< < Better Nights for Better Days

The GABA Gating System The brain chemical GABA opens chloride channels, quieting brain activity and allowing sleep. BDZs act with GABA to enhance sleep safely, but barbiturates can imitate GABA to a toxic degree.

People have used potions and pills to make them sleep for centuries - sometimes effectively, sometimes disastrously. Many people would probably rather "take something" than investigate a complex problem, physical or psychological. Few, however, have any idea how sleeping medications work or what their hidden dangers may be in any circumstance, let alone in specific situations like neuromuscular disease. Some of these - even nonprescription remedies with friendly-sounding names - can be dangerous for those with respiratory compromise. Even sleep aids prescribed by doctors have to be used with care in the face of weakening respiratory muscles.

Antihistamines

Probably the most common type of sleeping medication is the kind found in almost all over-the-counter sleep aids - antihistamines.

Next time you're in a drugstore or supermarket, stroll down the sleep aids aisle and read the ingredients on the packages. Nearly all - such as Simply Sleep, Unisom SleepGels, Sleepinal, Sominex and Nytol - contain diphenhydramine; a few, such as Unisom SleepTabs, contain doxylamine. These are known as sedating antihistamines. (If you've ever taken Benadryl, a brand name for diphenhydramine, for allergies, you probably know how sleep-inducing it can be.)

Antihistamines work against the central nervous system chemical histamine, and some, such as diphenhydramine, can be quite sedating. Sedation, however, isn't the same as good sleep, according to sleep specialist Karl Doghramji, and the sleep quality that results from taking them may be poor. Among their more serious side effects for people with neuromuscular disorders is their tendency to dry up respiratory secretions, making these harder to cough up and more likely to plug bronchioles (breathing tubes) in the lungs.

Pharmacologist Merrill Mitler says most of the sleep-related data on these drugs are based on patient questionnaires, an unreliable source of information compared to placebo-controlled studies. He says he can't justify using antihistamines instead of prescription sleep aids to treat insomnia.

Benzodiazepines

These are members of the Valium family of drugs and have been the first choice in prescription sleep aids since the 1970s. (Valium itself, although good for muscle relaxation and curbing anxiety, isn't really a good sleep aid and isn't usually prescribed for this purpose.) Some experts feel enzodiazepines (BDZs) have acquired an undeservedly bad reputation. Actually, Mitler says, these drugs are "far and away the safest medications for promoting sleep that we have available." Examples are temazepam (Restoril), estazolam (ProSom), flurazepam (Dalmane) and triazolam (Halcion).

Of course, no drug is completely safe, and no sleep drug should be taken for more than a few weeks without very careful supervision. They can have very serious side effects (up to coma and death) when combined with alcohol or other drugs, and their effects on respiratory drive can pose a real danger in people with serious respiratory weakness (for example, in ALS) or reduced brain control of respirations (for example, in myotonic dystrophy - MMD).

BDZs are among many sleep-promoting substances that work on a molecular structure in the brain known as the GABA receptor-chloride channel complex, or simply the GABA gating system.

When the central nervous system chemical GABA (see page 11) lands at a specific "docking site" on one of these structures, it allows the chloride channel in the middle to open temporarily and let chloride flow through it. This chloride flow keeps the cell from becoming activated and, when it happens to a lot of cells, the nervous system is quieted by this action.

Benzodiazepines can't do anything by themselves - that is, without GABA - which is why they're considered relatively safe. They seem to make it more likely that a GABA molecule will open the chloride channel, but they can't open the chloride channel alone. Therefore, their action is limited by how much natural GABA is around. All this safety is, of course, nullified if there's another drug present that alters these conditions.

In people with respiratory weakness, these drugs should be used cautiously, if at all, and probably only when breathing is already being helped by ventilation.

Barbiturates

These are the drugs used in suicides, and they have a deservedly bad reputation as drugs of abuse. They're quite lethal when combined with alcohol and can easily become overdoses if combined with a BDZ. Examples of barbiturates are phenobarbital (Luminal, Solfoton) and secobarbital (Seconal).

Today, they're hardly ever prescribed as sleep aids, although they do have other uses (such as seizure control and anesthesia). You're unlikely to get a prescription for a barbiturate sleeping pill, but it's good to know what these are in case you have to take one for another reason, such as before surgery (especially if you're already taking a sleep aid), and to understand the difference between these and newer drugs.

In contrast to the benzodiazepines, barbiturates not only can enhance the actions of GABA but also can imitate GABA. When they imitate GABA, they can open the chloride channel in the gating system without any help from this natural substance, so their action and their toxicity aren't limited by how much GABA is around. Their sedating action - all the way to coma and death - is limited only by their dosage.

If they're combined with a BDZ (for example, before a surgical procedure), they can be lethal, especially in someone with a respiratory problem.

Dietary Supplements

For the last several years, these have hardly been federally regulated at all, so there's no telling what they do or even what you're getting when you buy one. One of them, the valerian root, present in Alluna and other preparations, seems to act on the GABA gating system, according to studies in rats. Melatonin may help regulate the biological clock and probably helps most when sleep problems are due to shift work, jet lag and other "clock" dysregulation.

Finally, a glass of warm milk taken before bed may help, or it may not, Doghramji says. It probably won't hurt. 

< < Better Nights for Better Days