxicity (Spiller et ah, 1994). 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

Benzodiazepines are used as hypnotics because they have the ability to increase total sleep time. They demonstrate minimal cardiovascular effects, but do have the ability to increase heart rate and decrease cardiac output. Most CNS depressants, including the benzodiazepines, exhibit the ability to relax skeletal muscles. Clozapine, a dibenzodiazepine, is used in the treatment of schizophrenia. It has both sedative and antipsychotic actions, and is the only FDA-approved medication indicated for treatment-resistant schizophrenia, and for reducing the risk of suicidal behavior in patients with schizophrenia. This drug can have potentially life-threatening side effects, but appears to have no abuse potential and will not be considered further. 

Note Benzodiazepines have only a limited capacity to produce profound and potentially fatal CNS depression. Although coma may be produced at very high doses, benzodiazepines cannot induce a state of surgical anesthesia by themselves and are virtually incapable of causing fatal respiratory depression or cardiovascular collapse unless other CNS depressants also are present. Because of this measure of safety, benzodiazepines have substantially replaced older agents for the treatment of insomnia or anxiety. 

Adjunctive use of potent opioids (eg, fentanyl and related compounds) contributes cardiovascular stability, enhanced sedation, and profound analgesia. Other intravenous agents such as the benzodiazepines (eg, midazolam, diazepam) have slower onset and recovery features and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines can be used to provide a basal level of sedation and amnesia when used in conjunction with other anesthetic agents. 

Among the many toxicants that cause convulsions are chlorinated hydrocarbons, amphetamines, lead, organophosphates, and strychnine. There are several levels of coma, the term used to describe a lowered level of consciousness. At level 0, the subject may be awakened and will respond to questions. At level 1, withdrawal from painful stimuli is observed and all reflexes function. A subject at level 2 does not withdraw from painful stimuli, although most reflexes still function. Levels 3 and 4 are characterized by the absence of reflexes at level 4, respiratory action is depressed and the cardiovascular system fails. Among the many toxicants that cause coma are narcotic analgesics, alcohols, organophosphates, carbamates, lead, hydrocarbons, hydrogen sulfide, benzodiazepines, tricyclic antidepressants, isoniazid, phenothiazines, and opiates. 

Trazodone Hydrochloride Trazodone overdose causes severe toxic effects. These effects are severe if taken along with benzodiazepines or alcohol. Trazodone interacts with MAOIs, cardiovascular drugs, CNS depressants, and antiepileptics. 

Even though Hoffmann-LaRoche has reformulated Rohypnol tablets to be more easily identified when placed into someone s drink, Rohypnol is still a very potent benzodiazepine and is subject to abuse. Chronic or daily Rohypnol use causes dependence in humans. Once dependence has developed, abstention induces withdrawal symptoms, including headache, muscle pain, extreme anxiety, tension, restlessness, confusion, and irritability. Numbness, tingling of the extremities, loss of identity, hallucinations, delirium, convulsions, shock, and cardiovascular collapse also may occur. Withdrawal seizures can occur in chronic abusers with abrupt cessation of Rohypnol use. 

Benzodiazepine (BZ) intoxication is manifested as slurred speech, poor coordination, swaying, drowsiness, hypotension, nystagmus, and confusion. Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, haJlucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepam, alprazolam) has an onset within 12 to 24 hours of the last dose. Diazepam, chlordiazep-oxide, and clorazepate have elimination half-lives (or active metabolites with elimination half-lives) of 24 to greater than 100 hours. So, withdrawal may be delayed for several days after their discontinuation. Sedative-hypnotic dependence is summarized in Table 73-2. 

If undesired effects are noted in time, seizure activity can be treated with benzodiazepines or thiobarbiturates (see Ch. 9) and cardiovascular collapse can be treated symptomatically (volume expansion, adrenergic agonists, oxygen, sodium bicarbonate see Ch. 12). 

---