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Toxins, Poisons and drug toxicity (mechanisms of toxicity (Receptors/ion…

- - - - organophosphates
      - based on arsenical compounds
    - - Atrazine
  - - - neurotoxin (Na+ channel blocking)
    - - Muscarine - parasympathomimetic effects
      - Muscimol - psychoactive effects
    - - TTX - neurotoxin
- - - - cell death, necrosis
      - Paracetamol => liver injury
      - Aspirin => gastric ulceration
      - caustic/acidic agents
      - caused by active metabolites of drugs
      - drug metabolism may give rise to a more reactive
        product or give rise to damaging oxygen radicals
      - paracetamol hepatotoxicity is due to a
        metabolite produced by oxidation
    - - single/low exposure may suffice
      - cancer may develop after months/years (stibestrol)
      - rather few drugs other then chemotherapeutic are carcinogenic
    - - permanent change to DNA of germ cells - inherited
    - - cause gross abnormalie of babies
      - serious defects from exposure in first trimester
      - Tetratogenicity
        
        ACE inhibitors
        
        Renal damage
        
        Aminoglycosides
        
        nerve toxicity
        
        Cocaine
        
        limb and urinary tracts defects, congenital heart disease
        
        Ethanol
        
        Foetal Alcohol Syndrome
        
        Craniofacial defects
        
        growth retardation
        
        Phenytoin
        
        cleft lip and palate
        
        Tetracycline
        
        discoloration and defects of teeth
        
        altered bone growth
        
        Thalidomide
        
        phocomelia
        
        Valproic Acid
        
        spina bifida
      - effects determined by the time of exposure during pregnancy
    - - relatively common, especially common skin rasheds
      - antibody to drug or drug conjugate with protein
      - anaphylactic shock can be life threatening
  - - - local concentration
      - local generation of reactive metabolites
      - local targets
    - - Hepatotoxicity (liver failure)
    - - Nephrotoxicity (renal tubes, kidney failure)
    - - Crystalluria (bladder failure)
    - - Totoxicity (deafness)
    - - (teeth damage)
- - - - uncouples oxidative phosphorylation
    - - Na+/K+ ATPase