• Korean Journal of Clinical Pharmacy
• /
• v.21 no.1
• /
• pp.36-38
• /
• 2011

We report an unusual case of respiratory depression and prolonged apnea after the second dose of 100-mg intravenous tramadol. Due to continuous pain at foley catheter keep site, intravenous tramadol was administered to the patient. Soon after the second dose of tramadol injection, the patient became apneic. The patient did not respond to verbal command and started exhibiting oxygen desaturation. The patient was quickly treated with 100% oxygen, and it took 4 hours for the spontaneous respiration to return to regular. This case report demonstrates that even two doses of tramadol administered intravenously may manifest as sudden and prolonged apnea. Respiratory depression with tramadol has been reported in patients with impaired renal functions and Cytochrome P(CYP) 2D6 gene duplication.

• Biomolecules & Therapeutics
• /
• v.31 no.2
• /
• pp.168-175
• /
• 2023

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Na_v1.7 or the cardiac sodium channel Na_v1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Na_v1.7 and 0.43 mM for Na_v1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Na_v1.7 and Na_v1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Na_v1.7 and Na_v1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Na_v1.7 or show cardiotoxicity by blocking Na_v1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

• Journal of Veterinary Clinics
• /
• v.29 no.3
• /
• pp.226-232
• /
• 2012

This study was performed to evaluate the sedative and analgesic effects of intravenous (IV) administration of detomidine (D) and tramadol (T) to horses. Six warmblood horses each received D (10 ${\mu}g/kg$), T (2 mg/kg), and a combination of DT (10 ${\mu}g/kg$ and 2 mg/kg). No significant differences in the heart rate, respiratory rate, rectal temperature, indirect arterial pressure, and gastrointestinal motility between D and DT were observed. The sedative effect was evident within 5 min after D and DT administration, but no significant difference between D and DT was observed. D and DT induced a similar analgesic effect up to 50 min after injection and DT maintained a longer analgesic effect than D. A significant increase in blood glucose was shown for D after the injection, but not for DT. A horse with T and DT showed an excited behavior within 5 min of the injection. This study suggests that the DT combination could be used for diagnostic procedures and simple surgeries in standing horses, with caution for excitement in the early phase after the administration.

• Journal of Veterinary Clinics
• /
• v.27 no.6
• /
• pp.668-673
• /
• 2010

This study was to evaluate the effects of tramadol and medetomidine administration on minimum alveolar concentration (MAC) of isoflurane in dogs. MAC of isoflurane was determined in four occasions; 1 ml saline (Control), $2{\mu}g$/kg medetomidine (M2), 4 mg/kg tramadol (T4), $2{\mu}g$/kg medetomidine-4 mg/kg tramadol combination (M2T4). Heart rate, blood pressure, respiratory rate, end-tidal carbon dioxide concentration, saturation of hemoglobin with oxygen and body temperature were recorded. After administration of M2 ($0.81{\times}0.18%$), T4 ($0.81{\times}0.14%$) and M2T4 ($0.62{\times}0.12%$), less isoflurane was required than the control value ($1.13{\times}0.19%$). Significantly lower heart rate than the control value was detected after treatment of M2, T4, and M2T4. When only M2T4 was administered, blood pressure was significantly higher than the control value. In conclusion, administrations of tramadol, medetomidine and medetomidine-tramadol combination decreased the MAC of isoflurane in dogs. Especially, medetomidine-tramadol combinations could be useful as a premedication because of the anesthetic sparing effect and moderate changes in cardiovascular system.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.3
• /
• pp.191-198
• /
• 2010

The effects of different doses of tramadol on analgesia and electroencephalographic (EEG) spectralparameters were compared in rats. Saline or tramadol 5, 10, 20 or 40 mg/kg was administered. The degree of analgesia was evaluated by tail-flick latency, and the degree of seizure was measured using numerical seizure score (NSS). Additionally, band powers, median power frequency and spectral edge frequency 95 were measured to quantify the EEG response. All doses of tramadol produced spike-wave discharge. Tramadol significantly and dose-dependently increased the analgesia, but these effects did not correspond with the changes in the EEG spectral parameters. NSS significantly increased in the Tramadol 20 and 40 mg/kg treatment groups compared to the Control and TRA5 groups, and two rats given 40 mg/kg had convulsions. In conclusion, tramadol dose-dependently increased the analgesic effect, and the 10 mg/kg dose appears to be a reliable clinical dose for analgesia in rats, but dose-dependent increases in analgesia and seizure severity did not correlate with EEG spectral parameters.

• The Korean Journal of Pain
• /
• v.14 no.2
• /
• pp.150-155
• /
• 2001

Background: Tramadol is known to be a weak opioid. However, it has also been shown that tramadol is an effective norepinephrine and serotonin uptake blocker, which may be effective in the treatment of neuropathic pain. The present study was undertaken in order to assess the antinociceptive action of tramadol and to investigate possible antinociceptive mechanisms by using antagonists in an animal neuropathic pain models in rats. Methods: Rats were prepared with tight ligation at the left 5 and 6th lumbar spinal nerves (Kim and Chung's neuropathic pain model). The antinociceptive effects of tramadol (10, 20, and 50 mg/kg i.p.) in rats with neuropathic pain were assessed. Additionally, following coadministration of antagonists such as naloxone (1 mg/kg i.p.), yohimbine (1 mg/kg i.p.) and ritanserin (1 mg/kg i.p.) with 50 mg/kg of tramadol, the responses to mechanical and thermal stimuli were measured over a two-hour period. Results: Tramadol displayed potent antinociceptive effects in a dose-dependent manner on rats with neuropathic pain (P < 0.05). The effects of tramadol were inhibited by coadministered naloxone and yohimbine in rats with mechanical and thermal allodynia, respectively (P < 0.05). However, there were no significant changes in the pain behaviors in the case of ritanserin. Conclusions: Tramadol showed significant antinociceptive effects in rats with regards to neuropathic pain against both mechanical and thermal allodynia. The antinociceptive effect on the mechanical stimuli is medicated via an opioid receptor. However, it appears that the antinociceptive effects on thermal allodynia are mediated via a noradrenalin receptor vice a serotonergic receptor.

• The Korean Journal of Pain
• /
• v.11 no.1
• /
• pp.54-59
• /
• 1998

Background: Tramadol administered epidurally is known to have one-thirtieth the potency of morphine for treatment of pain following abdominal surgery. We designed a prospective, randomized, controlled study to evaluate the analgesic efficacy and safety of combined epidural infusion of bupivacaine and tramadol with 2-day infusor as ompared to bupivacaine and morphine combined epidural infusion. Methods: Sixty healthy women scheduled for Cesarean delivery were assigned randomly in double- blind fashion: Group 1 (n=20) were given a mixture of morphine 10 mg(1 ml), 0.5% bupivacaine 40 ml and normal saline(NS) 40 ml; Group 2(n=20) a mixture of tramadol 300 mg(6 ml), 0.5% bupivacaine 40 ml and NS 54 ml; Group 3(n=20) or a mixture of tramadol 500 mg(10 ml), 0.5% bupivacaine 50 ml and NS 50 ml, of continuous dose via epidural route following 1% lidocaine 6 ml as bolus dose for 48 hours postoperatively. We evaluated the analgesic efficacy and side effects of these three groups using visual analogue pain scale (VAPS) and verbal rating scale (VRS). Results: VAPS of group 1 and 3 were lower than group 2, and VAPS of group 1 was lower than group 3(12, 24, 36, 48 hours). VRS of group 1 and 3 were lower than group 2 (12, 24, 36 hours). There were incidences of pruritus was 16 patients in group 1. Conclusions: Tramadol does possess the analgesia effect of morphine, but has the added analgesia following increment. Further research to determine the most effective administration method and reguired dosage of tramadol is further needed.

• Analytical Science and Technology
• /
• v.31 no.3
• /
• pp.107-111
• /
• 2018

Currently, ultraviolet-visible spectrophotometry and titration methods are used for assay tests of tramadol hydrochloride injection and raw material in the Korean Pharmacopoeia XI (KP XI). Titration has also been used in the British Pharmacopoeia (BP 2013) for the assay test of tramadol hydrochloride, and the HPLC assay for tramadol hydrochloride raw material has been used in the United States Pharmacopeia (USP 39). In this study, we developed an alternative HPLC assay method for tramadol hydrochloride injection that is up to date and specific, and employs the same method as tramadol hydrochloride capsules. Validation of the HPLC method was conducted to determine linearity, precision, accuracy, system suitability, and robustness. The linearity of the calibration curves in the desired concentration range was good ($r^2$ > 0.9999). RSDs of intra-day precision obtained were 0.05-0.08 % and inter-day precision obtained were 0.08-0.19 %. Accuracy was obtained with recoveries in the range of 98.16 % and 100.90 %. As a result of the system's suitability, the RSD of both retention time and the peak area obtained were 0.07 %. The values of the plate number and tailing factor of tramadol hydrochloride obtained were 7076 and 1.16, respectively. Because of the intermediate precision and robustness of the developed assay, it is expected to become a valuable tool for revising the Korean Pharmacopoeia (KP XI).

• Journal of Veterinary Clinics
• /
• v.33 no.6
• /
• pp.325-331
• /
• 2016

This study investigated the antinociceptive effect of epidural tramadol with bupivacaine in 36 healthy Beagle dogs. The dogs were divided into 6 groups; 1) C (control), 2) B (0.5% bupivacaine 0.1 mL/kg), 3) BT0.5 (0.5% bupivacaine 0.1 mL/kg + tramadol 0.5 mg/kg), 4) BT1 (0.5% bupivacaine 0.1 mL/kg + tramadol 1 mg/kg), 5) BT2 (0.5% bupivacaine 0.1 mL/kg + tramadol 2 mg/kg), 6) BT3 (0.5% bupivacaine 0.1 mL/kg + tramadol 3 mg/kg). The epidural injection was performed under isoflurane inhalation, after then, nociceptive block and motor block scores were assessed with physiologic parameters (HR, RR, RT, MAP). BT groups showed significantly longer antinociceptive time than C and B, while motor block time of BT groups were not different from B except BT3. Durations of total nociceptive block of BT2 ($60.83{\pm}19.08min$) and BT3 ($74.17{\pm}8.61min$) were significantly longer than those of BT0.5 ($33.33{\pm}8.76min$) and BT1 ($37.50{\pm}19.43min$), but there was no significant difference between BT2 and BT3. Durations of total motor block in all groups were less than 20 minutes although that of BT3 was significantly longer than B. There were no significant differences in HR, RR, RT, MAP among groups. Consequently, epidural administration of tramadol (2 mg/kg) with 0.5% bupivacaine (0.1 mL/kg) can be used safely and effectively in dogs.

• Journal of Yeungnam Medical Science
• /
• v.37 no.4
• /
• pp.329-331
• /
• 2020

Negative myoclonus (NM) is a shock-like jerky involuntary movement caused by a sudden, brief interruption of tonic muscle contraction. NM is observed in patients diagnosed with epilepsy, metabolic encephalopathy, and drug toxicity and in patients with brain lesions. A 55-year-old man presented with NM in both his arms and neck. He has taken medications containing tramadol at a dose of 80-140 mg/day for 5 days due to common cold. He had no history of seizures. Acute lesions were not observed during magnetic resonance imaging, and abnormal findings in his laboratory tests were not noted. His NM resolved completely after the discontinuation of tramadol and the oral administration of clonazepam. Our case report suggests that tramadol can cause NM in patients without seizure history or metabolic disorders, even within its therapeutic dose.