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Diazepam is mainly used to treat anxiety, insomnia, and symptoms of acute alcohol or opiate withdrawal. It is also used as a premedication for inducing sedation, anxiolysis or amnesia prior to certain medical procedures (e.g. endoscopy).

Diazepam is rarely used as a primary drug for the long-term treatment of epilepsy. This is due to the fact that tolerance to the anticonvulsant effects of diazepam usually develops within 6 to 12 months of treatment, effectively rendering it useless for this purpose.

Diazepam has a broad spectrum of indications (most of which are off-label), including:

Treatment of anxiety, panic attacks, and states of agitation
Treatment of status epilepticus, adjunctive treatment of other forms of epilepsy
Treatment of the symptoms of alcohol and opiate withdrawal
Short-term treatment of insomnia
Treatment of tetanus, together with other measures of intensive-treatment
Initial management of mania, together with firstline drugs like lithium, valproate or other antipsychotics
Adjunctive treatment (with antidepressants) of depression with symptoms of anxiety
Adjunctive treatment (with antipsychotics), in patients who develop early extrapyramidal side-effectsAdjunctive treatment of painful muscle conditions
Adjunctive treatment of spastic muscular paresis (para-/tetraplegia) caused by cerebral or spinal cord conditions such as stroke, multiple sclerosis, spinal cord injury (long-term treatment is coupled with other rehabilitative measures)
Palliative treatment of stiff person syndrome
Pre-/postoperative sedation, anxiolysis and/or amnesia (e.g. before endoscopic or surgical procedures)
Treatment of overdosage with hallucinogens or CNS stimulants
Adjunctive treatment of drug-induced seizures, resulting from exposure to sarin, VX, soman (or other organophosphate poisons), lindane, chloroquine, physostigmine, or pyrethroids
Emergency treatment of eclampsia, along with IV magnesium sulfate
Prophylactic treatment of oxygen toxicity during hyperbaric oxygen therapy.

Veterinary uses
Diazepam is very useful as short term sedative and anxiolytic for cats and dogs. It can also be used for preoperative sedation of cats and dogs and as an anticonvulsive suitable for short-term and long-term treatment, if sedation is tolerated. The anticonvulsant dosage is typically 0.25 milligram/pound administered intervenously or, for emergency treatment, rectally in suppository form.

Warnings
Pregnancy:
Several studies have suggested an increased risk of congenital malformations associated with the use of diazepam, chlordiazepoxide and meprobamate during the first trimester of pregnancy. Therefore, the administration of diazepam is rarely justified in women of childbearing potential. If the drug is prescribed for a woman of childbearing potential, she should be warned to contact her physician regarding discontinuation of the drug if she intends to become or suspects that she is pregnant.
Precautions
Geriatrics:
Elderly and debilitated patients or those with organic brain disorders have been found to be prone to CNS depression following even low doses. For these patients it is recommended that the dosage be limited to the smallest effective amount to preclude development of ataxia, oversedation or other possible adverse effects.

Use in emotional disorders:
Diazepam is not recommended in the treatment of psychotic or severely depressed patients. Precautions are indicated for severely depressed patients or those who show evidence of impending depression, particularly the recognition that suicidal tendencies may be present and protective measures may be necessary. Since excitement and other paradoxical reactions may result from the use of the drug in psychotic patients, it should not be used in ambulatory patients suspected of having psychotic tendencies.

Use in epileptic patients:
Since diazepam may exacerbate grand mal seizures in some patients, caution is required when it is used in epileptic patients. An adjustment may be necessary in their anticonvulsive medication. Abrupt withdrawal of diazepam in these patients should also be avoided.

Potentiation of drug effects:
Patients should be advised to abstain from alcohol and other CNS depressant drugs during treatment with diazepam. Phenothiazines, barbiturates, MAO inhibitors and other psychoactive drugs may potentiate the action of the drug and should not usually be given concurrently.

Drug dependence:
Abrupt cessation of large doses of diazepam after prolonged periods may precipitate acute withdrawal symptoms and, in these cases, the drug should be discontinued gradually. Caution should be exercised when it is considered necessary to administer diazepam to addiction prone individuals.

Occupational Hazards:
Patients receiving diazepam should be advised to proceed cautiously whenever mental alertness and physical coordination are required.

The usual precautions in treating patients with impaired renal and hepatic functions should be observed. If diazepam is administered for protracted periods, periodic blood counts and liver function tests would be highly advisable.
Adverse Effects
The most common adverse effects reported are drowsiness and ataxia. Other reactions noted less frequently are fatigue, dizziness, nausea, blurred vision, diplopia, vertigo, headache, slurred speech, tremors, hypoactivity, dysarthria, euphoria, impairment of memory, confusion, depression, incontinence or urinary retention, constipation, skin rash, generalized exfoliative dermatitis, hypotension, changes in libido.

The more serious adverse reactions occasionally reported are leukopenia, jaundice, hypersensitivity and paradoxical reactions.

Paradoxical reactions such as hyperexcited states, anxiety, excitement, hallucinations, increased muscle spasticity, insomnia, rage, as well as sleep disturbances and stimulation, have been reported; should these occur, the drug should be discontinued.

Minor changes in EEG patterns have been observed in patients on diazepam therapy. These changes consist of low to moderate voltage fast activity, 20 to 30 cycles/second and are of no known significance.
Overdose
Symptoms:
Drowsiness, oversedation and ataxia. When the effects of drug overdosage begin to wear off, the patient exhibits some jitteriness and overstimulation. The cardinal manifestations of overdosage are drowsiness and confusion, reduced reflexes and coma. There are minimum effects on respiration, pulse and blood pressure unless the overdosage is extreme.

Treatment:
Gastric lavage may be beneficial if performed soon after oral ingestion of diazepam. If necessary, a CNS stimulant such as caffeine or methylphenidate may be administered with caution. Supportive measures should be instituted as indicated, such as, maintenance of an adequate airway, levarterenol for hypotension. Dialysis appears to be of little value.

Anxiolytic - Sedative - Muscle Relaxant

Diazepam is a benzodiazepine with CNS depressant properties and a somewhat flatter dose-response slope than the sedative-hypnotic drugs. In laboratory animals, it produces, in varying doses, taming, disinhibitory, sedative, anticonvulsant, muscle relaxant, ataxic and hypnotic effects.

Diazepam is relatively devoid of autonomic effects and does not significantly reduce locomotor activity at low doses, or depress amphetamine-induced excitation. In high doses, it activates the drug metabolizing enzymes in the liver. Diazepam also possesses dependence liability and may produce withdrawal symptoms, but has a wide margin of safety against poisoning.

Metabolism studies in animals and man have indicated that oral diazepam is rapidly absorbed from the gastrointestinal tract. Peak blood levels are reached within 1-2 hours after administration. The acute half-life is 6-8 hours with a slower decline thereafter, possibly due to tissue storage.

In humans, comparable blood levels of diazepam were obtained in maternal and cord blood indicating placental transfer of the drug. Diazepam may appear in human breast milk.

With the parenteral form, peak blood levels are reached within 15 minutes after i.v. administration and are of the same magnitude as after oral administration. The respective half-life is approximately 2-3 hours.

The distribution and fate of tritium-labeled diazepam in man has indicated that the drug has a rapid and extensive uptake by tissues. Although the radioactivity in the blood appears to represent mainly the intact drug, diazepam was shown to be excreted exclusively in the form of its metabolites. The two major metabolites are oxazepam glucuronide and N-desmethylated diazepam.