Toxicology Test 1

Any agent that is capable of producing injury or death when ingested or absorbed

• Basic science of poisons
• science of adverse effects of chemicals on living organisms

public health relevance of chemicals and chemical exposure

not all chemicals are drugs

binding at molecular level

• policy issues with chemical exposure
• FDA

• examining what damage a poison can produce
• ex. acetaminophen decreases glutathione and cause liver damage

• clinical: drug-drug, overdose, underdose
• Forensice: medical legal aspects of poison
• investigative

• physics: 1st order, 0 order
• biochem: feedback mech, molecular level
• medicine: treatment
• biology: algae growth, life outside body
• physiology: fxn of organ systems
• (pharmacology)

• yes depending on the dose or concentration
• timing also included in case of newborn (biological system can handle substance)

make sure all drugs on the market are safe and efficacious

gave FDA their power, gave to pregnant women for nausea and it caused major birth defects (no arms)

• delaney clause (1958)
• thalidomide incident
• diethylstilbestrol (DES)
• rachel carson's silent spring

The liver is the largest organ because of presence of poison in nature (we are exposed all the time.

used to prevent abortion or miscarriage or premature labor, caused major problems. (origionally recommended in all pregnancies)

• Wrote a book about the effects of pesticides on environment...DDT wiping out condor, egg shells soft
• DDT: man made and accumulates in naure.

• Allergic rxn
• idiosyncratic reactions
• immediate vs. delayed toxicity
• reversible vs. irreversible toxic effects
• local vx systemic toxicity
• interaction of chemicals
• tolerance

• hypersensitivity, illicit immune system response vs. local
• previous sensitivity
• can happen with really low doses

• genetically determined abnormal reactivity to a chemical
• reaction to chemical that general population doesn't have
• 5% or less

• imm: overdose by drinking gasoline, no time passes
• delay: exposed but not show effects until time passes, Ex. cancer

• rev: tylenol destroying liver cells, they regenerate if treated
• irr: higher doses of tylenol and alcohol causes permenant liver damage, fatty liver pscerosis

• local: hydrogen peroxide on skin, or skin rash
• systemic: sulfa drugs or penicillins.

• additive: 2+3=5
• synergistic: 2+3 = 20
• potentiation: 0+3=10
• antagonism

• functional
• chemical/inactivation
• dispositional
• receptor

body becomes less sensitive to a substance

• gastrointestinal tract: ingestion, bad mushrooms
• lungs: inhalation, perfumes
• skin: topical or dermal
• Parenteral: other than intestinal canal, IV drugs given the wrong conc

• acute
• subacute
• subchronic
• chronic

2 drugs offset each other effecting physiological changes

• chemical rxn between 2 things that renders them usless or less toxic
• ex: chelating agents

something effects ADME of drug and its effects are diminished

2 chemicals bind to same receptors and produces a lower effect

administered --> into systemic circulation

systemic circulation --> into tissue

systemic circulation --> metabolized or excreted

pharmacological effect

• clinical response
• toxicity

• toxicity
• efficacy

• goes to the liver to be metabolized
• inactivate it
• activate it
• or do nothing

• rate remains constant and is independent of concentartions or amount of chemical
• biological system is rate limiting
• t1/2: increases with dose (not a true t1/2)
• alcholol metabolized by this

• rate proportional to concentration or amount of chemical present
• chemical is rate limiting
• T1/2: independent of dose (true t1/2)
• most chemicals in the body are metabolized this way

become saturated and change from firstorder to zero order

amount or concentration changes by fraction per unit of time

• Therapeutic index(TI)
• ED50
• TD50
• LD50

• safe operation window
• area where you expect drugs to work

• effective dose that produces response in 50% of people
• animal or human

• Toxic dose expect to see in 50% of population
• animal or human

lethal dose observed in 50% of ANIMALS!

no observed adverse effect level

• as dose increases
• noael-->TI-->Toxicity-->death
• 0-250-->250-500-->500-2500-->2500 and above

deficiency

• toxicity
• and threshold for adverse effects
• eventually death

we identify the specifec target molecule which is attacked by toxin

eats up whatever it sees

• attack a specific target
• inital attack leads to cascade of events that will lead eventually to toxicity

• linked to target molecule that is damaged: vapor attack retina of eye, causes blindness, immediate toxicity
• a sequence of complexities: compound destroys pancrease, no immediate toxicity but diabetes eventually creates toxicity

• relate directly to the interaction between the toxicant and its specific target molecule
• may be comlicated by secondary effects

for the majority of toxicants, site(s) remain(s) unknown

result through a chain of events which begins with an action at a very specific target

• proteins
• lipids
• nucleic acids (RNA, DNA)

• enzymes
• mitochondrial respiratory chain
• receptors/ion channels
• transport proteins

replace acetylcholine to cause toxicity

• acetylcholenesterase acts on organophosphates like it is acetylcholine
• acetylcholenesterase ends up with phosphate group at end and the enzyme cant recover easily from this toxic effect

Is is recovered and makes free acetate, after it destroys acetylcholine