Term
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Definition
| a compound which has bad effects on cell function with NO positive effects |
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Term
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Definition
| a drug that displays selective toxicity. At a normal dose, is it used to treat psoriasis, but at slightly higher doses it can become toxic and cause diarrhea. |
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Term
| Pharmacodynamic specificity |
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Definition
| the mechanism of drug action |
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Term
| Pharmacokinetic selectivity |
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Definition
| the study of the distribution of a drug to a target site |
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Term
| For drug interactions to occur, the drug molecule must correspond perfectly to the appropriate receptor for it to produce a response |
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Definition
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Term
| Molecular features necessary for acetylcholine action |
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Definition
positively charged N
three CH3 groups on the nitrogen
ester linkage
spacing between N and carbonyl C |
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Term
| Why is acetylcholine able to bind to both muscarinic and nicotinic receptors? |
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Definition
the acetylcholine molecule is able to change its shape between the cis and trans form
cis: nicotinic
trans: muscarinic |
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Term
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Definition
an example of a selective therapeutic drug (used to treat schizo) developed to display fewer side effects. It works by selectively binding only to dopamine D2 and D3 receptors.
Because it only binds to D2 and D3 receptors, you don't get antipsychotic-induced Parkinsonism which occurs when all the dopamine receptors are blocked |
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Term
| Stereospecificity of a drug to a ligand |
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Definition
Some drugs may have some isomers that aren't effective and some that are. You'll need 3 points of attachment to a receptor
For example: only the l-form of norepinephrine elevates blood pressure |
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Term
| Chlorpromazine, Procaine, Diphenhydramine |
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Definition
| are examples of drugs that all have a local anaesthetic, antihistamine, and antiarythmic effect but also each have their own unique effects because of their different side chains? |
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Term
| Pharmacokinetic selectivity related to drug distribution |
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Definition
A drug can still display selectivity depending on where the target site is
topical application: selectivity comes from the fact that the drug absorbed from the target site will be diluted in a large volume of circulating blood
Artery injection: facilitates drug uptake in a particular tissue such as a tumor
Selectivity by ionization: Propantheline and atropine are both good muscarinic blockers but propantheline will not be distributed past the blood brain barrier because it's a cation
Differential blood flow: drugs given through I.V. will most likely be distributed to sites with high blood flow
Distribution by selective carriers:
Selective concentration by excretion: drugs that are concentrated in urine will be poorly reabsobed |
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Term
| Selectivity related to tissue differences |
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Definition
Some drugs only work on tissues with a certain cell type
Some tissues can concentrate drugs (increasing their effect?)
Some tissues also has the ability to activate drugs (change it from the pro form to the active form)
Some drugs may interact with a lot of different tissue types but can have only a therapeutic effect in a tissue that's functionally more important than others |
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Term
| Individuals and species differences of selectivity to a drug |
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Definition
Obviously across different species a drug will have different effects (an antibiotic in bacteria vs humans).
Also genetic differences may make one more sensitive to a drug than others |
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Term
| Chemical neurotransmission |
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Definition
| when an action potential travels down the axon of a neuron leading to nuerotransmitter release |
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Term
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Definition
| small molecules released by neurons that bind receptors and elicit effect |
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Term
| Excitatory postsynaptic potential |
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Definition
| increases the likelihood of action potential generation in the postsynaptic cell |
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Term
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Definition
| decreases the likelihood of action potential generation |
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Term
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Definition
receptor has a pore that opens when the neurotransmitter binds to it. This will allow ions to flow through.
Has a fast onset
Receptor is a multi-subunit protein complex
Tends to desensitize after exposure to agonist
pore can be selective to ions
(such as ACh receptor being selective to cations only) |
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Term
| Metabotropic receptor (also called G-protein coupled receptors) |
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Definition
| this type of receptor produces second messenger cascades when a ligand binds to it. Compared to ionotropic receptors, this has a slow and steady response |
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Term
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Definition
an example of an ionotropic receptor
has 4 subunits |
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Term
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Definition
| has 2 binding sites for acetylcholine. Pore will only open when both binding sites are bound to ACh |
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Term
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Definition
| diversity is achieved through the fact that receptors will have several classes and each of these classes will be broken into different kinds of subunits. So for example a particular GABA receptor could have 30+ different combinations of classes and subunits |
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Term
| The two major inhibitory neurotransmitters in the brain and spinal cord are |
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Definition
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Term
| Too much inhibition of GABA or Gly receptors cause |
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Definition
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Term
| Too much enhancement of GABA or Gly receptors cause |
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Definition
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Term
| Sutherland and Rall found what? |
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Definition
| They found out that cAMP is a second messenger by stimulating cardiac cells with epinephrine |
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Term
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Definition
| neurotransmitters, hormones and drugs that cannot cross the cell membrane |
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Term
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Definition
| molecules that act intracellularly as a result of a first messenger reacting with the cell membrane |
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Term
| A particular ligand can act on a number of different receptors producing different responses |
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Definition
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Term
| Three components required for G-protein signaling |
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Definition
receptor (on cell surface)
G protein
effector
all 3 are embedded in the cell membrane |
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Term
| G-protein coupled receptor characteristics |
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Definition
has 7 transmembrane domains
neurotransmitter - binds to GPCR on extracellular side
G protein - bind to intracellur side of GPCR |
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Term
| Receptor desensitization for GPCRs |
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Definition
| the extent of interaction between receptor and G protein can be decreased by phosphorylating serine and threonine residues |
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Term
| Receptor down-regulation for GPCRs |
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Definition
| if an agonist is bound to the receptor for a prolonged period of time, basically the cell will remove some of its GPCR receptors from the membrane. This decreases the number of GPCRs that can interact with G proteins |
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Term
| G protein characteristics |
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Definition
has 3 subunits (alpha, beta, and gamma)
alpha unit - the main subunit that allows the g protein to act on an effector. interacts with guanine nucleotides
beta and gamma support alpha interactions but can also act on effectors |
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Term
| G protein activation/inactivation cycle |
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Definition
1. resting state - all three G protein subunits are bound together. alpha has GDP attached to it
2. when an agonist binds, a conformational change occurs which leads to the g protein breaking off. additionally, GDP will be released from the alpha unit
3. GTP binds to alpha which makes alpha separate from the beta and gamma dimer
4. this allows the alpha to bind to an effector. also alpha will hydrolyze the GTP attached to GDP
5. this makes the alpha dissociate from the effector to bind to the beta and gamma dimer
6. rinse and repeat |
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Term
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Definition
| stimulates adenylyl cyclase leading to the production of cAMP |
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Term
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Definition
| inhibits adenylyl cyclase |
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Term
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Definition
| found only in the rods and cones of the eye |
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Term
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Definition
| binds ADP ribose to the guanyl nucleotide binding site of the Gs(alpha) protein which leads to persistent activation of Gs(alpha). Because it's a Gs protein, this leads to a lot of production of cAMP and eventually bad diarrhea |
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Term
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Definition
| prevents Gi protein from activating and so cAMP levels rise leading to whooping cough |
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Term
| Most common effector enzymes that G proteins act on |
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Definition
| Adenylyl cyclases and phospholipases C |
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Term
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Definition
| catalyze the synthesis of cAMP from ATP after a G protein acts on it |
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Term
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Definition
| once synthesized by andenylyl cyclase, it activated protein kinases which phosphorylate other proteins |
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Term
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Definition
activated by Gq proteins
acts on phospholipids to break down PIP2 into IP3 and DAG (second messengers, but really like third messengers) |
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Term
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Definition
| results in the release of calcium |
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Term
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Definition
| activates protein kinase C in the cell membrane |
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Term
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Definition
| whenever a ligand binds to a GPCR, several G proteins are activated before the ligand leaves. Each of thes G proteins produces many second messengers so the net result is the activation of many effectors |
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Term
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Definition
| how heredity and genes affect the response to drugs |
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Term
| Pharmacogenetic defects vs inborn errors of metabolism |
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Definition
| pharmacogenetic defects don't have visible signs until the drug is administered |
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Term
| Pharmacogenetics 3 subdivisions |
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Definition
Functional subdivision
Pharmacological subdivision
Genetic subdivision |
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Term
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Definition
| includes disorders where there is an increased sensitivity or resistance to drugs. Also disorders of unknown cause or associated with diet |
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Term
| Pharmacological subdivision |
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Definition
| distinguishes between how the drug is metabolized (pharmacokinetic) and the response to the drug (pharmacodynamic) |
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Term
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Definition
| more to do with monogenic vs multigenic variants |
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Term
| Monogenic variant example |
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Definition
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Term
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Definition
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Term
| Plasma cholinesterase defect |
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Definition
| example of a defect that's due to genetic differences (pharmacogenetics). used as a muscle relaxant but the anaesthesiac effect can last for much more longer than necessary in people with the defect |
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Term
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Definition
| some people are slow acetylation while some have rapid acetylation...the difference |
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Term
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Definition
| a reduction in the mount of NAT2 produced in the liver. this is turn could be caused by a mutation in the NAT2 gene, decreased translation of NAT2, or decreased stability of the enzyme |
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Term
| Slow acetylator consequence |
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Definition
| could lead to an overdose because the drug breaks down so slowly |
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Term
| Fast acetylator consequence |
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Definition
| require to give higher doses because the drug breaks down so quickly |
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Term
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Definition
| means you have insufficient concentrations of the reduced form of glutathione which is important in oxidizing stuff. Ultimately leads to the lysing of RBCs |
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Term
| Two variants in the G-6-PD deficiency |
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Definition
A- variant found in AAs: young RBCs have normal G-6-PDs when the person is young but the activity of the G-6-PD decreases as the person ages
In Mediterraneans the G-6-PD activity is decreased in all RBCs |
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Term
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Definition
with this on the onset of anaesthetics, calcium would be released causing a rise in body temp which eventually led to death
This was caused by a mutation in the ryanodine receptor |
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Term
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Definition
duration of treatment influences compliance: the longer the patieent take the drug, the more likely they'll stop taking it
inconvenience of drug regimen influences compliance
how serious the patient takes their ailments affects compliance
side effects of their treatment
ease of contact with the physician |
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Term
| Hypertension has a problem with patient compliance |
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Definition
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Term
| Bioavailability is affected by what? |
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Definition
| GI or liver pathology and the form the drug comes in |
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Term
| Things that affect metabolism (pharmacokinetic variation) |
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Definition
liver disease
age
smoking
variation in pharmacokinetic is normally seen in infants and the very old |
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Term
| Drug doses in adults vs children |
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Definition
Adults: determined by body size and body composition
Kids: determined by Young's Rule because the discrepancy in body surface area is too great |
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Term
| An obese person requires a smaller dose of water soluble drugs and a higher dose of a lipid soluble drug because they are mostly fat |
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Definition
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Term
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Definition
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Term
| Calculation of children's dose by body surface area (for babies) |
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Definition
| (1.5 * weight [in kg] + 10) |
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Term
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Definition
| the study of the adverse effects of drugs |
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Term
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Definition
| a remedy for counteracting the effects of a poison |
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Term
| BOth natural and synthetic compounds can be carcinogenic |
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Definition
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Term
| Cytochrome P450 is normally involved in the activation of precarcinogens |
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Definition
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Term
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Definition
| arrests the cell cycle and induces cell death |
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Term
| Alkylating agents (chemotherapy) |
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Definition
| interfere with the separation of DNA strands leading to cell death |
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Term
| Antimetabolites (chemotherapy) |
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Definition
interferes with the cancer cell's ability to make new DNA and so the cell ends up dying
Methotrexate
5-Flurouracil |
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Term
| Plant derivatives (chemotherapy) |
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Definition
| Vincristine and vinblastine |
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Term
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Definition
| Antiestrogens such as tamoxifen |
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