Clinical Experience with Oral Ketamine

Enarson, Mark C; Hays, Helen; Woodroffe, Mary Ann

doi:10.1016/s0885-3924(99)00011-1

Cited by 117 publications

(47 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, use of these inhibitors is limited because of the numerous side effects resulting from antagonizing NMDA receptors in the CNS (Enarson, Hays, & Woodroffe, 1999; Rabben et al., 1999; Schmid et al, 1999). Several reports have shown that NMDA receptors are present in both CNS and in the peripheral nerves (Carlton, 2001; Carlton & Coggeshall, 1999; Coggeshall & Carlton, 1998).…”

Section: Discussionmentioning

confidence: 99%

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

Liu¹,

Cheng

Hung

et al. 2016

Brain and Behavior

View full text Add to dashboard Cite

Background and Purpose RNA polymerase II promoters that drive the expression of rationally designed primary microRNA‐based shRNA, for example, shRNAmir, can produce more potent gene knockdown than RNA polymerase III promoters. Antagonists of peripheral N methyl‐D‐aspartate (NMDA) receptors that do not interfere with central glutamate processing would prevent the development of adverse central nervous system effects. Thus, in this study, we examined the effects of gene silencing and antinociception on formalin‐ and Complete Freund's adjuvant (CFA)‐induced pain in rats by subcutaneously injecting a lentiviral vector encoding a shRNAmir that targets the NR1 subunit of the NMDA receptor.MethodsRats received intradermal injections of different doses of NR1 shRNAmir at different time points before injection of formalin. Pain behavior was assessed by monitoring the paw flinch response, paw withdrawal threshold, and thermal withdrawal latency. We then analyzed NR1 messenger RNA and protein expression in skin and the L5 dorsal root ganglion (DRG).ResultsWe found that intradermal injection of 1, 5, and 10 μg of shRNAmir significantly inhibited flinch responses (p < .05). Administration of 5 μg of shRNAmir resulted in the attenuation of CFA‐induced mechanical allodynia, but did not affect the time spent on the rotarod. Real‐time polymerase chain reaction and western blotting revealed that NR1 mRNA and protein levels were significantly lower in all NR1 shRNAmir1 groups than in controls (p < .05). There was a significant reduction in the percentage of NR1‐ and pERK‐positive neurons in the DRG ipsilateral to shRNAmir treated paws (p < .05). The effect of antinociception and inhibition of NR1 expression by NR1 shRNAmir was evident on day 3 and persisted for 7 days after injection of 5 μg of vector.ConclusionPeripheral administration of the vector‐encoded NR1 shRNAmir is a promising therapy for persistent inflammatory pain.

show abstract

Section: Discussionmentioning

confidence: 99%

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

Liu¹,

Cheng

Hung

et al. 2016

Brain and Behavior

View full text Add to dashboard Cite

show abstract

“…However, There is no consensus in the literature on the most appropriate oral dose of this drug that has been used in a wide range of doses, of up to 500 mg.day -1 or more. Despite the lack of a consensus, several authors have used doses of 0.5 mg.kg -1 of racemic ketamine 16,31,32 . The pharmacokinetics of oral S(+) ketamine needs to be studied further.…”

Section: Discussionmentioning

confidence: 99%

“…Entretanto, não há um consenso na literatura sobre a dose mais apropriada desse fármaco pela via oral, que tem sido usada em uma ampla faixa, com relatos de doses de 500 mg.dia -1 ou mais. Apesar dessa indefinição, muitos autores têm utilizado doses de cetamina racêmica em torno de 0,5 mg.kg -1 em algumas tomadas por dia 18,31,32 . A farmacocinética da S(+) cetamina por via oral precisa ser mais bem estudada.…”

Section: Tabela I -Dados Demográficosunclassified

Avaliação da S(+) cetamina por via oral associada à morfina no tratamento da dor oncológica

Ishizuka¹,

Garcia²,

Sakata³

et al. 2007

Rev. Bras. Anestesiol.

View full text Add to dashboard Cite

RESUMOIshizuka P, Garcia JBS, Sakata RK, Issy AM, Mülich SL -Avaliação da S(+) Cetamina por Via Oral Associada à Morfina no Tratamento da Dor Oncológica. JUSTIFICATIVA E OBJETIVOS:A morfina é muito usada para o alí-vio da dor oncológica. Entretanto, pode ocorrer tolerância com seu uso prolongado. A associação de antagonista de receptores NMDA pode diminuir ou retardar esse fenômeno. A S(+) cetamina parece ser mais potente e com menos efeitos colaterais. O objetivo deste estudo foi avaliar a ação da S(+) cetamina associada à morfina no tratamento da dor oncológica. MÉTODO:Foram avaliados, de forma duplamente encoberta, 30 pacientes divididos em dois grupos. Os do G1 receberam 10 mg de morfina a cada seis horas, associada a 10 mg de S(+) cetamina a cada oito horas, por via oral. Os do G2 receberam 10 mg de morfina a cada seis horas, associada ao placebo a cada oito horas, por via oral. A dose de morfina foi aumentada em 5 mg, quando necessário. A intensidade da dor foi avaliada por meio de escala verbal. RESULTADOS:A porcentagem de dor ausente e leve foi semelhante nos grupos (G1 = 0 e G2 = 0 no M0; G1 = 22,2 e G2 = 53,8 no M1; G1 = 22,2 e G2 = 61,5 no M2; G1 = 44,6 e G2 = 61,5 no M3; e G1 = 44,5 e G2 = 53,8 no M4); teste do Qui-quadrado. Foi observada porcentagem de alívio moderado e completo semelhante nos grupos (G1 = 33,4 e G2 = 53,9 após uma semana; G1 = 44,4 e G2 = 69,2 após duas semanas; G1 = 66,6 e G2 = 69,2 após três semanas; G1 = 55,6 e G2 = 53,9 após quatro semanas); teste do Quiquadrado. A necessidade de aumento da dose de morfina foi semelhante nos dois grupos (G1 = 2,22 e G2 = 2,15), teste de MannWhitney. CONCLUSÕES:Não foi observado aumento do efeito analgésico com 10 mg de S (+) cetamina, administrada a cada oito horas por via oral associada à morfina no tratamento da dor oncológica.Unitermos: ANALGÉSICOS, Opióides: morfina; cetamina; DOR, Oncológica. SUMMARY BACKGROUND AND OBJECTIVES:Morphine is used frequently to treat oncologic pain. However, tolerance may develop with prolonged use. The association of a NMDA receptor antagonist may reduce or delay the onset of tolerance. S(+) ketamine seems to be more potent and with fewer side effects. The aim of this study was to evaluate the association of S(+) ketamine and morphine in the treatment of oncologic pain. METHODS:Thirty patients, randomly divided in two groups, participated in this double-blind study. Patients in G1 received 10 mg of morphine PO every 6 hours and 10 mg of S(+) ketamine PO every 8 hours. Patients in G2 received 10 mg of morphine PO every 6 hours and placebo PO every 8 hours. The dose of morphine was adjusted by 5 mg increments whenever necessary. Pain severity was evaluated through a verbal scale. RESULTS:The percentage of no pain and mild pain was similar in both groups (G1 = 0 and G2 = 0 at M0; G1 = 22.2 and G2 = 53.8 at M1; G1 = 22.2 and G2 = 61.5 at M2; G1 = 44.6 and G2 = 61.5 at M3; and G1 = 44.5 and G2 = 53.8 at M4); Chi-square test. The percentage of moderate relief and complete relief was similar in both groups (G1 = 33....

show abstract

“…both pain relief and tolerable undesirable effects, varies from <20% to about 50%. 10,11,47,112 Some practitioners routinely reduce the background opioid dose by 25e50% when starting parenteral ketamine. If the patient becomes drowsy, the dose of opioid should be reduced.…”

Section: Dose and Usementioning

confidence: 99%

Ketamine*

Quibell

Fallon

Mihalyo

et al. 2015

Journal of Pain and Symptom Management

View full text Add to dashboard Cite

The use of ketamine is associated with neuropsychiatric, urinary tract and hepatobiliary toxicity. Although most reports involve long-term recreational abusers, it has also arisen after only 1e2 weeks of therapeutic use (Box A). Accordingly, the use of ketamine should be restricted to specialists in pain or palliative care for patients who have failed to obtain relief from standard drug and non-drug treatments.Class: General anesthetic.Indications: Induction and maintenance of anesthesia; yneuropathic, inflammatory, ischemic limb and procedure-related pain unresponsive to standard treatments. 1,2 Contra-indications: Any situation in which an increase in blood pressure would constitute a hazard. PharmacologyKetamine, a derivative of phencyclidine (PCP), is a dissociative anesthetic which has analgesic properties in subanaesthetic doses. 2,3 Ketamine is the most potent NMDA-receptor-channel blocker available for clinical use, binding to the PCP site when the channels are in the open activated state (Fig. 1). 3 It also binds to a second membrane-associated site which decreases the frequency of channel opening. 3 The NMDA receptor-channel complex is closely involved in the development of central sensitization of dorsal horn neurons which transmit pain signals. 4 At normal resting membrane potentials, the channel is blocked by magnesium and is inactive. 3 When the resting membrane potential is changed as a result of prolonged excitation, the channel unblocks and calcium moves into the cell. This leads to neuronal hyperexcitability and results in hyperalgesia and allodynia, and a reduction in opioid-responsiveness. These effects are probably mediated by the intracellular formation of nitric oxide and cyclic guanosine monophosphate. 3 The reduction in opioid-responsiveness arises from cross-talk between opioid receptors and the NMDA receptor-channel. Opioid receptor activation results in phosphorylation and opening of the NMDA receptorchannel leading to a cascade of events which ultimately down-regulates the opioid receptor and its effects, thereby contributing towards tolerance and hyperalgesia. 3

show abstract

Clinical Experience with Oral Ketamine

Cited by 117 publications

References 12 publications

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

Avaliação da S(+) cetamina por via oral associada à morfina no tratamento da dor oncológica

Ketamine*

Contact Info

Product

Resources

About