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'''Intrathecal administration''' is a [[route of administration]] for drugs via an [[injection (medicine)|injection]] into the [[spinal canal]], or into the [[subarachnoid space]] so that it reaches the [[cerebrospinal fluid]] (CSF). andIt is useful in several applications, such as for [[spinal anesthesia]], [[chemotherapy]], or [[pain management]] applications. This route is also used to introduce drugs that fight certain infections, particularly post-neurosurgical. TheTypically, the drug needs to beis given this way to avoid being stopped by the [[blood–brain barrier]]. The same drug given orally must enter the blood, streamas andit may not be able to pass out and into the brain when given orally. Drugs given by the intrathecal route often have to be compounded specially by a pharmacist or technician because they cannot contain any preservative or other potentially harmful inactive ingredients that are sometimes found in standard injectable drug preparations.
 
Intrathecal pseudodelivery is a technique where the drug is encapsulated in a porous capsule that is placed in communication with the cerebrospinal CSF. In this method, the drug is not released into the CSF. Instead, the CSF is in communication with the capsule through its porous walls, allowing the drug to interact with its target within the capsule itself. This allows for localized treatment while avoiding systemic distribution of the drug, potentially reducing side effects and enhancing the therapeutic efficacy for conditions affecting the central nervous system.
The route of administration is sometimes simply referred to as "intrathecal"; however, the term is also an adjective that refers to something occurring in or introduced into the [[anatomic space]] or [[potential space]] inside a sheath, most commonly the [[arachnoid membrane]] of the [[brain]] or [[spinal cord]]<ref>{{cite web|title=Route of Administration|url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/DataStandardsManualmonographs/ucm071667.htm|work=Data Standards Manual|publisher=Food and Drug Administration|access-date=11 March 2011}}</ref> (under which is the [[subarachnoid space]]). For example, intrathecal immunoglobulin production is production of antibodies in the spinal cord.<ref>{{cite journal | last1 = Meinl | first1 = E | last2 = Krumbholz | first2 = M | last3 = Derfuss | first3 = T | last4 = Junker | first4 = A | last5 = Hohlfeld | first5 = R | title = Compartmentalization of inflammation in the CNS: a major mechanism driving progressive multiple sclerosis | journal = Journal of the Neurological Sciences | volume = 274 | issue = 1–2 | pages = 42–4 | year = 2008 | pmid = 18715571 | doi = 10.1016/j.jns.2008.06.032 | s2cid = 34995402 }}</ref> The abbreviation "IT" is best not used; instead, "intrathecal" is spelled out to avoid medical mistakes.
 
The route of administration is sometimes simply referred to as "intrathecal"; however, the term is also an adjective that refers to something occurring in or introduced into the [[anatomic space]] or [[potential space]] inside a sheath, most commonly the [[arachnoid membrane]] of the [[brain]] or [[spinal cord]]<ref>{{cite web|title=Route of Administration|url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/DataStandardsManualmonographs/ucm071667.htm|work=Data Standards Manual|publisher=Food and Drug Administration|access-date=11 March 2011}}</ref> (under which is the [[subarachnoid space]]). For example, intrathecal immunoglobulin production is production of antibodies in the spinal cord.<ref>{{cite journal | last1 = Meinl | first1 = E | last2 = Krumbholz | first2 = M | last3 = Derfuss | first3 = T | last4 = Junker | first4 = A | last5 = Hohlfeld | first5 = R | title = Compartmentalization of inflammation in the CNS: a major mechanism driving progressive multiple sclerosis | journal = Journal of the Neurological Sciences | volume = 274 | issue = 1–2 | pages = 42–4 | year = 2008 | pmid = 18715571 | doi = 10.1016/j.jns.2008.06.032 | s2cid = 34995402 }}</ref> The abbreviation "IT" is best not used; instead, "intrathecal" is spelled out to avoid medical mistakes.{{Citation needed|date=May 2024}}
==Intrathecal administration of analgesic agents==
{{see also|Spinal anaesthesia|Cancer pain}}
{{confusing section|date=March 2024}}
* Very popular for a single 24-hour dose of analgesia ([[opioid]] with [[local anesthetic]])
*Caution because of late onset [[hypoventilation]] due to intrathecal opioids
*Severe [[itch|pruritus]] and [[urinary retention]] may limit the use of intrathecal [[morphine]]
*[[Pethidine]] has the unusual property of being both a local anaesthetic and opioid [[analgesic]] which ''occasionally'' permits its use as the sole intrathecal anaesthetic agent
* An intrathecal catheter and pump can be used to deliver a local anaesthetic and sometimes also an opioid and/or [[clonidine]].
* The analgesic [[ziconotide]] is administered through an intrathecal pump system.
 
==Applications of intrathecal administration==
==Intrathecal administration of antifungal agents==
 
=== Analgesics ===
For CNS infections, amphotericin B is administered intrathecally.<ref name="PMID32349999">{{cite journal |last1=Nau |first1=R |last2=Blei |first2=C |last3=Eiffert |first3=H |title=Intrathecal Antibacterial and Antifungal Therapies. |journal=Clinical microbiology reviews |date=17 June 2020 |volume=33 |issue=3 |doi=10.1128/CMR.00190-19 |pmid=32349999|pmc=7194852 }}</ref>
Intrathecal administration is often used for a single 24-hour dose of analgesia ([[opioid]] with [[local anesthetic]]). Caution should be exercised with intrathecal opioids due to the risk of late onset [[hypoventilation]]. The use of intrathecal [[morphine]] may be limited by severe [[itch|pruritus]] and [[urinary retention]].{{Citation needed|date=May 2024}}
 
*[[Pethidine]] has the unusual property of being both a local anaesthetic and opioid [[analgesic]], which ''occasionally'' permits its use as the sole intrathecal anaesthetic agent.{{Citation needed|date=May 2024}}
==Intrathecal chemotherapy==
*Currently, only four agents are licensed for intrathecal chemotherapy:
**[[Methotrexate]], [[cytarabine]] (Ara-C), [[hydrocortisone]], and, rarely, [[thiotepa]].<ref name="pmid8445432">{{cite journal |vauthors=Grossman SA, Finklestein DM, Ruckdeschel JC, etal | title = Randomized prospective comparison of intraventricular methotrexate and thiotepa with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. | journal = Journal of Clinical Oncology | volume = 11 | issue = 3 | pages = 561–9 |date=March 1993 | pmid = 8445432 | doi=10.1200/jco.1993.11.3.561}}</ref>
*Accidental administration of any [[vinca alkaloid]]s—especially [[vincristine]] but also vinblastine, vinorelbine, or others—via the intrathecal route is nearly always fatal.<ref name="pmid15378106">{{cite journal | author = Schulmeister L | title = Preventing vincristine sulfate medication errors | journal = Oncology Nursing Forum | volume = 31 | issue = 5 | pages = E90–8 |date=September 2004 | pmid = 15378106 | doi = 10.1188/04.ONF.E90-E98 | doi-access = free }}</ref><ref name="pmid17355029">{{cite journal |vauthors=Qweider M, Gilsbach JM, Rohde V | title = Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report | journal = Journal of Neurosurgery. Spine | volume = 6 | issue = 3 | pages = 280–3 |date=March 2007 | pmid = 17355029 | doi = 10.3171/spi.2007.6.3.280 }}</ref><ref name="IMSN-gTMSBP">{{Citation |author=International Medication Safety Network |year=2019 |title=IMSN Global Targeted Medication Safety Best Practices |url=https://www.intmedsafe.net/imsn-global-targeted-medication-safety-best-practices/ |access-date=2020-03-11 |postscript=.}}</ref>
 
* An intrathecal catheter and pump system can be used to deliver a local anaesthetic, and sometimes also/or an opioid and/or an atypical analgesic agent as [[clonidineziconotide]].
==Intrathecal baclofen==
{{main|Intrathecal pump}}
Often reserved for [[spastic cerebral palsy]], intrathecally-administered [[baclofen]] is done through an [[intrathecal pump]] implanted just below the skin of the abdomen (or behind the chest wall, depending on the surgeon implanting the device, and patient preferences), with a tube (called the 'catheter') connected directly to the base of the spine, where it bathes the spinal cord using a dose about one thousand times smaller than that required by orally-administered baclofen. Intrathecal baclofen also carries none of the side effects, such as sleepiness, that typically occur with oral baclofen. However, intrathecal baclofen pumps carry serious clinical risks, such as infection or a possibly fatal sudden malfunction, that oral baclofen does not.
 
=== Antifungals ===
A tremendous amount of care is taken to ensure the optimal location of the pump and catheter, based upon medical considerations and patient requirements.
For CNS infections, amphotericin[[Amphotericin B]] is administered intrathecally to treat fungal infections involving the central nervous system infections.<ref name="PMID32349999">{{cite journal |last1=Nau |first1=R |last2=Blei |first2=C |last3=Eiffert |first3=H |title=Intrathecal Antibacterial and Antifungal Therapies. |journal=Clinical microbiologyMicrobiology reviewsReviews |date=17 June 2020 |volume=33 |issue=3 |doi=10.1128/CMR.00190-19 |pmid=32349999|pmc=7194852 }}</ref>
 
==Intrathecal= Cancer chemotherapy ===
**Currently, only four agents are licensed for intrathecal cancer chemotherapy: [[Methotrexatemethotrexate]], [[cytarabine]] (Ara-C), [[hydrocortisone]], and, rarely, [[thiotepa]].<ref name="pmid8445432">{{cite journal |vauthors=Grossman SA, Finklestein DM, Ruckdeschel JC, etal | title = Randomized prospective comparison of intraventricular methotrexate and thiotepa with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group. | journal = Journal of Clinical Oncology | volume = 11 | issue = 3 | pages = 561–9 |date=March 1993 | pmid = 8445432 | doi=10.1200/jco.1993.11.3.561}}</ref>
 
*Accidental administrationAdministration of any [[vinca alkaloid]]s—especiallys, especially [[vincristine]] but also vinblastine, vinorelbine, or others—viavia the intrathecal route is nearly always fatal.<ref name="pmid15378106">{{cite journal | author = Schulmeister L | title = Preventing vincristine sulfate medication errors | journal = Oncology Nursing Forum | volume = 31 | issue = 5 | pages = E90–8 |date=September 2004 | pmid = 15378106 | doi = 10.1188/04.ONF.E90-E98 | doi-access = free }}</ref><ref name="pmid17355029">{{cite journal |vauthors=Qweider M, Gilsbach JM, Rohde V | title = Inadvertent intrathecal vincristine administration: a neurosurgical emergency. Case report | journal = Journal of Neurosurgery. Spine | volume = 6 | issue = 3 | pages = 280–3 |date=March 2007 | pmid = 17355029 | doi = 10.3171/spi.2007.6.3.280 }}</ref><ref name="IMSN-gTMSBP">{{Citation |author=International Medication Safety Network |year=2019 |title=IMSN Global Targeted Medication Safety Best Practices |url=https://www.intmedsafe.net/imsn-global-targeted-medication-safety-best-practices/ |access-date=2020-03-11 |postscript=.}}</ref>
 
=== Baclofen ===
Often reserved for [[spastic cerebral palsy]], intrathecally-administered [[baclofen]] iscan donebe administered through an [[intrathecal pump]] implanted just below the skin of the abdomen (or behind the chest wall, depending on the surgeon implanting the device, and patient preferences), with a tube (called the 'catheter') connected directly to the base of the spine, where it bathes the spinal cord using a dose about one thousand times smaller than that required by orally-administered baclofen. Intrathecal baclofen alsopumps carries none of the side effects, such as sleepiness, that typically occur with oral baclofen. However, intrathecal baclofen pumpssometimes carry serious clinical risks, such as infection or a possibly fatal sudden malfunction,.{{Citation thatneeded|date=May oral baclofen does not.2024}}
 
=== Mesenchymal Stem Cell Therapy===
Treatment of chronic spinal injuries via the administration of [[mesenchymal stem cells]],<ref>{{Cite journal |last1=Li |first1=Man |last2=Chen |first2=Hong |last3=Zhu |first3=Mingxin |date=2022-12-13 |title=Mesenchymal stem cells for regenerative medicine in central nervous system |journal=Frontiers in Neuroscience |language=English |volume=16 |doi=10.3389/fnins.2022.1068114 |doi-access=free |pmid=36583105 |issn=1662-453X|pmc=9793714 }}</ref> either from adipose tissue or bone marrow, is experimental, with better results from the former method. Introduction of mesenchymal stem cells promote the microenvironment needed for axonal regrowth and reduction of inflammation caused by astrocytes proliferation and glial scar tissue.<ref>{{Cite journal |last1=Carrillo-Galvez |first1=Ana Belén |last2=Cobo |first2=Marién |last3=Cuevas-Ocaña |first3=Sara |last4=Gutiérrez-Guerrero |first4=Alejandra |last5=Sánchez-Gilabert |first5=Almudena |last6=Bongarzone |first6=Pierpaolo |last7=García-Pérez |first7=Angélica |last8=Muñoz |first8=Pilar |last9=Benabdellah |first9=Karim |last10=Toscano |first10=Miguel G. |last11=Martín |first11=Francisco |last12=Anderson |first12=Per |date=2015-01-01 |title=Mesenchymal Stromal Cells Express GARP/LRRC32 on Their Surface: Effects on Their Biology and Immunomodulatory Capacity |journal=Stem Cells |language=en |volume=33 |issue=1 |pages=183–195 |doi=10.1002/stem.1821 |issn=1066-5099 |pmc=4309416 |pmid=25182959 |doi-access=free}}</ref>
 
Animal models have showed improved motor control under the site of injury. A clinical trial also showed statistically significant improved sensitivity under the site of injury in patients.<ref>{{Cite journal |last1=Vaquero |first1=Jesús |last2=Zurita |first2=Mercedes |last3=Rico |first3=Miguel A. |last4=Aguayo |first4=Concepcion |last5=Bonilla |first5=Celia |last6=Marin |first6=Esperanza |last7=Tapiador |first7=Noemi |last8=Sevilla |first8=Marta |last9=Vazquez |first9=David |last10=Carballido |first10=Joaquin |last11=Fernandez |first11=Cecilia |last12=Rodriguez-Boto |first12=Gregorio |last13=Ovejero |first13=Mercedes |last14=Vaquero |first14=Jesús |last15=Zurita |first15=Mercedes |date=2018-06-01 |title=Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline |url=https://www.sciencedirect.com/science/article/pii/S1465324918304717 |journal=Cytotherapy |volume=20 |issue=6 |pages=806–819 |doi=10.1016/j.jcyt.2018.03.032 |pmid=29853256 |issn=1465-3249|doi-access=free }}</ref>
 
==See also==