Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Mar 2000
ReviewMigraine pharmacotherapy with oral triptans: a rational approach to clinical management.
The recent clinical development of a number of migraine specific 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and zolmitriptan display both increased stability to first pass metabolic inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to > 120-fold more than sumatriptan), leading to increased oral bioavailability (2- to 5-fold more than the 14% reported for oral sumatriptan). Central penetration and increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or less compared with 50-300 mg doses of sumatriptan) and reduced peripheral exposure to the coronary vasoconstrictor (5-HT1B) receptor. ⋯ Naratriptan would appear to have lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for headaches of long duration and with a tendency to recur naratriptan may be the most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and clinical profiles of the TELs facilitates the selection of a triptan which allows optimisation of the clinical benefits for individual patients, minimising the risk of drug interactions and a minimally effective dose to reduce potential adverse events (AEs).
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Ropivacaine (Naropin, AstraZeneca) is a long-acting amide local anaesthetic released for clinical use in 1996. Similar to bupivacaine, ropivacaine is equally effective for s.c. infiltration, epidural and peripheral nerve block for surgery, obstetric and post-operative analgesia. Ropivacaine differs from most other amide-type local anaesthetics in that it is marketed as a pure S-enantiomer, instead of as a racemate. ⋯ Ropivacaine is nearly identical to bupivacaine in onset, quality and duration of sensory block, but it produces less motor block. Whether or not the motor sparing effect of ropivacaine is due to a lower relative potency compared to bupivacaine is a matter of intense debate. Despite a better safety profile, the increased cost of ropivacaine may limit its clinical utility.
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Expert Opin Pharmacother · Nov 1999
ReviewNitric oxide scavengers in the treatment of shock associated with systemic inflammatory response syndrome.
Shock associated with systemic inflammatory response syndrome (SIRS) is a form of distributive shock affecting over 200,000 patients per year in the US that results in 50% mortality. The role of NO in a variety of shock states has been extensively studied and has been shown to be the primary effector in endotoxin lipopolysaccharide (LPS)-induced hypotension attendant to shock associated with sepsis or presumed sepsis. NO has also been shown to be a myocardial depressant, an inhibitor of mitochondrial electron transport, an inducer of vascular leakage and an enhancer of LPS-induced cytokine release. ⋯ NO scavengers are comprised of two basic classes: organic molecules and metal complexes. Pyridoxalated haemoglobin polyoxyethylene conjugate (PHP) is a chemically-modified haemoglobin. It is the furthest advanced NO scavenger in clinical trials and is about to enter pivotal Phase 3 trials in patients with shock associated with SIRS.