LMP301 Lecture 17: Toxicology Flashcards
define: mithridatism
taking poisons in small doses to develop tolerance
define: xenobiotics
pharmacologically active substance that is not produced in the body(e.g. drugs)
TDM
therapeutic drug monitoring
The difference between toxin and anecdote is…
dose
define: pharmacodynamics
how the drug affects your body
define: pharmacokinetics
what the body does to the drug
difference between pharmacodynamics and pharmacokinetics
what the drug does to the body vs. what the body does to the drug
absorption, distribution, metabolism of the drug is pharmacodynamics / pharmacokinetics?
pharmacokinetics
drug-receptor interaction is pharmacodynamics / pharmacokinetics?
pharmacodynamics
difference between toxicology & TDM
toxicology: harmful substance
TDM: medicine
define: biotransformation
converting fat soluble chemicals to hydrophilic chemicals to be excreted in the urine/bile
biotransformation alters the biological properties of xenobiotics so…
it become less toxic (detoxification)
what makes xenobiotics less toxic?
biotransformation
what happens in rare cases when biotransformation on xenobiotics don’t react as expected?
makes a more toxic metabolite (e.g. metabolism of alcohol)
enzymes that carry out biotransformation can be put into 4 categories… (main reactions that happen)
- hydrolysis
- reduction
- oxidation
- conjugation
examples of conjugation reactions
- glucuronidation (add glucuronic acid / B-glucuronide)
- sulfonation (add sulfate)
- add glycine
- add glutathione
define: glucuronidation
addition of glucuronic acid to a substrate
enzymes involved in biotransformation are usually ____, so activity differs among individuals
polymorphic
what limits exposure of orally ingested xenobiotics?
small intestines & liver
Phase I of toxin metabolism
- activation/inactivation of compounds
- change pharmacological activity (make drug less toxic)
where does most of the phase I activities take place?
liver mitochondria
which enzyme is involved in phase I?
cytochrome P-450 system
- oxidation
- reduction
- hydrolysis
how are drugs processed by the P450 class of enzymes? (slide 8)
- attached to P450-Fe3+
- Fe3+ gets reduced to Fe2+ (attached to P450-Fe2+)
- O2 is added = peroxide dianion
- 2H+ is added, which removes oxidized drug + water from P450-Fe3+
- P450-Fe3+ goes on to attach to more drugs
what reduces Fe3+ to Fe2+ in the P450 enzyme system?
reduced P450 reductase
reduced [P450 reductase] + [Fe3+] -> [P450 reductase] + [Fe2+]
what changes oxidized flavoprotein -> reduced flavoprotein?
NADPH
[NADPH] + [P450 reductase] -> [NADP+] + reduced [P450 reductase]
What element does the drug bind to on P450?
N
binding of the drug to P450 changes…
conformation of the enzyme, and exposes drug to other reactions
the active form of the drug is oxidated / reduced?
oxidated
Which is the oxidated state: Fe3+ or Fe2+?
Fe3+
steps of drug metabolism
- activation / inactivation
- conjugation products
- elimination