Intro to Toxicology Flashcards
Differentiates a poison from a remedy
Dose
Ability of a substance to cause injury to biologic material
Toxicity
Medially accepted term for poison
Toxicants
What is poisoning?
Difference w/ Adverse Reaction?
Overdose of drug, beyond therapeutic dose;
Always within therapeutic dose;
Field in Toxicology:
Identifying and understanding mechanisms; involve animal studies
Mechanistic Toxicology
Field in Toxicology:
Toxicity testing to provide info for safety and regulation
Descriptive Toxicology
Field in Toxicology
Deciding whether a chemical poses only a low risk; for marketing purposes; involves FDA and EMB, provide guidelines for drug use
Regulatory Toxicology
Field in Toxicology:
Impacts of chemical pollutants in the environment on biological organisms
Environmental Toxiclogy
Field in Toxicology:
concerned with medicolegal aspects of the harmful effects of chemicals
Forensic Toxicology
Field in Toxicology:
concerned with diseases caused by/associated w/ toxicants
Clinical Toxicology
Field in Toxicology:
studies the adverse effects of chemicals encountered by workers
Occupational Toxicology
Likelihood that injury will occur given a situation; Formula for this
Risk; Risk = Toxicity x Exposure;
its is INHERENT and CONSTANT
Amount of substance AVAILABLE FOR ABSORPTION; How do i lower this?
Exposure;
- Dec. the dose &
- Use a different mode of administration
What is Safety?
- Inverse of Risk
2. Probability that harm will NOT OCCUR
Exposure types:
<24 hrs single dose or continuous for 4hrs
Effects appear w/in 14 days
Acute
Exposure types:
Repeated daily exposure for 90 days
Subchronic
Exposure types:
Repeated daily exposure for <1 month or 21 days; effects seen within 21 days
Subacute
Exposure types:
How many years for chronic exposure in rats? in humans?
2 years; 70 years;
has transgenerational effects
Exposure / Time period
Frequency
What are the 6 major routes
DI PIMP
Dermal, Inhalation, Parenteral, Ingestion, Mucosal, Percutaneous
What is the order of effective toxicity?
Parenteral>Inhalation>Intraperitoneal>IM>
SQ>Intradermal>Oral/Dermal
The most critical factor in determining the expression of intrinsic potential. It is dependent on ______.
Dosage. dependent on patient’s weight
Other factors:
Sex? Genetics? Nutrition? General Health?
Pregnant women more prone;
Those with metabolic disorders have greater effects;
Malnutrition/Kwashiorkor exacerbates effects;
Liver, kidney, heart, blood disorders
3 Principles of Toxicokinetics
- Not dependent on dose administered but with the concentration absorbed by the organ
- Primarily 1st order kinetics, later become zero order during overdose –> slower elimination rate
- Volume of distribution
Factors affecting toxicokinetics:
Concentration? Absorption Rate? Distribution? Biotransformation? Permeability?
Greater Damage/ Toxicity if:
High Conc, Faster absorption, Wider distribution, Toxic metabolites, Placental and BBB infiltration
Factors affecting toxicokinetics:
Storage? Excretion rate?
Greater Damage/ Toxicity if:
Stored longer, slower excretion rate
T/F: Organs having the highest conc of the drug has the most damage
F. Organ could serve as a storage unit
Where is lead stored? What are its effects?
Where is DDT stored? What are its efects?
Bone, Hematologic and nervous disorders
Fat and proteins, toxic effects in reproductive system
T/F: Protein bound substance does not exert any toxic action
T.
2 Main conditions where BBB will not work/become permeable.
Hypoglycemia and acidosis
2 common mechanisms of elimination
Enterohepatic Circulation
Ion-trapping mechanism
Enterohepatic Circulation:
Where does absorption occur?
What converts the parent drug into its lipophilic form?
Small intestine, at the distal ileum.
Bacterial enzymes
Ion trapping mechanism:
How do I eliminate an acidic/basic drug from my body?
How do I absorb an acidic/basic drug into my body?
Alkalinize/Acidify my urine.
Acidify/Alkalinize my urine.
Nature of Toxic Action (5)
- Drug Exaggeration vs Behavior change
- Drug can have MULTIPLE MOA
- Toxic parent or toxic metabolite
- MOA: Acute exposure vs chronic exposure
- Conc and Persistence-dependent.
4 Main Stages of Toxicity Development
- Delivery
- Interaction with Target Molecule
- Cellular Dysfunction/Injury
- Dysrepair
Delivery:
- what causes DIRECT INJURY?
- what causes TOXICATION.
- Caustic agents (NaOH, HCl)
- Metabolized into harmful products
(Ethylene glycol into oxalic acid causing HYPERCALCEMIA and ACIDOSIS)
Interaction with target molecule:
4 types of interaction
- Non covalent binding
- Covalent binding
- Enzymatic reaction
- Electron transfer
Cellular Dysfunction/Injury
2 Main mechanisms?
Examples of each mechanism
- affects Cell Regulation (dysregulation of gene expression and of cellular activity)
- affects Cell Maintenance (Impaired internal and external maintenance)
Dysregulation of gene expression:
Chemicals that inc estrogen synthesis
Bisphenol A, DDT, phthalate
Dysregulation of cell activity [toxicant-receptor interaction]: 1. Stimulation Benzodiazepine? Amphetamine? 2. Inhibition Atropine? Isoniazid?
Benzodiazepine: stimulate GABA receptor
Amphetamine: stimulate adrenergic receptors
Atropine: Inhibit muscarinic receptor for Ach
Isoniazid: inhibit GABA production
Sympathomimetic vs Anticholinergic
Sympathomimetic: No skin dryness
Anticholinergic: dry and hot skin, high fever
Dysregulation of cell activity [Enzyme rxn]:
Isoniazid inhibits 2 enzymes in GABA formation
PPK (pyridoxine phosphokinase)
Glutamic acid decarboxylase
Impaired Internal Maintenance
3 Main ways
- ATP synthesis (Mt fxn)
- Oxidative Stress (Mt fxn)
- Membrane function (PM fxn)
Drugs that impair ATP synthesis: Give the mechanism
- fluoroacetate
- Cyanide
- CO
- Inhibit H delivery
- Inhibit electron transport in cytochrome oxidase (binds to Fe3+)
- Inhibit O2 delivery to ETC, competes with O2 at Hb sites
Oxidative Stress:
2 main processes involved in Paracetamol degradation?
Toxic metabolie? Its effect?
Glucuronidation, Sulfation
NAPQI (electrophilic moelcule), cause liver damage
Membrane Function - effect of the ff:
Ethanol? Lipid solvent? Hydrocarbon?
Inc membrane fluidity
Destroy PM
Destroy lysosomal membrane
What is an Idiosyncratic Response?
genetically determined abnormal reactivity to a chemical
Drug Interaction:
Interactions demonstrated by certain drugs can be extrapolated to closely related drugs (T/F)
F.
Drug Interaction:
Concurrent use of drugs does not affect drug interaction (T/F)
F.
3 types of drug interaction
Pharamceutical
Pharmacodynamic
Pharmacokinetic
Pharmaceutical Drug Interaction
Drug filler (excipient) interacts with active ingredient. Drug filler can inc. F of active ingredient --> toxicity
Pharmacodynamic Drug Interaction Direct Interaction (Pharmacological | Physiological)
Direct Pharmacological - agonist and antagonist interact at the same receptor
Direct Physiological - Cellular mechanisms acting in concert or in opposition
Mech of interaction between Naloxone and Opiates
Direct Pharmacological; antagonistic to each other
Mech of interaction between Antihistaminic and antihypertensive drugs
Direct Physiological; Antihistaminic also causes hypotension w/c is synergistic w/ antihypertensive drugs
Pharmacodynamic Drug Interaction
Indirect Interaction MOA and example
2 unrelated drugs affect different organs –> The organs produce its respective substances/physiological effect –> the substances/effects react with each other –> effect can be synergistic or destructive
How does motility and food affect drug absorption?
if Motility is dec (due to antimuscarinic drugs) –> inc in GET –> drug degradation in stomach or dec absorption in the SI
Food inc GET.
Physical and Chemical Properties of Substance:
Physical State? Solubility? Vapor Pressure? Vapor density? Reactivity?
- Liquid and gas spreads faster, more toxic
- Lipid soluble, easily absorbed
- Highly volatile, spreads easily, can affect more people
- When chemical is heavier than air, it is found below (more air toxins found in the 1st floor of buildings)
- Can be converted into a more reactive and toxic metabolite
Protective Kinetic Adaptations of the Body Against Hazardous Chemicals:
a
