W9 - Toxins Flashcards
What is toxicology
the study of the effect of poisons on the function of living systems
What are some examples of agents that can be toxic to the human body
drugs paracetamol penicillin thalidomide novichok sarin
What was Paracelsus’s statement on toxicity
all things are poison and nothing is without poison only the dose permits something not to be poisonous
What did we learn from paracelsus’s statement
the dose makes the poison
describe the range between the therapeutic effect and the toxic effect
Every drug has a therapeutic effect and a toxic effect, in an ideal drug the toxic effect limit will be much higher than the therapeutic effect. So that a dose can be increased to have a higher therapeutic effect before it would become toxic
What is an ADR
Adverse Drug Reactions. They are noxious or unintended responses occurring at therapeutic doses
What are the two types of ADR
Type A (Augmented)
Type B (Bizzarre)
What are the effects of an augmented ADR
related to known pharmacology but undesirable
common
dose related
predictable
what is an example of an augmented ADR
Hemorrhage with anticoagulants
What are the effects of a bizarre ADR
unrelated to known pharmacology
Rare
Unpredictable
Often idiosyncratic
What is an example of a bizarre ADR
anaphylaxis with penicilin
what are the 4 part of toxicokinetics
Think pharmacokinetics
ADME
Absorption
Distribution
Metabolism
Excretion
What are two ways in which toxic materials are absorbed
ingestion
inhalatin
what are two metabolic processes that can be found in toxicokinetics
Detoxification
Toxification
what is detoxification
compound rendered less toxic
what is toxification
relatively inert compound converted into toxin
What are the 4 types of basic clinical syndromes (gell and combes)
Type 1 - Hypersensitivity reaction
Type 2 - Antibody mediated cytotoxic hypersensitivity reaction
Type 3 - Immune complex mediated hypersensitivity reaction
Type 4 - Delayed type hypersensitivity
Describe the mechanism of a hypersensitivity reaction (histamine)
Hapten binds onto a low molecular weight allergen such as bee venom peanut oil or penicilin, this forms the immunogenic conjugate. This then binds to an IgE site on a mast cell which triggers the release of histamine.
What is the response of a hypersensitivity reaction
Bronchoconstriction
Vasodilation
Inflammation
What is a type one clinical syndrome treated with
adrenaline
Describe the mechanism of a type 2 hypersensitivity reaction
- Toxic antigen binds to red blood cell, an IgG then binds to the red blood cell which then allows a T cell to bind and cause a mediated cell lysis.
What can a type 2 hypersensitivity reaction cause the lysis of
red blood cells
neutrophile
platelets
what is hameolytic anemia
lysis of red blood cells
what is agranulocytosis
lysis of neutrophiles
wht is thrombocytopenia
lysis of platelets
What are the 4 types of molecular drug / toxin target
receptor
enzyme
carriers
othere e.g. protein in vesicle release
what are the 4 types of receptor
ligang gated ion channel
gpcrs
enzyme linked receptors
nuclear receptors
what do animal toxins block
ion conduction
what do dendrotoxins block
voltage gated K+ channels
What channel is an important toxin target
Ca2+
what does tetrodotoxin act on
Na+
What effects can be affected by the release of cellular effects
increased secretion e.g. eyes watering
convulsions
bradycardia hypotension
bronchoconstriction respiratory depression
What is ACHE
acetyl choline esterase
what happens if ache is inhibited
acetyl choline is not broken down safely and that can lead to deadly consequences
describe the effect of sarin of the the acetylcholinesterase active site
the molecule binds onto the serine molecule preventing aceytlcholine from being broken down as the active site has a competitive inhibitor blocking it
What role do oxines have in helping the body against sarin gas attacks
they are strong nucleophiles which take the molecule that has binded onto the serine particle and seperates it which in turn reactivates acetylcholinesterase
why is carbon monixide toxic
displaces oxygen from hameoglobin
Why is cyanide toxic
cyanide inhibits mitochondrial cytochrome c oxidase to prevent cellular respiration
what 2 organs are most susceptible to toxin damage
liver
kidney
what are the 3 types of hepatoxicity
hepatic necrosis
hepatic inflammation
chronic liver damage
what is hepatic necrosis
paracetamol poisoning
what is hepatic inflammation
hepatitis is when halothane can covalently bind to liver proteins to trigger an autoimmune reaction
what is chronic liver damage
long term ethanol abuse causes cellular toxicity and inflammation and malnutrition as ethanol becomes a food source
