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DRUG PROFILE

DRUG PROFILE:
Drug

:Tramadol

Drug category

: NSAID

Structure

Chemical name/ Nomenclature / IUPAC Name

: 2-[(Dimethylamino)methyl]-1-(3-

methoxyphenyl)cyclohexanol
Molecular Formula

: C16H25NO2

Molecular Weight

: 263.4 g/mol

Official Pharmacopoeia :BP,EP,IP,USP


PHYSICOCHEMICAL PROPERTIES:
Description(Physical State): white to off-white, crystalline, odourless powder
Solubility: soluble in water
Storage Conditions: stored at room temperature
Dosage: 50mg
Melting point: 180-181 C
pKa(strongest acidic): 13.8
Log P: 2.4
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DRUG PROFILE

PHARMACOKINETIC PROPERTIES:
Bioavailability

: 7075% (oral)

Half-life

: 6.3 1.4 hr

Absorption

: Racemic tramadol is rapidly and almost completely

absorbed after oral administration


Volume of Distribution

2.6 L/kg [male, 100 mg intravenous dose]


2.9 L/kg [female, 100 mg intravenous dose]

Protein binding
Metabolism

: 20 %
: Liver-mediated demethylation and glucuronidation via

CYP2D6 & CYP3A4


Metabolites

: O-Desmethyltramadol, N-Desmethyltramadol, O-

Desmethyl-tramado glucuronide
Time of peak action

: 2-3 hrs

Excretion

: Urine (95%)

Adverse effects/Side effects

: The most common adverse effects of tramadol

include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting,
constipation, drowsiness and headache. Compared to other opioids, respiratory depression
and constipation are considered less of a problem with tramadol.
PHARMACODYNAMICS:

Mechanism of action: 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
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DRUG PROFILE

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
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.

Therapeutic efficacy/ Indications: 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 musculosketetal pain and as an adjuvant to NSAID
therapy in patients with osteoarthritis.

Contraindications: Its use is not advised for people deficient in CYP2D6 enzymes which
accounts for about 610% of Caucasians and 12% of Asians, as they are crucial to the
therapeutic effects of tramadol, by means of enabling tramadol's metabolism to Odesmethyltramadol.
INTERACTIONS:
Drug interactions: Tramadol interacts with such serotonergics, monoamine oxidase
inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotoninnorepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants,
serotonin antagonist and reuptake inhibitors, certain analgesics (pethidine (meperidine),
tapentadol, oxycodone, dextromethorphan and fentanyl), certain anxiolytics (such as the
SSRIs and buspirone), certain antibiotics (namely, linezolid and isoniazid), certain herbs
(e.g.

St.

John's

wort,

passiflora,

etc.),

amphetamines/substituted

amphetamines,

phenethylamines/Substituted phenethylamines, phentermine, lithium, methylene blue as well


as numerous other therapeutic agents.As it is a substrate of CYP3A4 and CYP2D6, any
agents with the ability to inhibit or induce these enzymes will likely interact with tramadol.
Food interactions: Oral administration of tramadol hydrochloride with food does not
significantly affect its rate or extent of absorption, therefore, tramadol hydrochloride can be
administered without regard to food.

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