Toxicology Flashcards
What is a dose dependent on?
Concentration of toxicant
Time and frequency of exposure
Toxicant properties
Length of exposure and exposure pathway
Dose = mg/kg
Amount of chemical entering the body at a certain time
List Individual body movement of toxins and toxicants
Agent > Exposure dose > Skin+ lungs+ GI tract > Bloodstream (absorption) > Target organ dose (distribution and metabolism) > Organs + Tissues > Excretion
What occurs during absorption?
Absorption involves the delivery of the toxicant from the exposure site into systemic circulation via the bloodstream.
Individual body movement of toxins and toxicants
Environment > [Mucosa + Skin] > Intestinal Fluid > [Capillary Membrane] > Plasma > [Capillary Membrane] .> Intestinal Fluid > [Target Cell Membrane] > Intestinal Fluid > [Subcellular membrane] > Intracellular fluid
Type of Xenobiotic transport
Simple diffusion
Facilitated diffusion
Active transport
Exocytosis
Filtration
Differences between Passive and Active Mediated Transport
Passive : Transport occurs in the direction of the electrochemical potential gradient
No energy requirement
Symmetrical transport
Active: Transport occurs against the electrochemical potential gradient
Energy is required
Asymmetrical transport
Both use carrier proteins, are inhibitable structurally specific
Explain endocytosis and distinguish types
Endocytosis is the process whereby cell internalizes non-particulate materials by engulfing.
Three types:
Phagocytosis - ingesting and eliminating larger particles
Pinocytosis- Uptake of smaller molecules
Receptor Mediated
Processes are energy dependent
Primary Enter
Skin, Lungs & GI tract
Dermal: impermeable to ions and aqueous solutions
Permeable to toxicants in solid, liquid and gaseous forms.
Epidermis : passive barrier
Penetration is affected by surfactants, soaps and toxicants.
Penetration is reduced by osculation and organic solvents
Factors Affecting Penetration;
Concentration of toxicant
Age and condition of skin
Surface area of contact
Explain GI tract entry
GI absorption is site dependent:
Site 1: Stomach
Site 2: Buccal, Nasal and rectum
1st pass occurs in the liver, leads to detox
Enterohepatic absorption: toxicant is absorbed via the intestinal lumen and reabsorbed into systemic circulation
Explain distribution
Transport of toxicant from the systemic circulation to the target sites
Mechs that facilitate distribution
1. Porosity of capillary epithelium
2. Specialized transporters
3. Accumulation in organelles
Mechs that hinder distribution
1. Distribution of storage sites
2. Export from cells
Difference between normal capillary and brain capillary
Brain capillaries lack fenestrae with tight junctions, hence active transport is required to facilitate the entry of hydrophilic molecules.
Distinguish between pharmacodynamics and pharmacokinetics.
Pharmacokinetics: the way the body responds to the drug. The way the body acts on the drug
Genetics: Absorption, distribution, metabolism, excretion.
Pharmacodynamics: the response the drug induces on the body. The way the drug acts on the body.
Genetics: Enzymes, Ion channels, Immune system and receptors.
Explain the process of BIOTRANSFORMATIONS
Process whereby xenobiotics undergo elimination by being converted to a water soluble form.
Biotransformation convert xenobiotics from a lipophilic form which is difficult to excrete to a hydrophilic form which are be readily excreted as urine or bile.
Process is catalyzed by liver enzymes, where 1st pass also occurs.
Main goal of biotransformation in terms of evolution is to increase the rate of xenobiotic excretion.
Biotransformation can either detoxify or bioactivate toxicants making them more toxic.
Distinguish between phase I and II reactions.
Primary organs of biotransformation:
Liver
Kidney
Lungs
Small Intestine
Phase I:
Alteration- involves oxidation, reduction and hydrolysis. Process involves the addition of functional groups : -OH, -NH2 , -SH and -COOH in increase reactivity and hydrophilicity.
Involves the conversion of the parent drug into a more active metabolite with the addition of polar functional groups.
Phase II:
Conjugation: addition of a metabolite to a xenobiotic with a functional group.
Involves sulphuration, acetylation, methylation glutathione, glucuronidation to increase hydrophilicity.
Role of CYP 450 in Phase I metabolism.
CYP 450 is the most important enzyme in biotransformation.
Catalyzes the oxidation of lipophilic xenobiotics.
CYP 450 is a heme-containing protein which is very versatile.
CYP general oxidation:
RH + NADPH+ + H+ > ROH + NADP + H2O
