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Sunday, July 15

  1. page Paraquat edited ... Corticosteroids and cyclophosphamide have been suggested as treatment. There are two non-rando…
    Corticosteroids and cyclophosphamide have been suggested as treatment. There are two non-randomised trials with opposite results (Buckley, 2001) and a randomised trial which did not show benefit (Gawarammana, 2012). There are a large number of other theoretically appealing treatments including N-acetylcysteine, lung transplantation and superoxide dismutase; however, there is insufficient animal or human work to support their use.
    Elimination enhancement
    from early charcoal haemoperfusion with
    Patients who do not develop multiorgan failure and therefore do not die within the first week may still develop progressive pulmonary fibrosis. This may slowly develop up to six weeks later. Patients in this situation who had confirmed exposure to paraquat should have regular clinical follow up and chest X-rays. Paraquat has only occasionally been reported to cause chronic non-fatal pulmonary fibrosis, i.e., the development of pulmonary fibrosis appears to lead almost inevitably to death.
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    8:18 pm

Thursday, May 31

  1. page Sodium Valproate edited ... hours in 15% of patients in one series. Bioavailability is high (~100%). Distribution ... …
    hours in 15% of patients in one series. Bioavailability is high (~100%).
    at 350 micromol/L (50
    mg/L so at
    distribution is low (0.13 to 0.23 L/kg).
    Metabolism - Elimination
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    9:42 pm

Monday, February 12

  1. user_add gazzaly gazzaly joined WikiTox
    2:18 am

Tuesday, January 2

  1. page Teaching Resources edited This is an outline of a course which includes clinical problems and is designed to support a curric…
    This is an outline of a course which includes clinical problems and is designed to support a curriculum in clinical toxicology which can be delivered either online or face to face.
    Feel free to make suggestions in the discussion tab
    with tuition is beingwas delivered through the, the course has been more fully developed to a Diploma and Masters Course delivered through the PGIM of Colombo University click here
    Core Principles
    Section 1 Pharmacokinetics and Pharmacodynamics (Pharmacokinetics and Pharmacodynamics, Protein binding, Clinical Toxicology- Assessment of patients, Decontamination)
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    2:28 pm

Saturday, December 30

  1. page WikiTox Course by Distance edited Peoples-Uni & WikiTox Clinical Toxicology This course is now run as distance learning cours…

    Peoples-Uni & WikiTox Clinical Toxicology
    This course is now run as distance learning course through the University of Colombo as a a Diploma and Masters level degree course. Course home page
    This course is designed to give students a solid theoretical knowledge base for the practice of clinical toxicology.
    It is best suited to those who have active exposure to clinical toxicology.
    The course is run by subject convenors and tutors for each weekly problem
    Course Convener
    Professor Darren Roberts has been a clinical toxicologist for 12 years working in Australia and Sri Lanka

    Subject Convenors
    One advantage of an online course is that material may be added or modified during course delivery to reflect recent developments or identified areas of need. The following course description therefore reflects the current content and layout.
    As the course is essentially problem based some concepts are introduced early and or are revisited through out the course.
    Student selection would be based upon the student being able to demonstrate a need for training and an appropriate level of prior knowledge.
    Potential students should contact
    contact details for 2 referees
    and a statement about where they see this training fit with their career path and their local countries needs
    a letter of support from their institutions head or their supervisor

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    1:56 pm
  2. page Methanol edited ... INVESTIGATIONS Anion gap ... anion-gap metabolic acidosis.== acidosis. Osmolal gap Th…
    Anion gap
    anion-gap metabolic acidosis.==acidosis.
    Osmolal gap
    There are many pitfalls in using the osmolal gap to make the diagnosis of significant methanol exposure. An ethanol concentration is required to calculate a meaningful osmolal gap in methanol poisoning. Ethanol will contribute to any osmolal gap. A significantly raised osmolal gap is useful in providing evidence to confirm a significant methanol exposure, but a normal osmolal gap is not reassuring and does not exclude the diagnosis for a number of reasons:
    Corresponding Osmolal Gap (Osmol/kg H2O): 25
    Contribution of Alcohol to Osmolar Gap
    SI units:

    gap (Osmol/kg)=1.25
    – 0.35
    (from Purssell //et al//)
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    1:36 pm

Sunday, November 26

  1. page Metaraminol edited Metaraminol pharmacology Summary Metaraminol was first discovered in 1951. It is a mixed-actin…

    Metaraminol pharmacology
    Metaraminol was first discovered in 1951. It is a mixed-acting sympathomimetic amine—indirectly releasing noradrenaline (norepinephrine) and directly activating α-adrenoceptors. It has prominent direct effects activating α1-adrenoceptors on vascular, postganglionic, sympathetic nerve terminals (causing vasoconstriction) and is also is an indirectly-acting agent that stimulates the release of noradrenaline (norepinephrine). The release of noradrenaline (norepinephrine) from sympathetic nerves in the heart acts on β1-adrenoceptors and has a positive inotropic effect while the peripheral vascular effects will increase the vasoconstriction. Some β2-adrenergic-mediated vasodilation via the release of adrenaline (epinephrine) from the adrenal medulla occurs with metaraminol, but α effects predominate. The accumulation of metaraminol and its metabolites as false-transmitters in the presynaptic sympathetic ganglion can produce a persistent reduction in the content of noradrenaline (norepinephrine) at functionally critical sites.
    Physiological basis of adrenoceptor function
    The key factor in the response of any cell or organ to sympathomimetic amines is the density and proportion of α- and β-adrenoceptors. For example, noradrenaline (norepinephrine) has relatively little capacity to increase bronchial airflow, since the receptors in bronchial smooth muscle are largely of the β2 subtype. In contrast, isoprenaline and adrenaline (epinephrine) are potent bronchodilators. Cutaneous blood vessels physiologically express almost exclusively α-adrenoceptors; thus, noradrenaline (norepinephrine)and adrenaline (epinephrine) cause constriction of such vessels, whereas isoprenaline has negligible effect. The smooth muscle of blood vessels that supply skeletal muscles has both β2 and α receptors; activation of β2-adrenoceptors causes vasodilation and stimulation of α-adrenoceptors constricts these vessels. In such vessels, the threshold concentration for activation of β2-adrenoceptors by adrenaline (epinephrine) is lower than that for α-adrenoceptors, but when both types of receptors are activated at high concentrations of adrenaline (epinephrine), the response to α-adrenoceptors predominates.
    Adrenaline (epinephrine) reversal
    Physiological concentrations of adrenaline (epinephrine) primarily cause vasodilation. Blood flow to skeletal muscles is increased by therapeutic doses of adrenaline (epinephrine). This is due in part to a powerful β2-mediated vasodilator action that is only partially counterbalanced by a vasoconstrictor action on the α receptors that also are present in the vascular bed. If an α-adrenoceptor antagonist is also given, the vasodilation in muscle is more pronounced, the total peripheral resistance is decreased, and the mean blood pressure falls. In the presence of significant α-adrenoceptor antagonist activity, unopposed β2-adrenoceptor activity produces a fall in blood pressure instead of the expected rise. This is the well-described adrenaline (epinephrine) reversal phenomenon.
    Unlike adrenaline, small doses of noradrenaline do not cause vasodilation or lower blood pressure, since the blood vessels of skeletal muscle constrict rather than dilate; α-adrenoceptor antagonists, therefore, may decrease or even abolish the pressor effects but do not cause significant reversal (i.e. hypotension).
    False-transmitter concept
    Indirectly-acting amines like metaraminol are taken up into sympathetic nerve terminals and storage vesicles, where they replace noradrenaline (norepinephrine) in the storage complex. They must be substrates of both the noradrenaline (norepinephrine) plasma-membrane transporter and the vesicular monoamine transporter (VMAT; responsible for transport into the presynaptic storage vesicles) to produce effective increases in synaptic noradrenaline (norepinephrine). In a study of indirectly acting sympathomimetic amines, the degree of noradrenaline (norepinephrine) release correlated directly with their affinity for the noradrenaline (norepinephrine) transporter. Phenylethylamines that lack a β-hydroxyl group are retained there poorly, but β-hydroxylated phenylethylamines (metaraminol) and compounds that subsequently become hydroxylated in the synaptic vesicle by dopamine β-hydroxylase (metaraminol to octopamine) are retained in the synaptic vesicle for relatively extended periods of time. Such substances can produce a persistent diminution in the content of noradrenaline (norepinephrine) at functionally critical sites.
    When the nerve is stimulated, the contents of a relatively constant number of synaptic vesicles are released by exocytosis. If these vesicles contain phenylethylamines that are less potent thannoradrenaline (norepinephrine), activation of postsynaptic α- and β-adrenoceptors will be diminished. This phenomenon is the explanation for the period of hypotension that is often seen after ceasing a metaraminol infusion. Consequently, restarting the metaraminol in this clinical situation is exactly the wrong thing to do.
    Adrenal medulla
    Basic autonomic pharmacology teaches us that the adrenal medulla is effectively a post-ganglionic nerve in the sympathetic nervous system. Stimulation of the preganglionic nerve releases acetylcholine which acts on the postsynaptic adrenal medulla to release adrenaline (epinephrine) (and noradrenaline [norepinephrine]). The same mechanisms by which the indirectly acting agents provoke noradrenaline (norepinephrine) release from sympathetic postganglionic nerves are, not surprisingly, those that result in the release of both noradrenaline (norepinephrine) and adrenaline (epinephrine) from the adrenal medulla. Both the noradrenaline (norepinephrine) transporter and VMAT are found in the adrenal medulla.
    Putting this all together, metaraminol (and any other indirectly acting or mixed sympathomimetic agent) causes the release of adrenaline (epinephrine) from the adrenal medulla in the same way it causes noradrenaline (norepinephrine) release from sympathetic nerves. The amount of extra circulating adrenaline (epinephrine) is likely to be less than therapeutic doses of adrenaline (epinephrine). Nevertheless, in the context of extensive α-adrenoceptor blockade from one or more drugs taken in overdose, metaraminol will certainly have its pressor effect reduced and may even produce hypotension. While any hypotension is unlikely to be as severe as is seen with adrenaline (epinephrine), it makes metaraminol a poor choice as pressor agent in this situation.

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    1:17 am