Pharmacology Essay - Flunitrazepam

So, it's my recent essay for Pharmacology. Perhaps somehow it can be any use

FLUNITRAZEPAM

by Bulqis I. Sakinah

Drugs were initially aimed at improving human's life, but there was dark within the light, in the other side, drugs were also abused for horrible stuffs, one of them is sexual abuse. According to Catatan Tahunan 2016 Komnas Perempuan Indonesia, from the woman assaulted cases, the sexual one is ranked as second place high . One method of the sexual assaulted is using sedative drugs such as the derivat drug of Benzodiazepine, Flunitrazepam.

Flunitrazepam

Flunitrazepan was one of the drugs in the Group III of Psychotropic according to UU No. 5 Tahun 1997 that known used in treatment in therapy and science purpose, also has an intermediate potential in addiction. But, among two other drugs such as gamma hydroxybutyric (GHB) and Ketamine, Flunitrazepam or known with the trade name of Rohypnol (roh-HIP-nol) was unfortunately used as a date rape drug. Abuse of two similar drugs appears to have replaced Rohypnol abuse in some parts of the United States. These are clonazepam (marketed as Klonopin in the U.S.and Rivotril in Mexico) and alprazolam (marketed as Xanax) . Rohypnol is also known as:

• Circles

• Forget Pill

• LA Rochas

• Lunch Money

• Mexican Valium

• Mind Erasers

• Poor Man's Quaalude

• R-2

• Rib

• Roach

• Roach-2

• Roches

• Roofies

• Roopies

• Rope

• Rophies

• Ruffies

• Trip-and-Fall

• Whiteys

Flunitrazepam (C16-H12-F-N3-O3) is a benzodiazepine derivative whose hypnotic effect predominates over the sedative, anxiolytic, muscle-relaxing and anticonvulsant effects characteristic of benzodiazepines . Thus, it is used as a night-time hypnotic and in anaesthesiology; due to the pronounced hypnotic effect, it is not appropriate as a daytime sedative. In Indonesia, Rohypnol is commercially available in the form of 1mg and 2mg tablets. The price for 10 tablets each is around IDR 450.000.

Pharmacodynamics

Flunitrazepam has a similar pharmacodynamic as the Benzodiazepine. It has a selective effect on GABA-mediated synaptic processes that can affect the limbic system. The relative weight-for-weight potency of flunitrazepam is high, on an average about 10 times as potent as diazepam; however, there is wide variation in this potency coefficient for different effects.

This drug produces both dose and time-dependent amnesic effect with the potential rank is higher than Diazepam but smaller than Lorazepam. It also prevents patient experiencing unpleasant feelings during different stages of anesthesia and operation besides having a function as sleeping pills.

The most typical effect of Flunitrazepam on the cardiovascular system is peripheral vasodilatation due to direct relaxing of muscle fibers in the vascular wall. In the patients with cardiovascular disease, decreasing of cardiac output can also occur. This reaction can result in the reduction of systolic blood pressure.

Flunitrazepam has a depressive influence on respiration, even in small intravenous doses, and this effect is augmented by simultaneously administered analgesics or hypnotics. In occasional extreme cases, there may be a need for respiratory assistance. The effect on respiration results in a significant decrease in arterial oxygen tension; this may be corrected by increasing oxygen concentration in the inspired air.

As a sedative, Flunitrazepam causes partial amnesia; individuals are unable to remember certain events that they experience while under the influence of the drug. This effect is particularly dangerous when Rohypnol is used to aid in the commission of sexual assault; victims may not be able to clearly recall the assault, the assailant, or the events surrounding the assault.

Pharmacokinetics

Flunitrazepam is almost completely (80 to 90%) absorbed from the gastrointestinal tract, best with parenteral administration, followed by the oral and last by suppositories (only 50 %).  Flunitrazepam is 80% bound to plasma proteins. The overall elimination half-life is about 20 hours, which is much longer than the duration of clinical effects. 

Metabolism of flunitrazepam is nearly complete, although there are several metabolites, most important are the 7-amino, the 1-desmethyl, and the 3-hydroxy derivatives. Some of the metabolites are active and may have an important influence on clinical effects. Excretion is via the urine, and thus renal insufficiency results in accumulation of the metabolites. In patients with normal renal function, there is no progressive accumulation of metabolites with a daily dose of 2mg flunitrazepam. Metabolism and elimination are age-dependent, and the dose must be reduced in elderly patients. 

Addiction and Intoxication

According to grouping system of UU No. 5 Tahun 1997, the Group III of Psychotropic has a mild potential of addiction. When used for a long-term medication or abusive behavior, the brain becomes tolerant to the drug and not giving any desirable effect with the same dose as the initial dose, so the patient must increase the dose to get the effect.

As for the intoxication, Flunitrazepam overdose symptoms range from mild to severe. Overdose can occur when more than 2 milligrams of this medication is taken at one time. The risk of overdose is greater when flunitrazepam is taken in combination with central nervous system depressants, such as opiates.

Signs of an overdose on flunitrazepam include excessive drowsiness, loss of coordination, slurred speech, difficulty breathing, lethargy, confusion, and blacking out . 

While intoxication happens, inducing vomit can help to wash the drug out from the body, if the patient is conscious, if not the stomach-pumping mechanism in the hospital can be done. Symptomatic treatment for the patient with difficulty of breathing is with the administration of oxygen. For the pharmacological treatment, the antidote of Benzodiazepine, Flumazenil, can be used.

Flunitrazepam withdrawal symptoms begin with an overwhelming need for the drug and mood swings. Some of the withdrawal symptoms like sleeplessness, restlessness, and insomnia mimic the symptoms for which the drug was initially prescribed to treat. Sweating and fever can also manifest in addition to nausea and vomiting. Hallucinations, vivid dreams and nightmares, and delirium have also been documented in moderate to serious cases. Other withdrawal symptoms include shaking, tremors, and seizures. Dysphoria is a common occurrence, along with chest and body pains, numbness, and tingling. Severe symptoms like mania, extreme depression, violence, and more typically occur only if you abruptly stop a high-dosage regimen . 

Withdrawal treatment for addiction is replacing the drugs with longer acting Benzodiazepine, like Diazepam, to reduce seizure activity with gradual reduction of the dose. Propanolol can also be used for reducing the sympathetic effects. While some of the commons symptoms on therapeutic withdrawal are weight loss, paresthesia, and headache. The treatment is recommended to be done comprehensively at the rehabilitation center so the patient could completely recover.

Advises

The usage of Flunitrazepam in medication must be watched carefully with wise consideration like other psychotropic medications cause it can lead to addiction or even abusive behavior. When used for medical application, the monitoring of drug-taking and precautions for the patients who use this drug are highly recommended.

For the social aspect especially as the infamous date rape drugs, various roles are needed synergically to regulate the using of this drug due to the risk of misuses, like government, doctors, pharmacists, and patients. Due to those risks, the availability of this drugs outside the medical needs ought to be restricted so it can help decrease the rate of drug abuse especially Flunitrazepam.

References

1.   Lembar Fakta Catatan Tahunan (CATAHU) Komnas Perempuan 2016
2.   Weiss, Susan. Date Rape Drugs (2012). https://www.womenshealth.gov/a-z-topics/date-rape-drugs
3.   Mattila, M.A.K. & Larni, H.M. Drugs (1980) 20: 353.
4.   Blanja.com (accessed on 29 October 2017)
5.   Mattila, M.A.K. & Larni, H.M. Drugs (1980) 20: 353.
6.   Rohypnol. https://www.drugs.com/illicit/rohypnol.html
7.   Flunitrazepam Overdose. https://www.projectknow.com/research/flunitrazepam-overdose/
8.   Flunitrazepam. https://www.withdrawal.net/learn/flunitrazepam/