| C. EXCRETION VS REABSORPTION
1 the REMOVAL OF XENOBIOTICS FROM BLOOD and their RETURN to the EXTERNAL ENVIRONMENT
A PHYSICAL MECHANISM
2 A CHEMICAL MECHANISM for
ELIMINATING THE TOXICANT. | 1 Excretion
2 Biotransformation |
| C. EXCRETION VS REABSORPTION
1 The ROUTE & SPEED of EXCRETION of the
toxicant depend largely on the __
2 These organs, the __ EFFICIENTLY REMOVE HIGHLY HYDROPHILIC CHEMICALS such as ORGANIC ACIDS & BASES. | 1 Physicochemical Properties
2 Major Excretory Organs— the Kidney and the Liver— |
| C. EXCRETION VS REABSORPTION
(EXCRETION)
1 There are NO EFFICIENT ELIMINATION
MECHANISMS for __. If resistant to __, such chemicals are eliminated VERY SLOWLY and tend to ACCUMULATE in the body on repeated exposure
2 THREE INEFFICIENT PROCESSES are available for the elimination of such chemicals:
3 VOLATILE, NONREACTIVE TOXICANTS
such as __ DIFFUSE from PULMONARY CAPILLARIES into the __ | .
1) 1 Nonvolatile, Highly Lipophilic Chemicals.
2 Biotransformation
2)
1 Excretion from the MAMMARY GLAND in breast
milk
2 Excretion in BILE
3 Excretion into the INTESTINAL LUMEN from blood.
3) 1 Gases and Volatile liquids
2 Alveoli and are Exhaled |
| C. EXCRETION VS REABSORPTION
(REABSORPTION)
1 Toxicants delivered into the RENAL TUBULES may __ across the tubular cells into the __
This __ INCREASES the INTRATUBULAR CONCENTRATION as well as the RESIDENCE TIME of the chemical by __.
2 REABSORPTION BY DIFFUSION is
- Dependent on: __
- Inversely related to: __
3 because the NONIONIZED MOLECULE is
__ soluble | .
1) 1 diffuse back,
2 PERITUBULAR CAPILLARIES.
3 Tubular Fluid Reabsorption
4 slowing urine flow
2) 1 Lipid solubility of the chemical,
2 Extent of ionization,
- More Ionized = Less Diffusion
3 more lipid |
| C. EXCRETION VS REABSORPTION
(REABSORPTION)
1 Toxicants delivered to the GI tract by __ may be REABSORBED BY DIFFUSION across the INTESTINAL MUCOSA
2 REABSORPTION of COMPOUNDS EXCRETED into the BILE is POSSIBLE ONLY IF they are __ | .
1 BILIARY, GASTRIC, & INTESTINAL EXCRETION & SECRETION by SALIVARY GLANDS and EXOCRINE PANCREAS
2 LIPOPHILIC enough,
are CONVERTED to MORE LIPID SOLUBLE forms
in the INTESTINAL LUMEN(TUBE). |
| D. TOXICATION VS DETOXICATION - (TOXICATION)
1 BIOTRANSFORMATION TO HARMFUL PRODUCTS is called __
2 With some __, Toxication CONFERS PHYSICOCHEMICAL PROPERTIES that adversely ALTER the MICROENVIRONMENT of biological processes or structures | .
1 Toxication or Metabolic Activation
2 Xenobiotics |
| D. TOXICATION VS DETOXICATION - (TOXICATION)
1 Most often Toxication RENDERS XENOBIOTICS and occasionally other molecules in the body, such as __, REACTIVE toward __
2 This INCREASED REACTIVITY may
be due to conversion into: __ | .
1 nitric oxide,
Endogenous molecules with susceptible functional groups.
2)
(1) Electrophiles,
(2) Free radicals,
(3) Nucleophiles, or
(4) Redox active reactants.
NERF |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
What are the different types of DETOXICATION | 1 Detoxication of Toxicants with No
Functional Groups
2 Detoxication of Nucleophiles
3 Detoxication of Electrophiles
4 Detoxication of Free Radicals
5 Detoxication of Superoxide Anion Radical by Superoxide Dismutase, Glutathione peroxidase, and Catalase
6 Detoxication of peroxidase generated free radicals such as chlorpromazine free radical by
glutathione
7 Detoxication of Protein toxins |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
1 the BIOTRANSFORMATIONS that ELIMINATE THE ULTIMATE TOXICANT or PREVENT its FORMATION | .
1 Detoxication |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
1 In general, chemicals WITHOUT FUNCTIONAL GROUPS, such as __, are detoxicated in
TWO PHASES: __
2 The Final Product of the 2 phase detoxication is __ | .
1 Benzene and Toluene.
step 1 - hydroxyl or carboxyl (a functional group) is introduced into the molecule
step 2 - endogenous acid such as Glucuronic acid, Sulfuric acid, or an Amino acid is added to the
functional group by a Transferase.
2 INACTIVE, HIGHLY HYDROPHILIC ORGANIC ACIDS that are readily excreted. |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
1 NUCLEOPHILES generally are DETOXICATED by __,
preventing peroxidase from catalyzing the conversion of the nucleophiles to __ and the biotransformation of phenols, aminophenols, catechols, and hydroquinones into __ | .
1 Conjugation at the Nucleophilic functional group,
Free radicals,
Electrophilic QUININES & QUINONEIMINES. |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
1 Generally, detoxication of ELECTROPHILIC TOXICANTS involves __
2 This reaction occur SPONTANEOUSLY or can be FACILITATED by __.
3 COVALENT BINDING of ELECTROPHILES
TO PROTEINS can be regarded as DETOXIFICATION, provided that the protein has __ | .
1 Conjugation of Nucleophile Glutathione.
2 Glutathione transferases
3 NO critical function and
does NOT become harmful. |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
1 __ can be converted into much more reactive compounds, its elimination is an IMPORTANT DETOXICATION MECHANISM.
2 __, located in the CYTOSOL (Cu, ZnSOD) and the mitochondria (MnSOD), convert O2 to HOOH
3 Subsequently, HOOH is reduced to water by __ | .
1) O2
2 Superoxide dismutases
3 Cytosolic Glutathione Peroxidase or
Peroxisomal Catalase. |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
DETOXICATION OF PEROXIDASE GENERATED FREE RADICALS SUCH AS CHLORPROMAZINE FREE RADICAL BY GLUTATHIONE
1 The byproducts are __ and __, from which GSH
is regenerated by __ | .
1 Glutathione thiyl radical (GS• )
Glutathione disulfide (GSSG)
Regenerated by: Glutathione reductase (GR) |
| D. TOXICATION VS DETOXICATION - (DETOXICATION)
- Detoxication of Protein toxins
1 __ are INVOLVED IN THE INACTIVATION OF TOXIC POLYPEPTIDES.
2 Venom toxins, such as __, lose their activity | .
1 Extra and intracellular proteases
2 α and β bungaratoxin, erabutoxin, and phospholipase |
