Benzodiazepine diazepam

The first-line treatment for status epilepticus is intravenous benzodiazepines. Diazepam, lorazepam, or midazolam may be used to rapidly control clinical signs of seizures. Lorazepam is currently considered the first-line agent by most clinicians. 

Concomitant administration of methotrexate and Voltarol, a proprietary preparation of diclofenac, a non-steroidal anti-inflammatory drug, may result in accumulation of methotrexate as its excretion is reduced. The use of diclofenac and diuretics such as bendroflumethiazide may increase the risk of nephrotoxicity. Concomitant use of alcohol and an angiotensin-converting enzyme inhibitor such as lisinopril (Zestril) may result in an enhanced hypotensive effect. Alcohol and the benzodiazepine diazepam (Valium) may result in enhanced sedation. 

Phenergan contains the antihistamine promethazine. Valium contains the benzodiazepine diazepam. Both the antihistamine and the benzodiazepine tend to reduce the blink rate, leading to dry eyes. Cilest is a combined oral contraceptive, which, like other oral contraceptives, may cause reduced tolerance because of corneal and eyelid oedema. 

The synthesis of these compounds will be described in Section 3.1, Opioid analgesics. Besides opioids, benzodiazepines (diazepam, lorazepam, and midazolam), which have anxiolytic, sedative, and anticonvulsant effects, that cause amnesia and muscle relaxation, are frequently used to relieve patients anxiety during anesthesia. 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

The tranquillizers like benzodiazepines (diazepam 5-10 mg oral, or lorazepam 2 to 4 mg IM, IV are now preferred for preanaesthetic medication because they produce tranquillity, have better muscle relaxant property and smoothen induction. Other tranquillizer compounds include phenothiazines which possess sedative, antiemetic and antihistaminic properties. They can be given orally as well as parenterally. 

Hegarty JE, Dundee JW. Sequelae after the intravenous injection of three benzodiazepines—diazepam, lorazepam and flunitrazepam. BrMed J 1977 22 1384-1385. 

Some naturally occurring neurotransmitters may be similar to drugs we use. For example, it is well known that the brain makes its own morphine (i.e., beta endorphin), and its own marijuana (i.e., anandamide). The brain may even make its own antidepressants, it own anxiolytics, and its own hallucinogens. Drugs often mimic the brain s natural neurotransmitters. Often, drugs are discovered prior to the natural neurotransmitter. Thus, we knew about morphine before the discovery of beta-endorphin marijuana before the discovery of cannabinoid receptors and anandamide the benzodiazepines diazepam (Valium) and alprazolam (Xanax) before the discovery of benzodiazepine receptors and the antidepressants amitriptyline (Elavil) and fluoxetine (Prozac) before the discovery of the serotonin transporter site. This un-... 

High-potency benzodiazepines (alprazolam, clonazepam) generally are more effective in panic disorder than low-potency benzodiazepines (diazepam, lorazepam, etc.). Although less research has been done on the low-potency benzodiazepines, it is generally accepted that they frequently result in sedation prior to adequately relieving panic attacks. The reader is referred to the discussion of benzodiazepines in Chapter 8 for a detailed overview of mechanism of action. A critique of the issues of benzodiazepine dependence and appropriate use is given in Chapter 13-... 

Benzodiazepines Diazepam [Valium] Lorazepam [Ativan] Midazolam [Versed]... 

Frequently, a preoperative sedative is given to a patient 1 to 2 hours before the administration of general anesthesia.2,36 Sedatives are usually administered orally or by intramuscular injection, and are given while the patient is still in his or her room. This approach serves to relax the patient and reduce anxiety when arriving at the operating room. Commonly used preoperative sedatives include barbiturates (secobarbital, pentobarbital), opioids (butorphanol, meperidine), and benzodiazepines (diazepam, lorazepam) (Table 11-2). Different sedatives are selected depending on the patient, the type of general anesthesia used, and the preference of the physician. 

Smith and Sanagi reported the packed-column SFC of benzodiazepines (diazepam, lorazepam, lormetazepam, nordazepam, temazepam, es-trazolam, chlordiazepoxide, triazolam, cloxazolam, ketazolam, and lopra-zolam) with methanol-modified carbon dioxide as the mobile phase [29]. The effect of methanol concentration on separation was studied on three columns polystyrene-divinylbenzene, octadecylsilane, and cyanopropyl-bonded silica columns. They concluded that proportion of methanol has marked effect on the selectivity of compounds containing different functional groups. 

Diazepam is a benzodiazepine. Diazepam is more reliably absorbed following oral rather than intramuscular admininstration. This may be due to precipitation in the muscle. Diazepam appears to undergo enterohepatic recirculation with a second plasma peak occurring 4-6 hours after initial administration. This may be associated with re-sedation. Diazepam is oxidised in the liver to active metabolites including desmethyldiazepam (nordiazepam), which has a half-life of over 100 hours. Benzodiazepine oxidation may be impaired in patients with liver disease and in some elderly patients. Metabolism of benzodiazepines such as oxazepam and lorazepam is not impaired in the elderly and in those with liver dysfunction. 

From the influence of the autonomic nervous system it follows that all sympatholytic or sympathomimetic and parasympatholytic or parasympathomimetic drugs can produce corresponding effects on cardiac performance. These possibilities are exploited therapeutically for instance, p-blockers for suppressing excessive sympathetic drive (p. 96) ipratropium for treating sinus bradycardia (p. 108). An unwanted activation of the sympathetic system can result from anxiety, pain, and other emotional stress. In these cases, the heart can be protected from harmful stimulation by psychopharmaceuticals such as benzodiazepines (diazepam and others important in myocardial infarction). 

Cornelissen PJ, Beijersbergen van Henegouwen GM, Gerritisma KW. Photochemical decomposition of 1,4-benzodiazepine. Diazepam. Int J Pharm 1978 1 173-181. 

Treatment is basically symptomatic and supportive no specific antidotes are available. Artificial ventilation with 100% humidified oxygen is necessary in cases of respiratory distress. If patient is cyanotic and cyanosis does not respond to oxygen administration, methemoglobin levels should be determined. Methemoglobinemia can be treated by intravenous administration of methylene blue. Support of cardiovascular function may also be required. Bladder damage can be determined by urinalysis. Hypotension may be treated with isotonic intravenous fluids. Dopamine or norepinephrine may be used if hypotension does not respond to infusion of fluids. Convulsions may be treated with intravenous benzodiazepines (diazepam or loraze-pam) phenobarbital may be used if the convulsions are recurrent. Because chlordimeform is a monoamine oxidase inhibitor, foods with large amounts of... 

Exposed skin should be washed promptly with soap and water. Dermal application of vitamin E oil preparations may be used for both prophylaxis and treatment of paresthesia. Eor contact with eyes, flush immediately and for an extended period with generous amounts of clean water or saline. Gastric lavage is indicated if patient has ingested a large amount of pyrethroid and can be treated soon after exposure. For ingestion of smaller amounts or if treatment has been delayed, activated charcoal and catharsis are indicated. Seizures can be treated with intravenous benzodiazepines (diazepam or loraze-pam) phenytoin or phenobarbital may be helpful for recurrent seizures. No specific antidotes for pyre-throid-induced neurotoxic effects have been approved for use in humans. Spontaneous recovery usually occurs with mild or moderate intoxication. 

For ingestion of smaller amounts or if treatment has been delayed, activated charcoal and catharsis are indicated. Seizures can be treated with intravenous benzodiazepines (diazepam or lorazepam) phenytoin or phenobarbital may be helpful for recurrent seizures. No specific antidotes for pyrethroid-induced neurotoxic effects have been approved for use in humans. Spontaneous recovery usually occurs with mild or moderate intoxication. 

A genetic factor in Asians causes an undesirable side effect when administered the standard dose of benzodiazepines (diazepam [Valium]) alprazolam [Xanax], tricyclic antidepressants, atropine, and propranolol [Inderal],... 

Benzodiazepines (diazepam, clonazepam) Treat absence seizures... 

CYP2C19 Benzodiazepines diazepam Antidepressants imipramine, amitriptyline, clomipramine, citalopram Others propranolol, hexobarbital, mephobarbital, proguanil, omeprazole, S-mephenytoin 2 no activity 23%-39% in Asians 13% in Caucasians 25% in African Americans 3 no activity 6%-10% in Asians 0% in others... 

Clinically important, potentially hazardous interactions with alprazolam, barbiturates, benzodiazepines, diazepam, midazolam, valproic acid... 

Benzodiazepines are typically administered orally, and the rate of absorption is the principal determinant of the rate of onset and the intensity of action. Highly lipophilic benzodiazepines (diazepam and flurazepam) are rapidly absorbed (time to peak serum concentration <1.2 hours), and less hpophilic compounds (oxazepam and temazepam) are more... 

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