Compare and contrast ibuprofen and tramadol as analgesic agents in intensive care.
Ibuprofen - inhibition of the cyclooxygenase (COX) and synthesis ofprostaglandins, which are important mediators for peripheral sensitization and hyperalgesia. Act peripherally and spinal COX - non selective. Oral and PR only Associated with a number of side effects, including decreased haemostasis, renal dysfunction, gastrointestinal haemorrhage, and effects on bone healing and osteogenesis
Tramadol - is a synthetic opioid that exhibits weak μ-agonist activity and inhibits reuptake of serotonin and noradrenaline. Analgesic effects primarily through central mechanisms, it may exhibit peripheral local anaesthetic properties. Tramadol is comparable in analgesic efficacy to ibuprofen. Common side effects (overall incidence of 1.6% to 6.1 %) include dizziness, drowsiness, sweating, nausea, vomiting, dry mouth, and headache. Tramadol should be used with caution in patients with seizures or increased intracranial pressure and in those taking monoamine oxidase inhibitors. IV and oral preparations. No bleeding, GIT and renal complications. More expensive Both have advantage of lack of respiratory depression, major organ toxicity, and depression
of gastrointestinal motility and a low potential for abuse.
|Chemistry||Aryl-propionic acid||Synthetic phenylpropylamine opioid|
|Routes of administration||Oral, PR, IV is available in some places||Oral, IV|
|Absorption||Rapidly absorbed; oral bioavailability is close to 100%||100% absorbed orally, 70% oral bioavailability, but increases to 90-100% with sustained dosing because of hepatic enzyme saturation|
|Solubility||pKa 4.9; quite lipid soluble and poorly water soluble||pKa 9.41, highly lipophilic|
|Distribution||VOD-0.1L/kg; 99% protein bound (to albumin)||VOD = 2.6-2.9L/kg; 20% protein-bound|
|Target receptor||COX-1 and COX-2 isoforms of the cycloxygenase enzyme||mu-opiate receptor (pre-synaptic G-protein coupled receptor)|
|Metabolism||Almost 100% of the dose is metabolised in the liver: oxidation into water-soluble inactive metabolites||Hepatic metabolism; notable metabolites include O-desmethyltramadol, an active metabolite|
|Elimination||All products of metabolism are renally excreted||Minimal unchanged drug cleared renally, but most of the metabolites rely on renal excretion|
|Time course of action||Half-life is 1.8 to two hours (duration of COX inhibition is much longer)||Half life = 6 hours|
|Mechanism of action||Inhibition of cyclooxygenase enzymes leads to decreased synthesis of prostaglandins, which decreases the vascular regional response to inflammation, and decreases the sensitivity of peripheral nociceptors. COX-1 inhibition also leads to the dysregulation of vascular antihrombotic effects of PGI2 and to the decreased secretion of bicarbonate and mucus in the gastric mucosa||Hyperpolarisation of cell membrane by increasing potassium conductance; reduced production of cAMP and closure of voltage-gated calcium channels. Also acts as as a serotonin and noradrenaline reuptake inhibitor|
|Clinical effects||COX-1 inhibitor and nonselective NSAID side effects:
GI ulceration (decreased gastric mucosal pH and mucus synthesis)
Acute kidney injury (microvascular renal dysfunction)
COX-2 inhibitor side effects:
Anti-inflammatory activity is mainly due to COX-2 inhibition
Prothrombotic side effects are due to COX-2 inhibition
CCF exacerbation and hypertnesion
|Analgesia, respiratory depression, constipation, miosis, urinary retention. Lowers seizure threshold, interacts with serotonergic drugs to increase risk of serotonin syndrome|
|Single best reference for further information||TGA PI document||Crow et al (2021)|
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