forensic toxicology - plant toxins - alkaloids - Statistics

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Hint Answer % Correct
what is the LD50 of nicotine? 0.5 to 1.0mg/kg for adults
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what is the LD50 of strychnine? 1-2mg/kg in humans
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what is the LD50 of ricin? 22ug/kg from injection or inhalation (approx 1.8mg/adult - 20 castor seeds could kill an adult)
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what are alkaloids? a basic organic compound containing nitrogen
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what is the primary ligand for the cholinergic receptor? acetylcholine
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action potentials are triggered by very low levels of neurotransmitter, causing constant muscle contractions/twitching
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after excessive stimulation, receptor levels are depressed
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what is ricin? a lectin (carbohydrate-binding protein) from the seeds of the castor oil plant
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what is muscarine? an alkaloid found in many species of mushroom
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what is strychnine? an alkaloid found in the seeds of the Strychnos tree (one of the most bitter chemicals known)
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an essential precursor in the synthesis of porphyrins (most important porphyrin in haem)
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what is its function in the CNS? an inhibitory neurotransmitter
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what is nicotine? a parasympathomimetic alkaloid found in the Solanaceae (nightshade) family of plants
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autonomic nervous system (regulates homeostasis)
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bronchoconstriction and severe gastrointestinal symptoms
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what are the physiological consequences of muscarine toxicity? cardiac arrest via M2 receptors (through bradycardia & low blood pressure)
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where are cholinergic receptors found? central nervous system
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muscarinic central nervous system
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convulsion and hypothermia via M1, M4, and M5 receptors in the brain
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death usually occurs as a result of respiratory arrest and asphyxia
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death usually occurs from circulatory shock due to a shutdown of metabolism
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does it have a faster or slower response? faster
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does it have a faster or slower response? faster (direct channel opening)
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how are alkaloids synthesised? from the amino acids phenylalanine, tryptophan, and tyrosine
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muscarinic gastric secretions, CNS
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muscarinic glands (e.g. salivary, pancreas)
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G protein-coupled receptors
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muscarinic heart muscle (contraction)
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what are the two main classes? heterocyclic
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what are the physiological consequences of strychnine toxicity? initial symptoms include restlessness, muscle twitching, and stiffness of the neck
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what are the physiological consequences of nicotine toxicity? initial symptoms: nausea, vomiting, hypertension, tachycardia, dizziness, and seizure
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where are glycine receptors (GlyRs) found? in the CNS (especially in the brain cord, brain stem, and retina)
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what kind of receptors are they? ion channel-linked receptors
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what kind of receptor is the GlyR? ionotropic receptor
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what are the two main types of cholinergic receptors? ionotropic receptors (direct neurotransmitter action)
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what is the mechanism of action of strychnine? it acts as an antagonist, and prevents glycine from binding to GlyR
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it also interacts with nicotinic receptors in the adrenal gland, stimulating the release of adrenaline
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what is the mechanism of action of muscarine? it binds to the muscarinic receptors and activates them (same as ACh)
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what is the mechanism of action of nicotine? it binds to the nicotinic receptors in the CNS & acts as a 'volume control'
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it increases release of neurotransmitters, providing a stimulant effect
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how can this lead to a toxic effect? it irreversibly hydrolyses a glycosidic bond in the rRNA of the 60s ribosomal subunit
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what is the mechanism of action of ricin? it is a type 2 ribosome-inactivating protein (RIP) or holotoxin (a single ricin molecule can inactivate 1500 ribosomes per minute)
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how does it function as a neurotransmitter? it opens ligand-gated ion channels
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later symptoms include convulsions and dilation of the pupils
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muscarinic M1
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muscarinic M2
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muscarinic M3
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muscarinic M4 & M5
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metabotropic receptors (indirect neurotransmitter action)
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muscarinic acetylcholine receptors
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musculoskeletal system
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what are the main types of these receptors? N1
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nicotinic N2
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nicotinic neuronal receptors (nerve synapses)
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what are the two classes of cholinergic receptors? nicotinic acetylcholine receptors
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non-heterocyclic
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what does it do? regulates chloride movement
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what are the physiological consequences of ricin toxicity? severe diarrhea
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where are they found? skeletal muscle (neuromuscular)
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slower
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slower (act via secondary messengers)
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subsequent symptoms: hypotension, bradycardia, CNS depression, coma, and paralysis
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what is glycine? the smallest of the 20 common amino acids (MW: 75 Da)
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this creates an inhibitory post-synaptic potential, making the neuron less likely to generate an action potential
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this rapidly and completely inactivates the ribosome
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this shuts down protein synthesis within the cells
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how can this lead to a toxic effect? through excessive activation of the muscarinic acetylcholine receptors
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how can this lead to a toxic effect? through excessive stimulations of the nicotinic acetylcholine receptors
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what is the LD50 of muscarine? unknown in humans (0.23mg/kg in mice)
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when the receptor is activated, chloride enters the neuron
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how can this lead to a toxic effect? without the glycine inhibiting GlyR, the nervous system becomes hypersensitive
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