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Tox- Intro

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acramer's version from 2018-02-27 17:25

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Idiosyncratic reactions (pic included)Drug gets metabolized via liver- creates reactive metabolite- causes oxidative stress leading to necrosis and apoptosis- binds to protein- creates drug hapten- causes immune system response- humoral and t-cell mediated. FMO (enzyme) in liver-->fish odor dz. MPO (enzyme) in neutrophils.
idiosyncratic- Phenylbutazone- what is the resulting tox, what is the mechanism? who should you not use this in?Aplastic anemia due to Oxidation by peroxidases-- DO NOT USE IN CATS/DOGS
idiosyncratic- Fenbendazole- what is the resulting tox, when would you see a reaction? how common is this?Pancytopenia, bone marrow necrosis. RARE.
idiosyncratic- Flucytosine- what is the resulting tox, when would you see onset, what is the area seen? How do you help with this reaction?Skin eruptions, depigmentation and ulcerations. Onset after 2-6 weeks, affecting the mucocutaneous junctions. Discontinuation, supportive care.
idiosyncratic- Mitotane- what is the resulting tox, when do you see signs? how common?Hepatopathy, bone marrow necrosis. Seen after 1 month-- lesions are rare.
(these examples skipped in class) idiosyncratic- Griseofulvine- what is the resulting tox, what will you see and in who specifically? how can you help with this prob?Pancytopenia (or neutropenia in cats), Neutropenia in FIV cats, Use alternatives (not griseo)
idiosyncratic- Albendazole- what is the resulting tox, what is the mechanism? What can you do to help this?Bone marrow suppression in one cat (lol what). Mechanism unknown. Reversible with drug withdrawal
idiosyncratic- Meloxicam- what is the resulting tox, When would you see a reaction?Vasculitis with ulcers, vesicles and erosions within 2 days. Rare.
(these examples skipped in class) idiosyncratic- Sulphonamides- what is the resulting tox, what is the mechanism? What should you do?Hepatopathy, blood dyscrasia, skin eruptions. Oxidised hydroxyl amine metabolite (CYP450, MPO). Discontinue sulphonamide
(these examples skipped in class) idiosyncratic- Methimazole- what is the resulting tox, what is the mechanism? what should you do?Hepatopathy, blood dyscrasia, skin eruptions. N-methylthiourea metabolite (FMO) --> antibodies. Counsel owners, discontinue drug therapy
where is most of the FMO enzymes?liver
where are the MPO enzymes?neutrophils (leukocytes)
Tox can be immediate or delayed- it can be Rapid development of toxic effects after single administration, or occurrence after the lapse of some time. 3 examples?Asbestos toxicosis (delayed), Diethylstilbestrol- both delayed and acute?, Organophosphorus- delayed polyneuropathy
Reversible versus irreversible toxic effects- what does this often depend on?Depends on affected body system and it's ability to regenerate (liver versus CNS regeneration). Carcinogenic and teratogenic effects are usually considered irreversible
Local versus systemic toxicity--> How do local effects happen? What needs to happen for systemic effects to happen?Local effects: at the site of first contact (ingestion of caustic substances; inhalation of irritant material). Systemic effects: requires absorption and distribution from its entry point
things you should do for your tox diagnostic workup (3) What if you can't dx what is wrong?(1) History (do not believe everything!) (2) Exclusion of causes that may induce the same range of symptoms (differential diagnosis). (3) Analysis of feed, other materials, the environment, stomach content, body excretions (we can only measure what we know to look for though, and we can only measure what is present (so if it has been biotransformed we won't find it) ).... if you can't figure it out, Treat the patient first before you worry about the diagnostic uncertainties!!
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