What are the possible side effects of tramadol (Ultram, Ultram ER)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, concerta tramadol, or throat. Stop using tramadol and call your doctor at once if you have any of these serious side effects:
agitation, hallucinations, concerta tramadol, fever, fast heart rate, concerta tramadol, overactive reflexes, nausea, vomiting, diarrhea, concerta tramadol, loss of coordination, fainting;
seizure (convulsions);
a red, blistering, peeling skin rash; or
shallow breathing, weak pulse.
Less serious side effects may include:
dizziness, drowsiness, weakness;
nausea, vomiting, constipation, loss of appetite;
blurred vision;
flushing (redness, warmth, or tingly feeling); or
sleep problems (insomnia).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. What is the most important information I should know about tramadol (Ultram, concerta tramadol, Ultram ER)? You should not take tramadol if you have ever been addicted to drugs or alcohol. Seizures (convulsions) have occurred in some people taking tramadol. You may be more likely to have a seizure while taking tramadol if you have a history of seizures or head injury, a metabolic disorder, or if you are taking certain medicines such as antidepressants, muscle relaxers, or medicine for nausea and vomiting. Take tramadol exactly as it was prescribed for you, concerta tramadol. Do not take it in larger doses or for longer than recommended by your doctor, west livingston. Do not take more than 300 milligrams of tramadol in one day. Seek emergency medical attention if you think you have used too much of this medicine. A tramadol overdose can be fatal, tramadol 083. Overdose symptoms of a tramadol overdose may include drowsiness, shallow breathing, slow heartbeat, extreme weakness, cold or clammy skin, feeling light-headed, fainting, or coma. Tramadol may be habit-forming and should be used only by the person it was prescribed for. Tramadol should never be given to another person, especially someone who has a history of drug abuse or addiction, tramadol 083. Keep the medication in a secure place where others cannot get to it. Tramadol can cause side effects that may impair your thinking or reactions, concerta tramadol. Be careful if you drive or do anything that requires you to be awake and alert. Do not stop using tramadol suddenly, or you could have unpleasant withdrawal symptoms such as anxiety, sweating, nausea, diarrhea, tremors, chills, hallucinations, trouble sleeping, , or breathing problems. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication. Do not crush the tramadol tablet. This medicine is for oral (by mouth) use only. Powder from a crushed tablet should not be inhaled or diluted with liquid and injected into the body. Using this medicine by inhalation or injection can cause life-threatening side effects, overdose, or death. What should I discuss with my healthcare provider before taking tramadol (Ultram, Ultram ER)? You should not take tramadol if you have ever been addicted to drugs or alcohol, if you are currently intoxicated (drunk), or if you have recently used any of the following drugs:
alcohol;
narcotic pain medicine;
sedatives or tranquilizers (such as Valium);
medicine for depression or anxiety;
medicine for mental illness (such as bipolar disorder, schizophrenia); or
street drugs.
Seizures have occurred in some people taking tramadol. Your risk of a seizure may be higher if you have any of these conditions:
a history of drug or alcohol addiction;
a history of epilepsy or other seizure disorder;
a history of head injury;
a metabolic disorder; or
if you are also taking an antidepressant, muscle relaxer, concerta tramadol, or medicine for nausea and vomiting.
Talk with your doctor about your individual risk of having a seizure while taking tramadol. If you have any of these other conditions, , you may need a dose adjustment or special tests to safely take tramadol:
kidney disease;
liver disease;
a stomach disorder; or
a history of depression, mental illness, concerta tramadol, or suicide attempt.
FDA pregnancy category C. This medication may be harmful to an unborn baby. Tramadol may also cause serious or fatal side effects in a newborn if the mother uses the medication during pregnancy or labor. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Tramadol can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Tramadol should not be given to a child younger than 18 years of age. How should I take tramadol (Ultram, Ultram ER)? Take tramadol exactly as it was prescribed for you. Do not take it in larger doses or for longer than recommended by your doctor. Follow the directions on your prescription label. Do not take more than 300 milligrams of tramadol in one day. Take this medication with a full glass of water. Tramadol can be taken with or without food, but take it the same way each time. Do not crush the tramadol tablet. This medicine is for oral (by mouth) use only. Powder from a crushed tablet should not be inhaled or diluted with liquid and injected into the body. Using this medicine by inhalation or injection can cause life-threatening side effects, overdose, or death. Do not crush, , chew, break, , or open a controlled-release, concerta tramadol, delayed-release, or extended-release tablet or capsule. Swallow the pill whole. Breaking or opening the pill may cause too much of the drug to be released at one time. If you use the tramadol extended-release tablet, the tablet shell may pass into your stools (bowel movements). This is normal and does not mean that you are not receiving enough of the medicine. Tramadol may be habit-forming. Tell your doctor if you feel the medicine is not working as well in relieving your pain. Do not change your dose without talking to your doctor. Do not stop using tramadol suddenly, or you could have unpleasant withdrawal symptoms such as anxiety, , sweating, concerta tramadol, nausea, diarrhea, tremors, , chills, hallucinations, trouble sleeping, or breathing problems, large bruising and tramadol. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication. Store tramadol at room temperature away from moisture and heat. Keep track of how many pills have been used from each new bottle of this medicine. Tramadol is a drug of abuse and you should be aware if any person in the household is using this medicine improperly or without a prescription. What happens if I miss a dose (Ultram, Ultram ER)? Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose. What happens if I overdose (Ultram, Ultram ER)? Seek emergency medical attention if you think you have used too much of this medicine. A tramadol overdose can be fatal. Overdose symptoms may include drowsiness, shallow breathing, slow heartbeat, extreme weakness, cold or clammy skin, feeling light-headed, fainting, or coma. What should I avoid while taking tramadol (Ultram, Ultram ER)? Do not drink alcohol while you are taking tramadol. Alcohol may cause a dangerous decrease in your breathing when used together with tramadol. Cold or allergy medicine, concerta tramadol, narcotic pain medicine, , sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by tramadol. Tell your doctor if you regularly use any of these other medicines. Tramadol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. What other drugs will affect tramadol (Ultram, Ultram ER)? You may be more likely to have a seizure (convulsions) if you take tramadol while you are using certain other medicines. Do not take tramadol without telling your doctor if you also use any of the following medications:
an MAO inhibitor such as isocarboxazid (Marplan), tranylcypromine (Parnate), phenelzine (Nardil), or selegiline (Eldepryl, Emsam); large bruising and tramadol; or
an antidepressant such as amitriptyline (Elavil), citalopram (Celexa), , clomipramine (Anafranil), concerta tramadol, desipramine (Norpramin), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Tofranil), nortriptyline (Pamelor); paroxetine (Paxil), or sertraline (Zoloft).
Before taking tramadol, tell your doctor if you also use:
carbamazepine (Tegretol);
warfarin (Coumadin);
digoxin (Lanoxin, Lanoxicaps);
ketoconazole (Nizoral);
erythromycin (E-Mycin, E.E.S., Ery-Tab);
rifampin (Rifadin, Rimactane, Rifater);
St. John's wort;
quinidine (Quinaglute, Quinadex, Cardioquin, Quinora); or
drugs that make you sleepy (such as cold medicine, other pain medications, , muscle relaxants, concerta tramadol, and medicine for seizures, depression or anxiety).
This list is not complete and there may be other drugs that can interact with tramadol. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors, com ultram ultram html. Do not start using a new medication without telling your doctor. Where can I get more information? Your pharmacist can provide more information about tramadol. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
In this study, we demonstrated that tramadol inhibited both the ACh-mediated response of M1 receptors expressed in X, concerta tramadol. laevis oocytes and the muscarine-induced accumulation of cyclic GMP in cultured bovine adrenal medullary cells. To our knowledge, concerta tramadol, this is the first evidence demonstrating that tramadol inhibits the function of muscarinic acetylcholine receptors. According to the report by Lintz et al. (1986), the concentration of tramadol in human serum reaches approximately 600 ng/ml (about 2 μM) after intravenous injection of 100 mg of tramadol, which is the clinical dosage. In the mouse tail-flick test, the plasma concentrations of tramadol for the threshold and maximum effective doses are 0.8 and 10.8 μM, respectively (Friderichs and Becker, concerta tramadol, 1991). In the present study, tramadol inhibited the ACh-induced Cl− currents with an IC50 of 3.4 ± 2.3 μM. In adrenal medullary cells, tramadol suppressed the muscarine-induced cyclic GMP accumulation to 54 and 36% of control at concentrations of 1 and 10 μM, , respectively. From these findings, , it is likely that tramadol suppresses the function of muscarinic receptors at clinically relevant concentrations. The role of brain muscarinic receptors in antinociception and analgesic action has been investigated. Several lines of evidence have shown that muscarinic agonists enhance antinociceptive effects that are blocked by pretreatment with either M1, M2, or M3 muscarinic receptor antagonists, and that M1 receptors may play a major role in antinociception (Bartolini et al., , 1992; concerta tramadol; Naguib and Yaksh, 1997). Moreover, , Ghelardini et al, concerta tramadol. (2000) reported a loss of muscarinic antinociception by antisense inhibition of M1 receptors in mice by using the hot-plate test, suggesting that activation of the M1 receptor subtype may be fundamental for inducing central cholinergic analgesia. These data are not consistent with our findings that a centrally acting analgesic, tramadol, inhibits M1 muscarinic receptor function. In contrast, inhibition of the muscarinic signaling pathway induced by the reduction of acetylcholine levels, inhibiting its release or administering scopolamine in rat brains, concerta tramadol, decreases the minimal alveolar concentration of inhaled anesthetics (Zucker, 1991), concerta tramadol. Ketamine (Durieux, 1995a), concerta tramadol, halothane (Durieux, 1995b), concerta tramadol, and isoflurane (Minami et al., , 1994) are well known to depress muscarinic receptor function. Thus, the actions of analgesics or anesthetics on muscarinic receptors may be more complex than currently considered (Durieux, 1996), and further studies are needed to define the relationship between antinociception and muscarinic receptor function. Recently, Gomeza et al. (1999) reported that muscarine-induced analgesia is mediated predominantly, but not exclusively, by the M2 receptor subtype in behavioral experiments by using M2 knockout mice, large bruising and tramadol. Furthermore, a recent article reported an involvement of M3 receptors of the spinal cord in formalin-induced nociception in mice (Honda et al., 2000), concerta tramadol. To clear analgesic mechanisms of tramadol, it would be interesting to study the effects of tramadol on M2 or M3 receptors. There have been a number of reports that show cyclic GMP accumulation by acetylcholine or muscarine in adrenal medullary cells (Schneider et al., , 1979; Yanagihara et al., 1979; Derome et al., 1981; concerta tramadol; Lemaire et al., 1981). Previously, Yamanaka et al. (1986) characterized muscarinic receptors in bovine adrenal medulla by radioligand binding assay with [3H]QNB. They showed that at least two distinct subtypes of muscarinic receptors exist in the adrenal medullary cells, and these receptors are predominantly composed of M1 receptors. Because M1receptors are reported to couple with Gq type (Caulfield, 1993), in the present study muscarine may stimulate cyclic GMP accumulation via Gq protein in adrenal medulla, concerta tramadol. On the other hand, other subtypes, such as M2 (Aguilar et al., 1992), M3 (Aguilar et al., 1992), or M4 (Fernando et al., 1991), have been reported to exist in adrenal medullary cells. Although the molecular mechanism of cyclic GMP accumulation by acetylcholine or muscarine has not been well understood, the inhibition by tramadol on cyclic GMP accumulation suggests the anticholinergic effects in vivo. In a clinical situation, tramadol sometimes causes anticholinergic effects such as dry mouth and constipation (Katz, , 1996). Northern blot analysis (Maeda et al., 1988) and receptor-specific antibody immunoprecipitation studies (Dörje et al., 1991) demonstrate mainly the presence of M1 and M3 receptors in peripheral glandular tissue. These anticholinergic effects of tramadol in clinical treatment suggest that tramadol would inhibit not only M1 but also other subtypes of muscarinic receptor functions, concerta tramadol. This study raised the question of how tramadol inhibits M1 receptor-mediated responses. There is considerable evidence that PKC plays an important role in the regulation of G protein-coupled receptors (Sakuta et al., 1991; Minami et al., concerta tramadol, 1997a), west livingston. We recently reported that halothane, concerta tramadol, F3 (1-chloro-1,2,2-trifluorocyclobutane), and ethanol inhibited the function of the 5-hydroxytryptamine2A receptor (Minami et al., 1997b) as well as that of the M1receptor (Minami et al., 1997a) in a PKC-dependent manner, concerta tramadol. In addition, M1 receptors are phosphorylated by PKC (Haga et al., concerta tramadol, 1996), com ultram ultram html. In our experiments, concerta tramadol, however, GF109203X did not have any effect on the inhibitory effects of tramadol on muscarinic function, suggesting that PKC is not involved in the inhibitory effects of tramadol on M1 function, tramadol 083. Moreover, tramadol had few effects on AlF4−-induced currents, suggesting that tramadol does not interfere with the pathway after G protein-coupled signal transduction, such as phospholipase C activation, intracellular Ca2+ release, and Ca2+-activated Cl−current. From these results, it is likely that the effect of tramadol on the ACh-induced Cl− current is due to direct inhibition of M1 receptors. To confirm our hypothesis, we next examined the effects of tramadol on [3H]QNB binding to muscarinic receptors in cultured bovine adrenal medullary cells, tramadol 083. Tramadol inhibited the specific binding of [3H]QNB to the cells, and this was reversed by increasing the concentration of [3H]QNB. Scatchard plot analysis of [3H]QNB binding revealed that tramadol increased the Kd value without altering the Bmax, concerta tramadol, indicating competitive inhibition. These findings suggest that tramadol shares the binding sites on muscarine receptors with QNB, concerta tramadol. Yamanaka et al. (1986)reported that the [3H]QNB binding sites to bovine adrenal medulla are also able to be displaced with atropine, which binds to ACh binding sites on ACh receptors. From the present findings, tramadol may inhibit M1 receptor function by interacting with the binding sites of muscarine or ACh, tramadol 083. It is of interest to define the region of M1responsible for tramadol action by using site-directed mutagenesis and such studies are currently underway in our laboratory. In conclusion, tramadol at clinically relevant concentrations inhibits M1 muscarinic receptor function by interfering with the QNB binding sites on the receptor. Our findings help to unveil the pharmacological basis for the better understanding of the neuronal action and anticholinergic effects of tramadol.
|
