Z drugs: discover how they work

Z drugs are a type of medication that differs from other hypnotic agents in the duration of their action and their side effects. There are 3 Z drugs: zolpidem, zoplicone and zaleplon. There are many drugs for the treatment of insomnia, but Z drugs cause little or no alteration of sleep architecture.

Insomnia has numerous causes and may be involved in the onset, aggravation or relapse of many psychiatric disorders. However, it can also be a sign that something is wrong. Sleep is a basic human need and studies recommend that, as adults, it is advisable to sleep between 7 and 9 hours a day.

What are we talking about when we refer to sleep architecture?

Sleep is a physiological process regulated by hormones connecting and disconnecting with each other. It is a large electrical and chemical circuit. When we talk about dream architecture, We refer to the phases that the brain goes through from when we are awake until we are deeply asleep:

Phase I or numbness: Sleep occurs very lightly, our muscles begin to relax and our eyes move slowly.Phase II or light sleeper: The heart and respiratory rate decreases, the temperature decreases, and our eyes practically do not move.Phase III or transition: It is the phase in which our brain prepares for deep sleep. Our muscles are relaxed and a type of waves characteristic of deep sleep appear: delta waves.Phase IV or deep sleep: Both breathing and heart rate are slowed. Delta waves predominate. This is the restorative phase of sleep.Phase V or REM phase: It is called that because it is the phase in which we characteristically dream. When we dream, our eyes are moving as if we see what we are really dreaming, while awake.

Sleep is a cyclical process. Our brain takes approximately 90 minutes to start in phase I and end in phase V. These are repeated throughout the 8 hours that we usually sleep. So, On average we go through each of these phases about 5 times a night..

Z drugs have no side effects on consciousness, learning, and memory.

An approach to the neurobiology of sleep

We are awake (wake) or asleep depending on the stimuli we receive and the degree of activation we have. In our brains there are molecules called neurotransmitters that are responsible for regulating the mechanisms that make us awake. They are the molecules that control how much and how activated we are.

What is a neurotransmitter and receptor?

A neurotransmitter is a key. Two key neurotransmitters regulate sleep-wake switches: histamine and GABA.

Histamine: It is one of the neurotransmitters that regulate wakefulness. When there is a lot of histamine, we are awake. But when there is little, we get sleepy. For this reason, the antihistamines that we can take for the flu make us sleepy. Because they reduce (anti) the amount of histamine in the areas of the brain that are responsible for sleep.GABA: It acts with the opposite function to histamine. It is mainly responsible for us falling asleep. We can say that GABA is an inhibitory neurotransmitter because it “turns off” the brain regions that are responsible for us being awake.

In a pedagogical way, we can conceive brain functioning as an electrical system full of circuits. In neurobiology, circuits that control sleep and wakefulness are called s ascending activating reticular system . This system contains on and off switches. Those that are relevant to the topic we discuss here are:

The off switch: It is the brain region that is responsible for making us fall asleep, the promoter of sleep. It is located in a region called ventrolateral preoptic nuclei (POVL), in the hypothalamus. When this region is activated, it produces the neurotransmitter GABA.He ignition switch: It is the region with the opposite function and when it is activated, it produces the neurotransmitter histamine and we wake up. It is located inside the nuclei tuberomammillars (NTM) of the hypothalamus.

These mechanisms act in a special way known as the flip-flop mechanism.: They cannot both be on or off at the same time. When one is on, the other must necessarily be off and vice versa.

In our brain we have multiple keys for multiple locks.. The lock that interests us here, due to its relationship with Z Drugs, is called GABA-A. The GABA-A receptor or lock works very well for the GABA neurotransmitter or key. Thus, when GABA and GABA-A join together, like a key in its lock, they produce sleep.

In addition, the brain also responds to the amount of light in our environment. When we are in bright places or it is daytime, the light causes a region of the brain to turn off. This area is known as the suprachiasmatic nucleus, and it is located in the hypothalamus. When the light decreases, this area of ​​the brain stops being turned off: the suprachiasmatic nucleus is activated and secretes a hormone that also induces drowsiness: melatonin.

Pharmacological treatment of insomnia

We can understand the insomnia as a state of activation during the night, the product of an overactivated brain. From a neurobiological perspective we can explain it as the activation of the power switch at night.

Drugs that reduce brain activation are those that when we need to sleep, but can’t, force the off switch to activate. As this mechanism is, remember, a flip-flop mechanism, the power switch will necessarily be deactivated. Among the hypnotic drugs we can find benzodiazepines, antihistamines and Z drugs.

Benzodiazepines

Benzodiazepine hypnotics or Benzodiazepines act like keys to the GABA-A lock: they make you sleepy. They are drugs that serve both to induce sleep (hypnotics) and to reduce anxiety (anxiolytics). Examples of benzodiazepines are lormetazepam, lorazepam, clonazepam, diazepam, or alprazolam.

What side effects do they have? Among others:

They cause addiction with continued use. Therefore, we recommend that you consult with your specialist how to take them. They can generate symptoms similar to a hangover when we wake up. When we stop taking them, they can cause an increase in insomnia: rebound insomnia.They also interfere with long-term memory.

antihistamines

If we remember, histamine was the neurotransmitter that flipped the on switch. If we introduce a drug that reduces the amount of histamine, the power switch will no longer be active. And since the mechanism is a flip-flop, automatically the other switch, the off switch will turn on. This is what antihistamines do. Examples of antihistamine drugs are doxylamine or diphenhydramine.

What side effects do they have? Among others:

Drowsiness.Dizziness and headaches.Fatigue.Dry mouth and constipation. Blurred vision. Vertigo.

The use of antihistamines can cause dizziness, fatigue and headaches.

Z Drugs

Z drugs were synthesized during the early 1980s and their hypnotic and sedative effect is similar to that produced by benzodiazepines. The Z drugs, zaleplon, zolpidem and zoplicone, They also act as keys that attach to the GABA-A receiver or lock, but in a slightly different way than benzodiazepines do.

These drugs They bind to GABA-A in such a way that they do not produce as much tolerance (less effect after taking the drug for a long time), or dependence (rebound insomnia after abruptly stopping treatment). They have no known side effects on consciousness, memory and learning.

Zoplicone: It is a drug with sedative, hypnotic, muscle relaxant or muscle relaxant, and anticonvulsant effects. Although its use has only been approved for the treatment of insomnia. The most frequently described adverse effect is a persistent bitter taste in the mouth (dysgeusia), dry mouth (xerostomia), difficulty waking up, drowsiness and headache. Its effect lasts between 4 and 5 hours.Zolpidem: When administered in low doses it does not produce dependence or tolerance. Among the effects of zolpidem we can find its sedative action, greater than its anxiolytic action, that is, it puts us to sleep more than it relaxes us. It is indicated as short-term treatment of insomnia. One of its most particular adverse effects is hallucinations. Its effect lasts between 1.5 and 2.5 hours.Zaleplon: It is a drug to which several actions are attributed. It is sedative, hypnotic, muscle relaxant and anticonvulsant. It does not produce tolerance or amnesia, or motor alterations the day after taking the drug. Of the three Z drugs, it has the shortest effect: only 1 hour.

Due to their short duration, Z drugs are indicated for initial insomnia, that is, the one that occurs when we have difficulty sleeping. They are not as effective drugs in maintenance insomnia (when we wake up many times throughout the night), or for mixed insomnia (when we have a hard time sleeping and, in addition, we wake up many times during the night).

No matter how clear the presentation of this article has been, remember that we are talking about a drug that directly affects the activity of our brain. Thus, I recommend that before starting to use it, you talk to your doctor and follow his instructions.

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