Pharm3
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Drug Class Use Side Effects All Penicillins All Penicillins --Bactericidal Allergies Inhibit crosslinking in cell wall synthesis by PBP Short t1/2, Low toxicity & Renal Clearance Distributed in CSF only with meningitis Penicillin G -Lactam (Penicillin) (Standard Penicillin) Parenteral (IV & IM) Syphilis (DOC – given IM) Allergies Seizures (w/ ↑ dose in renal failure) IV DOC = strep,meningcocci, enterococci, pneumococci, bacillus & clostridium Penicilin V -Lactam (Penicillin) (Standard Penicillin) Oral Allergies Some anaerobes, minor infections Methicillin -Lactam (Penicillin) (Antistaphylococcal) Parenteral (IV) Allergies Nephrotoxic -Lactamase producing Staph Nafcillin -Lactam (Penicillin) (Antistaphylococcal) Parenteral (IV) Allergies Nephrotoxic -Lactamase producing Staph Preferred over methicillin Dicloxacillin -Lactam (Penicillin) (Antistaphylococcal) Oral Allergies Mild local staph infections Ampicillin -Lactam (Penicillin) (Aminopenicillin) Parenteral (IV) Allergies, GI Upset Superinfections Non-allergic skin rashes Anaerobes, enterococci, Listeria Gram- rods & bacilli, (E. coli, H. inf, Salmonella) Amoxicillin -Lactam (Penicillin) (Aminopenicillin) Oral URI, Sinusitis, Otitis & LRTI (DOC) Allergies, GI Upset Superinfections Non-allergic skin rashes Ticarcillin -Lactam (Penicillin) (Antipseudomonal) Allergies Gram – (Klebsiella, Enterobacter, Pseudomonas) Often combined with aminoglycoside (tobramycin) For hospitalized neutropenic patients Pipercillin -Lactam (Penicillin) (Antipseudomonal) Allergies Gram – (Klebsiella, Enterobacter, Pseudomonas) Often combined with aminoglycoside (tobramycin) For hospitalized neutropenic patients Augmentin (Amoxicillin & Clavulanic Acid) -Lactam (Penicillin) Oral Allergies, GI Upset Superinfections Non-allergic skin rashes 1st Generation Cephalosporins -Lactam (1 Generation Cephalosporin) --Bactericidal Allergies & Nephrotoxic Superinfections, Alcohol Intorelance Bleeding, Serum Sickness Cephalexin -Lactam (1st Generation Cephalosporin) Oral Allergies Potentially nephrotoxic Cefazolin -Lactam (1st Generation Cephalosporin) Parenteral Allergies Potentially nephrotoxic Surgical Prophylaxis (for skin microbes) Bone Penetration 2nd Generation Cephalosporins -Lactam (2nd Generation Cephalosporin) --Bactericidal Allergies Potentially nephrotoxic Haemophilus, Enterobacter, Neisseria & PEcK Less Gram + than 1st Generation st Interactions Other Prophylactically by dentists Sinusitis, Pneumonia, Otitis, Meningitis, etc Clavulanic Acid overcomes -Lactamases Gram +; Proteus, E. coli, Klebsiella (PEcK) More resistant to -Lactamases Not effective on Listeria & enterococci Drug Class Use Side Effects Cefuroxime -Lactam (2nd Generation Cephalosporin) Parenteral Allergies Potentially nephrotoxic Cefuroxime axetil -Lactam (2nd Generation Cephalosporin) Oral Allergies Potentially nephrotoxic Cefoxitin -Lactam (2nd Generation Cephalosporin) Parenteral Allergies Potentially nephrotoxic Bacteroides, abdominal & gynecological sepsis Surgical Prophylaxis (for intestinal microbes) 3rd Generation Cephalosporins -Lactam (3rd Generation Cephalosporin) --Bactericidal Allergies Potentially nephrotoxic HENPEcK, Serratia, Enterics Less Gram + than 2nd Generation Ceftriaxone -Lactam (3rd Generation Cephalosporin) Parenteral Meningitis & Lyme Disease (DOC) Allergies Potentially nephrotoxic Gets in CSF, Penetrates bone Great for N. gonrrorhea; Longest t1/2 Excreted in bile (not renal) Cefixime -Lactam (3rd Generation Cephalosporin) Oral Allergies Potentially nephrotoxic Once Daily Dosing Ceftazidime -Lactam (3rd Generation Cephalosporin) Parenteral Allergies Potentially nephrotoxic Pseudomonas 4th Generation Cephalosporins -Lactam (4th Generation Cephalosporin) --Bactericidal Allergies Potentially nephrotoxic Very resistant to -Lactamases Less Gram + than 3rd Generation Cefepime -Lactam (4th Generation Cephalosporin) Allergies Potentially nephrotoxic Very resistant to -Lactamases Imipenem (+ Cilastin) Carbapenem Parenteral (IV) Reserved Enterobacter (DOC) GI Upset, rash Reaction at infusion site Seizures with renal insufficiency Gram + & - & Anaerobes Gets in bones & CSF, Renal Clearance Given with Cilastin to prevent inactivation Aztreonam Monobactam Parenteral (IV) Rash Transaminase Elevation Vancomycin Vancomycin Parenteral (Slow IV) Oral (for colitis) Reserved Red Man Syndrome Fever, Chills, Phlebitis, Tachycardia Hypotension, Shock, Flushing Allergies, Ototoxic, Nephrotoxic Metronidazole Nucleic Acid Synthesis Inhibitor Oral Bactericidal Bacteroides (DOC) Nausea, Headache, Vertigo Alcohol Intolerance Peripheral Neuropathy Fluoroquinolones & Quinolones Nucleic Acid Synthesis Inhibitor (Fluoroquinolones & Quinolones) Ciprofloxacin Nucleic Acid Synthesis Inhibitor (Fluoroquinolones & Quinolones) Interactions Gets into CSF, Long t1/2 Bronchitis, Pneumonias, Immunocomprimised Gram - Rods Renal Clearance Resistant to -Lactamases Aminoglycosides Prevents formation of polymers in cell wall Gram +, MRSA, Clostridium, Enterococci Renal secretion, Penetrates CSF with inflammation Fragments anaerobic DNA, must be reduced Gets into bone & CSF Liver & Renal Metabolism/Excretion; Enterocolitis Inhibit Gram - DNA replication; enters via porins Acts on gyrase/topoisomerase; Gets in Bone Mycobacteria, Weakly on anaerobes, Gram + --Bactericidal UTI (DOC) Anti-TB (2nd line) Other Nausea, Headache, Dizziness Nephrotoxic & Phototoxic; Arthropathy Not for pregnant or under 18, Seizures ↑ Theophylline ↑ Warfarin ↑ Cyclosporine NSAID ↑ Antacids ↓ Gram – Aerobes Only! UTI, Prostatitis, Pseudomonas in CF Synergystic with -Lactams Drug Class Use Side Effects Interactions Rifampin Nucleic Acid Synthesis Inhibitor Oral Bactericidal Anti-TB Makes body fluids red Hepatotoxic GI Upset, bleeding, flu-like ↓ Anticoagulants ↓ Contraceptives ↓ Glucocorticoids ↓ Estrogen Sulfonamide Metabolic Inhibitor (Sulfonamide) Oral & Suppository Bacteristatic Renal problems (parent drug secreted) Sulfamethoxazole Metabolic Inhibitor (Sulfonamide) Oral Suppository Nephrotoxicity (crystalluria), Allergies Not for pregnant & newborns (kernicterus) Anemia (G6PD) Trimethoprim Metabolic Inhibitor Oral Same as sulfa Bad for AIDS w/ PCCP (Stevens-Johnson) Permanent renal damage if ↓ function Binds DHF reductase ;Concentrates in prostate & vaginal fluids; UTI, prostatitis, genital infxns, Legionella, Salmonella, “anythingitis” & PCCP Aminoglycosides Protein Synthesis Inhibitor Aminoglycoside --Bactericidal (Bacteriostatic for TB?) Post-antibiotic effect Enters porins & requires O2 , DNA Misreading, Inhibit ribosomes on aerobic bacteria only Penetrates bone, NOT CSF; Renal excretion Streptomycin Protein Synthesis Inhibitor Aminoglycoside Parenteral Anti-TB Vestibular damage/fetal hearing loss Neuromuscular paralysis (w/ ↑ doses) 2nd line TB, plaque, Tularemia (+penicillin) Resistance is a problem; Doesn’t cross BBB Binds 30S, not metaboolized Gentamycin Protein Synthesis Inhibitor Aminoglycoside Parenteral Ototoxicity (worst of all aminoglycosides) Nephrotoxicity, vestibular damage Neuromuscular paralysis (w/ ↑ doses) Endocarditis (+ -Lactam); Severe UTI Pseudomonas, Klebsiella, Proteus, Serratia, brucellosis, tularemia, peritonitis; Binds 30 & 50S Tobramycin Protein Synthesis Inhibitor Aminoglycoside Parenteral Ototoxicity, nephrotoxicity vestibular damage Neuromuscular paralysis (w/ ↑ doses) Similar to gentamycin, better w/ Pseudomonas Less w/ Serratia & enterococci Oftened combined with -Lactam; Binds 30 & 50S Tetracyclines Protein Synthesis Inhibitor Tetracycline --Bacteristatic Bones & Teeth, Hepatotoxic, GI upset Not for pregnant or children, Phototoxic Binds 30S of ribosome, blocks tRNA access Gram + & -, anaerobes, rickettsiae, Chlamydia, Legionella, Plasmodia, Gets in bones & CSF Tetracycline Protein Synthesis Inhibitor Tetracycline Doxycycline Protein Synthesis Inhibitor Tetracycline Oral Macrolides Protein Synthesis Inhibitor Macrolides Bacteristatic (some cidal) Erythromycin Protein Synthesis Inhibitor Macrolides Oral Parenteral (IV) Chlamydia UG infections (DOC) Clarithromycin Protein Synthesis Inhibitor Macrolides Azithromycin Protein Synthesis Inhibitor Macrolides Oral Rickettsias, cholera, Borrelia (DOC) Inhibits RNA Pol; Deacetylation for activation Gram + & -, Mycobacteria, N. meningitides; CSF Hepatic metabolism, enterohepatic recirculation Binds dihydropteroate synthetase (similar to PABA) Actinomycetes, Chlamydia, E. coli, Proteus, Strep H. influenza, PCC; Enters CSF, Liver Metabolized Methenamine ↑ Anticoagulants ↑ Anticonvulsants ↑ Hypoglycemics UTI, Otitis, Bronchitis, Sinusitis, PCC Pneumonia Trachoma, Nocardiosis Often combined with Trimethoprim Bones & Teeth, Hepatotoxic, GI upset Not for pregnant or children, Phototoxic Antacids ↓ ↓ Birth Control ↑ Anticoagulants Liver metabolism,renal excretion Chlamydia, Mycoplasma, Brucella, Tularemia, Acne Bones & Teeth, Hepatotoxic, GI upset Not for pregnant or children, Phototoxic Antacids ↓ ↓ Birth Control ↑ Anticoagulants Liver metabolism, Hepatic excretion Clindamycin Chloramphenicol Irreversibly bind 50S, inihibits translocation Same spectrum as Penicillin G, Mycoplasma, Chlamydia, Neisseira, Haemophilus, Legionella GI Upset (direct stimulation) Ototoxicity, not for hepatic disfxn pts Allergic Rash Ototoxicity Legionella (DOC) Other Ototoxicity ↑ Warfarin ↑ Steroids ↑ Digoxin ↑ Carbamexzapime Others ↑ Warfarin ↑ Steroids ↑ Digoxin ↑ Carbamexzapime Others Destroyed by gastric acid (coated), Hepatic elimination; Penicillin alternative Inhibits P450 Improved acid stability, same as above & Toxoplasma, M. leprae & avium, longer t1/2 Less GI upset, renal elimination, Inhibits P450 Similar to above; once/day dose; well tolerated Less GI upset, Few interactions Doesn’t inhibit P450 Drug Class Use Side Effects Interactions Clindamycin (Cleocin) Clindamycin Oral (well absorbed) & Parenteral Bactericidal Anaerobic Infections (DOC) Diarrhea, Colitis, ↓ hematopoietic Inhibits NMJ Chloramphenicol Macrolides Binds 50S, prevents translocation Gram + & - anaerobes; Gets in bone Metabolized in liver, excreted in bile Chloramphenicol Protein Synthesis Inhibitor Chloramphenicol Oral & Parenteral Bacteristatic S. typhi, Abscesses, Mixed Infections Gray Baby Syndrome, GI Upset ↓ Clotting (↓ Vitamin K), Allergies BM Depression, Black Tongue Macrolides Clindamycin Anticoagulants Anti-HIV meds Phenytoin Binds 50S, prevents bond formation Broad Spectrum, Gets in CSF Hepatic Metabolism (glucuronate), renal secretion Synercid (Quniupristin/ Dalfopristin) Protein Synthesis Inhibitor Streptogramin Parenteral (slow IV) Bacteristatic (some cidal) Reserved for resistant Gram + Pain & Phlebitis at infusion site Arthalgias & Myalgias ↑ Calcium Blockers ↑ Cyclosporine Binds two sites on 50S, prevents translocation Gram +, Few Gram – (Moraxella & Neiserria) Hepatic elimination (conjugation) Linezolid Protein Synthesis Inhibitor Linezolid Oral Bacteristatic (some cidal) Reserved for resistant Gram + Thrombocytopenia, GI Upset, Headache Rash Prevents formation of f-met tRNA w/ 70S Gram +; non-enzymatic oxidation Renal Elimination Isoniazid Tuberculocidal (Mycolic Acid Synthesis Inhibitor) Oral Peripheral Neuritis (Vitamin B6) Rash, fever, hepatotoxic Hypersensitivity Crosses BBB/CSF; Excreted in urine Metabolized by N-acetyl transferase Pyrazinamide Tuberculocidal (Mycolic Acid Synthesis Inhibitor?) Oral Hepatitis Hyperuricemia Bacteriostatic Resembles Nicotinamide; Crosses BBB Metabolized in liver; renal excretion Ethambutol Tuberculocidal Oral Optic Neuritis (blurring, loss of green) Anaphylaxis, Dermatitis, Anorexia Nausea CSF Distribution less than serum; Not metabolized Must be monitered for visual acuity since optic neuritis is reversible Rifapentine Rifamycin Similar to Rifampin Similar to Rifampin Similar to Rifampin Easier dosing than Rifampin (once weekly) Ofloxacin Fluoroquinolone Tuberculocidal (2nd Line) GI Upset, Photosensitivity CNS Effects Inhibits DNA Gyrase Bacteriocidal Kanamycin Tuberculocidal (2nd Line) IM Ototoxic Renal toxic Bacteriostatic Capreomycin Tuberculocidal (2nd Line) IM Ototoxic Renal toxic Bacteriostatic Ethionamide Tuberculocidal (2nd Line) Inhibitor of mycolic acid synthesis? Bacteriostatic Few Drug Interactions Cycloserine Tuberculocidal (2nd Line) Competes with D-Alanine in protein synthesis Bacteriostatic p-amino-salicylic acid Tuberculocidal (2nd Line) Competetive inhibitor of PABA/Folate Synthesis Clofazamine Tuberculocidal (2nd Line) Oral GI Effects Crystalline deposits in intestine Other Slow bacteriocidal effect on M. leprae Drug Class Use Side Effects Interactions Other Zanamavir Antiviral (Influenza A) Antiviral (Influenza A) Oral inhalation Few Inhibits neuraminidase Can shorten or prevent symptoms Amandtidine Antiviral (Influenza A) Antiviral (Influenza A) Anti-Parkinson’s Anticholinergic effects Prevents viral uncoating Prevents infections of Influenza A Prone to drug resistance Rimantidine Antiviral (Influenza A) Antiviral (Influenza A) Anti-Parkinson’s Anticholinergic effects Prevents viral uncoating Prevents infections of Influenza A Prone to drug resistance Acyclovir Antiviral (Herpes) Antiviral (Herpes) Oral or Parenteral (IV) Inhibits viral DNA synthesis, chain elongation Renal clearance, requires Thymidine Kinase Guanosine analog, binds viral DNA Polymerase Valacyclovir Antiviral (Herpes) Antiviral (Herpes) Oral Preffered over acyclovir for genital herpes & VZV Valine ester of acyclovir, better absorption Ganciclovir Antiviral (Herpes) Antiviral (Herpes) Oral Preferred for treatment of immunosuppressed Guanasine analog More effective against CMV than acyclovir Vidaribine Antiviral (Herpes) Antiviral (Herpes) Oral Purine nucleoside analog Inhibits viral DNA Polymerase & ribonucleotide reductase Ribavrin Antiviral (Herpes) Antiviral (Herpes) Oral inhalation Guanosine analog; only approved for RSV Both DNA & RNA viruses Inhibits polymerases & 5’ capping Ziduvidine Antiviral Reverse Transcriptase Inhibitor Antiviral (HIV) Oral Pyrimidine analog, targets reverse transcriptase Gets in CSF, renal elimination Lacks 3’ OH – Chain Terminator ddInosine Antiviral Reverse Transcriptase Inhibitor Antiviral (HIV) D4T Antiviral Reverse Transcriptase Inhibitor Antiviral (HIV) 3TC Antiviral Reverse Transcriptase Inhibitor Antiviral (HIV) Azidiuridine Antiviral Reverse Transcriptase Inhibitor Antiviral (HIV) Neviripine Antiviral Non-nucleoside RTI Antiviral (HIV) Delaviridine Antiviral Non-nucleoside RTI Antiviral (HIV) Blocks active site of reverse transcriptase Blocks active site of reverse transcriptase Side Effects Interactions Other Drug Class Use Loviride Antiviral Non-nucleoside RTI Antiviral (HIV) Phosphonophormate Antiviral Non-nucleoside RTI Antiviral (HIV) Blocks active site of reverse transcriptase Pyrophosphate analog Saquinavir Antiviral Protease Inhibitor Antiviral (HIV) Inhibit cleavage of pol & gag proteins by protease Progeny virions lack ability to reproduce Indinavir Antiviral Protease Inhibitor Antiviral (HIV) Inhibit cleavage of pol & gag proteins by protease Progeny virions lack ability to reproduce Ritonavir Antiviral Protease Inhibitor Antiviral (HIV) Inhibit cleavage of pol & gag proteins by protease Progeny virions lack ability to reproduce T20 Antiviral Fusion Inhibitor Antiviral (HIV) Parenteral (IV) Blocks HIV entry Binds coil domain on gp41 Miconazole Imidazole Sterol Synthesis Inhibitor (Lanosterol Demethylase Inhibitor) Antifungal TInea corporis, Tinea pedis, Vaginal Candidosis Altered drug metabolism/sterol synthesis Teratogen Burning, Itching, Irritation Fluconazole Triazole Sterol Synthesis Inhibitor (Lanosterol Demethylase Inhibitor) Antifungal; DOC = Candidosis DOC = Cryptococcal Meningitis DOC = Coccidiodal Meningitis Altered drug metabolism/sterol synthesis Teratogen Nausea, Vomiting, Rash Antifungal Itraconazole Femstat Antifungal Tioconazole Vagistat Antifungal Oxiconazole Allyamine Sterol Synthesis Inhibitor (Squalene Epoxidase Inhibitor) Antifungal Tinea Infections Nail Infections Bronchial Aspergillosis? Slower metabolism; Less effect on human sterols Crosses BBB Inhibits P450 Spectrazole Antifungal Butoconazole Warfarin Cyclosporine Phenytoin Lovastatin Protease Inhibitors Lotrimin, Mycelex Antifungal Econazole Topical use only Similar to fluconazole Sporanox Antifungal DOC = Oral Fungal Infections Clotrimazole Terbinafine Blocks active site of reverse transcriptase Oxistat Allergic reactions if given orally Not for use if hepatic impairment Dose adjustment for renal impairment Oral, Topical, Future use Systemically? Concentrates in skin and nails Drug Class Use Side Effects Interactions Other Amphotericin B Polyene Macrolide Fungal Membrane Disruption Systemic Administration (Broad Spectrum Antifungal) Fever, Chills, Allergic Reaction Renal Dysfunction, Hypotension, Hypokalemia, Anemia, Thrombophlebitis Binds ergosterol, Significant Renal Toxicity Not for oral use Nystatin Polyene Macrolide Fungal Membrane Disruption Oral Candidosis Topical Administration (Broad Spectrum Antifungal) Highly toxic if given IV Bitter Taste Minimal Oral Absorption Flucytosine Pyrimidine DNA & Protein Synthesis Inhibitor (Thymidilate Synthase Inhibitor) Oral Antifungal BM Depression Nausea, Vomiting, Diarrhea Requires cytosine specific permease, Crosses BBB Converted to 5-FU; Resistance via ↓ uptake Synergistic with Amphotericin B Griseofulvin Fungal Mitosis Inhibitor (Binds Microtubules) Oral Antifungal (Microsporum, Trichophyton & Epidermophyton) Drug Interactions Allergic Reactions, Headache, Nausea Liver Toxicity? Specific to fungi; Concentrates in skin Induces P450 Mechlorethamine Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrogen Mustard) Hodgkin’s Disease IV Myelosuppressive - Leukopenic Mucosal, Reproductive toxicicity Some Nausea, Vomiting & Anorexia Electrophile, reacts with nucleophiles (guanine N7) Most Reactive, short t1/2 Part of MOPP Regimen; CCNS Melphalan Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrogen Mustard) Myeloma, Breast, Ovary Oral & IV Electrophile, reacts with nucleophiles (guanine N7) Phenyl Stabilization, Longer t1/2 Amino Acid Derivative; CCNS Chlorambucil Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrogen Mustard) Oral & IV Electrophile, reacts with nucleophiles (guanine N7) Phenyl Stabilization, Least Myelosuppressive CCNS Cyclophosphamide Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrogen Mustard) Breast Carcinoma Lymphocytic Leukemia (ALL) Oral & IV Hemorrhagic Cystitis (treat w/ MESNA) Myelosuppression, Nausea, GI Ulcers Allopecia Electrophile, reacts with nucleophiles (guanine N7) Hepatic Metabolism, Part of FAC Regimen Toxicity due to Acryline; CCNS Carmustine Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrosurea) Lymphomas, Brain, Meningeal Leukemias IV BM Toxicity/Myelosuppression Lipophilic (Crosses BBB), Not cross resistant Most Useful CCNS Lomustine Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrosurea) Lymphomas, Brain, Meningeal Leukemias IV BM Toxicity/Myelosuppression Lipophilic (Crosses BBB), Not cross resistant CCNS Semustine Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrosurea) Lymphomas, Brain, Meningeal Leukemias IV BM Toxicity/Myelosuppression Lipophilic (Crosses BBB), Not cross resistant CCNS Streptozocin Cancer Chemotherapeutic Alkylating/Covalent Binding (Nitrosurea) Lymphomas, Brain, Meningeal Leukemias IV Renal/Hepatic Toxicicty Lipophilic (Crosses BBB), Not cross resistant Natural Nitrosurea, Little BM Toxicity CCNS Busufan Cancer Chemotherapeutic Alkylating/Covalent Binding (Alkyl Sulfonate) Chronic Granulocytic Leukemia Oral Cisplatin Cancer Chemotherapeutic Alkylating/Covalent Binding (Platinum Complex) Nephrotoxic - Irreversible Renal Fibrosis Worst Nausea, Vomiting & Anorexia of all Least myelosuppressive of Class Synergize with other cancer drugs Combination Therapy; CCNS Carboplatin Cancer Chemotherapeutic Alkylating/Covalent Binding (Platinum Complex) Nephrotoxic Least myelosuppressive Synergize with other cancer drugs Combination Therapy; CCNS CCNS Interactions Other Class Triethylenemelamine Cancer Chemotherapeutic Alkylating/Covalent Binding Ethlenimines CCNS Thiotepa Cancer Chemotherapeutic Alkylating/Covalent Binding Ethlenimines CCNS Hexamethylmelamine Cancer Chemotherapeutic Alkylating/Covalent Binding Ethlenimines CCNS Dacarbazine Cancer Chemotherapeutic Alkylating/Covalent Binding Triazine Hodgkin’s Disease Cancer Chemotherapeutic Alkylating/Covalent Binding Hodgkin’s Disease Carcinogenic? Part of MOPP Regimen Lipophillic – Crosses BBB CCNS Methotrexate Cancer Chemotherapeutic Antimetabolite/DNA Syn. Inhibitor Folic Acid Analog Choriocarcinoma, Lung, Breast ALL, Osteosarcoma Oral Myelosuppression, Nausea, GI Ulcers Cirrhosis (if chronic) Reduces Folate for A,G,T synthesis (DHFR) Combat toxicity with Leucovorin; CCS-S Doesn’t cross BBB, Cures Choriocarcinoma 5-Fluorouracil Cancer Chemotherapeutic Antimetabolite/DNA Syn. Inhibitor Pyrimidine Analog Breast Carcinoma IV Myelosuppression/GI Ulceration Unique Neurologic Toxicity Inhibit Pyrimidine Synthesis, Incorporated into DNA Thymidilate Synthetase Inhibitor, Part of FAC Reg Erratic Absorption;GI, Hepatic Degradation; CCS-S Cytarabine Cancer Chemotherapeutic Antimetabolite/DNA Syn. Inhibitor Pyrimidine Analog Acute Myelocytic Leukemia IV Mercaptopurine Cancer Chemotherapeutic Antimetabolite/DNA Syn. Inhibitor Purine Analog ALL, Immunosuppresives Antiviral, Gout IV Thioguanine Cancer Chemotherapeutic Antimetabolite/DNA Syn. Inhibitor Purine Analog IV Hydroxyurea Cancer Chemotherapeutic Antimetabolite/DNA Syn. Inhibitor Ribonucleotide Reductase Inhibitor Cervix, Head, Neck, Lung IV Myelosuppressive RNA Reductase Inhibitor; CCS-S (Rate limiting DNA in synthesis) Synergistic with Radiotherapy Vincristine Cancer Chemotherapeutic Natural Products/CCS Drugs Vinca Alkaloids Hodgkin’s Disease, Leukemia Breast Cancer IV ↓ Myelosuppresion & Epithelial ↑ NEUROTOXIC Anti-mitotic; binds tubulin, preventing polymerization Given IV (30% oral availability) Part of MOPP; CCS-M Vinblastine Cancer Chemotherapeutic Natural Products/CCS Drugs Vinca Alkaloids Hodgkin’s Disease Testicular Carcinomas Lymphomas ↑ Myelosuppresion & Epithelial ↓ Neurotoxic Part of ABVD CCS-M Vinorelbine Cancer Chemotherapeutic Natural Products/CCS Drugs Vinca Alkaloids Procarbazine Paclitaxel (Taxol) Cancer Chemotherapeutic Natural Products/CCS Drugs Use Side Effects Drug Part of ABVD Regimen CCNS Inhibit Pyrimidine Synthesis, Incorporated into DNA Improper stacking due to 2’-OH; CCS-S Erratic Absorption;GI, Hepatic Degradation Hyperuricemia Myelosuppressive (Gradual) Allopurinol Inhibitor of purine synthesis/HGRT Salvage CCS-S Inhibitor of purine synthesis/HGRT Salvage Less toxic than mercaptopurine CCS-S CCS-M Leukemia, Lymphoma, Breast & Testicular Cancer IV Myelosuppression Anti-mitotic; stabilizes microtubules, prevents depolymerizatrion; Hepatic metabolism Antagonized by anti-metabolites; CCS-M Use Side Effects Interactions Other Drug Class Doxorubicin (Adriomycin) Cancer Chemotherapeutic Natural Products/CCS Drugs Antibiotic Hodgkin’s Disease Solid Breast and Ovarian Cancers Myelosuprresive Irreversible Cardiomyopathy Causes DNA Breaks, Part of ABVD & FAC Regimen Inhibits DNA Topoisomerase, Free Radicals Intercalates; CCS-S Phase? Bleomycin Cancer Chemotherapeutic Natural Products/CCS Drugs Antibiotic Hodgkin’s Disease Minimal Myelosuppressive Pulmonary Fibrosis Causes DNA Fragmentation. Complexes with FeO2 Combination Therapies, Part of ABVD Regimen CCS-G2 Phase? Actinomycin D Cancer Chemotherapeutic Natural Products/CCS Drugs Antibiotic Some Childhood Cancers Very Myelosuppressive DNA Intercalation, Inhibits RNA Pol II CCS-? Etoposide Cancer Chemotherapeutic Natural Products/CCS Drugs Epipodophyllotoxin Testicular Cancer Dose Limiting Myelosuppression From Mandrake (May Apple); Synergistic w/ Platins Stimulates DNA Topoisomerase to cleave DNA CCS-S-G2 Interface L-Asparginase Elspar Cancer Chemotherapeutic Natural Products/CCS Drugs Enzyme Hypersensitivity due to antigenicicty Only enzyme used for cancer Depletes asparagines (inhibits protein synthesis) Minimal BM & GI side effects Hydrocortisone Cancer Chemotherapeutic Hormone/Antihormone Adrenocorticosteroid Hematological Cancers Oral Metabolic/Catabolic Manifestations Changes in fat distribution, muscle mass Osteoperosis Dexamethasone Cancer Chemotherapeutic Hormone/Antihormone Adrenocorticosteroid Hematological Cancers Oral Metabolic/Catabolic Manifestations Changes in fat distribution, muscle mass Osteoperosis Prednisone Cancer Chemotherapeutic Hormone/Antihormone Adrenocorticosteroid Hodgkin’s Disease Hematological Cancers Oral Metabolic/Catabolic Manifestations Changes in fat distribution, muscle mass Osteoperosis Leuprolide Cancer Chemotherapeutic Hormone/Antihormone Androgen Deprivation Prostatic Carcinoma Changes in fat distribution, muscle mass Osteoperosis GnRH agonist inhibits androgen synthesis Not curative, but palliative Second choice after surgery Cyproterone Cancer Chemotherapeutic Hormone/Antihormone Androgen Deprivation Prostatic Carcinoma Changes in fat distribution, muscle mass Osteoperosis Androgen receptor antagonist Second choice after surgery Flutamide Cancer Chemotherapeutic Hormone/Antihormone Androgen Deprivation Prostatic Carcinoma Changes in fat distribution, muscle mass Osteoperosis Inhibits translocation of androgen receptor Second choice after surgery Tamoxifen Cancer Chemotherapeutic Hormone/Antihormone Estrogen Deprivation Mammary Carcinoma Changes in fat distribution, muscle mass Osteoperosis Hot Flashes/Nausea Competitive Inhibitor of estrogen receptors Given for metastases Interferon Cancer Chemotherapeutic Biological Response Modifier Interferon Hairy Cell Leukemia Activates T Cells, Macrophages, NK Cells Interleukin-2 Cancer Chemotherapeutic Biological Response Modifier Interleukin Kidney Cancer Modulates T Cell proliferation and generation of Killer T Cells Filgrastim Cancer Chemotherapeutic Biological Response Modifier G-CSF Receptor Mediated Immunosuppresion Receptor Mediated Immunosuppresion Receptor Mediated Immunosuppresion Part of MOPP Regimen Counters myelosuppresion during chemo for ↑ dose Stimulates Granulocytes Use Side Effects Interactions Other Drug Class Sargramostim Cancer Chemotherapeutic Biological Response Modifier GM-CSF Aprotonin Protease Inhibitor (Kallikrein Inhibitor) Cardiopulmonary Bypass Surgery Cortisol Glucocorticoid Acute Flare Ups Only Immunosuppressive CNS effects – Mood, behavior Na+ and fluid retention (hypertension) Work on Intracellular (DNA) Receptor Directly Inhibits COX Indirectly inhibits COX & Lox by ↓ Arachidonic Acid Prednisone Glucocorticoid Acute Flare Ups Only Immunosuppressive CNS effects – Mood, behavior Na+ and fluid retention (hypertension) Work on Intracellular (DNA) Receptor Directly Inhibits COX Indirectly inhibits COX & Lox by ↓ Arachidonic Acid Dexamethasone Glucocorticoid Acute Flare Ups Only Immunosuppressive CNS effects – Mood, behavior Na+ and fluid retention (hypertension) Work on Intracellular (DNA) Receptor Directly Inhibits COX Indirectly inhibits COX & Lox by ↓ Arachidonic Acid Cortisone Glucocorticoid Acute Flare Ups Only Immunosuppressive CNS effects – Mood, behavior Na+ and fluid retention (hypertension) Work on Intracellular (DNA) Receptor Directly Inhibits COX Indirectly inhibits COX & Lox by ↓ Arachidonic Acid Acetaminophen Central COX Inhibitor Antipyretic & Analgesic (Useful when aspirin contraindicated) Hepatic Toxicicty (esp. with alcohol) Not an NSAID; Poorly inhibits COX No platelet function No effect on acid/base or uric acid Aspirin NSAID (Carboxylic Acid – Salicylate) Integument Analgesic, Migraine Antipyretic, Antiinflammatory (↑ dose) Anticoagulant, Colon Cancer, MI Not for use with Peptic Ulcers; Reye’s Tinnitus, Deafness, Vertigo Alkalosis,Acidosis,Fever, Dehydration COX Inhibitor (Covalently modifies COX1 & COX2) Suicide Inhibitor of COX1 & stimulator of LOX Highly Dose Dependent – Not for Gout! Salicylic Acid NSAID (Carboxylic Acid – Salicylate) Methyl Salicylate NSAID (Carboxylic Acid – Salicylate) Indomethacin NSAID (Acetic Acid) Anti-inflammatory Gout Toxic Inhibits prostaglandin inflammation of Gout Inhibits macrophage urate phagocytosis Sulindac NSAID (Acetic Acid) Breast Cancer? Gastric Distress A prodrug – converted by P450 Decreased incidence of breast cancer in animals Etodolac NSAID (Acetic Acid) Toxic Some COX2 selectivity Mefenamic Acid NSAID (Fenamic Acid) High incidence of diarrhea Little clinical use Meclofenamic Acid NSAID (Fenamic Acid) High incidence of diarrhea Little clinical use Counters myelosuppresion during chemo for ↑ dose Stimulates Granulocytes & Macrophages From Bovine Lung Drug Tolmetin Ketorolac Diclofenac Class Use Side Effects Interactions NSAID NSAID NSAID Other Similar to aspirin, but better tolerated Analgesic Allergic Conjunctivitis Occular Inflammation Poor inhibitor of inflammation Approved for topical, parenteral & oral use Short Term Use only Rheumatoid Arthritis Osteoarthritis Ankylosing Spondylitis Ibuprofen NSAID (Propionic Acid) Antiinflammatory, Migraine Analgesic, Antipyretic Rheumatoid Arthritis & Osteoarthritis Naproxen NSAID (Propionic Acid) Rheumatoid Arthritis Osteoarthritis Migraine, Fever Fenoprofen NSAID (Propionic Acid) Ketoprofen NSAID (Propionic Acid) Flurbiprofen NSAID (Propionic Acid) Nimesulide NSAID (Propionic Acid) Antiinflammatory Poorly inhibits COX1 in seminal vessicles Celecoxib NSAID (Selective COX2 Inhibitor) (1st Gen) Rheumatoid Osteoarthritis Reduced gastric toxicity Rofecoxib NSAID (Selective COX2 Inhibitor) (1st Gen) Antiinflammatory Rheumatoid Arthritis Osteoarthritis & Acute Pain Piroxicam NSAID (Enolic Acid) Breast Cancer? Colchicine Plant Alkaloid (Autumn Crocus) Gout Diagnosic Gout (Inflammation Relief) Given <4 mg per week IV Diarrhea, Nausea, Vomiting, Hair Loss Abdominal Pain, BM Suppression Peripheral Neuritis & Myopathy Allopurinol Xanthine Oxidase Inhibitor Severe Gout & Renal Stones Nausea, Vomiting, Diarrhea, BM Allergies May induce Gout, BM Depression Hepatic/Renal Toxicity, Cataracts Probenecid Probenecid Uricosuric (Increases Uric Acid Excretion) Gout Not for use with kidney stones Increases gout Use with caution if peptic ulcers Salicilate Allopurinol Better tolerated than aspirin Also for Ankylosing Spondylitis & Dysmenorrhea Better tolerated than Indomethacin Especially good for menstral migraine prophylaxis As good as Methysergide for migraines GI & CNS Side effects Not for pediatric use Increased risk of CV thrombosis Renal Toxicity Inhibits the inducible COX-2 Longer t1/2 & smaller dose than Celecoxib (but qid) Extremely long t1/2 (57 hrs) Suppressed breast cancer growth in animal models Relieves pain & inflammation of gout, not analgesic Inhibits tubulin polymerization/LTB4 (Neutrophils) Greater than 8 mg is lethal Not effective during acute attack Designed to inhibit penicillin excretion Additive with Sulfinpyrazone Drug Class Use Side Effects Interactions Low doses ↑ urate reabsorption Gastric Distress & Peptic Ulcers ↑ Acetominophen toxicity, ↓ Hematopoiesis Other Salicilates Like Probenecid – inhibits urate reabsorption Must use a loading dose Aspirin Sulfinpyrazone Inhibits urate-anion exchanger in proximal tubule Metabolized to monobromine (active) Bile excretion; Well tolerated as daily dose Sulfinpyrazone Uricosuric (Increases Uric Acid Excretion) Gout Benzbromarone Uricosuric (Increases Uric Acid Excretion) Gout (Europe Only) Ergotamine/ Dihydroergotamine (DHE) Nonselective 5-HT Agonist Migraine Headache (DHE = Nasal Spray) (Ergotamine = Oral) Diarrhea, Oxytocic (not for pregnant) ERgotism: cramps, paresthesia, angina edema & ischemia; Causes dependency Sumatriptan Triptan (Selective 5-HT Agonist) Migraine Headache (SubQ or Nasal Spray) Coroncary Vasospasm (Not for CV Disease or HBP) Ergotamine MAOI SSRI Frovatriptan Triptan (Selective 5-HT Agonist) Migraine Headache (SubQ or Nasal Spray) Coroncary Vasospasm (Not for CV Disease or HBP) Ergotamine MAOI SSRI Structurally similar to Serotonin Faster onset than DHE, but higher recurrence Longest t1/2 of class Naratriptan Triptan (Selective 5-HT Agonist) Migraine Headache (SubQ or Nasal Spray) Coroncary Vasospasm (Not for CV Disease or HBP) Ergotamine MAOI SSRI Structurally similar to Serotonin Faster onset than DHE, but higher recurrence Longt t1/2, Renal Clearance, High oral bioavailability Rizatritan Triptan (Selective 5-HT Agonist) Migraine Headache (SubQ or Nasal Spray) Coroncary Vasospasm (Not for CV Disease or HBP) Ergotamine MAOI SSRI Structurally similar to Serotonin Faster onset than DHE, but higher recurrence Fastest onset of class Butorphanol Opiod Migraine Headache (Nasal Spray) Propranolol 1 & 2 antagonist (Nonselective Prototype) 2) Class II Anti-Arrythmic Migraines, Arrythmias & HBP DOC for A. Fib rate control 2nd choice V. Tach suppression Airway Disease Exacerbation ↑ Peripheral Vascular Disease Diabetic Hypoglycemia; ↓ CNS Fxn Migraine MOA not due to CNS or cardiac effects Slows AV node conduction ( ↑ PR interval) ↓ Ca2+ overload & DADs, May ↑ TGs & ↓ HDL Metoprolol Selective 1 antagonist Migraine Headaches CHF & Hypertension Myocardial Ischemia ↓ CNS Fxn Migraine MOA not due to CNS or cardiac effects May ↑ Triglycerides & ↓ HDL Amitriptyline Tricyclic Antidepressant (TCA) Migraine Headache Depression Drowsiness, Weight Gain Anticholinergic Problems Methysergide 5-HT Agonist/Antagonist Migraine Headache Fibrosis Valproate/Divalproex Anticonvulsants Migraine Headache Weight Gain, Hair Loss, Tremor Teratogen (Neural Tube Defects) Metoclopramide Agonist or antagonist at 5HT, D2 & Adrenergic If oral, given with caffeine to ↑ absorption Given with metaclopramide for GI Upset Structurally similar to Serotonin Faster onset than DHE, but higher recurrence Self administered rapid pain relief 5-HT Antagonist in periphery, Agonist in CNS Don’t use for > 6 mos without 3-4 week “holiday” Only for not responsive to other prophylactics Drug Class Use Minor Use (10%) SCID (c gene) Side Effects Mutagenesis/Cancer (Leukemia?) Recombination with other retroviruses Interactions Other Requires target cells to have a specific receptor Only integrate into dividing cells Expression is long term; Particles quickly degraded Retrovirus Gene Therapy Virus (RNA Virus) Adenoviruses Gene Therapy Virus (DNA Virus) Conditionally Replicating Adenoviruses Gene Therapy Virus (DNA Virus) Cancer (ONYX-015) Replication-Defective Adenovirus Gene Therapy Virus (DNA Virus) DMD Less Immune Response Lacks viral genes; Packaged via helper cells Uses creatine kinase promoter (muscle specific) Adeno-associated Virus Gene Therapy Virus (DNA Virus) Minor Use (10%) Cystic Fibrosis (CFTR gene) DMD Limited size capacity for genes High Titers of pure virus is hard to get Mutagenesis/Cancer; Semen Infection? Requires 3 plasmids & helper virus (more work) Can infect wide range of cells Virus integrates into genome – Long Term Cationic Liposomes Gene Therapy Non-Viral Vector Cystic Fibrosis (CFTR gene) Naked Plasmid Gene Therapy Cardiovascular Disease (VEGF-2) Erythropoietin DNA Vaccine Ex Vivo Myoblast Transplant Gene Therapy DMD Major Use (40%) Inflammatory & Toxic Immune Response Cystic Fibrosis (CFTR gene) Viral Particles may be neutralized Cancer (ONYX-015), Erythropoietin Not long term Controlled via helper protein requirement Can infect any cells, High Titers Inflammatory & Toxic Immune Response Viral Particles may be neutralized Not long term Controlled via helper protein requirement Can infect any cells, High Titers Selectively lyses p53 deficient cells Relatively safe & noninfectious Not specific ,Transient Immune Response? Plasmid coated with lipophilic molecules Poorly understood; Doesn’t integrate No size limit; could use interfering RNA Low cost? Only transient expression Few cells survive, Large gene size Dystrophin expression lost Immune Response Uses retrovirus infection in culture then transplanted
