Structural Biochemistry/Alprazolam

Introduction

Alprazolam (also known as Xanax) is a psychoactive drug used to treat anxiety disorders along with panic disorders. It is in a class of medications called benzodiazepines and how it works is it decreases abnormal excitement in the brain. Alprazolam can come in a variety of shapes and sizes. They can come as a tablet, an extended-release tablet, an orally disintegrating tablet, and it is also available in a liquid form. Alprazolam is used to treat anxiety disorders and panic disorders (sudden and unexpected attacks of extreme fear and uneasiness about these thoughts). Alprazolam is in a class of medication called benzodiazepines, which works by decreasing abnormal excitement in the brain.

Alprazolam is also sometimes used to treat depression, fear of open spaces (agoraphobia), and premenstrual syndrome. This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

History

Alprazolam is now part of Pfizer, but it was first released by Upjohn. It was covered under U.S. Patent 3,987,052, which was filed on October of 1969 and expired in September 1993. In the year 1981, Alprazolam was released. When it came out, the first approved indication was panic disordered.

A young psychiatrist named David Sheehan suggested using the new distinction called DSM-III. Hence, DSM-III created in the classification of anxiety disorders between generalized anxiety disorders (GAD) and panic disorder in order to market alprazolam. In other words, this was a way for Sheehan to advertise the use of alprozolam. From his studies, Sheehen knew that panic disorder was both widespread among the populace and responsive to benzodiazepines. Therefore, he had an idea and suggested to Upjohn that marketing alproxolam for panic disorder would both cover new diagnostic territory and emphasize the unique potency of this drug. He was basically finding unique ways to show how great alprazolam is.

As his clinical study continues, Sheehen describes how the first group of patients he tested with aplprozolam say how effective this drug was. They were basically all very impressed with the action that alprozolam carries. Several months later, when the United States Food and Drug Administration approved alprozolam, alprozolam was sold out quick and they made a great profit. However, similar to many other drugs out there many published reports in the medical literature state that taking alprozolam created severe withdrawal symptoms including psychoses, seizures, and intense rebound anxiety.

Panic/Anxiety Disorders

Alprazolam is effective in relieving moderate to severe anxiety and panic attacks. It is no longer the first line of defense for these attacks due to concerns of tolerance, dependence, and abuse. Doctors limited Alprazolam for a patient from 4 to 10 weeks and is only allowed to distribute the drug to those of no history of tolerance or dependence of any drug.

Alprazolam and Pregnancy

By taking Alprazolam while being pregnant has potential risks. It can cause fetal drug dependence and withdrawal symptoms in the post-natal period. It can also cause neonatal flaccidity and respiratory problems. Alprazolam are known to excreted in human milk and passed down to the infants. Alprazolam causes the infants to lose weight and become lethargic.

Mechanism of Action

Alprazolam is a Central Nervous System drug from the benzodiazepine class of no known mechanism of action. It is predicted to have its effects through binding to different stereo-specific receptors in the CNS. Alprazolam has also been tested to show antidepressant properties, which isn't usually a common characteristic of regular benzodiazepine derivatives.

Side Effects

Alprazolam can cause several side effects. The most common side-effects are:

1. drowsiness
2. light-headedness
3. headache
4. tiredness
5. dizziness
6. irritability
7. talkativeness
8. difficulty concentrating
9. dry mouth
10. increased salivation
11. changes in sex drive or ability
12. nausea
13. constipation
14. changes in appetite
15. weight changes
16. difficulty urinating
17. joint pain

Besides these common side effects, it sometimes produces more side side effects such as:

1. shortness of breath
2. seizures
3. seeing things or hearing voices that do not exist (hallucinating)
4. severe skin rash
5. yellowing of the skin or eyes
6. depression
7. memory problems
8. confusion
9. problems with speech
10. unusual changes in behavior or mood
11. thinking about harming or killing yourself or trying to do so
12. problems with coordination or balance

Food and Drug interactions

Alprazolam is metabolized via CYP3A4. Inhibitors such as fluoxetine, ketoconazole, cimetidine, nedfazodone, ritonavir, propoxyphene, erthromycin, and itraconazole are all examples of combining CYP3A4 inhibitors. These inhibitors basically delay the hepatic clearance of alprazolam which create an excessive accumulation of alprazolam.

Through the concomitant administration of alprazolam tablets in doses up to 4 mg/day, Imipramine and Desipramine both have been reported to increase an average 31% and 20%. It is also known that combined oral contraceptive pills reduce the clearance of alproxolam. This leads to the increased of plasma levels of alprozolam and accumulation.

Furthermore, herb kava and alprazolam can have a great affect between each other when combined because it can result in the development of a semi-comatose state. Hypericum is a genus of about 400 species of flowering plants in the family Hypericaceae that can lower the plasma levels of alproxolam and reduce its therapeutic effect. However, looking at the big picture, alcohol is one of the most important and common interactions. This is due to the idea of combination. Alcohol and benzodiazepines such as alproxolam taken in combination have a synergistic effect on one another. Due to this reaction, it causes severe sedation, behavioral changes, and intoxication. Therefore, it is usually seen that the more alcohol and alprozolam taken, the worse the interaction will be.

How supplied

Generic:(Alprazolam)

• Oral Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg
• Oral Tablet, Disintegrating: 0.25 mg, 0.5 mg, 1 mg, 2 mg
• Oral Tablet, Extended release: 0.5 mg, 1 mg, 2 mg, 3 mg

Alprazolam Intensol (oral solution) : 1 mg/ml

Niravam: Oral Tablet, disintegrating: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Xanax: Oral Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg

Xanax XR: Oral Tablet, Extended release: 0.5 mg, 1 mg, 2 mg, 3 mg

Reference

http://www.nlm.nih.gov/medlineplus/druginfo/meds/a684001.html http://www.medicinenet.com/alprazolam-oral/page2.htm http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000807 http://en.wikipedia.org/wiki/Alprazolam