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52 Cards in this Set
- Front
- Back
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List the five chemotherapeutic targets for agents.
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1. DNA
2. Enzymes involved in DNA replication 3. Specific molecular entities with antibodies 4. Invasion, angiogenesis, metastases 5. Newer experimental approaches with drugs |
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Anticancer drugs tend to send the cell into ______________
(apoptotic/necrotic) mode |
apoptotic
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What are three characteristics of a cancer cell that are all potential targets for drug manipulation?
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1. Increased proliferation
2. Genomic stability 3. Loss of or mutation of regulatory proteins |
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The decision to divide occurs as cells pass a restriction point late in _________ (G1 / G2 / M / S) phase
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G1
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Oncogenic processes exert their greatest effect by targeting particular regulators of which phase progression?
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G1
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Describe the differences between CCS and CCNS drugs.
* percentage of cancer cells * growth fraction * types of cancers |
CCS
- high percentage of cancer cells in replication - high growth fraction - testicular and choriocarcinoma CCSN - low percentage of cancer cells in replication - low growth fraction - colon and lung carcinomas |
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The log kill concept kills a _____________ (constant proportion / constant number) of cells in a population
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constant proportion
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CALCULATE LOG KILL & DECREASE IN CELL POPULATION
1 log 2 log 3 log |
10^1 = 90%
10^2 = 99% 10^3 = 99.9% |
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DEFINITIONS
dose-limiting toxicity |
* dose-limiting toxicity
drug toxicity towards an organ is so serious that it puts a limit on the dose of that drug used in treatment * recruitment initial use of CCNS drugs to achieve a significant log kills results in recruitment of G0 cells into G1 cycling next, use CCS type drugs * synchrony hold cells in a particular phase (M phase, vinca alkoids OR S phase, cytarabine) |
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What is Pgp and mdr? How are the two connected?
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Pgp: drug transporter glycoprotein
mdr: a multidrug resistance gene that codes for the Pgp transporter protein |
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What characteristic of cancer cells gives them a built-in ability to develop resistance to anticancer drugs?
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They are gene labile
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Name the seven mechanisms of resistance.
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1. Changes in sensitivity of the gene product such as target enzymes
2. Changes in target receptor affinity characteristics 3. Changes in expression of the drug transporter glycoprotein (Pgp) 4. Modifications (increases) in the production of drug-inactivating enzymes 5. Increased DNA repair 6. Reduced activation of drugs 7. Alteration in the p53 pathway |
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Name the function of the following drugs:
fluorouracil mercaptopurine methotrexate |
* fluorouracil
inhibits thymidylate synthase * mercaptopurine inhibits enzymes in purine interconversions * methotrexate inhibits dihydrofolate reductase |
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Combination chemotherapy is a simple but effective formula - name it.
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Dose intensity + scheduling
= broad coverage against resistant cell lines within the heterogeneous tumor mass |
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What are the four principles which guide choices of drugs in combination chemotherapy?
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1. use drugs that have demonstrated single agent activity against a specific type of tumor
2. drugs that have different mechanisms AND act at different phases of cell cycle 3. drugs that DO NOT have overlapping toxicities 4. drugs should be used at their OPTIMAL DOSE and emply EFFECTIVE SCHEDULING |
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What route of administration is preferred for chemotherapeutic drugs?
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IV
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What route may be the route of choice when trying to prevent meningeal metastases?
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Intrathecal
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Name the drug used to fight the four groups of protozoal parasites:
* Amoeba * Flagellates * Ciliates * Sporozoa |
* Amoeba = metronidazole
* Flagellates 1. Intestinal = metronidazole 2. Urogenital = metronidazole 3. Hemo 1. T. Cruzi = Nifurtimox 2. Leishmania Donovanii = stilbogluconate sodium * Ciliate = tetracycline * Sporozoa 1. Intestinal = paromomycin 2. Toxoplasma = pyrimethamine + clindomycin + folinic acid 3. Plasmodium = see others |
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Name the periodicity for the different forms of plasmodium.
Name the erythrocyte stage they infect. |
P. falciparum = tertian, all stages
P. ovale = tertian, young P. vivax = tertian, young P. malariae = quartan, senescent |
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Name the drug based on these features:
* Exerts prophylactic suppressive activity * Suppresses acute attack of P. falciparum and P. vivax * When combined with atovaquone (malarone) = treat chloroquine-resistant and MDR resistant strains of P. falciparum and P. vivax |
Proguanil
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Name the drug based on these features:
* Treats latent tissue forms of P. ovale and P. vivax * Active against exo-erythrocutic schizonts * Gametocytocidal for all malarial parasite * Hypnozoitocidal for P. ovale and P. vivax |
Primaquine
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Name the drug based on these features:
* Acts on asexual erythrocytic stage of malarial parasites to interrupt erythrocytic schizogony. |
Chloroquine
Quinine Quinidine Doxycycline |
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This drug is not for patients suffering from G6PD deficiency as it may cause intravascular hemolysis and methemoglobinemia
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Primaquine
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This drug is used to treat malaria caused by all four strains of plasmodium (only if they are sensitive to it).
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Chloroquine
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This drug is only used against latent tissue forms of P. ovale and P. vivax.
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Primaquine
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These drugs are used against MDR strains of plasmodium.
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Doxycycline (mefloquine)
Pyrimethamine-sulfadoxine Quinidine |
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Chloroquine
* Uses * MOA * Resistance |
Cholorquine
USES * treatment of choice for all four plasmodium MOA * concentrates in acid environment of the food vacuole of plasmodia inside erythrocyte = increases pH * prevents polymerization of hemozoin * prevents polymerization of heme RESISTANCE * plasmodial chloroquine-uptake transporter and transporter in food vacuole both have gene mutations * chloroquine efflux pump found in tumor cells |
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Quinine
* Uses * MOA * Resistance |
Quinine
USES * gametocidal for P. vivax and P. malariae * treats chloroquine resistant and MDR strains of P. falciparum MOA * concentrates in acid environment of the food vacuole of plasmodia inside erythrocyte = increases pH * prevents polymerization of hemozoin RESISTANCE * amplification of pfmdr1 (P. falciparum mdr resistance gene product - efflux pump) |
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Pyrimethamine + sulfadioxine
* Uses * MOA * Resistance |
Pyrimethamine + sulfadioxine
USES * chloroquine resistance P. falciparum * used in combo with quinine to treat mdr P. falciparum MOA * competitively inhibts parasitic DHFR enzyme RESISTANCE * mutations in DHFR gene and its enzyme product = not effective drug |
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Metronidazole
* Uses * MOA * Resistance |
Metronidazole
USES * amebiasis, trichomoniasis, giardiasis MOA * acts as an electron sink, depriving anaerobes of reducing equivalents RESISTANCE * high localized oxygen conc. in cells * less free radical formation (altered redox) |
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Nifurtimox
* Uses * MOA * Resistance |
Nifurtimox
USES * acute Chagas' diases (T. cruzi) MOA * intracellular reduction & auto-oxidation to increase oxygen free radicals RESISTANCE |
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Stilbogluconate sodium
* Uses * MOA * Resistance |
Stilbogluconate sodium
USES * treatment of Leishmaniasis and kala-azar |
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Proguanil + ________________
= useful in the treatment of chloroquine resistant and mdr strains of P. falciparum and P. vivac |
atovaquone (malarone)
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This drug is gametocytocidal for all species of human malarial parasite
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Primaquine
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A erythrocytic schizonticide + antifolate drugs treat mdr P. falciparum
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quinine + pyrimethamine-sulfadioxine
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Which of the erythrocytic drugs are safe and unsafe in pregnancy?
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Safe = chloroquine
Unsafe = quinine |
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What are the factors which affect the parasitization of man?
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1. Disease spread by human soil (feces)
2. Helminthic infections circulating within children b/c of minimal hygiene 3. Presence of secondary hosts or vectors 4. Mixed worm burdens |
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What are the factors for selecting drugs to treat helminthic infections?
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1. Cost
2. Selectivity 3. Toxicity 4. Efficacy 5. Appropriate dosing schedule -- preferably oral and one dose 6. Side effects |
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Which factors (relating to pathogenicity of worm) influence treatment strategies?
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1. Penetration of gut wall
2. Nutrition deprivation of host 3. Bloodsucking activities 4. Allergic reactions |
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What is the best route for distribution of anti-helminthics?
What is the best dose? |
Oral
1 or 2 |
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What does the presence of mixed worm burden dictate?
Why is it dangerous to eliminate one class of worm in a mixed population in the gut? |
You must use more than one drug to combat several worms
Eliminating one class of worm may cause other to move 'en masse' and tear the gut wall |
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What is the drug of choice in:
Nematodes Cestodes Trematodes |
Nematodes: mebendazole
Cestodes & Trematodes: praziquantel |
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What is the DOC for Strongyloides stercoralis?
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Ivermectin
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What is the DOC for Ascaris lumbricoides in a pregnant woman?
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Pyrantel pamoate
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What is the DOC for:
W. bancrofti B. malayi Loa loa O. volvulus Dracunculus |
W. bancrofti: diethyl carbamazine or Ivermectin (DOC)
B. malayi : diethyl carbamazine Loa loa : O. volvulus: diethyl carbamazine + Ivermectin Dracunculus: roll out female worm |
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What is the DOC for "river blindness"?
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Ivermectin
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What is a Mazotti like reaction?
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pruritis
fevers arthralgias |
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Mebendazole
USES MOA ADVERSE EFFECTS |
Mebendazole
USES pins, whips, rounds, hooks, pork MOA inhibits polymerization of tubulin and microtubulin - dependent glucose transport = decr. glucose ADVERSE EFFECTS teratogenic and embryotoxic |
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Pyrantel Pamoate
USES MOA ADVERSE EFFECTS |
Pyrantel Pamoate
USES pins, round, hooks MOA 1. release Ach at NMJ and block AchE 2. Excess Ach at nicotinic receptor ADVERSE EFFECTS GI stress, headache, weakness |
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Ivermectin
USES MOA ADVERSE EFFECTS |
Ivermectin
USES Onchocera volvulus, W. bancrofti, Strongyloides stercoralis MOA increases GABA-mediated neurotransmission = paralysis of larvae ADVERSE EFFECTS Mazotti-like reactions |
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Diethyl Carbamazine
USES MOA ADVERSE EFFECTS |
Diethyl Carbamazine
USES Human filariasis MOA may involve interfering with arachidonic acid metabolism ADVERSE EFFECTS Mazotti-like reactions |
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Praziquantel
USES MOA ADVERSE EFFECTS |
Praziquantel
USES Cestodes and Trematodes MOA Increases membrane permeability to Ca++ = paralysis ADVERE EFFECTS dizziness, drowsiness, skin rash, heat "feeling" |
