Block A Flashcards

Question

what is structure-activity relationships (SAR) and their importance

Answer 1

SARs = chemical structure determines a compounds physical and chemical properties ergo it determines biological properties -important for toxicity as we can predict by a chemicals structure how it will interact witha biological system, a drug made for morning sickness generated severe birth defects, could have been prevented if care was given to how its isomer would react within the body

Answer 2

a drug that in R configuration acts as a seditive but in S formation is a teratogenic (causes birth defects)

Answer 3

the capacity to produce abnornalities of the unborn child or foetus (birth defectsss)

Answer 4

the capaity to produce disease from the side effects or inappropriate prescribing of drugs, e.g: anti-malarial drug mefloquine (lariam) associated with neuropsychiatric side effects (same brand of defect as dementia)

Answer 5

animal testing, looking at: -long-term administration of drug -regular monitoring for abnormalities -detailed post-mortem check for histological abnormalities -dose administered well above therapeutic range to check for likely targets under overdose conditions -recovery studies to examine reversible effects

Answer 6

-descriptive toxicology -analytical toxicology -regulatory toxicology -mechanistic toxicology -clinical toxicology -forensic toxicology -ocupational toxicology -enviromental toxicology

Answer 7

adverse drug reactions, effects can be related to known pharmalogical action of drug (e.g vascodilator causing exadurated effects of low blood pressure) or unrelated to known pharmalogical action of drug, e.g morning sickness cure causing birth defects

Answer 8

the qualitive and quantitive study of adverse or toxic effects of substances on organisms

Answer 9

the inherent ability of a substance to cause harm to a living organism

Answer 10

the potential for harm under specific conditions of use or exposure. hazard considers both toxicity of substance ad likelyhood of exposure (seen in risk assesment for labs)

Answer 11

the likelyhood of being harmed, taking into consideration the degree or nature of exposure to hazard and how serious the consequnces would be

Answer 12

a foriegn substance taken into body that may produce benifical effects or may be toxic, like gambling wether a mushroom is extremely poisonous or goes well in a soup

Answer 13

a general term for any material capable of a harmful effect in a biological system, can be chemical, physical, or biological in nature

Answer 14

a substance producing adverse biological effect, generaly a main product or by-product of human activity

Answer 15

peptides or proteins produced by living organisms capable of harm, venoms are toxins injected by a bite or sting, poisonous animals release toxins when touched or ingested

Answer 16

-what is the substance? (inherintly toxic) -what is the amount? (you can overdose on water nothing is safe in excess) -what is the situation? (exposure, how much actually made contact and entered the body) -what is the timeframe? (exposure again, depending on route of exposure it can happen fast or sloqly, repeated exposure increases risk)

Answer 17

-industrial chemicals -therapeutic agents (overdose) -house-hold chemicals like bleach -food adatives -enviromental contaminants (industrial waste, polution) -drugs of abuse (alcohol, cocaine, steroids)

Answer 18

-acute: within 24 hours eg drug overdose -subacute: repeated exposure up to 1 month, e.g toxic response to new medicine in early stage of therapy -subchronic, repeated exposure 1-3 months, e.g contaminated drinking water -chronic, 3 months or greater, e.g occupational exposure to chemicals, like all the guys who fitted asbestos before we realised it was super cancer

Answer 19

-local toxicity which occurs upon initial contact with body in highly reactive chemistry, think acid burns -systemic toxicant, able to affect the whole body or many organs rather then a specific site -target organ toxins, which dont produce damage to the body as a whole but affects only certain tissues, like asbestos in the lungs

Answer 20

-dose is the quantity of toxin received by an individual represented in mass or molar amount. -dosage is an expression of the dose in terms of recipient characteristics, e.g body weight, milligrams of toxin/kg body weight -internal dose reflects actual amount of substance within body which can vary between individuals even when external exposure is the same

Answer 21

the corelation of how exposure changes body function or health, in general the higher the dose the more severe the response

Answer 22

the lowest dose where a induced effect occurs

Answer 23

a toxin having induced expected observable effects

Answer 24

the rate at which adverse effects accumulate, indicitive of potency. steeper slope indicates a higher potency as it reaches effect quicker/at lower dosage

Answer 25

the dose estimite where 50% of the group of organisms given toxin would be expected to die

Answer 26

ED can refer to a benificial effect (pharmacology) or a toxic effect (toxicology) as effective dose is the effectiveness of a substance reaching these results reliably at a specific endpoint/dose

Answer 27

doses at which adverse toxic effects occur

Answer 28

the dose of drug/toxicant required to produce a specific effect of given intensity e.g LD50

Answer 29

no observable adverse effect limit, the highest dose at which there was not an observed toxic or adverse effect

Answer 30

lowest observable adverse effect limit, the lowest dose at which a toxic or adverse effect is observed

Answer 31

the therapeuticly effective dose to the toxic dose of a pharmaceutical agent, TI is the ratio of dose that produces toxicity to the dose needed to produce the desired therapeutic response, basically TD50 devided by ED50

Answer 32

the maximum effect that a drug can produce regardless of dose

Answer 33

a ratio of the toxic dose to 1% of population (TD01) to the dose that is 99% effective to the population (ED99) this is done where the effective dose of a drug overlaps with the Toxic dose since a 100% effective dose which has a toxic dose of 75% is not great since 75% of the population dying is not ideal in medicine

Answer 34

they both deal with the absorption, distribution, biotransformation, and excretion of chemicals, pharma relates to helpful effects and toxico refers to harmful effects

Answer 35

phase 1: oxidation, reduction, and hydrolysis reactions, convert a parent drug to a more polar water soluble active metabolite by unmasking or inserting a polar functional group. phase 2: conjugation, a drug or its metabolite is conjugated with an endogenous substance e.g glucuronide conjugate, converting a parent drug to a more polar inactive metabolite by conjugation of subgroups to -OH, -SH, -NH2 functional groups on drug

Answer 36

the time required to reduce blood concentration of chemical to half, often represented as (t1/2)

Answer 37

co-exposure is when an organism comes into contact with multiple chemicals concurrently or sequentially. the dangers arise from how the chemicals compound in their function to worsen the effect, e.g: sleeping pills with some drugs can cause vomiting in sleep which if not cleared of airways can drown the person

Answer 38

to identify and protect subsets of people predisposed to toxicity from chemicals or drugs, this is due to populations having varying ressistance to various toxins dependant on age, gender, life style, genomic makeup and sickness.

Answer 39

The ALDH2 enzyme is located within hepatic mitochondria and is responsible for converting the acetaldehyde that forms during alcohol metabolism into acetic acid. Allelic variants in aldehyde dehydrogenase-2 (ALDH2) cause decreased ability to clear acetaldehyde and other aldehyde substrates.

Answer 40

Clostridium botulinum is a bacterium that produces dangerous toxins (botulinum toxins) under low-oxygen conditions, such as contaminated sealed cans (duck paste from the horrible science book)

Answer 41

Botulinum toxins are one of the most lethal substances known, 100 billion times more toxic than cyanide - included in the category A list of agents that could be used in bioterrorism. it blocks nerve function and causes respiratory and muscular paralysis with a incubation period of 12 to 36 days, onset time is dose-dependant

Answer 42

BoNT consists of a heavy chain and a light chain linked together by a single disulfide bond, it works by inhibiting acetylcholine release from nerve terminals

Answer 43

the biochemical and physiological effects of chemicals to the body and the mechanism of their actions

Answer 44

heavy chain binds to glycoprotein receptors specific to cholinergic nerve terminals and toxin enters via endocytosis. the light chain posseses protease activity (capable of inducing hydrolysis) and can proteolytically degrade SNAP-25, a SNARE protein (responsible for the combining of vesticles and transported molecules) it inhibits synaptic vesicle fusion with presynaptic membrane inhibiting the release of acetylcholine into the synapse, blocking communication of nerve cell causing flaccid paralysis and death from respiratory arrest

Answer 45

the endospores of C. botulinum can contaminate food, the bodies natural defenses stop this from progressing into active bacteria. Infant intestines lack the protective bacterial flora and chlostridium-inhibiting bile acids allowing the endospores to germinate, multiply, colonise the intestinal lumen in the colon and prodduce neurotoxin. characteristic floppy body and loss of head control as symptoms, avoid giving infants honey as it can carry endospores

Answer 46

-polyclonal antibody fragments, F(ab')2 and Fab, which bind free botulinum toxin in blood, preventing it being internalised in nerve cells, must be administered quickly as it only binds free botulinum toxin, preventing the progression of symptoms but not reversing any paralysis already present.

Answer 47

purified type A BoNT was the first bacterial toxin used as medicine, liscenced by the FDA for use in treating 2 eye conditions; blepharospasm (twitch of eyelid) and strabismus (eye misalignment), both were caused by excesive muscle contractions. later purified botulinum was used for cervical dystonia (neurological disorder causing severe neck and shoulder muscle contractions), persistant migraines and cosmetic uses as botox

Answer 48

-oral administration -Cmax occurs at ~1 hour after ingestion -half life of therapeutic dose is 2-4 hours -uncommon side effect is an allergic skin reaction

Answer 49

10% oxidised byphase 1 reactions of cytochrome P450, producing a reactive intermediate of N-acetyl-p-benzoquinone imine/NAPQI (toxic reaction w proteins and nucleic acid) which is further neutrilised by glutathione. 90% inactivated in liver via sulfatiob and glucuronidation, non toxic product is then excreted via urine

Answer 50

proportion oxidised by CYP enzymes (producing NAPQI) during an ovedose leading to far more toxic reactions w proteins and nucleic acids. sulphation pathway becomes saturated at therapeutic dose leaving glucuronide over-used making it critically depleted and causing liver damage via ballooning degeneration

Answer 51

-identifies risk o co-exposure -identifies suceptable populations -informs regulation -develops therapeutic intervention

Answer 52

alcohol, as it increases activity of CYP enzymes causing more NAPQI to be produced bringing the lethal dose of paracetamol down

Answer 53

-those with polymorphism in the CYP450 gene causing rapid and hyperactive CYP450 activity producing a large amount of NAPQI even at therapeutic dose. -Glutathione serves as the liver's main method of neutrilising paracetamol so low levels produce vulnerability, as seen in infants, malnurished individuals, alcoholics, and the elderly.

Answer 54

acetylcysteine (NAC) within 8 hours of overdose can orevent excessive cell death in liver, NAC is a precursor of glutathione and increases removal of NAPQI by conjugation with GSH (glutathione)

Answer 55

-structure, it is thin allowing for deposition beyond cillated airways, long making macrophages unable to enclose their structure making frustrated phagocytosis, reducing motility and failing to degrade the fiber. and is biopersistent as it retains its fibrous shape over long term residance in the lungs

Answer 56

the physical and chemical relationship that drives toxicity of a substance. physicochemical characteristics linked to biological reactivity can be used to predict toxicity of novel materials

Answer 57

-cannot be cleared passively as asbestos is long and indigestable, leading to failure of passive clearance through stomata (pores that drain lubrication fluid) as asbestos can block the pores, leading to a buildup of pleural fluid in the lungs -cannot be cleared actively y immune cells like macrophages as they are far too long and indigestable to be broken down and removed, instead being stuck in macrophage severely limiting its functionality until death.

Answer 58

glass and mineral fibers present in asbestos are only disolvable in phagolysosomal fluid's low pH, breaking into short fibres and getting cleared, otherwise it can live in the lungs for decades blocking pores that handle passive clearing, leading to buildup of fluid in lungs, increased cancer risk, and failure to clear any and all irritants from the lungs via the stomata pores.

Answer 59

long-fibre-induced-lesions, signified by changes in mRNA levels in the whole diapgragm lysate, comon gene expresion across all lesions of the same type, changes of inflamation, macrophage recruitment and cytokine production

Block A Flashcards

(85 cards)