Term
| Describe the 7 mechanisms of antidote covered in class |
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Definition
1. Antidote complexes with poison, rendering it inactive
2. Antidote accelerates metabolic conversion of poison to non-toxic product
3. Antidote blocks metabolic conversion of poison
4. Antidote accelerates excretion of poison
5. Antidote competes with poison for essential receptors
6. Antidote blocks receptors responsible for toxic effects
7. Antidote restores normal function by repairing/bypassing effect of poison |
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Term
| (T/F) The use of chelating agents in heavy metal poisoning uses the tactic described by mechanism 1 |
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Definition
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Term
| Describe what chelating agents do? |
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Definition
| Form tight bonds with the metal, decreasing the amount of metal availible for binding to tissue molecules. The metal-chelating agent complex is then excreted, and there is a decrease in the total body load |
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Term
| What chelating agent is used to treat heavy metal poisoning by arsenic, mercury, lead, bismuth, and polonium? |
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Definition
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Term
| What is the rationale for the use of BAL? |
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Definition
| Arsenic ring of the poison binds to the SH groups of DAL, and the chelates of 5- or 6- membered rings are stable, so the goal is to make a stable ring with BAL so the poison can be excreted |
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Term
| What is the function of the OH group on dimercaprol? |
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Definition
| To increase its solubility in water |
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Term
| (T/F) Dimercaprol itself is also toxic, and DMSA is used (orally) instead because it is less toxic |
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Definition
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Term
| What is the chelating agent calcium disodium edetate (EDTA) used for? |
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Definition
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Term
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Definition
| Lead has an affinity 10 million times higher for EDTA than for Ca, so the Ca is displaced from EDTA by lead |
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Term
| What is oral penicillamine used for? |
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Definition
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Term
| What is deferoxamine used for? |
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Definition
| Iron poisoning (ie eating too many vitamins) |
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Term
| (T/F) Organophosphate insecticides and pralidoxime (2-PAM) interaction is another example of mechanism 1 |
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Definition
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Term
| Why is organophosphate harmful? |
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Definition
| It binds to acetylcholinesterase, and blocks the mechanism of NT ACh. ACh then accumulates in synapses, neuroeffector junctions etc, and constant depolarization is seen. |
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Term
| What is the result of this? |
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Definition
| A depolarization blockade, and death from paralysis of breathing muscles |
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Term
| What does pralidoxime do to combat this? |
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Definition
| Binds to organophosphorous molecuels and removes them for AChesterase |
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Term
| What are the antidotes Sodium nitrite and amyl nitrite used for? |
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Definition
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Term
| How is cyanide harmful to the body? |
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Definition
| Cyanide combines with ferric iron contained in cytochromes and prevents their oxidation/reduction, therefore preventing the ETC |
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Term
| (T/F) CN is a very potent poison |
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Definition
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Term
| With this in mind, how does CN still cause rapid death? |
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Definition
| Inactivates cytochrome oxidase in the tissues, therefore no ATP production in mitochondria |
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Term
| What is the treatment used to combat this? |
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Definition
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Term
| What is used to bind the CN ion? |
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Definition
| HbFe2+ is converted to HbFe3+ increases the amount of Fe3+ available for binding, which can then bind the cyanide ion |
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Term
| Why does Hemoglobin need to be converted into methemoglobin (HbFe3+) to treat CN poisoning? |
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Definition
| Because CN will not combine with cyanide |
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Term
| What is the rationale behind using methemoglobin? |
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Definition
| There is a much larger amount of Hb in the body than cytochrome oxidase, so an individual can afford to lose some Hb |
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Term
| When does serious anoxia occur, with CN poison treatment? |
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Definition
| When over half of Hb is converted to Methemoglobin |
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Term
| What is protamine used to treat? |
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Definition
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Term
| (T/F) Cynaide poisoning can also be treated by using mechanism two |
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Definition
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Term
| What is cyanide usually converted into by transsulfurase? |
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Definition
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Term
| Why does this reaction usually occur at a very slow rate? |
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Definition
| Because the supply for sulfur is very low, and thus, the amount of free sulfur limits the reaction |
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Term
| How does thiosulfate solve this problem? |
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Definition
| It can accelerate the rate of reaction, thus increasing the rate of metabolism to thiocyanate and thus reducing toxicity |
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Term
| (T/F) Cyanide poisoning is only ever treated by one mechanism or another, never both at the same time |
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Definition
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Term
| (T/F) Using NaNO2 and Thiosulfate together increases the LD50 by 18x, far greater than either treatment alone |
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Definition
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Term
| What mechanism is usually used to treat methanol poisoning? |
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Definition
| Mech 3: Blocking metabolic conversion of the poison |
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Term
| Describe the conversion pathway of methanol in the body |
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Definition
| CH3OH - alcohol dehydrogenase -> HCHO - aldehyde dehydrogenase -> HCOOH |
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Term
| What two substances in this pathway are responsible for the toxic effects of methanol poisoning? |
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Definition
| HCHO (formaldehyde) and HCOOH (formic acid) |
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Term
| Which drug is used preferentially as a common treatment for methanol poisoning, fomepizole or ethanol? |
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Definition
| Fomepizole (4-methylpyrazole) |
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Term
| How does fomepizole work? |
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Definition
| It inhibits alcohol dehydrogenase, which decreases the rate of formation of toxic reaction products |
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Term
| What is often given with fomepizole, and why? |
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Definition
| An alkyl product (bicarbonate usually) to combat the acidosis |
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Term
| (T/F) Although not used today, ethanol is an effective treatment for methanol poisoning |
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Definition
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Term
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Definition
| Ethanol is metabolized by the same enzymes as methanol, and ethanol has a higher affinity for ethanol than methanol, thus, methanol conversion is slowed down. |
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Term
| What mechanism is usually used to treat bromide intoxication? |
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Definition
| Mech 4: Accelerated excretion |
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Term
| What does accumulation of bromide (found in OTC sleep aids and minor analgesics) lead to? |
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Definition
| CNS, gastrointestinal disturbances and dermatitis |
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Term
| What is used to treat bromide toxicity? |
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Definition
| Administration of other halides |
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Term
| (T/F) The kidney can distinguish between different halide elements |
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Definition
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Term
| Describe how administration of halides combats bromide poisoning |
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Definition
| Kidney acts to maintain a constant extracellular concentration of halides, so administration of chloride causes an increase in halide excretion. This increased excretion causes increased bromide excretion. |
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Term
| Why is this treatment effective, if it doesn't target bromide specifically? |
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Definition
| Bromide poisoning is usually an acute emergency, so this works |
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Term
| What mechanism is used to treat exposure to Strontium-90? |
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Definition
| Mechanism 4: accelerated excretion |
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Term
| What is used to treat Sr-90 poisoning? |
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Definition
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Term
| (T/F) EDTA is equally as effective for treatment of Sr90 poisoning |
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Definition
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Term
| What mechanism is used to treat carbon monoxide poisoning? |
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Definition
| Mechanism 5: antidote competes with poison for essential receptors |
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Term
| What occurs to Hb upon exposure to CO? |
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Definition
| CO binds reversibly to Hb |
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Term
| What is the consequence of COHb formation? |
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Definition
| Reduced binding sites for O2, which increases Hb affinity for O2, meaning less deposition at tissues |
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Term
| What are the symptoms seen at 50% COHb? |
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Definition
| Headache, flushing (bright red skin), weakness, vomiting |
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Term
| What is seen above 50% COHb? |
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Definition
| Convulsions, respiratory failure |
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Term
| (T/F) CO has a much higher affinity for Hb than O2, so small amounts (.08%) in the air can be dangerous |
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Definition
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Term
| What is used to treat CO poisoning? |
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Definition
| O2 - competes for Hb binding with CO |
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Term
| What 3 ways is oxygen given to the patient? |
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Definition
1. Normal air
2. Pure O2
3. Hyperbaric O2 |
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Term
| What mechanism is used to treat tubocurarine poisoning? |
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Definition
| Mechanism 5: competing for essential receptors |
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Term
| (T/F) Tubocurarine is the active ingredient in curare |
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Definition
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Term
| What is curare usually used for? |
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Definition
| It is the substance used for poison blow darts |
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Term
| What does tubocurarine do within the human body? |
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Definition
| Blocks ACh receptors at the neuromuscular junction |
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Term
| What is used to treat this? |
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Definition
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Term
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Definition
| AChesterase inhibitors slow the breakdown of ACh in the neuromusc junction, and ACh will outcompete tubocurarine for binding to the AChR |
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Term
| By what method does atropine act to combat poisoning by a cholinesterase inhibitor (ie organophosphate insecticide, nerve gas)? |
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Definition
| Mechanism 6: antidote blocks receptors responsible for toxic effect |
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Term
| (T/F) Atropine prevents bronchoconstriction and hypersecretion of fluids in the respiratory tract |
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Definition
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Term
| Why is artificial respiration also needed with atropine administration? |
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Definition
| Because the NMJ is not responsible to atropine |
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Term
| (T/F) In organophosphate poisoning, atropine is usually administered alone |
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Definition
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Term
| What is the common antidote used to treat organophosphate poisoning, and which mechanism does each component act through? |
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Definition
1. Atropine - mechanism 6
2. Pralidoxime - mechanism 1 |
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Term
| What is used for treatment of non-organophosphate cholinesterase inhibitor poisoning? |
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Definition
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Term
| Why is pralidoxime not used? |
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Definition
| Because it is a weak cholinesterase inhibitor, and it will not chelate with the toxin because the toxin is not metallic |
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Term
| What is methylene blue used to combat? |
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Definition
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Term
| What mechanism does it accomplish this with? |
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Definition
| Mech 7: Antidote restores normal function by by-passing or repairing poison effect |
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Term
| What can methemoglobimia result from? |
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Definition
- Nitrite poisoning
- Excess conversion of Hb to methemglobin during CN treatment (nitrites responsible for the conversion) |
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Term
| How does methylene blue combat methemoglobinemia? |
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Definition
| It increases the rate of reduction of Fe3+ to Fe2+ |
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Term
| (T/F) Methylene blue is only an effective treatment when combating methemglobinemia caused by CN treatment |
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Definition
| False, it is effective regardless of the cause |
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Term
| How does it work as an antidote? |
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Definition
| The dye acts as an intermediate electron acceptor between NADPH and methemoglobin, enhancing the rate of reaction |
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Term
| What are potassium salts and anti-dysrhythmics used to treat? |
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Definition
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Term
| What does 5-Fluorouracil do, and what is it used to treat? |
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Definition
| Prevents thymidine production; treats cancers |
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Term
| What does 6-mercaptopurine treat? |
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Definition
| Excessive purines - inhibits purine synthesis |
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