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205 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Classes of molecular drug modes of transport |
Bulk flow Diffusional |
2 |
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Diffusional transfer: location Mechanisms |
Across boundaries lipid, channels, carrier |
3 |
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Blood Brain Barrier |
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Bioavailability |
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Chronic dosing |
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Chronic dose scheduling |
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Clearance |
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Distribution |
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Distribution |
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Mechanisms of Biotransportation |
Passive Diffusion
Facilitated Diffusion Active Transport Receptor-Mediated Endocytosis |
4 |
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Factors that influence passive diffusion |
Solubility Permeability pH Partition Mechanism Fick's Law |
4 |
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Partition coefficient |
[D]eq lipid/[D]eq H2O |
ratio |
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Permeability |
quality of a substance that is correlated with partition coefficient and molecular size |
correlated (2) |
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Loading dose |
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Plasma Protein Binding Saturation |
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Ion Trapping |
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Receptor-mediated endocytosis |
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Redistribution |
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Routes of administration |
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Speed of injection for acute dose of IV |
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Volume of Distribution |
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Fick's Law of Diffusion |
Flux=molecules/time =([D]i-[D]0)(Area)(PermCoeff)/Thickness |
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pH Partition Mechanism: Bases Diffusion increased |
pH>pKa |
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pH Partition Mechanism: pH>pKa |
Diffusion of Bases increase Acids decrease |
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pKa |
pH at which half the compound is in a charged state |
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Concentrations of weak acids and bases at equilibrium across boundaries |
Neutral species are equal Ionic species depend on balance of charge |
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Henderson-Hasselbach |
pH=pKa+log([base]/[acid]) |
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Endogenous dopaminergic neurotoxicants |
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extrapyrimidal dopaminergic nigrostriatal system |
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haloperidol |
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Lipid peroxidation |
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Pyridines MPP+ neurodegen Paraquat |
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MPTP formation mechanism |
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Neuronal Protein alkylated by dopaminergic quinone |
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Paraquat |
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Dopaminergic Neurotoxicants fall under which class of compounds? |
quinone |
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L-DOPA |
L-3,4-dihydroxyphenylalanine Carboxylated precursor to dopamine |
precursor |
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Dopaminergic neurotoxicants cause neuronal death by |
inhibition of complex IV of Mitochondrial ETC |
ATP producer |
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Complex IV relation to neuronal death Location |
inhibited by dopaminergic neurotoxicants Mitochondrial ETC |
inhibited by |
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Dopamine and norepinephrine are |
Catecholamines
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Oxidation of what by what forms H2O2? |
catecholamine NTs MAO |
NT |
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MAO produces what from oxidizing catecholamine amines by what? |
H2O2 Transferring electrons to O2 |
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Haber Weiss equation |
H2O2+superperoxide= neurocytotoxic hydroxy radical |
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H2O2+superperoxide= neurocytotoxic hydroxy radical |
Haber Weiss equation |
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Oxidation of the dopamine amine group produces |
ammonia NH3 DOPGAL |
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Byproduct of faulty MPPP-reverse ester synthesis |
MPTP |
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MPPP full name Street name |
N-methyl-4-propionoxy-4-phenylpiperidine designer heroin |
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MPTP full name |
Methyl-phenyl-tetrahydro-pyridine |
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reverse ester of MPPP |
Meperidine Demerol |
Street name Trade name |
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Herbicide trade name of MPP+ |
Cyperquat |
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haloperidol is what that does what? |
antipsych drug PD-like, side effects |
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Genetic mutation found in familial cases of PD
Effect |
alpha-synuclein
synucleinpathy |
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Synucleinpathy |
aggregation of protein in dopaminergic neurons causing pathological inclusions/plaques |
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Endogenous Neurotoxicants are formed by what producing what? |
auto-oxidation of dopamine quinones and hydroxy radicals |
reaction of 2 |
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Quinones are a compound class that can be used to describe what formed from what? |
Endogenous neurotoxicants
autooxidation of dopamine |
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Dopaminergic quinone neurotoxicants react with what via what? |
Amine group of neuronal proteins oxygenated carbon |
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What enzyme forms MPDP+ from which molecule? |
MAO-B MPTP |
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MAO-B oxidizes which exogenous molecule to form what? |
MPTP MPDP+ |
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Exogenous neurotoxicants vs Endogenous Neurotoxins |
Pyridines
Quinones |
Compound classes |
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This autocoid is a NT |
histamine
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2 |
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H1 receptors are located where on the neuron? |
presynaptic membrane |
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what H1 G-protein subunit stimulates PLC pathway? |
alpha q |
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What H1 G-protein subunit stimulates AC? |
alpha s |
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PLC pathway stimulates what causing what? |
PKC by Ca2+ release
smooth muscle contraction
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The activation of the H1 Galpha_s stimulates what (1) which produces what (2) that stimulates what (3) that produces what (4) from what (5)? |
AC cAMP PKA DOPA tyrosine |
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The endpoint of H1 Galpha_s activation is.... |
dopamine formation |
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The endpoint of H1 Galpha_q activation is.... |
smooth muscle contraction |
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Which H1 Gprotein subunit has the endpoint of dopamine formation? |
Galpha_s |
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Which H1 Gprotein subunit has the endpoint of smooth muscle contraction? |
Galpha_q |
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trans-PAT is a conformationally H1 selective drug that selects for the activation of which Gprotein subunit? |
Galpha_s |
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cis-PAB is a conformationally H1 selective drug that selects for the activation of which Gprotein subunit? |
Galpha_q |
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What molecule is used in comparative binding studies of trans-PAT? |
Mepyramine |
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What are the major classes of G-protein dimer formation models? |
Contact Domain-swapped |
2 |
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What are the types of contact dimerization models for G-proteins? |
Lateral packing/microaggregation disulfide bond formation coiled coil interactions |
3 |
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Mechanism for the domain-swapped G-protein dimer models |
Trans-complementation |
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COMT |
Catechol-O-Methyltransferase |
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Dopamine+MAO |
Oxidizes amine group double bond to amine Water attacks tri-subbed C O double bond and formation of ammonia + DOPGAL |
4 last step=2 products |
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Mechanism of MAO inhibition made possible by |
third-order substitution of nitrogen on dopaminergic molecule |
resonance |
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A dopaminergic molecule with a tertiary nitrogen provides the capability of what? E.g. drug |
inhibiting of MAO Deprenyl |
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dopaminergic drug substrate with tertiary N |
deprenyl |
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deprenyl |
dopaminergic drug substrate with tertiary N |
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Alzheimer's is a product of what neurochemical condition? |
ACh deficiency |
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ACh deficiency is the neurochemical cause of what? |
Alzheimer's |
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Neuropathology of Alzheimer's |
degeneration of cerebral cholinergic neurons |
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What areas of the brain does Alzheimer's effect? |
Frontal Temporal Parietal Occipital lobes |
4 |
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The initial precursor of Ach |
serine |
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Serine is the initial precursor to which NT? |
Ach |
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Serine modification to choline involves what chemical modifications? |
Decarboxylation tertiary-methylation of amine N |
2 |
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What components form Ach? What enzyme allows for this conjugation? |
Choline Acetyl-CoA choline acetyltransferase |
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What triggers ACh release from presynaptic neuron? |
Depolarization allowing for Ca2+ influx |
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How are ACh molecules condensed while in storage? |
N attracted to phosphate Os on ATP |
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The interaction of AChase phenyl groups with quaternary N of ACh |
pi-pi stacking |
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pi-pi stacking can be used to describe what enzyme-ligand interaction |
AChase phenyl groups with quaternary N of ACh |
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What chemical modification inhibits the protease activity of the AChase serine residue? |
Carbomylation |
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Carbomylation of AChase serine residue mechanistically inhibits hydrolysis by what means? |
Resonance of N electrons |
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Achase Serine carbomylation |
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Rivastigmine |
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Pyridostigmine |
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Neostigmine |
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Physostigmine |
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Donepezil-AChase competitive inhibition |
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ACh-AChase |
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ACh formation |
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BBB |
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MAO inhibition by Deprenyl |
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(MAO+2e-) +O2+(2H+)>H2O2 |
MAO mechanism |
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cis-PAB vs trans-PAT and histamine |
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Dopamine formation |
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histamine |
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AC-cAMP formation |
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H1 AC cAMP pathway |
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PLC-IP3-DAG |
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H1 PLC pathway |
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Bioavailability equation |
C_oral abosrption/C_IV |
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Bioavailability integration of curve for |
Concentration vs Time graph |
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Integration of a Drug Concentration vs time drug curve gives what value? |
bioavailability |
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Dosage formulations of sustained release tablets |
coated multiple layer with slow release core |
2 |
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Dosage formulations of sustained release capsules |
Microencapsulation mixed release granules coated release beads |
3 |
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Volume of distribution equation |
Vdist=dose/C_0 equilibrium concentration |
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Initial equilibrium concentration of drug is determined by |
extrapolation of curve on drug plasma concentration vs time graph |
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Extrapolation of the curve for a plasma concentration vs time graph yields |
initial equilibrium concentration of drug |
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equation of Vdist% for deuterated water |
![or [V_(dist_D2O)/V_body] x 100%](https://images.cram.com/images/upload-flashcards/31/92/34/14319234_m.png)
or [V_(dist_D2O)/V_body] x 100% |
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What happens to the compartmentalization of drug when there is no elimination? |
it becomes biphasic |
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First order elimination Integrated equation |
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Integrated equation first order elimination |
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bioequivalence |
how the bioavalabilitiesof two preparations of a drug compare |
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how the bioavailabilities of two preparations of a drug compare |
bioequivalence
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Cp equals |
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Toxicology is a product of |
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Top reasons for drug attrition 1991 |
Pharmacokinetics Lack of efficacy |
2 |
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Top reasons for drug attrition besides Lack of efficacy 2001 |
Animal Toxicity Adverse Effects on man |
2 |
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Toxicity |
degree of damage that a substance can cause a living system |
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Inherent properties of Toxicity |
Immediate vs Delayed (time of onset) (ir)Reversible (duration of effect) Local vs Systemic (Location) Graded vs Quantal |
4
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Factors that determine degree of toxicity |
dose route of exposure age gender genetics lifestyle health medication |
8 |
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Factors of toxicity: Route of exposure |
rate of exposure extent of exposure |
2 |
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Factors of toxicity: Age |
Variation in absorption variation in organ function |
2 |
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Factors of toxicity: Genetics |
variation in acetyltransferase activity variation in expression or mutation in enzymes that effect absorption/distribution |
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Factors of Toxicity: Lifestyle |
Diet Nutritional Status Smoking Alcohol Consumption |
4 |
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How does food affect toxicity? |
food decreases absorption certain foods effect enzyme activity |
2 |
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How does smoking affect toxicity? |
increases susceptibility to inhaled poisons Enhances metabolic activation |
2 |
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How does drinking affect toxicity? |
increases susceptibility to hepatotoxicity alters nutritional status |
2 |
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Poisons |
any agent producing toxicity |
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Major types of toxicants |
Solvents/vapors Pollutants Pesticides Drug (side effects) Metals |
5 |
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Pesticides are largely these classes of compounds |
organo- phosphorous chlorine |
2 |
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Phenytoin side effect |
teratogenicity |
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Essential metals |
iron manganese zinc copper |
4 |
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How does Arsenic interfere with normal physiology? |
binds to enzyme thiol groups |
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This nonessential metal binds to enzyme thiol groups |
Arsenic |
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what variation of Iron produces molecular oxygen radicals? |
Ferrous Fe(II) |
adjective
oxidation state abbreviation |
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Ferrous Iron |
Fe(II) |
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Fe(II) |
Ferrous Iron |
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Fe(III) |
Ferric Iron |
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Ferric Iron |
Fe(III) |
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Fenton Rxn |
Ferrous iron produces either produces superperoxides from O2 or hydroxyl radicals from H2O2 or Cu does the same from H2O2 |
3 |
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When Ferrous iron either produces superperoxides from O2 or hydroxyl radicals from H2O2 or Cu(I) produces hydroxyl radicals from H2O2 |
Fenton Rxn |
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Antioxidase System |
Superoxide dismutase (SOD) Catalase (CAD) Glutathione Peroxidase (GPx) |
3 |
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SOD: name and role |
superoxide dismutase converts superoxide to H2O2 |
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SOD1 location and metal |
cytosolic Cu and Zn |
2 |
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SOD2 location and metal |
Mitochondrion Mn |
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SOD3 location and metal |
Extracellular Cu and Zn |
2 |
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Catalase Tissues Metal Inhibitors |
liver; kidney; erythrocytes Fe for heme Heavy metals and cyanide |
2 inhibitors |
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Catalase: role |
convert 2 H2O2s to O2 and 2x H2O |
2 |
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GPx: name and role |
Glutathione Peroxidase Reduction of lipid hydroperoxide |
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GSH: name and role |
Glutathione Regenerates GPx by forming GSSG |
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GR: name Regenerates two molecules of GSH with protons from which molecule? |
Glutathione Reductase NADPH |
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GPx and GR mechanisms |
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Antioxidant system |
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Excess zinc causes |
anemia |
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Zinc deficiency causes |
neuronal damage |
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Excess iron causes |
hepatotoxicity |
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Manganese deficiency causes |
bone deformation |
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Excess manganese causes |
neurotoxicity |
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Copper deficiency causes |
neurodegeneration |
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Excess copper causes |
hepatotoxicity |
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Arsenic causes |
neurotoxicity |
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Cadmium causes |
Nephrotoxicity |
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Lead causes |
Anemia |
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Mercury causes |
neurotoxicity |
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nickel causes |
cancer |
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Excess of these metals cause hepatotoxicity |
Iron Copper |
2 |
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Excess of these metals cause Neurotoxicity |
Mercury Arsenic Manganese |
3 |
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Excess of these metals cause anemia |
Lead Zinc |
2 |
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Deficiency of these metals negatively influences the nervous system |
Copper Zinc |
2 |
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Metals |
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Subfields of toxicology |
Mechanistic Regulatory/Occupational Forensic Clinical Environmental Developmental Reproductive |
7 |
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Hazard |
the ability to cause damage |
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the ability to cause damage |
hazard |
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Chance of toxicity from exposure to a hazardous substance |
Risk |
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Risk |
chance of toxicity from exposure to a hazardous substance |
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Curve for toxicokinetics |
Concentration vs time |
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Curve for toxicodynamics |
Effect vs concentration |
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concentration of toxin vs time |
toxicokinetics |
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effect vs concentration of toxin |
toxicodynamics |
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effect of toxin vs time |
toxicology |
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toxicology curve |
effect vs time |
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Factors that influence dose-effect |
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Factors that influence dose-effect of toxins/toxicants |
Route of administration Disposal/elimination Comedication Disease Age Genetics Formulation Environment Lifestyle |
9 |
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What do the factors of dose-effect response of toxins determine per physiology? |
Tissue weight Tissue composition blood flow Enzyme activity Transporter activity Renal/biliary function GI function |
7 |
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differential equation of zero-order elimination |
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Integrated equation of zero-order elimination |
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Integrated equation of first-order elimination |
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differential equation of first-order elimination |
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Straight-line equation of first-order kinetics |
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How to determine elimination half life. Formula |
solve Straight-line first order equation for t when Ct=50 and C0=100 |
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half-life of elimination |
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