By Dr Tomislav Meštrović, MD, PhD
Sedatives are a diverse group of drugs manufactured for medical purposes to relax the central nervous system. Also known as tranquillizers or central nervous system (CNS) depressants, they encompass drug classes such as barbiturates, benzodiazepines, non-benzodiazepine sedative-hypnotics, anesthetics, antihistamines and opioid narcotics, as well as herbal compounds.
History of sedatives
Before the era of modern medicine, the most commonly prescribed sedative to ease tension, cause relaxation and help forget problems was alcohol. Its beneficial effects were definitely the reason why alcohol gained such popularity and is still the most commonly abused sedative of all time.
Attempts to find sedatives other than alcohol for treating anxiety and nervousness began in the 19th century with the introduction of bromides, which were discovered in 1826. These drugs were extremely popular for this purpose until their propensity to build up in the body and produce toxic effects became known in the medical community.
Because of their toxicity, bromides were replaced by barbiturates in the early 20th century, which were initially also heralded as effective and safe sedative drugs. However, in a short period of time problems with dependence, tolerance and lethal overdosing became evident. As the margin of safety for barbiturates was too narrow, research endeavors for safer sedatives continued.
In 1950s the first benzodiazepines were marketed as valid substitutes for dangerous barbiturates. Although initially viewed as completely safe and free from problems of dependence, tolerance and withdrawal, today we know that benzodiazepines are less than ideal antianxiety drugs, and that their long-term usage can cause all the aforementioned effects associated with their sedative predecessors.
During the 1970s and 1980s, there was an epidemic of prescriptions written for sedatives (for example, 100 million prescriptions were written for benzodiazepines alone in 1973). They are still one of the most prescribed classes of drugs, even though the medical community has become more aware of the problem.
Mechanism of action and effects
Sedatives are usually classified according to the way they affect the human body. They represent a diverse group of drugs that share an ability to reduce activity of CNS and diminish the brain’s level of awareness. The lack of similarity between the structures of drugs that belong to different classes made it difficult to propose a common receptor or mechanism of action.
This is best explained if we observe two commonly prescribed groups of drugs – barbiturates and benzodiazepines. For example, barbiturate-type drugs cause general depression of most neuronal activity, thus they are considered nonselective. That is the reason why their use is practically always accompanied by certain degree of cognitive function impairment.
In contrast, benzodiazepines selectively affect the neurons that have receptors for the neurotransmitter gamma-aminobutyric acid (GABA), which is a crucial inhibitory transmitter in several regions of the brain. In the presence of these drugs, the inhibitory effects of GABA are increased, which explains the selective CNS depression caused by benzodiazepines.
Absorption of most sedatives is fairly rapid and it goes through gastrointestinal tract. Two mentioned groups of drugs are primarily absorbed in the small intestine, and clinical effects are determined by their ability to penetrate the blood-brain barrier. Most sedatives are metabolized to pharmacologically active intermediates, and elimination occurs predominantly by hepatic metabolism.
The effects of the sedatives tend to be dose dependent, and often the only difference between anxiolytic and hypnotic effect is the dose. Consequently, the same drug can be used for both purposes just by varying the dose. By increasing the dose even further, an anesthetic state can be reached.
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Last Updated: Nov 23, 2015