Diazepam intramuscular

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

Diazepam Being extremely lipophilic, diazepam penetrates quickly into the CNS, but can rapidly redistribute into body fat and muscle. This results in a faster decline in CNS levels and early recurrence of seizures. It is dosed at 5 to 10 mg (or 0.15 mg/kg) and infused no faster than 5 mg/minute. Repeated doses can be given every 5 minutes until seizure activity stops or toxicities are seen (e.g., respiratory depression). Diazepam can also be administered as a rectal suppository, making it possible for non-medical personnel to provide rapid therapy for seizures that develop at home or in public areas.11 The adult dose is 10 mg given rectally and this dose may be repeated once if necessary. Diazepam is erratically absorbed via the intramuscular route therefore, IM administration is not recommended. 

Midazolam Midazolam is water-soluble and can be administered intravenously, intramuscularly,13 buccally,14,15 and nasally.16,17 At physiologic pH, it becomes more lipophilic and can diffuse into the CNS. Compared to diazepam and lorazepam, it has fewer effects on the respiratory and cardiovascular systems. Its short half-life requires that it be re-dosed... 

Diazepam, a long-acting benzodiazepine can be used either intravenously (risk of thrombophlebitis) or intramuscularly or rectally (both of the last two routes are associated with slow absorption). 

The intramuscular dosage of diazepam solution for injection is 5-10 mg, repeated if necessary after 4 hours. A rectal solution also exists. If respiratory depression occurs, it can be reversed with the antagonist flumazenil. 

Most BZs are completely absorbed from the gastrointestinal (GI) tract. The one exception is clorazepate, a pro-drug that undergoes acid hydrolysis in the stomach and is decarboxylated to form N-desmethyl-diazepam, which is then completely absorbed into the bloodstream (Bellantuono et ak, 1980 Hobbs et ak, 1996 Chouinard et ak, 1999). In contrast, most BZs, with the exception of lorazepam and midazolam, are not consistently absorbed from intramuscular injection (Chouinard et ak, 1999). Lorazepam is available as a sublingual form that reaches clinical effect at the same rate as an oral dose. In general, intravenous administration is used only for anesthesia or for the acute management of seizures. When BZs are given via this route, the onset of action is almost immediate (Chouinard et ak, 1999). 

Conscious sedation implies that patients have a depressed level of consciousness but nevertheless have intact protective reflexes, the ability to maintain their airway, and the ability to respond appropriately to requests and physical stimulation (Kennedy and Luh-mann, 1999). Sedative agents familiar to psychiatrists that are used in this manner for procedures include chloral hydrate, given orally or rectally in a dose of 25 to 100 mg/kg midazolam, given intramuscularly or intravenously in a dose of 0.05 to 0.15 mg/kg, rectally in a dose of 0.3 to 0.5 mg/kg, or orally in a dose of 0.2 to 0.75 mg/kg and midazolam, which is felt to be preferable to diazepam for this purpose (Kennedy and Luhmann, 1999). Midazolam is also available in a nasal spray (Ljungman et ah, 2000). 

The clinical duration of action of benzodiazepines does not correlate witii die elimination half-life. Intramuscular lorazepam is well absorbed. We do not recommend intramuscular chlordiazepoxide or diazepam. Source. Adapted from Teboul and Chouinard 1990. 

This pattern is not true for all drugs, however. For example, diazepam and chlordiazepoxide are unstable at a pH of 7.4 and tend to crystallize in tissue when given intramuscularly (14, 17, 18). Therefore, they are less bioavailable when given intramuscularly versus orally. Their absorption also tends to be erratic and variable, depending on where the injection was given (i.e., near blood vessels, in fat, or in muscle), as well as slower and less complete. 

Topiramate, another antiepileptic drug, may also be helpful in a dose of 400 mg daily, built up gradually. Small quantities of alcohol may suppress essential tremor but only for a short time. Alprazolam (in doses up to 3 mg daily) or gabapentin (100-2400 mg/d) is helpful in some patients. Others are helped by intramuscular injections of botulinum toxin. Thalamic stimulation by an implanted electrode and stimulator is often worthwhile in advanced cases refractory to pharmacotherapy. Diazepam, chlordiazepoxide, mephenesin, and antiparkinsonism agents have been advocated in the past but are generally worthless. Anecdotal reports of benefit from mirtazapine were not confirmed in a double-blind study, which found no effect on the tremor in most patients. 

The pharmacologic basis of the acute dyskinesia or dystonia sometimes precipitated by the first few doses of a phenothiazine is not clear. In most instances, parenteral administration of an antimuscarinic drug such as benztropine (2 mg intravenously), diphenhydramine (50 mg intravenously), or biperiden (2-5 mg intravenously or intramuscularly) is helpful, whereas in other instances diazepam (10 mg intravenously) alleviates the abnormal movements. 

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. 

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

The rates of oral absorption of benzodiazepines differ depending on a number of factors, including lipophilicity. Oral absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Oxazepam, lorazepam, and temazepam are absorbed from the gut at slower rates than other benzodiazepines. The bioavailability of several benzodiazepines, including chlordiazepoxide and diazepam, may be unreliable after intramuscular injection. Most of the barbiturates and other older sedative-hypnotics are absorbed rapidly into the blood following their oral administration. 

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. 

In patients unable to take medication by the oral route, diazepam may be administered by intramuscular or slow intravenous injection (into a large vein, at a rate of not more than 5 mg/min), at a dose of 10 mg, repeated if necessary after not less than 4 hours. Alternatively, diazepam may be administered via the rectal route as a rectal solution or suppository. The intramuscular route should only be used when both the oral and intravenous routes are not possible. 

Intramuscular injection of diazepam is absorbed erratically and may be slower in acting than an oral dose lorazepam and midazolam i.m. are absorbed rapidly. 

Brazeau, G.A. Fung, H-L. Effect of organic solvent-induced skeletal muscle damage on the bioavailability of intramuscular [14C] diazepam. J. Pharm. Sci. 1990, 79 (9), 773-777. 

A 26-year-old woman undergoing bronchoscopy received lidocaine jelly 2% to each nostril, lidocaine solution 2% sprayed on the throat, and 10 ml of lidocaine solution 2% into the trachea. She was also given intravenous diazepam 5 mg and pethidine 75 mg and intramuscular atropine 0.6 mg. She developed dyspnea and cyanosis after the procedure and despite 100% oxygen, her Sp02 was 85%. Her methemoglobin concentration was 14%. 

Figure 9.18 Plasma diazepam levels 90 min after intramuscular injection by one doctor and several nurses, showing the importance of technique and site of injection, which was variable in the latter group (individual values horizontal lines denote average levels). Redrawn from J. W. Dundee, J. A. Gamble and R. A. Assaf, Lancet, 2, 1461 (1974) with permission.

The most common route of exposure to the benzodiazepines is ingestion of oral dosage forms. Several of these agents are also available for parenteral administration (intramuscular or intravenous). Diazepam may be administered through an... 

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