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Drugs Overview

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  Page 1 of 8 Pharmacology: Fast and Dirty Board Review Edward Cooper, VMD Emergency Fellow Veterinary Hospital of the University of Pennsylvania General Format    Drug (Trade name)    Mechanism of action    Uses/applications    Side effects/toxicities/contraindications    * = particularly board worthy Chemotheraputics    Doxurubicin (Adriamycin)    Intercalating agent – DNA fragmentation. Cell-cycle non-specific    Very broad spectrum – big gun. Single agent or combo for carcinoma, sarcoma, lymphoma, leukemia    BM suppression, hemorrhagic enterocolitis, dose-dependant cardiomyopathy*. Perivascular sloughing. Metabolized by liver, caution in liver disease.    Cyclophosphamide (Cytoxan)    Alkylating agent – DNA fragmentation and crosslinking. Cell cycle non-specific    Used in combo protocols for carcinoma, sarcoma, lymphoma, leukemia. Not affected by multi-drug resistance (MDR) gene*. Orally active.    BM suppresion, GI signs, sterile hemorrhagic cystitis*. Caution in liver and kidney disease Melphalan    Alkylating agent – same as cytoxan    Particularly used in multiple myeloma*    Same as cytoxan    Vincristine (Oncovin)    Inhibits microtubule formation, blocks mitotic spindle. Cell cycle specific    Combination protocols for lymphoma, carcinomas, sarcomas. Single agent for transmissible venereal tumor (TVT)*    Relatively GI and BM sparing*, peripheral neural toxicity-cumulative. Sever peri-vascular irritant.    Vinblastine    Same as vincristine    Agent of choice for mast cell tumors    Severe BM toxicity (as compared to vincristine)    Methotrexate    Dihydrofolate reductase inhibitor blocks nucleotide synthesis. Cell cycle specific.    Primarily used in combination protocols for lymphoma and leukemia    Causes GI toxicity and BM suppression. Caution in renal failure.    Cytosine arabinoside (Cytosar)    Inhibits DNA synthesis. Cell cycle specific.    Primarily used in combination protocols for lymphoma and leukemia    Causes GI toxicity and BM suppression.    Cisplatin    Incorporates into DNA strands and inhibits replication  Page 2 of 8    Single agent or combo for osteosarcoma*, malignant melanoma, squamous cell carcinoma, other carcinomas/sarcomas    Acute renal toxicity*, nausea/vomiting, peripheral neuorpathy, seizures. Extremely toxic to cats (CISPLATIN SPLATS CATS)*. BM sparing.    Carboplatin    Same as cisplatin    Same as cisplatin     No renal toxicity but more BM and GI    L-Asparginase (ELSPAR)    Degrades intracellular asparagine. Lymphoid cells can’t make new amino acid reulting in cell death    Almost exclusively for lymphoma. Also not affected by MDR.*    Very little toxicity. Immune mediated reactions and (rarely) pancreatits.    5-Flurouracil (5FU)    5-FU inhibits synthesis of thymidine. Interferes with DNA replication.    Primarily carcinomas, esp. mammary gland but also GI, pancreas, etc    BM suppression, GI signs. Severe neurotoxicity in cats (5-FU F’s Up cats).    Piroxicam (Feldane)     NSAID – COX inhibitor    Believed to be effective in palliating carcinoma, esp prostatic and TCC    GI ulceration Antimicrobials    Enrofloxacin (Baytril)    DNA gyrase inhibitor. Interfers with DNA replication. Bactericidal.    Broad spectrum – big gun. Especially good with gram-negative bacilli and cocci, few gram positive. NO anaerobic coverage (requires oxygen to work)*. Uses: pneumonia, UTI, sepsis, prophylaxis for GI translocation.    Damages growth plate in growing animals.* Also has been shown to cause blindness in cats when used above 5mg/kg/dose.*    Metronidazole    Mechanism of action unknown – believed to disrupt DNA. Bactericidal.    Primarily anaerobes and protozoa (especially giardia*). Also has anti-inflammatory/immune-modulatory affects – IBD. Also used for HE/CLF.*     Neurological signs (acute high dose or chronic use)*, hepatotoxicity, GI signs. Not to exceed 15mg/kg/dose IV.    ß-lactams (Penicillin, Amoxicillin, Ampicilllin)    Inhibit cell synthesis by blocking crosslinking of peptidoglycan mollecules. Bactericidal.    Penicillin G – gram + and gram - cocci (staph and strep), gram + bacilli, spirochetes. Inactivated by ß-lactamases.    Methcillin – used for penicillinase producing staph infections    Ampicillin – less potent against cocci but have extended spectrum against gram + and – bacilli. Good anaerobic spectrum. Most commonly used antimicrobial in hospital setting.    Clavamox (Amoxicillin + clavulanic acid) – similar spectrum to ampicillin. Clavulanic acid (ß-lactamase inhibitor) potentiates amoxicillin* and expands spectrum. Used for cat bites, UTIs.    Ticarcillin/piperacillin – very big guns. Covers pseudomonas infections in addition to spectrum of ampicillin. Ticarcillin + clavulanic acid = Timentin.*    Synergistic affects with aminoglycosides.*    Generally very safe drugs. Very little toxicity associated. Hypersensitivty can occur, can trigger IMHA/ITP. Some GI signs when given orally.    Cephalosporins    Also ß-lactams which inhibit cell wall synthesis. Generally more resistant to ß-lactamases than penicillins.    1st generation - predominantly G+ with little G-. Good anaerobic. Includes cefazolin and cephalexin (Keflex). Commonly used for skin infections (Keflex) and intra-op (cefazolin).    Cephalosporins (con’t)    2nd generation – same G+ but expanded G- and anaerobic coverage (including Bacteroides spp). Very good for pneumonia, sepsis, GI bacterial translocation. Cefoxitin (Mefoxin) best in this group.  Page 3 of 8    3rd generation – sl. less G+ but further expanded G-. Cefotaxime and Ceftiofur (Naxcel) most common. Naxcel used commonly in large animals – no withdraw time.    Also fairly safe. Side effects similar to penicillins.    Carbapenems    Similar to ß-lactams    Very broad spectrum, very big gun. Covers everything as single agent. Imipenum combined with cilastatin (inhibits metabolism).    Can cause GI, CNS, and renal signs if given too rapidly.    Aminoglycosides (Gentamicin, Amikacin, Neomycin)    Binds to 30s ribosomal subunit blocking protein synthesis. Cidal.    Predominantly G- spectrum. NO anaerobic coverage.* Due to toxicity, reserved for use only in hospitalized patients with severe infections resistant to other options. Only dosed once a day (post – antibiotic affect). Neomycin only used topically.    Primarily causes nephrotoxicity and ototoxicity.* Cats more severely affected. Should measure  peak and trough blood levels.    Erythromycin      Macrolide - binds to 50s subunit blocking protein synthesis. Generally considered static but cidal at high concentrations.    Has mostly G+ spectrum similar to Penicillin G. Often given for campylobacter infections. Also has prokinetic effects on GI motility.*    GI signs when given orally. Should not be given with liver disease .    Tetracyclines (doxycycline, oxytetracycline)    Binds 30s subunit blocking protein synthesis. Bacteriostatic.    Activity against multiple organisms including mycoplasma, Rickettsial organisms (RMSF, erlichia)*, hembartonella*, chlamydia, some G+, G- and spirochetes (Lyme disease and leptospirosis*). Most enteric G- are resistant. Doxycycline also believed to have some immune-modulatory affects.    Contraindicated in pregnancy – retard fetal skeletal growth and stain deciduous teeth. Tet and oxytet cause renal toxicity, doxy does not. Also can cause phototoxicity, superinfections (SIBO), and esophageal stricture (cats).      Clindamycin (Antirobe)    Lincosamide - binds 50s subunit blocking protein synthesis. Static or cidal, depending on concentration.    Spectrum includes aerobic G+ cocci, many anaerobic, protozoa and mycoplasma. Used for Toxo/Neospora,* abcesses, osteomyelitis and to treat dental diasese.*    Can cause clostridial overgrowth, gastroenteritis.    Chloramphenicol    Binds 50s subunit blocking protein synthesis. Bacteriostatic.    Broad spectrum of G+, G-, and anaerobes. Also, rickettsia, chlamydia, and mycoplasma. Seldom used because of toxicity.    Bone marrow suppression, reversible (aplastic anemia in humans). Prohibited use in food animals. Caution with renal, liver dz.    Sulfonamides (Sulfadiazine, Sulfadimethoxine, Sulfasalazine)    Inhibit folate synthesis which limits bacterial DNA replication. Bacteriostatic alone, cidal when combined with trimethoprim.    Good G+ and G- spectrum. Also protozoal organisms. Most commonly used for UTI’s. TMS (Trimethorprim/sulfadiazine) most common. Sulfsalazine used in IBD – alter GI flora and have local anti-inflamatory effects.    Many side effects associated. KCS,* polyarthitis, immune mediated disease (IMHA,ITP)*, ideosyncratic hepatic necorsis,* panceatits, urticaria, PU/PD, crystalluria, renal tubular destruction, vomiting, diarrhea, anorexia  Page 4 of 8 Gram + Bacteria    S: Staph    S: Strep    B: Bacillis    E: Erysipelothrix    C: Clostridium    C: Corynebacterium    L: Listeria    A: Actinomyces    R: Rhodococcus    D: Dermatophylis    A: Archanobacter    M: Mycobacteria     N: Nocardia Anthelmintics    Benzimidazoles (fenbendazole, febental)    Bind to tubulin and inhibit formation of cytoskeleton    Activity against metastrongyles (lung worms), strongyles, trichostrongyles, tapeworms, liver flukes. Requires long exposure.    High margin of safety. Has teratogenic affects.    Imidazothiazoles (levamisole)     Neurotoxic - spastic paralysis of nematodes    Primarily nematodes and lungworms (no tapes or flukes)    Side-effects related to cholinergic overstimulation – SLUDGE.    Tetrahydropyrimidines (pyrantel, morantel)    Similar to levamisole     Nematodes (hooks, rounds, strongyles, pinworms)    Similar to levamisole    Avermectins (Ivermectin, Selemectin, Moxidectin)    GABA mediated hyperpolarization leading to paralysis    Everything except tapes, flukes and adult heartworm. Also active against external parasites – mites,  bots, ticks, lice    Wide margin of safety. Neuro signs with severe overdose. Collies/herding dogs especially sensitive.    Praziquantel (Droncit)    Interferes ion balance and cell membrane potential.    Primarily tapeworms in dogs and cats.    Very wide margin of safety. Antifungals    Amphotericin B    Irreversibly binds to ergosterol in fungal cell membrane    Broad spectrum of activity – Blasto, Histo, Crypto, Coccidioides, Candida, Aspergillus. Does not cross BBB.    Severely nephrotoxic.* Need to give fluid diuresis. Severe perivascular irritant,* anemia, GI signs.    Flucytosine (5FC)    Pyrimidine analog – interferes with DNA synthesis
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