Buy Valium Online
Diazepam is a long acting 1,4-benzodiazepine .It acts on the CNS and produce sedation ,sleep and inhibition of anxiety. It is also used for muscular disorders and seizures. It is also sometimes used to manage alcohol withdrawal effects. Benzodiazepines are most widely used anxiolytic drugs and have replaced barbiturates and meprobamate because of their efficacy and safety. (Explained below)
Anxiety is an upsetting condition of strain, worry, or uneasiness (a dread that appears to emerge from an obscure source). Anxiety disorders are the most common mental disturbances. Anxiety causes both psychological symptoms and physical symptoms. The physical symptoms of severe anxiety are:
- muscular tension,
- tightness in the abdominal region,
- inability to catch ones breath
It involves sympathetic activation. Episodes of mild anxiety are common life experiences and do not require any treatment. However, the symptoms of severe, persistent, debilitating anxiety may be treated with anti-anxiety drugs (sometimes called anxiolytic or minor tranquilizers) and/or some sort of behavioral therapy or psychotherapy.
What causes Anxiety?
Anxiety may occur due to apparent causes, such as a person may be anxious because he is suffering from some serious debilitating disease ,for example, cancer, Myocardial infarction or he may have some serious problems in social life for example, death of a close relative or friend can cause anxiety in a person. A second type of anxiety is without any apparent cause, characterized by severe anxiety called as Anxiety disorders/Anxiety neurosis. Anxiety Disorder is caused by genetically inherited neurochemical dysfunction.
In CNS, the major mediators of the symptoms of anxiety disorders are norepinephrine, serotonin, dopamine and gamma-amino butyric acid(GABA)Peripherally, the sympathetic nervous system mediates many of the symptoms.
Emotional processing is done in the limbic system of the brain where GABA receptors are present. Benzodiazepines are the anxiolytics which act on these receptors and potentiates the effect of GABA receptors and in turn depresses CNS, relieving anxiety, depression and convulsions.
Sedatives and Narcotics have a long been used for the purpose of medication and leisure, starting with alcohol which is foremost and original sedative in the history. Paraldehyde, bromides, chloral hydrates were created during the 1800s, trailed by barbiturates and meprobamate in early twenties. These substances are restricted by their high potential for misuse and reliance and their possibly deadly results of overdose.
By 1950s, Leo-Sternbach of Hoffmann-La Roche Company started struggling to invent a tranquilizer which can be safe and efficacious at the same time. Librium ad then diazepam was invented as successful benzodiazepines. First combined in 1959, diazepam was found 3-10 times as effective as Librium with extremely low toxicity and then it entered the market in 1963 and turned into the top selling drug in the United States from 1968 until 1978 with 2.3 billion pills sold that year.
However, with time it came into attention that due to its high efficacy, it can be abused. With female abusers significantly outnumbering males, this drug was sardonically called as ‘Mother’s Little Helper’. Despite the risk of abuse, a very important specification of this drug is its relative safety in comparison to other tranquilizers because the lethal dose is over 1000 folds greater than the typical therapeutic dose. This proves that it is rarely fatal when taken alone, but can lead to severe consequences when used alongside certain medication.
1. Anti-anxiety: It makes the person calm by binding to alpha 2 GABA receptors and potentiating their effect of CNS depression, causing CNS depression.
2. Sedative and hypnotic actions: Diazepam causes sedation by acting on alpha1 GABA receptors.
3. Anterograde amnesia: Diazepam causes amnesia by acting on same alpha1 GABA receptors.
4. Anticonvulsant: This action is partially, although not completely, mediated by alpha1-GABA receptors.
5. Muscle relaxant: At high doses, the diazepam relaxes the spasticity of skeletal muscle, probably by increasing presynaptic inhibition in the spinal cord, where the α2-GABAA receptors are largely located.
Diazepam is highly effective and safe drug for variant uses. Some of the common uses of the drug are:
Diazepam is one of the most highly prescribed drugs for the anxiety disorders due to its efficacy, safety and long lasting effects. It is used to control panic attacks, generalized anxiety disorder (GAD), social anxiety disorder, performance anxiety, posttraumatic stress disorder, obsessive-compulsive disorder, and the extreme anxiety sometimes encountered with specific phobias such as fear of flying.
Caution: It should not be used to alleviate the normal stress of everyday life. They should be reserved for continued severe anxiety, and should only be used for short periods of time because of their potential of causing addiction.
As Diazepam is long it is often preferred in those patients with anxiety who may require treatment for prolonged periods of time. N
It is given in the dose of 2 mg to 10 mg, 2 to 4 times daily depending on the severity of symptoms.
Diazepam is used as the anticonvulsant. Diazepam is the FIRST LINE DRUG for the treatment of grand-mal epilepsy and status epilecticus. It is used in Partial seizures and tonic –clonic seizures. However, it can be used for all other types of epilepsies as an alternative drug of choice
It is given in the dose of 2 mg to 10 mg, 2 to 4 times daily for convulsions orally.
In status epilepticus,it can be given in a dose of 10-20mg IV at a rate of 1-2mg/minute. If the attacks are not controlled the same dose can be repeated after 20-30 minutes to a maximum total dose of 20-30mg.
Diazepam is effective in causing relaxation by acting on neurons in spinal cord. It is used in the treatment of muscle spasm (acute),muscle spasm in palliative care, muscle spasms such as that occur in muscle strain, and in treating spasticity from demyelination disorders, such as multiple sclerosis and cerebral palsy. It can also be used in Tetanus and myoclonus.
Given 2 mg to 10 mg, 3 or 4 times daily
Diazepam can be used before the administration of anesthesia prior to surgeries and procedures to relieve anxiety and tension in the patient.
It is also used to cause anterograde amnesia during surgeries and procedures for example endoscopy, bronchoscopy
Initially, loading dose of 5 to 10 mg , followed by a maintenance dose of 0.03 to 0.10 mg/kg every 0.5 to 6 hours
Diazepam can be used as hypnotic but it should be better avoided because it has prolonged action, and therefore, may cause hangover effects on the following day. Short acting benzodiazepines can be used for this purpose as they cause little or no hangover effects the following day.
Diazepam can be used as an anti-depressant. According to a study, diazepam when compared with the proven antibiotic, meclobomide proved to be better at 4 weeks but not at 8 weeks. All patients stopped diazepam inside one year and none announced withdrawal responses.
Treatment of Acute alcohol withdrawal:
Diazepam is used for alcohol withdrawal.
Dose is 10 mg orally every 6 to 8 hours within the first 24 hours, then 5mg every 6 to 8 hours thereafter as needed.
Routes of administration:
- Diazepam rectal gel is prescribed for emergency control of seizures in people who are already taking other medication to treat epilepsy.
- For pediatric patients, initiate therapy with lowest dose and increase as required. It should not be given to children age less than 6 months.
Diazepam is rapidly absorbed from GIT and produce active metabolites that act for several hours. It has minimal or no residual effects on occasional use due to redistribution as compared to clonazepam, lorazepam and flurazepam.
Overdosing causes cardiovascular depression and severe respiratory depression.Diazepam is relatively safe as compared to barbiturates because of wide therapeutic index. It’s lethal dose is 1000 fold greater than the typical therapeutic dose making rare chances for its toxicity.
Withdrawal effects like anxiety, tremors, hyper reflexia and seizures can occur Drugs having long half-life, like diazepam, withdrawal effects may occur slowly and last for days after the discontinuation of drug which further increases its safety value while other benzodiazepines having short half-life, causes abrupt withdrawal effects and can lead to severe consequences.
When compared with other anxiolytics like barbiturates, diazepam has less severe withdrawal effects and also takes some days to appear whereas barbiturates can produce withdrawal symptoms on 3 4 days which are more lethal.
Dependence and Tolerance:
Tolerance is the decrease in the responsiveness, occurs when drugs are used chronically. Dependence is addiction to drug. Psychological and physical dependence on benzodiazepines and barbiturates can occur if high doses of the drugs are given over a prolonged period. Diazepam is less likely to cause tolerance and dependence when compared with barbiturates but as it is widely prescribed and more easily available, it has higher rates of abuse and addiction.
However, long term use of benzodiazepines for insomnia is not recommended because of tolerance and dependency and hangover effects, but these drugs are ideal for occasional use by air travellers ,shift workers etc.
Hangover effects are headache and residual drowsiness on waking. Due to the prolonged effect of diazepam, it has strong hangover effect as compared to barbiturates and other short acting benzodiazepines so their long term use should be discourage.
Change in the response of a drug due to administration of another drug is known as drug-drug interaction. This occurs when two or more drugs are used side by side. Interaction can occur during absorption, distribution, metabolism and excretion of drug .
They have no enzyme inducing property, hence drug interactions are less as compared to barbiturates and thus less chances of fatality.
Benzodiazepines have specific Benzodiazepine receptor antagonist like flumazenil as compared to barbiturates, thus diazepam can be reversed in case of overdosing. Presence of specific antidote further increases its safety index.
OTHER ANXIOLYTICS AND DIAZEPAM:
There are other anxiolytics that can be used ,for example, some antidepressants like selective serotonin reuptake inhibitors(SSRI) and buspirone.These drugs are less likely to cause dependence and addiction and thus sometimes is preferred in patients with the concerns of dependence and addiction.
Serotonin reuptake inhibitors can be used alone or in combination with benzodiazepines for treatment of generalized anxiety disorder. After four to six weeks, this is tapered by benzodiazepines. Due to its efficacy and less side effects,SSRIs have become first line treatment for generalized anxiety disorder.
Buspirone can be used for chronic generalized anxiety disorder and is considered as efficacious as benzodiazepines. It has fewer side effects except nausea, dizziness and headache. It is less likely to cause dependency and psychomotor/cognitive dysfunction. Due to its less interference with motor functions, it is particularly important in elderly patients.
Figure 3: Comparison of buspirone with one of the benzodiazepine.
Depression of Central Nervous system:
It can cause decrease in motor skills, drowsiness and decrease in cognition. Cognitive activities that require learning and recalling of previous knowledge is impaired. It can also effect the decision making power of a person. Routine work can be severely affected. Ataxia can also occur on higher doses. Activities requiring fine motor functions can be impaired.
The dosage of diazepam should be reduced in elderly, as they are more susceptible to drugs that case psychomotor dysfunctions.
When used for prolonged period of time, diazepam can cause dependence. In such cases, withdrawal effects can occur when drug is suddenly stopped. As Diazepam is long acting drug so withdrawal symptoms occur slowly within three weeks and are less lethal. Withdrawal effects include
- unpleasant dreams
- tremors, anorexia
- sleep abnormalities
- Convulsions can occur, in severe cases.
- Addiction of diazepam is more common in people with personality disorder and previous history of sedative or alcohol abuse.
Tolerance can occur with chronic use of diazepam Tolerance is the decrease in the responsiveness, occurs when drugs are used chronically. Thus to maintain the pharmacological action of the drug ,dose of the drug have to be increased with the passage of time.
Long term use of benzodiazepines for insomnia is not recommended because of tolerance, dependency and hangover effects, but these drugs are ideal for occasional use by air travellers, shift workers etc
Hangover effects are headache and residual drowsiness on waking. Due to the prolonged effect of diazepam, it has strong hangover effect, so their long term use should be discourage
Floppy baby syndrome:
Using benzodiazepines during labor may cause respiratory depression and hypotonia known as floppy baby syndrome in newborn and even the withdrawal effects can occur in new born.
Overdose of diazepam can seldom occur and can cause respiratory and cardiovascular depression. Coma can occur. Other symptoms may include:
- Bluish-colored lips and fingernails.
Overdose can be revered effectively by Benzodiazepine antagonist named flumazenil. It can reverse the Central Nervous system depression produced but over dose but is not efficacious against respiratory depression.
It can be given intravenously in the dose of 200micro gram initially in 15 seconds, then 100 micro grams at 1 minute intervals.
- Blood dyscrasias
- Skin Rashes
- Allergic Reaction:
It should be used with caution in patients with aspirin hypersensitivity as it may induce allergic reaction
Other SIDE EFFECTS
Other symptoms include:
- Mental confusion
- Light-headed ness
- Anterograde amnesia(memory lose for short time) during effect.
- Disorganization of thoughts
- Dry mouth
- Bitter taste
- Blurring of vision
- Epigastric pain
Phlebitis, changes in libido, pain at injection site poor appetite, constipation and hematuria are some other side effects.
Diazepam should be used with caution in patients with liver diseases and in patients with narrow-angle glaucoma. It should be given least amount to patients in whom depression is also present along with anxiety.
Diazepam is contraindicated in patients with myasthenia Gravis.
Can I take Diazepam if I am pregnant or breastfeeding?
No, Diazepam is harmful for the baby both during pregnancy and breast feeding. Diazepam has the potential to cross the Placental barrier in pregnancy and also excrete in breast milk .It can cause lethal effects in newborn such as respiratory depression which can lead to mortality of the newborn. It can also cause hypotonia known as Floppy baby syndrome, in which baby don’t have any tone and feel limp, like a rag doll.
Diazepam is classified in FDA pregnancy category D, which means there is possible risk to fetus.
cause other symptoms of CNS depression and withdrawal effects even in new born. It can lead to congenital malformations such as cleft palate.
How quickly does treatment work?
Diazepam generally has fast onset of action. When administered through Intravenous route, it acts within 1-3mintes, while when given orally its onset of action ranges between 15-60 minutes.
Is it safe to take Diazepam?
Yes, it’s highly safe to use diazepam due to its wide therapeutic index i.e. lethal dose is 1000 times greater than typical therapeutic dose.
How long does a dose of Diazepam last?
As diazepam is long acting benzodiazepine so its dose last for 1-3 days days.
Are there any side effects of the treatment?
Yes, therapeutic doses of diazepam have side effects but these are less likely to be lethal.
Do I require a prescription for taking Diazepam?
Yes, you should have prescription for taking diazepam because it is available on prescription by a certified doctor only. This is due to its fatal effects if misused. Having diazepam without prescription is illegal.
Why is it not safe to buy Diazepam online?
It is not safe because this drug may be fake. FDA strongly discourages consumers from buying online because of the issue of counterfeit. World Health Organization has reported 700 adverse events that have occurred due to consumption of mislabeled diazepam.
I cannot swallow tablets, what should I take?
You can take Oral Diazepam Solution or diazepam Intensol. This intensol is mixed with liquid and semi-solid food such as water ,soda and soda lie beverages.Always use calibrated dropper with this product for accurate dosage
You can also use diazepam rectally, through Intramuscular IM or Intravenous route IV.
Is this treatment safe option for children?
It is contraindicated in children age less than 6 months. In children above 6 months, it should be used with caution because of varied responses to CNS-acting drugs. It is used for muscle spasticity and febrile seizures in children.
How long do I have to take diazepam for?
It is usually recommended for short period of no more than 4 weeks. Prolong use of these medication can cause dependency and withdrawal effects, once you stop the medication. So these medications if used for more than 4 weeks, should be tapered gradually to prevent withdrawal effects. For depression and anxiety,sometimes this medication is prescribed for 6 months in low dose.
Can I take Diazepam with other medication?
There are certain drugs which shouldn’t be used alongside diazepam because some drugs decreases its efficacy and interaction of some drugs wit it ,can cause lethal effects.Severe interaction of diazepam can be caused by sodium oxalates.
Serious interactions of diazepam include:
- Anti-epileptic such as carbamazepine
- erythromycin lactobionate
- erythromycin base
- erythromycin strearate
Diazepam causes moderate interactions with at least 238 different drugs. Concomitant use of opioids and benzodiazepines may result in respiratory depression, severe sedation, soma and death
Is Diazepam hard on liver?
Clinically, liver injury from diazepam is rare. However, it should be used with caution in patients with liver diseases.
Is it true that diazepam should not be used in glaucoma?
Yes, it is contraindicated in narrow angle glaucoma.