Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
142 Cards in this Set
- Front
- Back
|
Alcohol
|
Fetal alcohol syndrome (FAS): intrauterine growth restriction (IUGR); mental retardation, microcephaly; ocular anomalies; joint abnormalities; short palpebral fissures
|
|
|
Androgens and high doses of progestogens
|
Varying degrees of masculinization of female fetuses: ambiguous external genitalia resulting in labial fusion and clitoral hypertrophy
|
|
|
Aminopterin
|
IUGR; skeletal defects; malformations of the central nervous system (CNS), notably meroencephaly (most of the brain is absent)
|
|
|
Cocaine
|
IUGR; prematurity; microcephaly; cerebral infarction; urogenital anomalies, neurobehavioral disturbances
|
|
|
Diethystilbestrol
|
Abnormalities of uterus and vagina; cervical erosion and ridges
|
|
|
Isotretinoin (13-cis-retinoic acid)
|
Craniofacial abnormalities; neural tube defects (NTDs), such as spina bifida cystica; cardiovascular defects; cleft palate; thymic aplasia
|
|
|
Lithium carbonate
|
Various anomalies usually involving the heart and great vessels
|
|
|
Methotrexate
|
Multiple anomalies, especially skeletal, involving the face, cranium, limbs, and vertebral column
|
|
|
Phenytoin (Dilantin)
|
Fetal hydantoin syndrome: IUGR; microcephaly; mental retardation; ridged frontal suture; inner epicanthal folds; eyelid ptosis; broad depressed nasal bridge; phalangeal hypoplasia
|
|
|
Tetracycline
|
Stained teeth; hypoplasia of enamel
|
|
|
Thalidomide
|
Abnormal development of limbs, e.g., meromelia (partial absence) and amelia (complete absence); facial anomalies; systemic anomalies; e.g., cardiac and kidney defects
|
|
|
Trimethadione
|
Development delay; V-shaped eyebrows; low-set ears; cleft lip and/or palate
|
|
|
Valproic acid
|
Craniofacial anomalies; NTDs; often hydrocephalus; heart and skeletal defects
|
|
|
Warfarin
|
Nasal hypoplasia; stippled epiphyses; hypoplastic phalanges; eye anomalies; mental retardation
|
|
|
Methylmercury
|
Cerebral atrophy; spasticity; seizures; mental retardation
|
|
|
Polychlorinated biphenyls
|
IUGR; skin discolorization
|
|
|
Cytomegalovirus
|
Microcephaly; chorioretinitis; sensorineural hearing loss; delayed psychomotor/mental development; hepatosplenomegaly; hydrocephaly; cerebral palsy; brain (periventricular) calcification
|
|
|
Herpes simplex virus
|
Skin vesicles and scarring; chorioretinitis; hepatomegaly; thrombocytopenia; petechiae; hemolytic anemia; hydranencephaly
|
|
|
Human parvovirus B19
|
Eye defects; degenerative changes in fetal tissues
|
|
|
Rubella virus
|
IUGR; postnatal growth retardation; cardiac and great vessel abnormalities; microcephaly; sensorineural deafness; cataract; microphthalmos; glaucoma; pigmented retinopathy; mental retardation; newborn bleeding; hepatosplenomegaly; osteopathy; tooth defects
|
|
|
Toxoplasma gondii
|
Microcephaly; mental retardation; microphthalmia; hydrocephaly; chorioretinitis; cerebral calcifications; hearing loss; neurologic disturbances
|
|
|
Treponema pallidum
|
Hydrocephalus; congenital deafness; mental retardation; abnormal teeth and bones
|
|
|
Venezuelan equine encephalitis virus
|
Microcephaly; microphthalmia; cerebral agenesis; CNS necrosis; hydrocephalus
|
|
|
Varicella virus
|
Cutaneous scars (dermatome distribution); neurologic anomalies (limb paresis [incomplete paralysis], hydrocephaly, seizures, etc.); cataracts; microphthalmia; Horner syndrome; optic atrophy; nystagmus; chorioretinitis; microcephaly; mental retardation; skeletal anomalies (hypoplasia of limbs, fingers, and toes, etc.); urogenital anomalies
|
|
|
High levels of ionizing radiation
|
Microcephaly; mental retardation; skeletal anomalies; growth retardation; cataracts
|
|
|
Methotrexate cell cycle specificity
|
cell-cycle specific
|
|
|
Methotrexate Drug class
|
antimetabolite; antifolate (folate acid analogue)
|
|
|
Methotrexate chemistry
|
has same structure as folate except it has an amino group on C4 & a methyl group on N10
|
|
|
Methotrexate MoA
|
inhibits dihydrofolate reductase & directly inhibits folate-dependent enzymes of de novo purine & thymidylate synthesis; prevents conversion of FH2 ->FH4; FH2 builds up as toxic inhibitory substrate; reactions requiring FH4 cannot continue; interrupts synthesis of DNA & RNA; also blocks N5, N10-methylene tetrahydrofolate conversion back to FH2 & TMP (headed for DNA synthesis) b/c it is a preferred cofactor for thymidylate synthetase
|
|
|
Methotrexate pharmacologic effects
|
inhibition of DHFR results in block of reduction of FH2->FH4; also inhibits formation of thymidylate & purines and arrests DNA, RNA & protein synthesis in rapidly dividing cells (S phase)
|
|
|
Methotrexate MoR
|
impaired transport of methotrexate into cells; production of altered forms of DHFR with lowered affinity for the inhibitor; increased intracellular [DHFR] through gene amplification or altered gene regulation; lowered ability to synthesize methotrexate polyglutamates; increased expression of drug efflux transporter of MRP class; lowered folate transporter; mutated DHFR, excessive DHFR
|
|
|
Mechanism of leucovorin rescue when administered 24 hours after methotrexate
|
Given 24 hours after methotrexate to reduce competition; bypasses FH 4 pathway and replenishes N5, N10 methylene tetrahydrofolate cofactor so that cells can make dTMP; normal cells are better at transporting leucovorin than tumor cells so this "rescues" normal cells will tumor cells are still being killed by methotrexate
|
|
|
Cyclophosphamide cell cycle specificity
|
cell-cycle nonspecific
|
|
|
Treatment for retinoblastoma (small tumors)
|
Surgery; radiation therapy cryotherapy; photocoagulation
|
|
|
Treatment for retinoblastoma (any size tumor)
|
Chemo/size reduction (so that one of the treatments for small tumors can be used, such as surgery); opthalmic arterial infusion; subtenon chemo; high does chemo w/stem cell transplant in severe cases
|
|
|
What does the log kill hypothesis say?
|
The sooner tumor cells are detected and the fewer tumor cells that are present, the less likely the patient is to die
|
|
|
What is the definition of the log till hypothesis?
|
A given dose of the chemotherapeutic drug kills a constant proportion of a cell population rather than a constant number of cells. The log kill hypothesis proposes that the magnitude of tumor cells killed by anticancer drugs is a logarithmic function.
|
|
|
Why is it effective to use chemotherapeutic drugs in combination?
|
Prevents resistance; combination of cell cycle specific and cell cycle nonspecific allows growing and at rest cells to be targeted; additive and synergistic mechanisms of action; different toxicities = less myelosuppression
|
|
|
Cell cycle specific versus cell cycle nonspecific
|
Cell cycle specific inhibits DNA synthesis during the as phase. Cell cycle nonspecific alkaloids and damages DNA, pushes cells into apoptosis, works on replicating or non-replicating cells and thus works for slow gross tumors
|
|
|
Cyclophosphamide trade names
|
cytoxan, neosar
|
|
|
Cyclophosphamide cell cycle specificity
|
Cell cycle nonspecific but best on G1 or S-phase cells
|
|
|
Cyclophosphamide drug class
|
Alkylating agent
|
|
|
Cyclophosphamide structure/chemistry
|
bis-chloroethyl amine compound in a group of reactive compounds called nitrogen mustard; activated via CYP450 isoenzyme; it is hydroxylated to 4-hydroxycyclophospliamide in equilibrium with aldophosphamide; non-ends and I cleavage of aldophosphamide produces toxic metabolites: phosphoramide mustard and acrolein
|
|
|
Cyclophosphamide mechanism of action
|
Alkylating agents from strong electrophilic cyclic carbonium ions (carbocations) that form covalent linkages with the various nucleophilic moieties via alkylation; allow 2-chloroethylsidechains to alkylation separate guanines resulting in cross-linking the of nucleic acids sidechains; disrupts normal nucleic acid function; phosphoramide is an anti-neoplastic cytotoxic metabolite; acrolein causes hemorrhagic cystitis but conjugated by MESNA in urine
|
|
|
Methotrexate tox
|
neutropenia; GI and oral mucostitis; myelosuppression; nephrotoxicity; hepatotoxicity; teratogenic effects (inhibits DNA synthesis & depletes FH4)
|
|
|
Methotrexate interactions
|
w/penicillin - may reduce renal clearance; w/NSAIDs - with high doses of methotrexate elevates and prolongs serum methotrexate levels
|
|
|
Methotrexate therapeutic uses
|
Treatment of stage I, stage II, or stage III non-metastatic or low risk metastatic gestational trophoblastic neoplasia-low-dose methotrexate as single agents, hysterectomy for stage II or stage III if future fertility is not a concern; treatment of stage II or stage III high-risk metastatic gestational trophoblastic neoplasia-high-dose methotrexate as single agents with leucovorin rescue; treatment of stage IV high-risk metastatic gestational trophoblastic neoplasia-surgery, radiation, high-dose methotrexate as single agent with leucovorin rescue; used with misoprostol to induce abortion; acute lymphoblastic leukemia in children; severe debilitating psoriasis; induction of remission in refractory rheumatoid arthritis
|
|
|
Cyclophosphamide pharmacological effects
|
Disturbs DNA synthesis; lethality of DNA operating agents depends on creation of DNA strand breaks by repair enzymes and in intact apoptotic response (p53 has to be working)
|
|
|
Cyclophosphamide method of resistance
|
Resistance develops quickly if administered as single agents; decreased permeation of dragons the cells; increased intracellular glutathione-glutathione is a nucleophile
scavenger and is better than DNA so it competes for alkylation by reacting with the drug; increased activity of DNA repair pathways; increase metabolism of the activated forms of cyclophosphamide |
|
|
Cyclophosphamide toxicity
|
hemorrhatic cystitis (prevented by coadministration with MESNA and fluids); myelosuppression; nausea, vomiting, alopecia; neurotoxicity
|
|
|
Cyclophosphamide drug interactions
|
Caution when used in combination with other immunosuppressants
|
|
|
Cyclophosphamide therapeutic uses
|
Breast cancer; lymphomas; chronic lymphocytic leukemia in combination of for non-Hodgkin's lymphoma; ovarian cancers; solid tumors in children; can also be used to reduce organ rejection after transplantation
|
|
|
Doxorubicin cell cycle specificity
|
Cell cycle nonspecific
|
|
|
Doxorubicin drug class
|
intercalating agents; anthracycline antibiotic
|
|
|
Doxorubicin structure/chemistry
|
Anthracycline antibiotics have the tetra cyclic ring structure attached to an unusual sugar, daunosamine; cytotoxic agents of this class all have quinone and hydroquinone moieties on adjacent rings that permit the gain and loss of electrons
|
|
|
Doxorubicin mechanism of action
|
intercalates between nucleoside bases of DNA and inhibits template utilization, directly affecting transcription and replication; forms free oxygen radicals that damage DNA when reduced; most importantly forms of tripartite complex with topoisomerase II into DNA-this complex allows for the double-stranded breaks but inhibits ligase activity and replication leading to apoptosis
|
|
|
Doxorubicin mechanism of resistance
|
Overexpression of transition linked DNA repair may contribute to resistance; multidrug resistance of P-glycoprotein-try to overcome with calcium channel blockers; increased efflux via MRP transporter family; increased glutathione activity into decreased activity or mutation of topoisomerase II or enhanced abilities to repair breaks
|
|
|
Doxorubicin toxicity
|
Myelosuppression; leukopenia; sometimes anemia; thrombocytopenia; alopecia, stomatitis, and G.I. problems; erythmatous streaking (allergic reaction);* cardiomyopathy-free radicals contribute to cardiac toxicity, give iron chelator to eliminate formation of Fe so free radicals don't form
|
|
|
Doxorubicin drug interactions
|
Used in combination with cyclophosphamide and vinca alkaloids for lymphoma treatment
|
|
|
Doxorubicin therapeutic uses
|
Treatment of AIDS-related Kaposi's sarcoma, malignant lymphomas and in solid tumors (breast cancer); small cell carcinoma of long; pediatrics/adult sarcomas (osteogenic, Ewing's, soft tissue)
|
|
|
Oxaliplatin cell cycle specificity
|
Cell cycle nonspecific
|
|
|
Oxaliplatin drug class
|
Alkylating agent
|
|
|
Oxaliplatin mechanism of action
|
Enter cell by diffusion and active cut transporters, reacts with DNA forming intra-and inter-strand cross-links particularly at N7 of guanine nucleotides which forms cross-links by inducing DNA adducts and inhibits replication and transcription; formation of breaks and miss coding if recognized by P 53 and other checkpoint proteins leading to apoptosis; plan and activated by water; covalently binds to nucleophilic sites on DNA; invented to be less cytotoxic than cisplatin
|
|
|
Oxaliplatin mechanism of resistance
|
Does not display across resistance with other drugs in class; resistance is not mediated through loss of function of MMR proteins; repair of cross-link DNA adducts of by methods such as nucleotide excision repair; less resistance than cisplatin
|
|
|
Oxaliplatin toxicity
|
Peripheral neuropathy with large doses; mild to moderate hematologic toxicity unstable in chloride or alkaline solutions
|
|
|
Oxaliplatin interactions
|
Does not display cross resistance with cisplatin or carboplatin
|
|
|
Oxaliplatin therapeutic uses
|
Antitumor activity in gastric and colon cancer due to MMR independent effects; suppresses expression of thymidylate synthase (target of 5-fluorouracil)and ferments synergy of the two drugs
|
|
|
5 -fluorouracil cell cycle specificity
|
Cell cycle specific
|
|
|
5-fluorouracil drug class
|
Anti-metabolite
|
|
|
5-fluorouracil mechanism of action
|
Prodrug; activated by addition of a ribose and a phosphate group; active form is FdUMP; directly inhibits thymidylate synthase so tumors can't make dTMP, inhibiting DNA replication; also inhibits RNA processing by incorporating into DNA; almost always give us leucovorin in order to increase thymidylate synthase production
|
|
|
5-fluorouracil pharmacologic effects
|
Inhibition of thymidylate synthase which blocks DNA synthesis
|
|
|
5-fluorouracil mechanism of resistance
|
Decreased enzymes involved in the activation of 5-fluorouracil; amplification/overexpression of thymidylate synthase by and autoregulatory feedback mechanism; mutant forms of thymidylate synthase don't bind FdUMP well
|
|
|
5-fluorouracil toxicity
|
Myelosuppression; nausea vomiting and other gastrointestinal effects; alopecia; mucocutaneous effects
|
|
|
5-fluorouracil drug interactions
|
With leucovorin-provides cofactor so FdUMP can bind and enhanced thymidylate synthase inhibition; with methotrexate given 24 hours prior-enhanced 5-fluorouracil activation/anabolism and RNA incorporation; with irinotecan, oxaliplatin-overcome resistance, decreased synthesis of thymidylate synthase
|
|
|
5-fluorouracil therapeutic uses
|
Produces partial responses in 10 to 20% of patients with metastatic colon carcinomas, upper gastrointestinal carcinomas, and breast carcinomas
|
|
|
6-mercaptopurine cell cycle specificity
|
Cell cycle specific
|
|
|
6-mercaptopurine drug class
|
antipurine (purine analogue)
|
|
|
6-mercaptopurine structure/chemistry
|
has the structure of purine, adenine, w/exception of an -SH attached at C6 instead of -NH2; readily converted to nucleotides in normal and malignant cells; nucleotides formed from 6-MP inhibit de novo purine synthesis and become incorporated into nucleic acids
|
|
|
6-mercaptopurine mechanism of action
|
6-MP must be activated by conversion to 6-thionosine-5'-monophosphate (T-IMP) by hypoxanthine guanine phosphoribosyl transferase (HGPRT) - a purine salvage enzyme; T-IMP inhibits 1st step in purine synthesis, PRPP amidotransferase inhibits conversion of IMP to AMP in purine metabolism; T-IMP is converted to T-GMP and incorporated into DNA and RNA
|
|
|
6-mercaptopurine pharmacologic effects
|
inhibits purine ring synthesis; inhibits nucleotide interconversion
|
|
|
6-mercaptopurine mechanism of resistance
|
primarily due to lack of activating enzyme - HGPRT; decreased drug transport into cell; increased drug efflux out of cell
|
|
|
6-mercaptopurine toxicity
|
myelosuppression that develops more gradually that with folic acid antagonists; jaundice and hepatic enzyme elevations, anorexia, nausea or vomiting, may lead to leukemia
|
|
|
6-mercaptopurine drug interactions
|
synergistic with methotrexate - methotrexate increases the intracellular concentration of PRPP which Is required for 6-MP activation; allopurinol markedly reduces metabolism of purine analogues leading to severe leukopenia (abnormal decrease of white blood cells)
|
|
|
6-mercaptopurine therapeutic uses
|
acute lymphocytic and juvenile chronic granulocytic (myelogenus) leukemias
|
|
|
Vinblastine/Vincristine cell cycle specificity
|
cell cycle specific
|
|
|
Vinblastine/Vincristine structure/chemistry
|
asymmetric dimeric compound capable of binding beta-tubulin monomers and preventing their joining with alpha-tubulin to form microtubules
|
|
|
Vinblastine/Vincristine mechanism of action
|
blocks cells in mitosis by binding specifically to beta-tubulin, blocking its ability to polymerize w/alpha-tubulin to form microtubules; cell division is arrested in metaphase, dissolution of mitotic spindle --> cell death
|
|
|
Vinblastine/Vincristine pharmacologic effects
|
cell cycle specific; blocks cells in mitosis; cell division is arrested in Mphase due to inability to form mitotic spindles & chromosomes, unable to alighn along metaphase plate, disperse randomly throughout cytoplasm exploded mitosis) or clup irregularly into balls or stars; undergo changes characteristic of apoptosis
|
|
|
Vinblastine/Vincristine mechanism of resistance
|
chromosomal abnormalities consistent with amplification of genes corresponding to the P-glycoprotein, a membrane efflux pump that transports drugs from cells - this amplification found in tumor cells after administration of single drug is responsible for cross resistance - calcium channel blockers can reverse this; other membrane transporters - MRP/multidrug resistance associated protein; mutations in beta-tubulin or in relative expression of beta-tubulin isoferms leads to less effective binding
|
|
|
Vinblastine/Vincristine Drug class
|
anti-mitotic, vinca alkaloid
|
|
|
Vinblastine toxicity
|
severe myelosuppression; alopecia and local cellulitis; nausea, vomiting, anorexia, diarrhea, stomatitis and dermatitis (but less gastrointestinal effects than Vincristine)
|
|
|
Vinblastine therapeutic uses
|
in combination with bleomycin and cisplatin - treat metastatic testicular tumors; Hodgkins disease and choriocarcinoma
|
|
|
Vincristine toxicity
|
less myelosuppression than Vinblastine; neurotoxicity - paresthesia (numbness and tingling of extremities) and loss of deep tendon reflexes followed by motor weakness; inadvertent intrathecal administration produces devastating and fatal neurotoxicity; gastrointestinal toxicty
|
|
|
Vincristine therapeutic uses
|
with glucocorticoids - treatment of choice to induce remission in childhood leukemias - tolerated better in children than adults
|
|
|
2 factors that contribute to MDR
|
P-glycoprotein pump acquired resistance and drug efflux; mutations/loss of p53 which confers loss of apoptosis and defects in the mismatch repair enzyme family
|
|
|
3 drugs that require an active p53 in order to work
|
cyclophosphamide, cisplatin, oxaloplatin; in Li Fraumeni you must be careful with giving chemotherapy because you may deactivate p52 in normal cells and promote another tumor
|
|
|
Treatment for basal cell carcinoma
|
surgery, topical chemotherapy (5-FU); laser therapy
|
|
|
Treatment for squamous cell carcinoma
|
surgery; topical chemotherapy (5-FU); laser therapy, regional lymph removal or irradation, cisplatin used for stage III SCC
|
|
|
Treatment for melanoma, based on stage
|
Stage I - surgery; Stage II - surgery + immunotherapy; Stage III - surgery + lymph dissection + maybe chemotherapy; Stage IV - no treatment is available
|
|
|
Letrozole mechanism of action
|
decreases estrogen biosynthesis by selective inhibition of aromatase (estrogen synthase) (nonsteroidal competitive inhibitor) in peripheral tissues
|
|
|
Letrozole pharmacologic effects
|
3rd generation type 2 inhibitor - nonsteroidal and binds reversibly to the heme group of aromatase enzymes by way of a basic nitrogen atom; blocks estradiol synthesis from androstendione and testosterone
|
|
|
Lerozole mechanism of resistance
|
tumor may progress and become hormone insensitive (no longer requires hormone for growth)
|
|
|
Letrozole absorption
|
given orally
|
|
|
Irinotecan drug class
|
antineoplastic
|
|
|
Irinotecan structure/chemistry
|
5-ring structure called camptotneun; the piperidine side chain is cleaved by carboxylesterase - converting enzyme to form SN-38 which is 1000-fold more biologically active than the patent prodrug; lactone ring must be intact for cytotoxic activity
|
|
|
Irinotecan mechanism of action
|
inhibits topoisomerase I in tumor cells by binding to and stabilizing DNA-topoisomerase I cleavable complex; inhibits religation of DNA during topoisomerase I induced relaxation step of DNA replication and causes single stranded breaks in DNA of tumor cells; collision of DNA replication fork with broken DNA strand causes irreversible double-stranded DNA breakd and cell death, making Irinotecan an S-phase specific agent
|
|
|
Irinotecan pharmacologic effects
|
by inhibiting DNA replication in rapidly dividing cells, it slows the growth of susceptible tumors
|
|
|
Irinotecan mechanism of resistance
|
lack of carboxylesterase-converting enzyme so prodrug activation to SN-38 cannot occur; P-glycoprotein pumps drug out of tumor cell (MDR); decreased expression of topoisomerase I in tumor cells or mutation in topoisomerase I that makes it unable to bind SN-38; tumor cells shift from topoisomerase I to topoisomerase II expression
|
|
|
Letrozol toxicity
|
associated with 100% incidence of osteoporosis (estradiol synthesis in bones causes breakage); mild nausea, headache, fatigue, hot flashes, joint pain
|
|
|
Letrozole therapeutic uses
|
25 mg administered PO i qd - efficacy in treatment of postmenopausal women with early stage/advanced hormone-receptor positive breast cancer
|
|
|
Irinotecan cell cycle specificity
|
cell cycle specific
|
|
|
irinotecan trade name
|
camptosar
|
|
|
Irinotecan toxicity
|
delayed diarrhea (severe); myelosuppression with severe neutropenia; cholinergic syndrome resulting from inhibition of acetylcholinesterase (responds well to atropine)
|
|
|
Irinotecan drug interactions
|
many other drugs either inhibit activity or induce expression of cytochroe P450 enzyme, CYP3A which effects the metabolism; these include antibiotics, erythromycin (inhibits CYP3A) and rifampin (inducer)
|
|
|
Irinotecan therapeutic uses
|
primarily used for colorectal cancer treatment; can be used in combination with 5-FU to treat advanced colon cancer; can also treat lung, cervical, ovarian and gastric tumors
|
|
|
Bleomycin cell cycle specificity
|
cell cycle specific
|
|
|
Bleomycin drug class
|
peptide antibiotics
|
|
|
Bleomycin structure/chemistry
|
water-soluble, basic glycopeptide - the core is a complex metal-binding structure containing a pyrimidien chromophore linked to propionamide, an amide side chain, and 2 sugars; a terminal bithiazole carboxylic acid binds DNA
|
|
|
Bleomycin mechanism of action
|
causes oxidative damage to the deoxyribose of thymidylate and other nucleotides leading to singe/double stranded breaks in DNA; causes accumulation of cells in G2 phase because Fe interacts with oxygen causing senescence
|
|
|
Bleomycin pharmacologic effects
|
Cells senesce and are trapped in G2 phase
|
|
|
Bleomycin mechanism of resistance
|
increased hydrolase activity cleaves it to inactive form (but this is decreased in skin and lungs, contributing to toxicity in these sites)
|
|
|
Bleomycin toxicity
|
pulmonary toxicity (pulmonary fibrosis because lungs lack hydrolase); little myelosuppression, so synergistic when used in combination therapy; cutaneous side effects; patients that hve been on bleomycin have to have more oxygen when under anaesthetic
|
|
|
Bleomycin drug interactions
|
used in combination therapy for neoplasias because of minimal toxicities
|
|
|
Bleomycin therapeutic uses
|
highly effective agains germ cell tumors of testis and ovary - especially with cisplatin and vinblastine or etoposide; also pleural effusions, hodgkin's disease, and squamous cell carcinomas of cervix
|
|
|
Cisplatin cell cycle specificity
|
cell cycle nonspecific
|
|
|
Cisplatin drug class
|
platinum alkylator
|
|
|
Cisplatin pharmacologic effects
|
alkynator - causes cross linking
|
|
|
Cisplatin mechanism of resistance
|
shares cross-reisitance with carboplatin; other drug interactions inactivate cisplatin; overexpression of nucleotide excision repair; loss of function in mismatch repair proteins (MMR) that would normally initiate apoptosis; *requires active p53, can't use with Li Fraumeni patients
|
|
|
Cisplatin mechanism of action
|
enters cells by diffusion and active copper transporter - chloride is replaced by water yielding positive charged molecule - the aquated species then reacts with nucleophilic sites on DNA and proteins (favored at low choloride levels in cell); platinum reacts with DNA forming intra/interstrand cross-links (especially at N7 of guanine) - may induce apoptosis; inhibits replication and transcription - most pronounced in S phase
|
|
|
Cisplatin toxicity
|
nephrotoxicity (to prevent this, establish a chloride diuresis prior to treatment with saline) - don't use aluminum needles or infusion equpiment - given with a cytoprotective agent, amifostine; ototoxicity; severe nausea and vomiting, moderate myelosuppression; at high doses, can cause neuropathy; mutagenic, teratogenic, carcinogenic
|
|
|
Cisplatin drug interaactions
|
drug accumulations with glutathione and other sulfhydryls bind to and inactivate cisplatin
|
|
|
Cisplatin therapeutic uses
|
given only IV; used in combination with bleomycin, vinblastine for testicular cancer; ovarian carcinoma, cancers of bladder, head, neck, cervix, endometrium, lung, rectum, childhood neoplasms; also sensitizes cells to radiation therapy
|
|
|
Neural Crest
|
PNS: CNs III-XII, spinal nerves, ganglia (cranial: V, VII, IX, X; spinal: dorsal root; autonomic: sympathetic and parasympathetic), schwann cells, sensory and motor nerve endings NEWLINE melanocytes, chromaffin cells, enterochromaffin cells, adrenal medulla, parafollicular C-cells in thyroid, heart (valves, cardiac skeleton, pulmonary trunk, chorda tendinae, ascending aorta, cushions, membranous atrial and ventricular septae), corneal endothelium
|
|
|
Neural Tube
|
CNS: Brain, spinal cord, neuroglia, ependyma, CNs I and II, posterior pituitary, pituicytes, hypothalamus, thalamus, pineal gland
|
|
|
Surface Ectoderm
|
epidermis; hair; nails; glands' anterior pituitary; gonadotropic, somatotropic, folliculostellate, precursor, thyrotropic, corticotropic, and mammotropic cells; lens; cornea; enamel
|
|
|
Sclerotome + neural crest
|
Cervical, Thoracic, Lumbar, & Sacral mesenchyme forms bone, cartilage, CT, BVs, LVs of axial and appendicular skeletons, leptomeninges (pia and arachnoid) covering the spinal cord
|
|
|
Myotome + neural crest
|
Cervical, Thoracic, Lumbar, & Sacral mesenchyme forms skeletal muscle, BVs, LVs of axial and appendicular skeletons
|
|
|
Dermatome + neural crest
|
Cervical, Thoracic, Lumbar, & Sacral mesenchyme forms dermis, connective tissue, BVs, LVs of axial and appendicular skeletons
|
|
|
Lateral Plate Somatic Mesoderm
|
bone, cartilage, dermis, CT, skeletal muscle, BVs, LVs of trunk
|
|
|
Lateral Plate Splanchic Mesoderm
|
Stroma: smooth muscle, fat, connective tissue, fibroblasts, BVs. LBs for respiratory, lower 1/3 of esophagus, stomach, small intestine, appendix, large intestine, colon, rectum, liver, gall bladder, pancreas, urinary bladder NEWLINE Heart: endocardium, myocardium, pericardium, epicardium, endothelium NEWLINE intra-embryonic blood formation of RBCs & WBCs begins @ week 5 NEWLINE Spleen: parenchyma: red pulp, whilte pulp; stroma: capsule, trabeculae NEWLINE Adrenal Cortex: parenchyma: z. fasciculata, z. glomerulosa, z. reticularis; stroma: capsules and BVs
|
|
|
Endoderm
|
Parenchyma: thyroid gland; respiratory system; GI system; NEWLINE lining of pharyngeal pouches: I - middle ear; II - pharyngeal tonsils, III- thymus and inferior parathyroids, IV - superior parathyroids; NEWLINE ultimo-branchial bodies, parafollicular C-cells of thyroid
|
|
|
Extra-embryonic splanchnic mesoderm
|
Hofbauer cells
|
