Flashcards in Exam 3 Toxicology Deck (38):
4 areas of study in toxicology
1. occupation safety
2. environmental toxicology
3. analytic toxicology
4. forensic toxicology
term describing the range of response per dose, an individual may require a higher/lower dose to produce the desired effect
term describing a greater than normal reaction to a drug
term describing the response of the patient to the drug when it is qualitatively different from the usual or expected response
Geriatric patients have less ___ ___ (decreased plasma proteins), less _____ (decreased liver function) and decreased renal function which allows for normal doses of drugs to act at ____ levels. Give ___ dose
In a pt with liver disease, drug ___ is reduced due to diminished function of ____ ____ system, dosing must be reduced.
In a pt with renal disease, renal impairment of ___ ___ occurs, dosing must be modified on the basis of renal ____ ___ of the drug
___ ____: increasing amounts of drug are required to produce a consistent effect, usually associated with drugs that cause ____ ____.
____: rapid development of tolerance
what does TD50/ED50 mean?
TD50 = dose of the drug that causes a toxic response in 50% of the popultion
ED50 = dose of the drug that is therapeutically effective in 50% of the population
The therapeutic index provides a single number that quantifies the relative ____ of ___ of a drug in population of people. A large Ti represents a ___ therapeutic window and a small TI represents a ___ therapeutic window = requires monitoring
margin of safety
____ toxicity occurs as a result of a single, large ___ to the toxic agent. Effects are usually ____ within minutes to hours. Occasionally, signs of acute toxicity are not visible for ___ to ___ following the initial exposure.
weeks to months
____ toxicity = the effect of toxic insult that occurs over a ____ period of time. Often it is manifested after ___ of exposure. May also manifest long after the individual is no longer exposed to the ____.
Study of the absorption, distribution, metabolism, and excretion of toxic parent compounds and metabolic products
4 types of GI toxins
2. contaminants in food (mercury in fish)
3. majority of therapeutic agents (drugs)
4. lead in dirt and paint
4 types of inhaled toxins
1. air pollutants
2. cigarette smoking
3. industrial chemicals
4. agents of chemical warfare
What toxin can passively diffuse through the 7 layers of skin after prolonged contact?
8 mechanism of toxicity
1. Interference with cellular function
2. Macromolecular damage
3. Reactive species
4. inflam/immune mediated mechanisms
5. Enzyme/receptor mediated
8. Organ directed toxicity
What type of toxicity mechanism is described: carbon monoxide binds strongly to the iron in the active site of hemoglobin, preventing oxygen binding and reducing oxygen carrying capacity.
What type of toxicity mechanism is described: nerve gasses/pesticides are acetylcholinesterase inhibitors which causes excessive concentration of ach in synaptic cleft resulting in slowed HR, difficulty breathing, sweating, pinpoint pupils
Enzyme mediated (common toxins interfere with NT, cardiac rhythm, oxygen deliver, ATP generation, or intracellular ca balance)
What type of toxicity mechanism is described: cyanide binds to the heme iron in the active site of the enzyme cytochrome C oxidase causing reduction in the generation of ATP
Enzyme mediated (many compounds are toxic bc they alter important metabolic pathways, signaling pathways, or interact with critical receptors)
What type of toxicity mechanism is described: toxins damage tissue by altering the structure of proteins, lipids, carbs, and nucleic acids so severely that cellular integrity is lost
macromolecular damage - tissue damaging agents are nonspecific
What type of toxicity mechanism is described: React chemically with biologic macromolecules and other chemicals, more specific in their site of action, example: carbon tetrachloride
Reactive species - when carbon tetrachloride is metabolized by the liver, reacts with oxygen to form toxic organic free radicals which cause toxicity
What type of toxicity mechanism is described: hypersensitivity and autoimmune reactions
Inflammatory and immune mediated mechanisms - the immune system removes cell damaged by toxins and releases immune mediators that are important in repairing tissue damage
What type of toxicity mechanism is described: the transformation of a normal cell to a neoplastic cell
carcinogenesis - involves multiple genetic changes
Development of cancer: Initiators damage ____, interfere with DNA replication or ___ mechanisms. Most initiators are ___ ___ that chemically modifies the structures of DNA, preventing accurate ____ which causes DNA _____. Mutations are passed along during cell ____.
Carcinogens can also promote the development of cancer by causing what?
chronic tissue damage in organs capable of tissue repair (alcoholism -> cirrhosis -> liver cancer)
What type of toxicity mechanism is described: substances that can inhibit intracellluar signals are potent, they can induce a birth deft and also alter DNA or chromosomes
Teratogenesis - effect of any substance is dependent on the development timing of the exposure
What type of toxicity mechanism is described: organs with regenerative capacity may recover after toxic exposure and organs with limited or no regenerative function lose function as tissue is destroyed from toxic exposure (heart/nerves)
Organ directed toxicity - blood brain barrier prevents many toxins from entering the CNS
3 mechanisms of selected toxicity by drugs
1. Attack targets that are unique to the pathogen but are not ______
2. Attack target in the pathogen or cancer cell that are similar ___________
3. Attack targets in the pathogen/cancer cell that are shared _________
1. present in the host
2. but not identical to those in the host
3, by the host but that vary in importance between pathogen and the host
Drugs exhibit the ____ toxicity when they target a ___ ___ between the pathogen and host cell
Drugs exhibit the ___ toxicity when they target ___ ___ shared by both the pathogen and the host cell.
A highly ___ drugs like penicillin is prescribed ___ because of the large difference between the therapeutic and ___ concentrations.Drugs that are less selective means that they affect both the pathogen and host cells and are ___ ___ and have a ____ therapeutic index.
4 examples of unique targets (present in pathogen bu lacking in host)
1. metabolic pathways
3. mutated genes
4. gene products
_______: when the host and the pathogen share a common biochemical or physiologic pathway
Common targets - narrow therapeutic index
With common targets their are adverse side effects, name 5
1. loss of hair
2. mouth sores
3. skin problems
4. GI problems
drugs that affect only 1 phase of the cell cycle
cell cycle specific
drugs that affect any/all phases of the cell cycle
cell cycle non specific (most antineoplastic drugs affect either S or M phase)