Central nervous system depression

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Central nervous system (CNS) depression is a physiological state that can result in a decreased rate of breathing, decreased heart rate, and loss of consciousness, possibly leading to coma or death.

Contents

It is the result of inhibited or suppressed brain activity. [1]

Causes

Depression of the central nervous system is generally caused by the use of depressant drugs such as ethanol, opioids, barbiturates, benzodiazepines, general anesthetics, and anticonvulsants such as pregabalin used to treat epilepsy. [2] [3]

Drug overdose is often caused by combining two or more depressant drugs, although overdose is also possible by consuming a large dose of one depressant drug. Central nervous system depression can also be caused by the accidental or intentional inhalation or ingestion of certain volatile chemicals such as butanone (contained in plastic cement) or isopropyl alcohol. Other causes of central nervous system depression are metabolic disturbances such as hypoglycemia. [4]

Comparison

In a study comparing the central nervous depression due to supra-therapeutic doses of triazolam (a benzodiazepine), pentobarbital (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. 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. This is often not the case with opioids as they cause respiratory depression. [5]

Treatment

Significant central nervous system depression is treated within a hospital setting by maintaining breathing and circulation. Individuals with reduced breathing may be given supplemental oxygen, while individuals who are not breathing can be ventilated with bag valve mask ventilation or by mechanical ventilation with a respirator. Sympathomimetic drugs may be used to attempt to stimulate cardiac output in order to maintain circulation. Central nervous system depression caused by certain drugs may respond to treatment with an antidote.[ citation needed ]

There are two antidotes that are frequently used in the hospital setting and these are naloxone and flumazenil. Naloxone is an opioid antagonist and reverses the central nervous depressive effects seen in opioid overdose. [6] In the setting of a colonoscopy, 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 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 seizures 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 sedatives but only 0.8% of them result in the administration of one of these antidotes. 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. [7]

Related Research Articles

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Naloxone</span> Opioid receptor antagonist

Naloxone, is a medication used to reverse or reduce the effects of opioids sold under various brands. It is used to counter decreased breathing in opioid overdose. Effects begin within two minutes when given intravenously, and within five minutes when injected into a muscle. The medicine can also be administered by spraying it into a person's nose. Naloxone blocks the effects of opioids for 30 to 90 minutes. Multiple doses may be required, as the duration of action of some opioids is greater than that of naloxone. Emergency medical services data from Massachusetts found that 93.5% of people given naloxone survived their overdose.

<span class="mw-page-title-main">Diazepam</span> Benzodiazepine sedative

Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. Orally, effects begin after 15 to 60 minutes.

A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity.

<span class="mw-page-title-main">Drug overdose</span> Use of an excessive amount of a drug

A drug overdose is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Typically it is used for cases when a risk to health will potentially result. An overdose may result in a toxic state or death.

Depressants, or central depressants, are drugs that lower neurotransmission levels, or depress or reduce arousal or stimulation in various areas of the brain. Depressants are also colloquially referred to as "downers" as they lower the level of arousal when taken. Depressants do not change the mood or mental state of others. Stimulants, or "uppers," increase mental or physical function, hence the opposite drug class from depressants are stimulants, not antidepressants.

Hypoventilation occurs when ventilation is inadequate to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. Hypoventilation is not synonymous with respiratory arrest, in which breathing ceases entirely and death occurs within minutes due to hypoxia and leads rapidly into complete anoxia, although both are medical emergencies. Hypoventilation can be considered a precursor to hypoxia and its lethality is attributed to hypoxia with carbon dioxide toxicity.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

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 properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Flumazenil</span> Chemical compound

Flumazenil is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines, through competitive inhibition.

Pentobarbital 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 has been largely replaced by the benzodiazepine family of drugs.

<span class="mw-page-title-main">Butabarbital</span> Chemical compound

Butabarbital is a prescription barbiturate sleep aid and anxiety medication. Butabarbital has a particularly fast onset of effects and short duration of action compared to other barbiturates, which makes it useful for certain applications such as treating severe insomnia, relieving general anxiety and relieving anxiety before surgical procedures; however it is also relatively dangerous particularly when combined with alcohol, and so is now rarely used, although it is still prescribed in some Eastern European and South American countries. Its intermediate duration of action gives butabarbital an abuse potential slightly lower than secobarbital. Butabarbital can be hydrolyzed to Valnoctamide.

<span class="mw-page-title-main">Opioid antagonist</span> Receptor agonist that acts on one or more of the opioid receptors

An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors.

<span class="mw-page-title-main">Butorphanol</span> Opioid analgesic

Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans.

<span class="mw-page-title-main">Ro15-4513</span> Chemical compound

Ro15-4513(IUPAC: Ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-1,4-benzodiazepine-3-carboxylate) is a weak partial inverse agonist of the benzodiazepine class of drugs, developed by Hoffmann–La Roche in the 1980s. It acts as an inverse agonist, and can therefore be an antidote to the acute impairment caused by alcohols, including ethanol, isopropanol, tert-butyl alcohol, tert-amyl alcohol, 3-methyl-3-pentanol, methylpentynol and ethchlorvynol.

Desbutal was a brand name drug by Abbott containing 5mg methamphetamine hydrochloride (Desoxyn) and 30mg pentobarbital sodium (Nembutal); a substituted amphetamine and a barbiturate combined within the same pill. Desbutal was marketed as an antidepressant as well as a medication for the treatment of obesity, narcolepsy, parkinsonism, and alcoholism, although it was commonly also prescribed off-label for miscellaneous ailments. It had a high abuse potential and is no longer manufactured.

<span class="mw-page-title-main">Opioid overdose</span> Medical condition

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 condition that can cause hypoxia from slow and shallow breathing. Other symptoms include small pupils, and unconsciousness, however its onset can depend on the method of ingestion, the dosage and individual risk factors. Although there were over 110,000 deaths in 2017 due to opioids, individuals who survived also faced adverse complications, including permanent brain damage.

<span class="mw-page-title-main">Benzodiazepine overdose</span> Medical condition

Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. The most common symptoms of overdose include central nervous system (CNS) depression, impaired balance, ataxia, and slurred speech. Severe symptoms include coma and respiratory depression. Supportive care is the mainstay of treatment of benzodiazepine overdose. There is an antidote, flumazenil, but its use is controversial.

<span class="mw-page-title-main">Coma cocktail</span>

A coma cocktail is a combination of substances administered in an emergency to comatose individuals when the cause of the coma has not yet been determined. The intention is to work against various causes of a coma seen in an emergency setting including drug overdoses and hypoglycemia. The coma cocktail is sometimes colloquially referred to as a “party pack” by professionals in the pre-hospital emergency medical services field.

<span class="mw-page-title-main">Barbiturate</span> Class of depressant drugs derived from barbituric acid

Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as well as overdose potential among other possible adverse effects. They have been used recreationally for their anti-anxiety and sedative effects, and are thus controlled in most countries due to the risks associated with such use.

<span class="mw-page-title-main">Barbiturate overdose</span> Medical condition

Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe. Complications of overdose can include noncardiogenic pulmonary edema. If death occurs this is typically due to a lack of breathing.

References

  1. ↑ "How do CNS depressants affect the brain and body?". National Institute of Health. October 2011.
  2. ↑ "What are CNS depressants?". National Institute of Health. October 2011.
  3. ↑ Adam Cloe (June 30, 2010). "What Is CNS Depression?". www.livestrong.com.
  4. ↑ Baskaran, Anusha; Milev, Roumen; McIntyre, Roger S. (2013). "A review of electroencephalographic changes in diabetes mellitus in relation to major depressive disorder". Neuropsychiatric Disease and Treatment. 9: 143–150. doi: 10.2147/NDT.S38720 . ISSN   1176-6328. PMC   3552551 . PMID   23355785.
  5. ↑ Carter, Lawrence P.; Richards, Brian D.; Mintzer, Miriam Z.; Griffiths, Roland R. (November 26, 2006). "Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB". Neuropsychopharmacology. 31 (11): 2537–2551. doi: 10.1038/sj.npp.1301146 . PMID   16880774.
  6. ↑ Sivilotti, Marco L. A. (2016). "Flumazenil, naloxone and the 'coma cocktail'". British Journal of Clinical Pharmacology. 81 (3): 428–436. doi:10.1111/bcp.12731. ISSN   1365-2125. PMC   4767210 . PMID   26469689.
  7. ↑ Bamias, Giorgos; Morse, John (April 26, 2010). "Ability to Reverse Deeper Levels of Unintended Sedation". Digestion. 82 (2): 94–96. doi: 10.1159/000285519 . PMID   20407253.
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