Gabapentin: Difference between revisions

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Gabapentin is also an effective tool for treating social anxiety disorder, panic disorder<ref>The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17502773</ref><ref>Manual of Clinical Psychopharmacology | https://books.google.co.uk/books?id=D3zz1NCm3qcC&pg=PA345&hl=en</ref> and generalized anxiety disorder.<ref>Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission | https://books.google.co.uk/books?id=dnAlO_Veu2QC&pg=PA124&hl=en</ref><ref>https://books.google.co.uk/books?id=82oiYYHGNTQC&pg=PA765&hl=en</ref> It is these effects which provide gabapentin with some recreational potential in a manner that can be accurately compared to a mild [[benzodiazepine]]. However, these recreational effects diminish very quickly with repeated usage and are most commonly reported by those who do not have a tolerance to this compound.

The bioavailability of gabapentin is relatively low and is inversely proportional to the dose. This means that higher doses have lower biovailability than lower doses. The bioavailability of gabapentin is approximately 60%, 47%,

34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> Gabapentin has minimal hydrophilicity, with saturation values of up to 4490mg/L of pure water<ref>https://pubchem.ncbi.nlm.nih.gov/compound/gabapentin#section=Solubility</ref>. It is instead mostly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>

Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses. Due to a lack of available unsaturated gabapentin transporters, this results in an inability of transporters to carry gabapentin, resulting in large amounts of gabapentin passing through the digestive system without being used by one's body.

This effect can easily be significantly lessened by taking lower doses more often instead of higher doses less frequently. As a general rule for most individuals, using any more than 250-300mg of gabapentin every 30-40 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit absorption of gabapentin, so lowering the pH of one's stomach using acidic substances such as soda/pop will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>

==Chemistry==

Gabapentin, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter [[GABA]]. It contains a cyclohexane ring bound to a methylamino chain CH3NH2. At the same location, R1, the cyclohexane ring is also substituted with an acetic acid group. Gabapentin is structurally analagous to GABA. GABA contains an amino group bound to the terminal carbon of a butanoic acid chain. The structure of gabapentin contains the secondary carbon R3 of the butanoic acid chain in GABA incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.

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Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.

The bioavailability of gabapentin is relatively low and is inversely proportional to the dose (i.e. higher doses have lower biovailability than lower doses). The bioavailability of gabapentin is approximately 60%, 47%,

34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> Gabapentin is highly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>

Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses.

==Subjective effects==

The decreasing bioavailability of gabapentin can be lessened by taking lower doses more often instead of higher doses less frequently. As a general rule, using any more than 250-300mg of gabapentin every 30-40 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit absorption of gabapentin, so lowering the pH of one's stomach using acidic substances (such as soft drinks) will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>

{{effects/base

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==Toxicity and harm potential==

[[File:Gabapentin FDA prescription document.jpg|300px|thumbnail|This document, provided with prescription gabapentin, contains detailed information regarding its toxicity and harm potential.]]

GABApentin has a [[Toxicity::low toxicity]] relative to dose. The most common side effects of gabapentin in adult patients include dizziness, fatigue, drowsiness, weight gain, and peripheral edema (swelling of extremities).<ref>http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020235s041,020882s028,021129s027lbl.pdf</ref> Gabapentin may also produce sexual dysfunction in some patients whose symptoms of which may include loss of libido, inability to reach orgasm, and erectile dysfunction.<ref>https://books.google.co.uk/books?id=jTc3AAAAQBAJ&pg=PA137&hl=en</ref><ref>https://books.google.co.uk/books?id=_VzzAgAAQBAJ&pg=PT482&hl=en</ref> Gabapentin should be used carefully in patients with renal impairment due to possible accumulation and toxicity.<ref>http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020235s057,020882s041,021129s039lbl.pdf</ref>

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===Lethal dosage===

People who accidentally or intentionally overdose may experience drowsiness, sedation, blurred vision, slurred speech, somnolence and possibly death (if a very high amount was taken and particularly if combined with alcohol). Serum gabapentin concentrations may be measured to confirm diagnosis.<ref>R.C. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 677–8. ISBN 978-0-9626523-7-0.</ref>

===~~Tolerance~~ and ~~addiction~~ potential===

===Dependence and abuse potential===

Gabapentin is not considered psychologically addictive. However, it is possible to develop a physical dependence on the drug. In fact, people can experience withdrawal symptoms for up to 45 days after they stop taking gabapentin. Although gabapentin does give some people a euphoric “high” which can cause abuse, gabapentin abusers do not present with the kind of compulsive, drug-seeking behavior or strong cravings associated with other more common depressants such as [[opioids]], [[alcohol]] or [[benzodiazepines]].

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===Dangerous interactions===

*'''[[DangerousInteraction::Opioids]]''' - Combining opioids with gabapentin can cause death from respiratory failure.

*'''[[Opioids]]''' - Combining opioids with gabapentin can cause death from respiratory failure.

*'''[[DangerousInteraction::Depressants]] (GABAergic)''' - Gabapentin significantly potentiates the effects of [[alcohol]], [[benzodiazepines]] and other [[GABA]]genics which may lead to blackouts, and dangerous behaviour.

*'''[[Depressants~~|GABAergic depressants~~]]''' - Gabapentin significantly potentiates the effects of [[alcohol]], [[benzodiazepines]] and other [[GABA]]genics which may lead to blackouts, and dangerous behaviour.

==Legal status==

@@ Line 6: / Line 6: @@
 Gabapentin is also an effective tool for treating social anxiety disorder, panic disorder<ref>The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17502773</ref><ref>Manual of Clinical Psychopharmacology | https://books.google.co.uk/books?id=D3zz1NCm3qcC&pg=PA345&hl=en</ref> and generalized anxiety disorder.<ref>Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission | https://books.google.co.uk/books?id=dnAlO_Veu2QC&pg=PA124&hl=en</ref><ref>https://books.google.co.uk/books?id=82oiYYHGNTQC&pg=PA765&hl=en</ref> It is these effects which provide gabapentin with some recreational potential in a manner that can be accurately compared to a mild [[benzodiazepine]]. However, these recreational effects diminish very quickly with repeated usage and are most commonly reported by those who do not have a tolerance to this compound.
-The bioavailability of gabapentin is relatively low and is inversely proportional to the dose. This means that higher doses have lower biovailability than lower doses. The bioavailability of gabapentin is approximately 60%, 47%,
-%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> Gabapentin has minimal hydrophilicity, with saturation values of up to 4490mg/L of pure water<ref>https://pubchem.ncbi.nlm.nih.gov/compound/gabapentin#section=Solubility</ref>. It is instead mostly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>
-Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses. Due to a lack of available unsaturated gabapentin transporters, this results in an inability of transporters to carry gabapentin, resulting in large amounts of gabapentin passing through the digestive system without being used by one's body.
-This effect can easily be significantly lessened by taking lower doses more often instead of higher doses less frequently. As a general rule for most individuals, using any more than 250-300mg of gabapentin every 30-40 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit absorption of gabapentin, so lowering the pH of one's stomach using acidic substances such as soda/pop will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>
 ==Chemistry==
 Gabapentin, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter [[GABA]]. It contains a cyclohexane ring bound to a methylamino chain CH<sub>3</sub>NH<sub>2</sub>. At the same location, R<sub>1</sub>, the cyclohexane ring is also substituted with an acetic acid group. Gabapentin is structurally analagous to GABA. GABA contains an amino group bound to the terminal carbon of a butanoic acid chain. The structure of gabapentin contains the secondary carbon R<sub>3</sub> of the butanoic acid chain in GABA incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.
@@ Line 19: / Line 13: @@
 Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.
+The bioavailability of gabapentin is relatively low and is inversely proportional to the dose (i.e. higher doses have lower biovailability than lower doses). The bioavailability of gabapentin is approximately 60%, 47%,
+%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> Gabapentin is highly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>
+Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses.
 ==Subjective effects==
+The decreasing bioavailability of gabapentin can be lessened by taking lower doses more often instead of higher doses less frequently. As a general rule, using any more than 250-300mg of gabapentin every 30-40 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit absorption of gabapentin, so lowering the pH of one's stomach using acidic substances (such as soft drinks) will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>
 {{Preamble/SubjectiveEffects}}
 {{effects/base
@@ Line 66: / Line 67: @@
 ==Toxicity and harm potential==
+{{toxicity}}
 [[File:Gabapentin FDA prescription document.jpg|300px|thumbnail|This document, provided with prescription gabapentin, contains detailed information regarding its toxicity and harm potential.]]
 GABApentin has a [[Toxicity::low toxicity]] relative to dose. The most common side effects of gabapentin in adult patients include dizziness, fatigue, drowsiness, weight gain, and peripheral edema (swelling of extremities).<ref>http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020235s041,020882s028,021129s027lbl.pdf</ref> Gabapentin may also produce sexual dysfunction in some patients whose symptoms of which may include loss of libido, inability to reach orgasm, and erectile dysfunction.<ref>https://books.google.co.uk/books?id=jTc3AAAAQBAJ&pg=PA137&hl=en</ref><ref>https://books.google.co.uk/books?id=_VzzAgAAQBAJ&pg=PT482&hl=en</ref> Gabapentin should be used carefully in patients with renal impairment due to possible accumulation and toxicity.<ref>http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020235s057,020882s041,021129s039lbl.pdf</ref>
@@ Line 75: / Line 77: @@
 ===Lethal dosage===
 People who accidentally or intentionally overdose may experience drowsiness, sedation, blurred vision, slurred speech, somnolence and possibly death (if a very high amount was taken and particularly if combined with alcohol). Serum gabapentin concentrations may be measured to confirm diagnosis.<ref>R.C. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 677–8. ISBN 978-0-9626523-7-0.</ref>
-===Tolerance and addiction potential===
+===Dependence and abuse potential===
 Gabapentin is not considered psychologically addictive. However, it is possible to develop a physical dependence on the drug. In fact, people can experience withdrawal symptoms for up to 45 days after they stop taking gabapentin. Although gabapentin does give some people a euphoric “high” which can cause abuse, gabapentin abusers do not present with the kind of compulsive, drug-seeking behavior or strong cravings associated with other more common depressants such as [[opioids]], [[alcohol]] or [[benzodiazepines]].
@@ Line 81: / Line 83: @@
 ===Dangerous interactions===
+*'''[[DangerousInteraction::Opioids]]''' - Combining opioids with gabapentin can cause death from respiratory failure.
-*'''[[Opioids]]''' - Combining opioids with gabapentin can cause death from respiratory failure.
+*'''[[DangerousInteraction::Depressants]] (GABAergic)''' - Gabapentin significantly potentiates the effects of [[alcohol]], [[benzodiazepines]] and other [[GABA]]genics which may lead to blackouts, and dangerous behaviour.
-*'''[[Depressants|GABAergic depressants]]''' - Gabapentin significantly potentiates the effects of [[alcohol]], [[benzodiazepines]] and other [[GABA]]genics which may lead to blackouts, and dangerous behaviour.
 ==Legal status==