Download Chemotherapy Basics

Chemotherapy Basics
Sites of Exclusion:
CSF
Ocular fluid (duh)
Synovial fluid
Pleural fluid cysts
Necrotic tissue
Sites of Concentration:
Liver & bile
Kidney & urine
Bone
Fat
RBCs
Skin
Antibiotics
Cell wall Synthesis Inhibitors
Penicillins:
Penicillin G (benzylpenicillin) -- against Gm +
Benzathine penicillin G -- depo preparation
Nafcillin -- -lactamase resistance
Oxacillin -- -lactamase resistance
Cloxacillin -- -lactamase resistance
Carbenicillin -- Proteus & Pseudomonas
Ticarcillin -- Proteus & Pseudomonas
Piperacillin -- Pseudomonas & Klebsiella
Ampicillin -- increased Gm - activity
Amoxacillin -- increased Gm - activity
* Penicillins also activate murein hydrolases
Cephalosporins:
1st Gen. = Cephalothin
Cephalexin -- can be given orally
Cefadroxil -- can be given orally
2nd Gen. = Cefoxitin
Cefaclor -- can be given orally
3rd Gen. = Ceftriaxone
Ceftazidime
Cefixime -- can be given orally
Moxalactam
Monobactams:
Aztreonam -- not inactivated by -lactamases; mostly
used for Gm - organisms, not effective vs. Gm +
Carbapenems:
Imipenem -- given IV; broad spectrum
Non--lactams:
Vancomycin -- oral for GI superinfections, IV for most
other uses; does not cross the blood-brain barrier (BBB)
Bacitracin -- Gm + only; used as a topical antibiotic
because of its nephrotoxicity
-Lactamase inhibitors:
Sulbactam
Clavulanic acid
Inhibitors of Protein Synthesis
Aminoglycosides: -- bind irreversibly to the 30S subunit of
bacterial ribosomes; particularly useful vs. Gm Streptomycin – given IM, not orally
Kanamycin -- mainly reserved for topical applications
Neomycin -- mainly reserved for topical applications
Gentamicin
Tobramycin -- slightly less nephrotoxic than gentamicin
Amikacin
Netilmicin
* since the aminoglycosides are poorly absorbed orally,
they are usually given IM or IV
* Ototoxicity, nephrotoxicity, and neuromuscular
blockade (very rare) are among their adverse effects
Tetracyclines: -- broad spectrum; bind reversibly to the
30S subunit of bacterial ribosomes (bacteriostatic)
Chlortetracycline -- <30% absorbed orally
Oxytetracycline -- 60-80% absorbed orally
Tetracycline -- 60-80% absorbed orally
Doxycycline -- complete oral absorption
Minocycline -- complete oral absorption
* all are potent chelators of metal cations
* do not cross the BBB in significant concentrations
* DO cross the placenta...contraindicated in pregnancy
* Frequently used for: Mycoplasma, chlamydia,
rickettsiae and Lyme disease
Macrolides:
Erythromycin -- bind reversibly to the 50S subunit; primarily
cleared in the bile;
Erythromycin esters
* potent inhibitor of certain P-450 enzymes
* frequently used for: Mycoplasma, chlamydia,
corynebacteria, and legionnaire’s disease
Others:
Chloramphenicol -- broad spectrum; will get into the CNS;
entirely excreted in urine; binds reversibly to the 50S
subunit; can (rarely) induce aplastic anemia which is
usually irreversible; use is limited to anaerobic and
mixed CNS infections, sensitive Salmonella and H. flu
Spectinomycin -- simialr to aminoglycosides; only given IM
Clindamycin -- given orally or IV; inhibits the 50S subunit;
resistance is chromosomal, and C. difficile is one of
the most common ones that has developed
resistance
Drugs that alter cell membrane function:
Polymixins
Nystatin
Gramicidin
Amphotericin B
Inhibitors of Nucleic Acid Synthesis
Sulfonamides: -- broad spectrum; great for UTIs; will get
Into the CNS readily
Sulfisoxazole
Sulfacytine
Sulfamethoxazole
Sulfasalazine
Silver sulfadiazine
Sodium sulfacetamide
Co-trimoxazole (sulfamethoxazole+trimethoprim)
* Sulfas are similar to p-aminobenzoic acid (PABA); in this
way they competitively inhibit the formation of
dihydrofolic acid (the enzyme is dihydropteroate synthase)
* Trimethoprim is a substrate analogue for dihydrofolate
reductase...inhibits formation of folic acid; although
it is much more specific for bacterial forms, it does
act on human isoforms of the same enzyme -- and
those effects can lead to those seen with folate deficiency!
* Must remember to hydrate the patient well to avoid
crystallization of sulfas in the urinary tract
DNA Gyrase inhibitors:
Nalidixic acid -- is a quinolone; used mostly against Gm organisms; excretion is too fast to be an effective agent
Ciprofloxacin -- is a fluroquinolone; used for both Gm and Gm + bugs
Norfloxacin -- is a fluroquinolone; used for both Gm and Gm + bugs
* Fluroquinolones inhibit theophylline clearance; they
can also cause abnormal liver function tests and skin
rashes.
Antimycobacterial Agents
First-line drugs:
Isoniazid (INH) -- blocks mycolic acid synthesis...key
components of their cell wall; hepatotoxicity occurs
in fast acetylators
Ethambutol -- RBCs concentrate this one...so they can
act as a depo source; can cause a reversible(usually)
optic neuritis...dose dependent
Rifampin -- also effective vs. GM + and Gm - cocci; inhibits
bacterial RNA synthesis; potent inducer of P-450s
Pyrazinamide -- resistance develops quickly; can
cause
hyperuricemia and hepatotoxicity
Second-line drugs:
Para-aminosalicylic acid -- rapidly excreted in urine; it
blocks the folate pathway in mycobacteria
Ethionamide -- causes intence gastric pain, and may be
neurotoxic as well
Cycloserine -- inhibits alanine racemase; CNS toxicity
and drug-induced psychoses limits its use
Antileprosy drugs:
Dapsone -- gets into skin better than rifampin; also good
against Pneumocystis carinii;frequently causes a
hemolytic anemia, and it also induces a
methemoglobinemia; GI disturbances and skin rashes
are also encountered