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298 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What toxins are in daffodils?
What do they do? |
-lycorine
-galanthamine -bind acetylcholiresterase -calcium oxalate crystals irritate mucous membrane |
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What toxins are in lily-of-the-valley/oleanders?
|
cardiac glycosides
(cause death by cardiac arrest) |
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What toxin is in castor beans?
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ricin
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What is the structure and mechanism of ricin?
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-B binds to cell surface
-A is toxic -inhibition of protein synthesis -subunits are linked by a disulfide bond |
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Name a phytotoxin:
|
Solanine (potatoes), a neurotoxin
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Name an animal toxin
|
tetradoxin (puffer fish)
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Name two mycotoxins:
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-ergot alkaloids
-aflatoxin |
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What is the most common type of household poisoning?
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NSAIDS
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What is biomagnification?
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When toxins accumulate up the food chain
e.g. DDT |
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What is toxicology?
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The study of the nature and mechanisms of adverse effects.
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What is a poison?
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A compound that is toxic even at low doses and has no benficial effect.
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How can you evaluate the safety of a drug (2)?
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-Therapeutic index (LD50/ED50)
-Safety margin (LD01/ED99) |
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What are the NOAEL and the LOAEL?
|
no observed adverse effect level
lowest observed adverse effect level |
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What is hormesis? Give 2 examples.
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When high and low doses of a drug have varying effects.
e.g. Vitamins, antibacterials |
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What is a cohort study?
|
-Study of a group of individuals exposed to a chemical over time, compared to a control group.
-Can be prospective/retrospective. |
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What is a case control study?
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Compare individuals with a disease to those without (control) to try and determine associations with prior exposures.
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What are cross-sectional studies?
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Test if a certain group is more susceptible to a certain condition. e.g. golf green tenders
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What are ecological studies?
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Incidence of a disease in one geographical area compared to another.
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What is an Odds Ratio?
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(Risk of disease exposed)/(Risk of disease unexposed)
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What is a Standard Mortality Ratio?
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SRM = relative risk of death of exposed compared to non-exposed
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What is a relative risk?
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RR = (disease in exposed/disease in unexposed)
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What do epidemiological studies test?
|
Risk of illness in exposed popultion vs. control
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What kinds of things can lead to false outcomes of epidemiological studies (3)?
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-selection bias: group non-representative of the population
-information bias: subjects misclassified -confounding factors: other elements not taken into consideration |
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What is a highly important component of toxicology?
|
Risk Assessment
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What toxin was found in toys when you were little?
|
Lead
|
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Where is lead found?
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-airborne
-gasoline (formerly) -house paint (formerly) -lead pipes -pottery (certain countries) |
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Name some symptoms of lead poisoning:
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-fatigue
-GI problems -reproductive issues -memory (NS) -kidney problems -weight loss -weak wrists/ankles |
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Where is lead stored in the body?
|
in bone
|
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What kind of effects does mercury have as a toxin?
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-NS
-"mad hatters" -vision/hearing -can kill you |
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Describe mercury's life cycle:
|
anthopogenic + natural mercury (volcanoes)
Hg in water sediment acted on by bacteria to form methyl mercury Bioaccumulates in the food chain |
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What is a relative risk?
|
RR = (disease in exposed/disease in unexposed)
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What do epidemiological studies test?
|
Risk of illness in exposed popultion vs. control
|
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What kinds of things can lead to false outcomes of epidemiological studies (3)?
|
-selection bias: group non-representative of the population
-information bias: subjects misclassified -confounding factors: other elements not taken into consideration |
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What is a highly important component of toxicology?
|
Risk Assessment
|
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|
What toxin was found in toys when you were little?
|
Lead
|
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|
Where is lead found?
|
-airborne
-gasoline (formerly) -house paint (formerly) -lead pipes -pottery (certain countries) |
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Name some symptoms of lead poisoning:
|
-fatigue
-GI problems -reproductive issues -memory (NS) -kidney problems -weight loss -weak wrists/ankles |
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Where is lead stored in the body?
|
in bone
|
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What kind of effects does mercury have as a toxin?
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-NS
-"mad hatters" -vision/hearing -can kill you |
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Describe mercury's life cycle:
|
anthopogenic + natural mercury (volcanoes)
Hg in water sediment acted on by bacteria to form methyl mercury Bioaccumulates in the food chain |
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What is the "grasshopper effect"?
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When mercury in the tropics blows north and settles
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What is a positive side of insecticides/pesticides?
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-better crop yield
-less disease (malaria) |
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What is the main problem with DDT?
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It bioaccumulates in birds/wildlife!!
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Name 2 classes of insecticides:
|
-organochlorines (DDT)
-pyrethroids -organophosphates |
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What is the mechanism of action of DDT?
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Open Na+ channels in insects so they cannot close = neurotoxicity
Bind to alpha subunit Insect Na+ channel more susceptible than human Na+ channel |
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Name 3 organochlorines + usage:
|
-DDT
-Lindane (lice - blocks GABA receptors) -Chlordane (termites) |
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What is a safer alternative to DDT that uses the same mechanism of action?
|
Pyrethroids (more easily metabolized)
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What is the mechanism of action of organophosphates?
|
Block acetylcholinesterase (e.g. malathione)
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Do DNA mutations occur equally in the genome?
|
No!! There are "hot spots"
|
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Describe the Ames test:
|
-His-negative bacteria
-Mutagen -Liver homogenate (metabolizing enzymes) -->If there is growth on His -ve agar, there are mutations |
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How does the cell deal with DNA damage?
|
It has repair processes that can be activated.
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Name 4 DNA repair mechanisms:
|
1) Mismatch repair
2) Nucleotide excision repair 3) Base excision repair 4) Recombination repair system |
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What does mismatch repair do?
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Solves base mispairing
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What does nucleotide excision repair do?
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Solves base adducts, crosslinks, base modifications
|
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What does base excision repair do?
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Base modifications, single strand breaks
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What do recombination repair systems do?
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Ss breaks, ds breaks
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What kind of disorder can result from a deficiency in one nucleotide excision repair enzyme?
|
Xeroderma pigmentosum
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What carcinogen is responsible for a major proportion of lung cancer incidences?
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Tobacco
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What elements in the diet can lead to cancer?
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Aflatoxin
also: fatty and fried foods play a role |
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Is there a safe exposure level to carcinogen?
|
No!!!
|
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Define a toxin.
|
You're a toxin.
|
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Transformed cells may have which genes altered?
|
-growth factors
-gf receptors -signal transduction -transcription regulation |
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What is the difference between an 'initiator' and a 'promoter'?
|
-initiator is irreversible
|
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What kind of carcinogen is NOT a mutagen?
|
a 'promoter'
|
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What kind of carcinogen can lead to cancer?
|
a complete carcinogen
|
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What is the difference between genetic and epigenetic carcinogens?
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Genetic = direct changes to DNA
Epigenetic = gene repression/stimulation of cell division/clonal expansion |
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Name some carcinogenic compounds in tobacco smoke besides tobacco:
|
-Polycyclic Aromatic Compounds (e.g. benzo(A)pyrene)
-N-Nitrosamine (e.g. NNK) |
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When do PAHs become carcinogenic?
|
after they are metabolized by p450 enzymes to form reactive diol epoxides that form DNA adducts
|
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When do NNKs become carcinogenic?
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after they are metabolized by p450 enzymes to form reactive diazonium ions and aldehydes that form DNA adducts
|
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What is characteristic of the urine of smokers?
|
it is carcinogenic
|
also, it is transparent |
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Are all benzo(A)pyrene metabolites the same (in structure and carcigonicity)?
|
No! The major projuct (7,8-diol-9,10-epoxide) is not the least mutagenic -- pretty bad.
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What can the diol-epoxide metabolites of benzo(A)pyrene induce?
|
Lung tumors
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Which CYP450 is involved in Benzo(A)pyrene metabolism?
|
1A1
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What can induce more 1A1 production?
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B(A)P
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Which gene is responsible for induction of 1A1?
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Aromatic hydrocarbon response element
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If you have no AhReceptor will you get tumours from aryl hydrocarbons?
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No!!
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What other issue can inducibilty of AHH's cause
|
cataracts
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What kinds of genes must be activated/inactivated to get a malignant tumour?
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activate oncogenes
inactivate tumor suppressor genes |
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What kinds of elements can be proto-oncogenes (6)?
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1-growth factors
2-gf receptors 3-signal transduction 4-transcription factors 5-apoptosis 6-cell cycle |
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Name a proto-oncogene:
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Ras p21
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Name 2 tumor suppressor genes:
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-p53
-Rb |
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What does wildtype p53 do?
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arrests cells with damaged DNA in G1 or G2 to allow DNA repair mechanism to take place
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Without p53, what happens?
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mutations accumulate
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Name some carcinogens that cause p53 mutations:
|
aflatoxin
cigarette smoke alcohol radiation |
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Is there a genetic component to cancer?
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yes, it is heretable
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Name some teratogenic agents:
|
-radiation
-infections -metabolic imbalances |
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What are the 5 principles of teratology?
|
1. Access of a toxic agent to developping tissues depends on the agent
2. The manifestation of deviant development increase as dosage increases from no effect to the lethal effect 3. The final manifestations of abnormal development are death, malformation, growth retardation, and functional disorder 4. Susceptibility varies with the developmental stage at which the exposure occurs 5. Teratogenic agents act in specific ways to initiate abnormal development |
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How can potential teratogens be tested?
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1. epidemiological studies
2. in vivo (2 species, during development) 3. in vitro (whole embryo/embryonic stem cells) |
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Which form of Thalidomide causes birth defect?
|
S-thalidomide
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What does Thalidomide cause?
|
phocomelia (seal-like limbs)
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Name a possible mechanism for the damage done by Thalidomide:
|
oxidative DNA damage`
|
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Is Thalidomide teratogenic in all organisms?
|
No! In rabbits it is, but not in mice!
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What can protect against Thalidomide damage in rabbits?
|
free radical scavengers
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What is new beneficial use for thalidomide?
|
use in treating:
-leprosy -multiple myseloma -HIV (must have no other safe alternative, etc...) |
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Retinoids are metabolites of which vitamin?
|
Vitamin A
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At what level do retinoid receptors act?
|
at the level of gene transcription
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What factor affects the outcome of retinoid defects?
|
Time of exposure
|
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Name an example of retinoid deformations:
|
limb deformities (increase in apoptosis in limbs)
|
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Explain the mechanism of retinoids:
|
RA binds RAR, activates genes, activates caspases, causes apoptosis (exact pathway unknown)
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Which CYP450s metabolize retinoids?
|
CYP26 (without it, we get mermaid mice)
|
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Do retinoid metabolites interact with RAR's?
|
No!
|
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What kind of genes come into play in the retinoid mechanism of action?
|
-homeobox genes
|
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|
Describe fetal alcohol syndrome:
|
-growth retardation
-craniofacial abnormalities -CNS abnormalities |
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What is the leading cause of mental retardation in the Western world?
|
ethanol consumption during pregnancy (no safe dose)
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What effects do maternal smoking play on infants?
|
-decreased birth weight
-increase of infant irritability and weakness -increase risk of overweight children |
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What can prevent neural tube damage formation?
|
folic acid
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Can paternal exposure influence malformations in progeny?
|
yes!
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Name a drug taken by males that could have an effect on offspring?
|
cyclophosphamide (an anti-cancer drug)
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What are some uses for estrogens and progestins as drugs?
|
-fertility control
-hormone replacement therapy -cancer chemotherapy -others |
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Which hormone is released from the hypothalamus to control angrogen/estrogen production and follicle maturation?
|
GnRH
|
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Which hormones are released from the anterior pituitary in response to GnRH?
|
LH
FSH |
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What does FSH regulate? Where does it act?
|
-follicle growth and maturation
-cholesterol side chain cleavage and aromatase activity Granulosa cells (inside theca cells) |
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What does LH regulate?
Where does it act? |
-steroid synthesis
-induces synthesis of FSH receptor Theca cells (layer around developing oocyte) |
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What is the steroidogenesis pathway?
|
cholesterol --> progesterone --> testosterone --> estradiol
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Where in the body do estrogen and progesterone exert their action?
|
-female reproductive tract
-mammary glands -fat/liver/bone/kidney/lung/testes/prostate/vasculature... |
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How do LH and FSH differ?
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-common alpha subunit
-distinct beta subunit |
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What subunits are there in steroid hormone receptors? (3)
|
-ligand binding domain
-DNA-binding domain -NH2-terminal domain (varies) |
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What are the two isoforms of the estrogen receptor?
|
alpha
beta (tissue specific, but estradiol binds both) |
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How do the A and B isoforms of the progesterone receptor result?
|
alternative splicing
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Describe the feedback mechanisms in the estrogen/progesteron pathway:
|
-estrogen and progesterone negatively feedback on hypothalamus and anterior pituitary
-inhibin (produced in the ovary) also inhibits the pituitary -once estrogen/progesterone reach a certain threshold, there is positive feedback on hypothalamus/pituitary |
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What is involved in estrogen action?
|
-endometrium proliferation
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What is involved in progesterone action?
|
-antagonizing of E2 action (secretory changes in endometrium)
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Describe the mentrual cycle:
|
-Estradiol progressivly increases (proliferation)
-Reaches thresholed, causing positive feedback on hypothalamic axis -LH surge/follicular rupture -progesterone increase (differentiation) |
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Name the targets for female contraception:
|
-block ovulation
-block egg transport -block fertilization -block zygote formation -affect implantation ...many targets!!! |
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What are the four types of female contraceptives (oral)?
|
-combination (estrogen + progestin)
-progestin-only -emergency (either type) -contragestation (antiprogestin) |
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What do combination contraceptive pills contain?
|
-estrogen
-progestin |
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What is their percent effectiveness?
|
98-99%
|
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How is the pill generally taken?
|
21 days with 7 days rest
or monophasic or bi/triphasic |
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What is the mechanism for the contraceptive pill?
|
Flattening of LH/FSH by the exogenous steroid (no LH surge = no ovulation)
|
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What does the contraceptive pill do on each component of the axis:
|
-Hypothalamus: P decreases GnRH pulses
-Pituitary: Decreased responsiveness to GnRH; E suppresses FSH release; decrease in follicle growth; P suppresses midcycle LH surge |
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|
Name the targets of the combination contraceptive:
|
-higher brain
-hypothalamus -pituitary -ripe follicle -ovulation -ovum/capacitated sperm -zygote implantation ....many targets! |
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Name two estrogen drugs?
|
ethinyl estradiol
levonorgestral NOT inactivated in the GI tract |
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Are oral contraceptives reversible?
|
yes
|
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Why is there a drug-drug interaction between combination contraceptives and large-spectrum antibiotics?
|
need bacteria to activate estrogens and progestins
|
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Name some long term benefits of combination oral contraceptives:
|
-decreased risk of ovarian and endometrial cancer
-decreased risk of fibrocytic breast disease -50% reduction in pelvic inflammmatory disease |
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Name some short term benefits of oral contracteption:
|
-help with headaches
-improve acne -lessen facial hair growth -reduce heavy bleeding; makes cycles regular -reduce painful periods/cramps |
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Name some adverse effects of combination oral contraceptives:
|
-clotting
-myocardial infarct -stroke -breast cancer -drug interactions lead to contraceptive failure |
|
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Are oral contraceptives considered safe?
|
YES
|
|
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Name some side effects of oral contraceptives:
|
-nausea
-breast tenderness -mid-cycle bleeding (first month) -weight gain -increased appertive -mood swings -depression -headaches... CYCLE OUT AFTER 6 MONTHS |
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What kind of women should NOT take oral contraceptives?
|
women who smoke cigarettes
|
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Name two forms of the "morning-after pill":
|
-preven: levonorgestrel + ethinyl estradiol
-plan B: levonorgestral alone |
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What is the mechanism of the morning after pill?
|
Interferes with ovulation, preventing fertilization.
|
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How effective is the morning-after pill?
|
95%, depending on time since intercourse
|
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|
Name two drugs used as contragestation/medical abortion:
|
Mifepristone
RU486 (progesterone and glucocorticoid receptor antagonist) |
|
|
Can you compare oral contraceptive drugs to delivery doses?
|
No!!!
|
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Name the two cell types in the testes, their location and what they produce:
|
Leydig cells - outside seminiferous tubule; produce T
Sertoli cells - inside tubules; support germ cell development |
|
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Where does LH act? FSH?
|
LH - Leydig cells
FSH - sertoli cells |
|
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What is the requirement for germ cell maturation?
|
10X more [T] in tubules than in circulation
|
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|
Which enzyme converts testosterone to DHT?
|
5alpha-reductase
|
|
|
Which enzyme converts testosterone to estradiol?
|
aromatase
|
|
|
Which testosterone products end up in urine?
|
androsterone
etiocholanolone glucuronide + sulface |
|
|
How much T is produced daily by a man?
|
5-7mg
|
|
|
Describe the male reproductive feedback loops:
|
-Leydig cells producte T and E2 which negatively feedsback on hypothalamus/pituitary
-Sertoli cells produce inhibin which negatively feedsback on pituitary |
|
|
Name some targets of androgen action:
|
-testis
-penis -prostate and seminiferous vesicles -striated muscle ect... -CNS-aggressive behaviour |
|
|
What is the effect of androgens on muscle?
|
-hypertrophy
-cell number does NOT change!! |
|
|
Which hormone plays an effect on libido?
|
E2!!
|
|
|
What does E2 do in rats?
|
increases libido and activity
|
|
|
What are 2 uses for androgens as drugs?
|
-hormone replacement
-male contraception |
|
|
What are the stages in development when T levels increase?
|
-gestation (2 peaks)
-infancy -puberty |
|
|
How do T levels change with age?
|
They decrease
|
|
|
What are the targets for male contraception?
|
-spermatogenesis
-sperm transport -seminal fluid composition |
|
|
How long would it take male contraception to have an effect?
|
2-3 months (for human spermatogenesis)
|
|
|
What is the reversal of a vasectomy called?
|
vasovasotomy
|
|
|
Name three methods of hormonal male contraception:
|
-testosterone alone
-testosterone + progestin/estrongen/GnRH analog -Selective Analog Receptor Modulators |
|
|
How does male hormonal contraception work?
|
-add exogenous testosterone
-feedback inhibition on hypothalamus/pituitary -block synthesis of LH -Leydig cells are not stimulated to produce testosterone -not enough T to support spermatogenesis |
|
|
Does T suppression of sperm production work in all species?
|
No! Works well in rabbits, but not rats or monkeys.
|
|
|
How can rats be treated to cease spermatogenesis?
|
T + E2
|
|
|
How effective must male contraception be to be useful?
|
100%
|
|
|
How long does it take for spermatogenesis to cease in rats on hormonal contraception?
|
2 months
|
|
|
Is hormonal contraception reversible in men?
|
yes! Takes 2.5 to 3 months
|
|
|
Name 2 T analogs:
|
undecanoate
DHTU |
|
|
How effective is hormonal contraception in human men?
|
62% of population
95% efficiency |
|
|
In which ethnicity is male hormonal contraceptive particularly effective?
|
Asian men
|
|
|
What is an advantage of SARMs?
|
Selectively target specific Androgen Receptors for selective actions
|
|
|
Name a nonhormonal method that could be used as a male contraceptive method:
|
Immunocontraception
(seminiferous tubule are outside the body's immune system) |
|
|
What is an issue with immunocontraception?
|
problem with reversibility
|
|
|
Name two current drugs that cause azoospermia:
|
-busulfan
-colchisine (anti-cancer drugs/block proliferating cells) |
|
|
What is a Chinese contraceptive method?
|
gossypol
made not be reversible potential anti-cancer drug |
|
|
What do retinoids target to control acne?
|
-comedogenesis
-sebum production -bacterial control -inflammation |
|
|
What is a second use of retinoids? (all-trans)
|
Modify small wrinkles through increase of skin turnover
|
|
|
What kind of receptors do retinoids act on?
|
nuclear receptors (heterodimerization)
stimulate genes by binding to RAREs |
|
|
What are some discovered target genes of retinoid receptors?
|
-T-cells and the immune system
-Inflammation -Cellular differentiation |
|
|
What is a side-effect of accutane?
|
It is a teratogen!
|
|
|
Do you need special anti-bacterial soaps?
|
no!
|
|
|
What is the best moisterizer?
|
the cheapest kind! all the same...
|
|
|
Can a cream cause weight loss?
|
NO!!!!
cellulite doesn't really exist |
|
|
What is an anti-viral for herpes' mechanism?
|
nucleotide analog inhibits viral DNA polymerase selectively
|
|
|
What are the phases of hair growth?
|
-anagen
-catagen -telogen |
|
|
Give an example of hormones affecting hair growth:
|
During pregnancy, anagen phase is maintained, so hair thickens
|
|
|
What does chlorine damage do to hair?
|
surface is bubbled
|
|
|
How does hair spray work?
|
glues hairs together to hold in place
|
|
|
How is hair styled?
|
Reform H-bonds
|
|
|
What happens in a permanent?
|
Disulfide bonds are reformed
|
|
|
How does permanent dye work?
|
Two small molecules pass into hair cortex, then bind so they cannot get out
|
|
|
What about temporary dye?
|
Dye binds to surface of hair
|
|
|
Name a drug that can promote hair growth:
|
Minoxidil
-prolongs anagen phase -applied topically |
|
|
Which drug blocks 5alpha reductase to promote hair growth?
|
finasteride
|
|
|
What is a problem with finasteride?
|
terotogenic for male fetus
|
|
|
Which drugs can cause tooth discolouration as a side-effect?
|
tetracycline antibiotics
|
|
|
Which drug prevents cavities?
|
fluoride
|
|
|
How does fluoride exert its action?
|
-forms fluoroapetite in tooth enamel
-more resistant to bacterial action |
|
|
What is a side-effect of fluoride?
|
Fluorosis: white spots/flecks to darker freckles on teeth
|
|
|
Is there fluoride in the water in Montreal?
|
No! Although in many other cities there is!
|
|
|
What drug in mouthwash can prevent gingivitis?
|
phenols
|
|
|
What is another name for Vitamin C?
|
ascorbic acid
|
|
|
Name a process in which vitamin C is essential:
|
collagen synthesis
|
|
|
What is the disease caused by vitamin C deficiency?
|
scurvy
|
|
|
Outlide vitamin C's actions:
|
-oxidation of lysine
-reduction of Fe3+ to 2+ in stomach -conversion of folic to folinic acid -steroidogenesis in adrenals -also: an antioxidant! |
|
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Can vitamin C have adverse effects?
|
Yes! GI disturbance, kidney stones, rebound deficiency
|
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What is a general trait of B vitamins?
|
serve as cofactors in enzymatic reactions
|
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What is another name for vitamin B1?
|
thiamin
|
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What is the disease caused by B1 deficiency?
|
beriberi
|
|
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What is another name for vitamin B2?
|
riboflavin
|
|
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A deficiency in riboflavin causes what?
|
subnormal growth in children
|
|
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What is another name for vitamin B3?
|
niacin
|
|
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What is B3 deficiency called?
|
pellagra
3Ds: dermatitis, diarrhea, dementia |
|
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What is another name for vitamin B6?
|
Pyridoxine
|
|
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What is another name for vitamin B12?
|
cyanocobalamin
|
|
|
What is caused by B12 deficiency?
|
megaloblastic anemia (a type of pernicious anemia)
|
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|
What are the roles of folate?
|
-production of rbcs
-DNA synthesis -DNA methylation |
|
|
What can folate possibly prevent?
|
neural tube defects in deloping fetuses
-also may prevent colorectal cancer |
|
|
How can folate decrease coronary heart disease?
|
by lowering levels of homocysteine
|
|
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What is another name for vitamin A?
|
retinol
|
|
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What is a precursor to retinol?
|
carotene
|
|
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What does retinol help with?
|
night vision
|
|
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What can a deficiency in retinol cause?
|
hyperkeratinization of skin
growth impairment decrease night vision |
|
|
What can an excess of retinol cause?
|
terotogenic
|
|
|
What are two sources of Vitamin D?
|
-sun
-dietary |
|
|
Where is cholesterol metabolized to synthesize vitamin D?
|
-skin
-liver -kidney |
|
|
What does Vitamin D do?
|
positively regulates Ca2+ homeostasis
increase: -calbindins -RANKL in osteoblasts -mineralization |
|
|
Which enzyme in the liver is responsible for the first hydroxylation of vitamin D?
|
CYP450
|
|
|
What is caused by a deficiency of Vitamin D?
|
-rickets (failure to mineralize new bone)
|
|
|
What can an excess of Vitamin D cause?
|
-increase in bone resorption
-activation of RANKL/osteoblasts |
|
|
Whch signals cross-talk with vitamin D?
|
-cyclin D1
-cell cycle factors -apoptosis factors ==> cell-cycle arrest |
|
|
What does Vitamin E do?
|
antioxidant
-e- donor in redox rxs |
|
|
Has vitamin E been shown scientifically to benefit cancer/CV patients?
|
no..but there is a lot potential
|
|
|
What is another name for vitamin K?
|
menaphthone
|
|
|
What does Vitamin K do?
|
promotes synthesis of blood clotting factors
|
|
|
What does Vitamin K do?
|
gamma-carboxylates the precursor of prothrombin to prothrombin on a glutamin aa
(redox reaction) |
|
|
What results from a Vitamin K deficiency?
|
increase in bleeding
|
|
|
What can cause a vitamin K deficiency?
|
-anticonvulsants
-antibiotics (neomycin) |
|
|
What compounds can prevent cancer?
|
phytochemicals/antioxidants
|
|
|
Which chemical in red wine prolongs life by mimicking calorie restriction?
|
resveratrol
|
|
|
What are two important principles in drug evaluation?
|
1. double-blind
2. randomization |
|
|
What effect must always be taken into account when testing a drug?
|
the placebo effect
|
|
|
What is homeopathy?
|
Dilution of the same thing that caused the disease (succussions)...fraudulent!
|
|
|
What are some problems with herbal remedies?
|
-not tested
-can be dangerous -can be ineffective |
|
|
What is the problem with Comfrey-treatment for cirrhosis?
|
-hepatotoxin
-carcinogen |
|
|
What is the problem with Ephedra?
|
-relative of amphetamine
-myocardial infarct |
|
|
What is the problem with Lobelia?
|
-leads to coma, death
|
|
|
What is the problem with Yohimbine?
|
-impotence
-seizures -paralysis |
|
|
What is Kava marketted for? What are it's negative effects?
|
-relieve stress, anxiety
-negative effects on heart and brain |
|
|
What is Chaparral for? What are it's negative effects?
|
-acne...cancer...
-causes hepatitis! |
|
|
What is coriolos fungus marketed for?
|
cancer adjuvant therapy
--no clinical trials!!! |
|
|
Is Echinaceae effective?
|
No!
|
|
|
What is BioPectin sold for?
|
breast and prostate cancer
|
|
|
What is St-John's Wart sold for? What is the problem with using it?
|
Sold for depression
Many drug-drug interactions that are potentially FATAL |
|
|
What is the problem with using Garlic remedies?
|
drug-drug interactions
|
|
|
What ingredient is in cold nasal spray?
|
oxymetazoline - stimulates adrenergic receptors to cause vasocontriction
|
|
|
What drug is an anti-tussive?
|
codeine
|
|
|
What drug is used for allergies?
|
anti-histamines (targets H1 receptors)
|
|
|
Where are H2 receptors found?
|
in the stomach
|
|
|
Name two anti-fungals:
|
Tolnaftate
Lotrimin AF |
|
|
How can anti-fungals act?
|
-cell wall
-cell membrane -nuclear division -nucleic acid synthesis |
|
|
What drug is used against lice?
|
nix
|
|
|
What two drugs can be used against heartburn?
|
PPIs
selective H1-receptor blockers |
|
|
What do laxatives do?
|
increase bulk/provide fiber
|
|
|
Why does loperamide stop diarrhea but cause no opioid-like effects?
|
does NOT cross BBB
|
|
|
What drug prevents osteoporosis?
|
CaCO3
also: Vitamin D for absorption |
|
|
What is the pharmacokinetic mechanism for drug-drug interactions?
|
-altered plasma level of the drug
-altered absobtion/distribution/metabolism/excretion |
|
|
What should not be eaten along with tetracycline antibiotics?
|
milk
also: Al(OH)3 antacid |
|
|
What inhibits thyroxine absorption?
|
CaCO3
|
|
|
What happens to TSH levels when CaCO3 is given with thyroxine?
|
they increase
|
|
|
What do P-glycoproteins do?
|
pump of drugs of cells (anti-cancer drugs -- up-regulated in cancer cells)
|
|
|
What do CYP450s do in phase I? phase II?
|
-redox
-conjugation |
|
|
Which CYP450 enzyme is involved in metabolism of most drugs?
|
3A4
|
|
|
How can genetic variation play a role in drug metabolism?
|
variation in CYP450 enzymes
|
|
|
Why should ketoconazole and warfarin NOT be taken together?
|
Ketoconazole knocks out CYP450s so Warfarin serum concentration increases (can hemorrhage)
|
|
|
Which CYP450 enzyme is induced by smoking?
|
1A2
|
|
|
Which CYP450 is induced by ethanol?
|
2E1
|
|
|
Which drugs should not be taken when taking oral contraceptives?
|
-rifampin (anti-tubercular)
-tetracyclines (anti-biotics) -barbiturates |
|
|
What does CYP3A metabolize?
|
-Ca2+ channel blockers
-benzodiazepines -HIV protease inhibitors -statins etc... |
|
|
What kinds of drugs inhibit CYP3A?
|
-antifungals
-antibiotics -grapefruit juice! |
|
|
Which CYP450 converts codeine to morphine?
|
2D6
|
|
|
What effect does St.-John's Wart have on CYP3A?
|
induces it (higher metabolism of drugs)
|
|
|
Besides drug-drug interactions, what else does St-John's wart cause?
|
photosensitivity
|
|
|
What food drug decreases Saquinavir levels?
|
Garlic
|
|
|
Which drugs in grapefruit juice inhibit CYP3A4? (and other CYPs)
|
naringen
naringenin furanocoumarins |
|
|
Besides inhibiting CYP3A4, what does grapefruit juice activate?
|
P-glycoproteins
|
|
|
Why are drug-drug interactions particularly dangerous if Warfarin is involved?
|
It has a low TI
|
|
|
What decreases lithium clearance?
|
-diuretics
-some NSAIDS |
|
|
What is the mechanism for pharmacokinetic drug interactions?
|
-Altered dose-response curve of drug
|
|
|
Describe a beneficial drug-drug interaction:
|
levodopa + carbodopa (blocks conversion of levodopa in the periphery, before crossing BBB)
|
|
|
What is another inhibitor involved in this mechanism?
|
COMT inhibitor
|
|
|
What beneficial effect of aspirin is blocked by ibuprofen?
|
antiplatelet effect (prevention of myocardial infarcts)
|
|
|
What drug in wine and cheese can interact with anti-depressants (MAOs) to cause neurotoxicity?
|
tyramine
|
|
|
What is tyramine's mechanism of action?
|
releases extra neurotransmitter, which is not broken down b/c of MAO
|
|
|
How much does it cost to develop a new drug?
|
up to a billion $
|
