Thomas Pharm Flashcards
5-FU
Given IV
Must be activated to FdUMP -> inhibits thymidylate synthase
Other actions: inhibition of RNA processing and incorporation into DNA
Combos: + Leucovorin -> enhanced TS inhibition; + Methotrexate -> enhanced 5-FU anabolism and RNA incorporation
Capecitabine
Oral version of 5-FU
Basic principles of oral agents
1) Polar sugar group provides water solubility
2) Lipophilic side group allows the drug to pass through the membranes of the gut and be absorbed orally
3) MUST BE ACID STABLE
Irinotecan
Inhibits topo I
Must be activated to SN38
Used in combo with leucovorin and 5-FU (FOLFIre)
T: diarrhea
Oxaliplatin
Synergistic with 5-FU FOLFOX (leucovorin+5-FU+oxaliplatin)
Binds DNA at promoter region of TS to overcome 5-FU resistance
Intercalates DNA
Erlotinib
Orally active epidermal growth factor receptor (EGFR)-tyrosine kinase reversible inhibitor which blocks EGFR phosphorylation and subsequent signal transduction pathways involved in proliferation, metastasis, angiogenesis, and apoptosis inhibition
Only work in pts that have activating mutation in EGFR gene
Tx: colon cancer
T: diarrhea, rash
Cetuximab
Chimeric monoclonal Ab that binds to the EGFR and inhibits proliferation, angiogenesis, metastasis, and promotes apoptosis
T: Ab-dependent cellular toxicity rxn, transfusion rxns
Panitumumab
Humanized monoclonal Ab that blocks the binding of EGF and TGFalpha ligands to the receptor
No Ab-dependent cellular toxicity rxn
Bevacizumab
Humanized monoclonal Ab primarily against VEGFa that inhibits its interaction with VEGF receptors -> inhibits angiogenesis in tumors and in normal tissues
Tx: colon cancer
R: shift to VEGFc or VEGFd; upreg of angiogenic factors
T: Severe HTN, hemorrhage, proteinuria, CHF, hemorrhage, gastric perforation; dose-related
Cisplatin
Produces crosslinks between adjacent guanines in DNA
Water replaces the Cl to activate the drug
T: myelosupp, N/V
Oxaliplatin
Intrastrand crosslinker
Contains platinum atom complexed with ocalate and DACH -> oxalate leaves and the bulky DACH is thought to contribute greater cytotoxicity than cisplatin
T: peripheral neuropathy
Mitomycin
Crosslinks DNA (alkylator) -> apoptosis
Tx: pancreatic, stomach, and colon cancer
T: myelosupp
Streptozocin
Methylnitrosurea + glucose -> glucose makes it bind to islets of Langerhans in pancreas -> specific for pancreatic cancer
Forms only the alkylating froup and not the carbamoylating group -> alkylates DNA (no carbamoylated proteins formed)
Causes lass myelosupp than other nitrosoureas (that produce carbamoylated proteins)
Paclitaxel
Binds to B-tubulin subunit of tubulin and blocks the disassembly of the microtubule bundles to prodice aberrant mictrotubule structures -> inhibits mitosis
Tx: carcinoma of the esophagus, ovary, breast, cervix, lung, and bladder
R: incr expression of p-glycoprotein POP and B-tubulin mutations
T: neutropenia and peripheral neuropathy
Gemcitabine
Inhibits DNA synthesis and is incorporated into DNA to induce apoptosis -> active against both rapidly dividing tumor cells and solid tumors
Tx: first choice agent for metastatic pancreatic cancer and esophageal cancer
T: myelosup; slowly progressive hemolytic uremic syndrome
C/I: radiation therapy
Vancomycin
Given IV; poorly absorbed orally
Binds to D-Ala-D-Ala precursor to inhibit transglycosylase
Teicoplanin
Given IV or IM; poorly absorbed orally
Inhibits peptidoglycan polymerization -> inhibits bacterial cell wall synthesis
Bacitracin
Used topically in dermatologic and ophthalmic ointments; not absorbed orallyInhibits bacterial cell wall synthesis by interfering with dephosphorylation of a lipid transport molecule which carries the building blocks of the peptidoglycan bacterial cell wall
T: nephrotoxicity if given parenterally
Orally absorbed PCNs
Penicillin V; Oxavillin; Cloxacillin; Dicloxacillin; Ampicillin; Amoxicillin; Carbenicillin indanyl
Orally absorbed Cephalosporins
First generations: Cephalexin; Cefadroxil
Second generations: Cefaclor; Loracarbef
Third generation: Cefpodoxime proxetil
Oral absorption of tetracyclines
Minocycline > Doxycycline > Methacycline > Demeclocycline > Oxytetra > Chlortetra (95% -> 30%)
Remain in body for a long time because of enterhepatic circulation
Doxy most widely used because of no nephrotoxicity and it’s excreted in poop
Tigecycline
Not absorbed orally; parenteral use only with rapid and wide distribution into tissues
Glycycline (butyl-glycylamido derivative of minocycline)
Tx: tetracycline-resistant bacteria
Chloramphenicol
Administered orally as the active drug
Effective against tetracycline-resistant bacteriaT: dose-related toxicity that presents as anemia, leukopenia, or thrombocytopenia; idiosyncratic toxicity manifested by aplastic anemia leading to fatal pancytopenia
C/I: fetuses and young kiddos because they can’t glucuronidate the drug causing gray baby syndrome (HTN, cyanosis)
Sulfonamides
Competitive inhibitor of dihydropterate synthase (only found in bacteria) due to PABA analog
T: crystal urea (crystals in the bladder -> pain) in older sulfonamides
Classes of Sulfonamides
1) Absorbed and excreted rapidly: Sulfisoxazole (has increased solubility -> decreased crystal urea) and Sulfamethoxazole -> only ones used in US
2) Poorly absorbed-active in bowel lumen: Sulfasalazine (used to treat colitis)
3) Topically used
4) Long-acting
Treatment of bacterial diarrhea and antibiotics with special GI indications
Diarrhea is typically self limiting in young adults -> usually does NOT require treatment
Treat diarrhea in traveler’s diarrhea, neonates, elderly, and immunocompromised
Clostridium difficile
Metronidazole
Discontinue all other abxs if possible
Helicobacter pylori
Omeprazole + amoxicillin-clarithromycin + metronidazole
Quickly develops resistance to single abx treatment; Bismuth is also used
TMP-SMX
TMP inhibits DHFR; SMX inhibits dihydropterate synthase
Sometimes used to treat diarrhea
Ciprofloxacin or Levofloxacin
Used for the treatment of diarrhea
Resistant mutant forms of DNA gyrase in bacteria are increasing
T: GI distress
Macrolides
Can induce GI motility -> diarrhea
Erythromycin: degraded by stomach acid
Clarithromycin: acid stable
Telithromycin
Binds and inhibits 50S subunit
Ketolide that is less susceptible to methylase-mediated and efflux mediated resistance than macrolides
T: less hepatotoxicity
Clindamycin
Binds to 50S subunit and inhibits translocation step; works against bacteria that are resistant to macrolides and can kill everything but C. dif
SE: produces diarrhea in up to 20% of pts that can develop into fatal pseudomembranous colitis
Metronidazole
Chemically activated to form a highly reactive hydroxylamine on the nitro group which degrades DNA in ANAEROBIC organisms
*Only activated in anaerobes because they possess ferredoxin -> activates drug
Tx: Giardia; Entamoeba histolytica
T: less GI toxicity seen with Tinidazole (same MOA)
Paromomycin
Luminal aminoglycoside used in combination with metronidazole
Not absorbed in intestine -> stays in intestine
Tx: Giardia; Entamoeba histolytica
Nitazoxanide
Interferes with the ferredoxin oxidoreductase enzyme-dependent electron-transfer reaction which is essential in anaerobic metabolism
Tx: Cryptosporidium
No resistance; little toxicity
Iodoquinol
Luminal agent that eliminates intestinal colonization of E. histolytica
Little toxicity at therapeutic doses
Tx for Roundworms (nematodes and hookworms)
Benzimidazoles, mebendazole, albendazole, and ivermectin
Tx for Flukes (trematodes)
Praziquantel
Tx for Tapeworms (cestodes)
Praziquantel
Benzimidazoles
Thiabendazole; Mebendazole; Albendazole
Inhibit microtubule polymerization by binding to parasite B-tubulin
Not toxic
Praziquantel
Causes influx of calcium to produce paralysis of the musculature of the worm
T: dose-related transient abdominal distress
Ivermectin
Causes tonic paralysis of the worm musculature by activating glutamate-gated chloride channels
Well tolerated
Tx for HepB
Better to get vaccine!
All drugs are inhibitors of the DNA polymerase/reverse transcriptase
Adefovir dipivoxil: most widely used; also a DNA chain terminator; T: nephro- and hepatotoxic
Lamivudine: anti-HIV and HepB
Tenofovir: also a DNA chain terminator; anti-HIV and HepB
Entecavir: anti-HIV and HepB
Telbivudine: also a DNA chain terminator; competes with natural TTP of HepB
Tx for HepC
IFNalpha: inhibits viral replication and the translation steps of viral protein synthesis; combo with ribavirin -> 40% response rate; SE: acute influenza-like syndrome several hours after injection
Sofosbuvir: nucleotide analog inhibitor of RNA polymerase; SE: fatigue and headache; 95% cure rate; expensive
Simeprevir: non-covalently binds to and inhibits NS3/4A protease (critical in life cycle); primarily metabolized by hepatic CYP3A and inhibits CYP1A2 and intestinal CYP3A; SE: rash, pruritus, nausea; expensive
Tx for HepA
Vaccine!
