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Plant Toxins, Screenshot 2023-08-27 at 10.53.43 am, Screenshot 2023-08-27…

- - - - Volume control - binding to nicotinic receptors in CNS
      - Increases release of neurotransmitters - stimulant
      - Interacts with nicotinic receptors in adrenal gland - stimulating release of adrenaline - physiological stimulant
      - Increased release of dopamine will act on 'reward' pathways
      - N1 = skeletal muscle (neuromuscular)
      - N2 = neuronal receptors (nerve synapses)
      - Toxicity
        
        LD50 is 0.5 to 1.0 mg/kg for adults
        
        Nicotine poisoning results in excessive stimulation of nicotinic acetylcholine receptors
        
        Initial symptoms - nausea, vomiting, hypertension, tachycardia
        
        After excessive stimulation, receptor levels depressed
        
        Subsequent symptoms - hypotension, bradycardia, CNS depression, coma, paralysis
        
        Nicotine toxicity - measuring levels of nicotine or cotinine in blood
        
        Cotinine - metabolite of nicotine
    - - Competitive, reversible inhibitors of the nicotinic acetylcholine receptor
      - LD50 in humans - 0.75 mg.kg
      - Lead for development of anesthetics & muscle relaxants
    - - Blocks neurotransmission via ACh, leading to paralysis
      - Quick onset (5 minutes) & long duration of action (up to 2 hours)
      - Was used as a mucsle relaxant (e.g. intubation) but now synthetic derivatives are used
    - - Interruption of neurotransmission leading to paralysis
      - Death due to respiratory paralysis or cardiac arrest
  - - - Binds to muscarinic acetylcholine receptors & activates them (same as ACh)
      - Alkaloid found in many species of mushroom
      - Slow metabolism seems to contribute to toxicity
      - Toxicity
        
        Muscarine receptors are located throughout body - effects of muscarine poisoning widespread
        
        Symptoms caused by excessive activation of receptors
        
        Muscarine can trigger cardiac arrest via M2 receptors
        
        Trigger convulsion & hypothermia via M1, M4 and M5 receptors in brain
        
        Bronchoconstriction & severe GI symptoms
    - - Increase heart rate by blocking M2 receptors
      - Alkaloid from deadly nightshade (Atropa belladonna)
      - Competitive antagonist at the muscarinic receptors
      - Antidote to muscarine poisoning
      - Toxicity
        
        Symptoms - anticholinergic toxidrome
        
        Incapacitating at doses of 20mg/person
        
        LD50 - 450mg/person
    - - Alkaloid found in the nightshade family of plants
      - Competitive antagonist at muscarinic receptors
      - Overdose - tachycardia & arrythmia
    - - Related to M2 receptors in heart (decrease heart rate)
  - - - Prevents glycine from binding to GlyR
      - Without inhibition, nervous system becomes hypersensitive
      - Constant muscle contractions
      - Alkaloid found in seeds of Strychnos tree
      - Action potentials triggered by very low levels of neurotransmitter
      - Toxicity
        
        LD50 in humans - 1 - 2mg/kg
        
        Exposure often through rodenticides containing strychnine
        
        Initial symptoms - restlessness, muscle twitching, stiffness of neck
        
        Later symptoms - convulsions & dilation of pupils
        
        Death - respiratory arrest & asphyxia
    - - Antagonism at glycine receptors
      - Less toxic than strychnine LD - 10 - 20mg/kg
      - Alkaloid from Strychnos tree, closely related to strychnine
    - - Essential precursor in synthesis of porphyrins
      - CNS - glycine functions as an inhibitory neurotransmitter
    - - Regulates chloride movement
      - When receptor activated, chloride enters neuron
      - Inhibitory post-synaptic potential, making neuron less likely to generate an action potential
      - Inhibition important to stop neuromuscular system from being too sensitive (i.e. triggering action potentials with very low levels of neurotransmitter)
  - - - Comprises chemical processes that cells must carry out in order to survive & reproduce
    - - Comprises chemical processes that are unique to a given organism & are not universal
      - Secondary metabolites aren't necessary for survival, but provide a competitive advantage
      - Plant secondary metabolites can be toxic to human cells
  - - - Heterocyclic
      - Non-heterocyclic
  - - - Central nervous system
      - Autonomic nervous system
      - Musculoskeletal system
    - - Functions as a neurotransmitter by opening ligand-gated ion channels
      - After its action, ACh degraded by acetylcholinesterase, clearing it from the synpase
    - - Direct neurotransmitter action (ionotropic receptor)
      - Indirect neurotransmitter action (metabotropic receptor)
- - - - Stored in vacuoles in plant - keeps plant cells safe
      - Released if plant attacked, activated by enzymes
      - Enzymes remove sugar & release toxic HCN
    - - Glycoside found in bitter almonds
      - B-glucosidase is a common enzyme in gut - breaks down amydalin to release HCN
    - - In solution, HCN produce cyanide ions (CN-)
      - CN- attaches to iron in cytochrome c oxidase (a + a3)
      - Binding prevents transfer of electrons from cytochrome c to oxygen
      - Shuts down mitochondrial electron transport chain
      - Cell no longer capable of aerobic respiration
      - Fatal dose 1.5 mg/kg
      - Poisoning - hypoxia, cells unable to use oxygen for metabolism
      - Initial symptoms - weakness, confusion, headache
      - Skin cherry red due to increased Hb oxygen saturation (oxygen not used, accumulates)
  - - - Ca2+ levels in cell increases, taken up into sarcoplasmic reticulum
      - When Ca2+ released, myocyte contraction is faster & more powerful
    - - Glycoside from foxglove (Digitalis sp.)
      - Treatment of heart conditions
      - Primary action - increasing contractility - heart takes longer to fill, slowing down heart rate
    - - Glycoside from foxglove (Digitalis sp.)
      - Similar to digoxin, but longer lasting
      - Initial symptoms - nausea, vomiting, diarrhea
    - - Glycoside found in seeds and bark of some African plants
      - Low concentrations can stimulate Na+/K+ pump
      - Largely replaced by digoxin, as digoxin is more lipophilic, more bioavailable
  - - - Saponin glycoside found in potatoes & tomatoes
      - Potatoes exposed to light will produce solanine
      - LD50 3-6 mg/kg
      - Toxicity - disruption of mitochondrial membrane
- - - - Type 2 ribosome-inactivating protein (RIP) or holotoxin
      - Irreversibly hydrolyses a glycosidic bond in rRNA of the 60s ribosomal subunit
      - Rapidly & completely inactivates ribosome
      - Shuts down protein synthesis within cells
  - - - Respiratory distress, GI symptoms