Tramadol is a synthetic codeine analog, tramadol has central analgesic properties with effects similar to opioids, such as morphine and codeine, acting on specific opioid receptors. Used as a narcotic analgesic for severe pain, it can be addictive and weakly inhibits norepinephrine and serotonin reuptake.
Tramadol is an opioid analgesic used for the therapy of mild-to-moderate pain. Tramadol overdose can cause acute liver failure. Pharmacologic use of tramadol has not been associated with cases of the clinically apparent drug-induced liver disease.
Tramadol is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually occurs within an hour. It is often combined with paracetamol (acetaminophen) as this is known to improve the efficacy of tramadol in relieving pain.
Mechanism of Action of Tramadol
Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. The analgesic properties of Tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has a higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha(2)-adrenergic receptors.
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Tramadol is a racemic mixture (R & S) that has a complicated mechanism of action. It has some mu-opioid receptor action, but this effect is 10 times lower than codeine and 6000 times lower than morphine. Tramadol also inhibits the reuptake of norepinephrine (NE) and serotonin (5 HT) and produces secondary effects on alpha-2 adrenergic receptors in pain pathways. One isomer has a greater effect on 5 HT reuptake and greater affinity for mu-opiate receptors. The other isomer is more potent for NE reuptake and less active for inhibiting 5 HT reuptake. Taken together, the effects of tramadol may be explained through inhibition of 5 HT reuptake, action on alpha2 receptors, and mild activity on opiate mu-receptors.
or
The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice. Reportedly, tramadol and its metabolite (M1) bind to mu-opioid receptors and/or inhibit reuptake of monoamines in the central nervous system, resulting in the activation of the descending inhibitory system. However, the fundamental mechanisms of tramadol in pain control remain unclear. TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively. We examined whether and how tramadol and M1 act on human embryonic kidney 293 (HEK293) cells expressing human TRPV1 (hTRPV1) or hTRPA1 by using a Ca imaging assay and whole-cell patch-clamp recording. Tramadol and M1 (0.01-10 uM) alone did not increase in intracellular Ca concentration ([Ca]i) in HEK293 cells expressing hTRPV1 or hTRPA1 compared with capsaicin (a TRPV1 agonist) or the allyl isothiocyanate (AITC, a TRPA1 agonist), respectively. Furthermore, in HEK293 cells expressing hTRPV1, pretreatment with tramadol or M1 for 5 minutes did not change the increase in [Ca] I induced by capsaicin. Conversely, pretreatment with tramadol (0.1-10 uM) and M1 (1-10 uM) significantly suppressed the AITC-induced [Ca] I increases in HEK293 cells expressing hTRPA1. In addition, the patch-clamp study showed that pretreatment with tramadol and M1 (10 uM) decreased the inward currents induced by AITC. These data indicate that tramadol and M1 selectively inhibit the function of hTRPA1, but not that of hTRPV1 and that hTRPA1 may play a role in the analgesic effects of these compounds.
Indications of Tramadol
- Fibromyalgia
- Pain due to road traffic accident.
- A headache
- Severe fever
- Chest pain
- A migraine headache
- Acute pain due to trauma
- Accidental pain
- Acute abdominal pain due to gastritis/appendicitis
- Ankylosing spondylitis
- Pain due to especially musculoskeletal system
- Ankylosing spondylitis
- Pain due to especially musculoskeletal system
- Lumbago
- Low back pain
- PLID
- Polyarthralgia
- Muscles stiffness in nerve diseases
- Multiple joint pain
- Muscles stiffness in the spinal cord
- Pain caused by nonarticular rheumatism
- Periarthritis of scapulohumeral
- Indicated in the treatment of moderate to severe pain. Consider for those prone to constipation or respiratory depression. Tramadol is used to treat postoperative, dental, cancer, and acute musculoskeletal pain and as an adjuvant to NSAID therapy in patients with osteoarthritis.
Therapeutic Indications of Tramadol
- Analgesics, Opioid; Narcotics
- Tramadol hydrochloride tablets, USP are indicated for the management of moderate to moderately severe pain in adults.
- Tramadol hydrochloride extended-release tablets are indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time.
Contra-Indications of Tramadol
Tramadol is contraindicated in those with hypersensitivity,
- Allergy to tramadol hydrochloride or any other ingredients in the medicine;
- Allergy to medicines called opioid antagonists (e.g. codeine, morphine);
- Consumed alcohol taken another drug which affects your brain. These include:
- Some painkillers, including opioid painkillers;
- Hypnotic drugs;
- Psychotropic drugs;
- Used monoamine oxidase inhibitors (MAOIs) such as phenelzine or tranylcypromine
- Epilepsy;
- Addiction or are recovering from addiction to another medication.
- History of peptic ulcer disease,
- Gastrointestinal bleeding,
- Alcohol intolerance,
- Renal impairment,
- Cerebrovascular bleeding,
- Nasal polyps,
- Angioedema, and asthma
- Acute intoxication with alcohol,
- Hypnotics,
- Heart failure,
- Coagulation disorders,
- Renal impairment,
- Hepatic impairment.
Dosage of Tramadol
Strengths: 50 mg; 100 mg/24 hours; 200 mg/24 hours;
Pain
Immediate-release
- 50 to 100 mg orally every 4 to 6 hours as needed for pain
- Maximum dose: 400 mg per day
Chronic Pain
Immediate-Release (IR)
- Initial dose: 25 mg orally once a day; titrate in 25 mg increments every 3 days to reach a dose of 25 mg four times a day; thereafter increase by 50 mg as tolerated every 3 days to reach a dose of 50 mg four times a day
- Maintenance dose: After titration, 50 to 100 mg orally as needed for pain every 4 to 6 hours
- Maximum dose: 400 mg per day
Extended-Release (ER)
- Initial dose (tramadol-naive): 100 mg orally once a day
- Individually titrate in 100 mg increments every 5 days to an effective dose that minimizes adverse reaction
- Maximum Dose: 300 mg orally per day
Geriatric Pain
- Age: 75 years or older: Maximum dose: 300 mg per day
Geriatric, Chronic Pain
- Age: 75 years or older: Maximum dose: 300 mg per day
Pediatric Dose for Pain
17 years or older
- Immediate-release: 50 to 100 mg orally every 4 to 6 hours as needed for pain
- Maximum dose: 400 mg per day
Immediate-Release
- Initial dose: 25 mg orally once daily; titrate in 25 mg increments every 3 days to reach a dose of 25 mg four times a day; thereafter increase by 50 mg as tolerated every 3 days to reach a dose of 50 mg four times a day
- Maintenance dose: After titration, 50 to 100 mg orally as needed for pain every 4 to 6 hours
- Maximum dose: 400 mg per day
Side Effects of Tramadol
The most common
- GI disorders (e.g. dyspepsia, abdominal pain, nausea, vomiting, diarrhea, flatulence, constipation,, ulcerative stomatitis, ), indigestion,
- Disturbances of the gut such as diarrhea, constipation, nausea, vomiting or abdominal pain.
- Drowsiness and lightheadedness
- Nausea and vomiting
- joint pain
- Nausea and vomiting
- Severe stomach ache
- Severe diarrhea
- Vaginal thrush
- Skin rash
- Headache
- Chest pain
- Diarrhea or loose stools
- Difficulty with breathing
- Dizziness
- Heartburn
- Muscle pain
More common
- Abdominal or stomach pain,
- Chills or fever
- Headache,
- Joint or back pain
- Muscle aching or cramping
- Muscle pains or stiffness
- Chest pressure or squeezing pain in the chest
- Excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- Constipation
- Diarrhea
- Loss of muscle coordination
- Sleepiness or unusual drowsiness
- Clumsiness or unsteadiness
- Drowsiness
Rare
- Anxiety
- change in vision
- seizures
- abnormal or fast heart rate
- tremors
- weight loss
- chest pain or tightness
- confusion
- a cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- a headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
Drug Interactions of Tramadol
Tramadol may interact with following drugs, supplements & may change the efficacy of drugs
- anti-emetic medications (serotonin antagonists; e.g., granisetron, ondansetron)
- antihistamines (e.g, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- aminoglycoside antibiotics (e.g., amikacin, gentamicin, tobramycin)
- angiotensin-converting enzyme inhibitors (ACEIs; e.g., captopril, enalapril, ramipril)
- angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
- beta-adrenergic blockers (e.g., metoprolol, atenolol)
- baclofen
- barbiturates (e.g., butalbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- celecoxib
- cilostazol
- clopidogrel
- corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, )
- 5-ASA medications (e.g. sulfasalazine)
- glucosamine
- haloperidol
- heparin
- methotrexate
- multivitamins
- other non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, ketorolac, naproxen)
- Omega-3 fatty acids
- phenytoin
- phenobarbital
- pentoxifylline
- quinolone antibiotics (e.g., ciprofloxacin, norfloxacin, ofloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- serotonin/norepinephrine reuptake inhibitors (SNRIs; e.gduloxetine, )
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- warfarin
Pregnancy & Lactation of Tramadol
FDA pregnancy category C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately
Lactation
Tramadol can increase serum prolactin.However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.A randomized study compared tramadol and naproxen for post-cesarean section pain. Patients received the drugs either on a fixed schedule or as needed. No difference in breastfeeding rates was seen among the groups.
