CNS Depression
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Central nervous system depression (or CNS depression) is a
nervous system In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
disorder characterized by a severely impaired physiological state in which patients may exhibit decreased rate of breathing, decreased
heart rate Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the nee ...
, and loss of consciousness; in extreme cases, CNS depression can possibly lead to
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
or
death Death is the end of life; the irreversible cessation of all biological functions that sustain a living organism. Death eventually and inevitably occurs in all organisms. The remains of a former organism normally begin to decompose sh ...
.


Causes

Central nervous system depression is generally caused by the improper or excessive use of
depressant Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various ...
drugs such as
opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
s,
barbiturate Barbiturates are a class of depressant, depressant drugs that are chemically derived from barbituric acid. They are effective when used medication, medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological a ...
s,
benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...
s,
general anesthetic General anaesthetics (or anesthetics) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of aware ...
s,
anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...
s, and certain sleep medications. These drugs, although useful for treating severe cases of depression that may manifest as CNS depression, can easily be misused. The medications above depress the functions of the spinal cord and brain, both vital components of the central nervous system. In cases of misuse due to addiction, accidents, or unregulated dosage increases, individuals can very easily slip into unconscious coma states because neural activity drops below safe levels. Other causes of central nervous system depression are metabolic disturbances such as
hypoglycemia Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...
. Because the brain relies so heavily on glucose for normal functioning, a hypoglycemic state that severely deprives the brain of glucose would damage the brain's fuel sources. In most cases, specific neurobiological systems are set in place to produce defensive actions in response to such drops in glucose concentrations in attempts to raise concentrations back to normal functioning levels. However, in rare cases, if hypoglycemic episodes cause CNS depression that goes unchecked, brain death can be fatal.


Comparison

In a study comparing the central nervous depression due to supra-therapeutic doses of
triazolam Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properti ...
(a benzodiazepine),
pentobarbital Pentobarbital (US) or pentobarbitone (British and Australian) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies. It can also be used for short-term treatment of insomnia but ...
(a barbiturate) and gamma-hydroxybutyric acid (GHB), it appeared as if GHB had the strongest dose-effect function. Since GHB has a high correlation between its dose and its central nervous system depression, it has a high risk of accidental overdose. In the case of accidental overdose of GHB, patients can become drowsy, fall asleep and may enter a
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
. Although GHB had higher sedative effects at high doses as compared to triazolam and pentobarbital, it had less of an amnestic effect. Arousal of subjects who received GHB sometimes even required a painful stimulus; this was not seen in patients who received triazolam or pentobarbital group. During the heavy sedation with GHB, the subjects maintained normal respiration and
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
. This is often not the case with opioids as they cause respiratory depression.


Treatment

There are two
antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon antidoton)'', "(medicine) given as a remedy". An older term in English which is ...
s that are frequently used in the hospital setting and these are naloxone and flumazenil. Naloxone is an
opioid antagonist An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors. Naloxone and naltrexone are commonly used opioid antagonist drugs which are competitive antagonists that bind to ...
and reverses the central nervous depressive effects seen in
opioid overdose An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal conditio ...
. In the setting of a
colonoscopy Colonoscopy () or coloscopy () is a medical procedure involving the Endoscopy, endoscopic examination of the large bowel (colon) and the distal portion of the small bowel. This examination is performed using either a Charge-coupled device, CCD ...
, naloxone is rarely administered but when it is administered, its half-life is shorter than some common opioid agonists. Therefore, the patient may still exhibit central nervous system depression after the naloxone has been cleared. Naloxone is typically administered in short intervals with relatively small doses in order to prevent the occurrence of withdrawal, pain, and sympathetic nervous system activation. Flumazenil is a benzodiazepine antagonist and blocks the binding of benzodiazepines to
gamma-aminobutyric acid GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...
receptors. Similarly to naloxone, flumazenil has a short half-life, and this needs to be taken into account because the patient may exhibit central nervous depression after the antidote has been cleared. Benzodiazepines are used in the treatment of
seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
s and subsequently, the administration of flumazenil may result in seizures. Therefore, slow administration of flumazenil is necessary to prevent the occurrence of a seizure. These agents are rarely used in the setting of a colonoscopy as 98.8% of colonoscopies use
sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...
s but only 0.8% of them result in the administration of one of these
antidotes An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon antidoton)'', "(medicine) given as a remedy". An older term in English which is ...
. Even if they are rarely used in colonoscopies they are important in preventing the patient from entering a coma or developing respiratory depression when sedatives are not properly dosed. Outside of the colonoscopy setting, these agents are used for other procedures and in the case of drug overdose.


References

{{DEFAULTSORT:Central Nervous System Depression Central nervous system Central nervous system disorders