Penicillins

Bacterial: Cell wall synthesis

β -lactam. Bactericidal. Combination between L-cysteine and D-valine  resemble D-Ala-D-Ala terminus. Acylate active site of transpeptidase (enzyme recognizes β -lactam)  inactive. Bacteria with β -lactamase will cleave acylation. Autolysins (murein hydrolyases) nick cell wall. Good for gram+ cocci and bacilli. Extended spectrum: also for grambacilli. Actively secreted by proximal tubule  short half-life. Add probenecid to block active renal secretion (competitive inhibitor). Toxicity: Anaphylactic/allergic response via IgE  bronchospasm, urticaria, shock, rash. Diarrhea via destroying natural GI flora. Group I: penicillin G (benzylpenicillin), penicillin V (phenoxymethylpenicillin). Narrow spec, penicillinase-sensitive. Penicillin G has two depot forms for deep IM injection: procaine, benzathine suspensions. Crystalline form increases half-life. Lowest MIC so drug of choice for G+c, G+b, G-c. β -lactam ring is acid labile  need parenteral. Inhibits GABA-gated chloride ion flux. Penicillin V more stable at acid pH. Good for oral administration. Group II: methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin. Narrow spec, penicillinase-resistant, “antistaphylococcal,” bulky sidechains. Methicillin, nafcillin, oxacillin: IV. Oxacillin acid stable. Cloxacillin, dicloxacillin: oral. Used for gram+ only (S. aureus). Methicillin causes nephrotoxicity  no longer used. MRSA bacteria overcome penicillinase-resistant drugs  use vancomycin. Nafcillin is drug of choice for S. aureus: cellulitis, endocarditis, sepsis. Group III: ampicillin, amoxicillin (aminopenicillins). Broad spec, penicillinase-sensitive. Good for Proteus, Haemophilus, Salmonella, E. coli, Enterobacteriaceae, H. pylori. One of the few drugs for gram+ enterococcus. Good for URI infections from S. pyogenes, S. pneumoniae, H. influenzae. Ampicillin is acid-stable but absorption is affected by food intake  variable. Often give with gentamicin: “Amp-gent.” Gives broader spec. Amoxicillin is acid stable, absorbed by GI tract. Spectrum extended to G-b. Drug of choice for Listeria. Group IV Carboxypenicllins: carbenicillin (prototype), carbenicillin indanyl, ticarcillin. Carbenicillin high dose  high soium load, plately dysfunction, hypokalemia. Ureidopenicillins: piperacillin, azlocillin, mezlocillin. “Antipsedumonal,” penicillinase-sensitive. Good for P. aeruginosa, Enterobacteriaceae, Bacteroids. β -lactam. Irreversibly bind to and inhibit class A, C, D β -lactamases (plasmid encoded). Inactive against chromosomal (class B) β -lactamases. Weak intrinsic activity so use with penicillin’s. Covers β -lactamases of G+ and G- bacteria. Most active for plasmid-

vomiting. ceftibuten. Enterococcus. M. Same spec as third generation but some β -lactamase resistance. Administer with cilastatin—inhibits dehydropeptidase-1. cephalexin. cefotetan. loracarbef. Narrow spec. Thienamycin: chemically unstable. Cephalothin: deacetylated by liver esterases to less active metabolites. Later generations gain G. Use with community-acquired bacterial pneumonia if you don’t know cause. Toxicities: IgE-mediated immune reaction with rash. cefmetazole have anaerobic coverage: B. Proteus. Cephalexin and cefradoxil: effective orally. Meropenem.bacilli. ceftazidim. Binds PBP’s. Serratia. . Other two are byproducts of it. Prolong prothrombin time due to MTT group. Klebsiella. Cefpirome not in U. aeruginosa. cefazolin. ceftizoxime. aeruginosa. Cefotetan. Nausea. cefdinir. Ceflacor: oral administration. cefaclor. community pneumonia. cefprozil. First generation: cephalothin. Good for S. seizures. Streptococci. Second ring has C instead of S (penicillin has S).Cephalosporins (Class of Penicillin) Bacterial: Cell wall synthesis Carbapenems β -lactam. Hydrolysis product is a toxic metabolite.S. Broad spec. bactericidal.. β -lactam. catarrhalis). Ceftazidine. Good for G-r: E. good for G. Enterobacter. Inhibit platelet aggregation. coli. good for G+. Same strep activity. Imipenem. cephradine. cephapirin. Good for P. Bactericidal. Cefuroxime: sinusitis and otitis media (from H. cefadroxil. cefoperzone. Klebsiella. meningitis. Synergistic nephropathy with aminoglycosides. Resistance: cephalosporinases. cefoxitin. Fourth generation: cefepime. Intolerant to alcohol. ceftriaxone. cefuroxime. cefepime are only ones for P. Resistant to β -lactamases. Resistant to dehydropeptidase-1. cefoperazone. Broadest spectrum of all Abx. Good for Pseudomonas. cefpodoxime. Hydrolyzed by dehydropeptidase-1 in kidney brush border  short half-life. cefpirome. fragilis. can cause superinfections.but lose G+ activity. MRSA. Very resistant to most β -lactamases. aureus. Third generation: cefotaxime.organisms but not as much for G+ organisms. Acyl-enzyme isomerizes from eneamine to imine  slower to hydrolyze. cefonicid. cefoxitin. influenza. Shouldn’t be used first: expensive. block nephrotoxicity. Broad-spectrum: gram+ cocci and gram. Treatment of pyelonephritis from UTI. cefmetazole. Intermediate spec. Don’t give to patients with reactions to penicillin: cross-reactivity. enterococci. Second generation: cefamandole. cefixime. Hemophilus.

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urticaria. CNS dysfunction (depression. difficile colitis. . Bind to D-ala-D-ala terminus of peptidoglycan. Structure resembles D-ala. Good for G+ and G. Reserved for MRSA. Good for G+ bacteria. Inhibit dephosphorylation of bactoprenyl diphosphate (used to transfer NAG-NAMpentapeptide subunits across cell membrane to cell wall). Rapidly bactericidal. Toxicity: Rapid infusion causes histamine release. Systemic toxicity: nephrotoxicity  proteinuria. Available in Europe but not in U. patients allergic to β -lactams. Good for G+ bacteria. nitrogen retention. psychoses)  use as second choice for T. UTI’s (concentrated in urine). Good for G+ and G. Use IV. Binds PBP’s  make long filamentous structures in bacteria. Neosporin: bacitracin + neomycin (aminoglycoside. hematuria. Can be given IM. Resistant acquired: chromosomal or plasmid. Thrombophlebitis and pain at site of IV injection.bacteria. including MRSA and VRE. Inactive against G. Use as a combo if you also are treating G+: add vancomycin or clindamycin. Inhibit alanine racemase (convert L-ala to D-ala) and D-ala-D-ala ligase. Forms covalent adduct to transporter used in formation of muramic acid.Monobactams Vancomycin Bacterial: Cell wall synthesis Teicoplanin Fosfomycin (Phosphonomyci n) Bacitracin Cycloserine Bacterial: Cell membrane function Daptomycin β -lactam. Renally cleared.B.B. Neisseria. tachycardia. Resistant bacteria have D-ala-D-lac instead (i. Excreted renally by filtration. Orally not absorbed  use for S.bacteria. Bacterial resistance: shut down transferase and use glutathione transferase. enterocolitis. IM causes intense pain. MRSE. hypotension.S.outer membranes). Nephrotoxic: decrease renal function if not excreted by kidney (toxic cycle). G-) + polymixin B (detergent for G. Good for G+ bacteria. vanA: catalyze formation of D-ala-D-lac. Good for G-R but inactive for G+ bacteria and anaerobes (magic bullet for G-). Lactobacilli). C. Used almost exclusively for T. Bind to D-ala-D-ala terminus of peptidoglycan. from conjugation. Oral and parenteral. usually unmetabolized.e. Analog of phosphoenolpyruvate. Cyclic lipopeptide. GI superinfection.bacteria.S. Topical use only (external wounds). Single-ring structure: only binds to transpeptidase of G-. Only oral used in U. Ototoxicity (partial hearing loss at high frequencies) if excessive in serum. Aztreonam. Resistant to β -lactamases. flushing (“red man/neck”). Good to use for patients allergic to penicillins and cephalosporins. Good for all G+ bacteria. Oral bioavailability = 40%. Dose-dependent toxicity: peripheral neuropathy. Alters membrane electrical charge and transport.

GI irritation are common.Bacterial: Reversibly inhibit protein synthesis via 30S or 50S Chloramphenico l Oxazolidinones (Linezolid) Bacteriostatic (can be bactericidal at higher concentrations). not dose-related. Free hydroxyl groups needed for activity. hypothermia. Serious and fatal dyscrasias  reserve use for meningitis. Used mainly for MRSA. clindamycin. mild GI disturbances. only one isomer is active. Two asymmetric centers. Can use for bacterial meningitis when cause is unknown. crosses placenta. typhoid fever. Faster onset than vancomycin. Irreversible. ribosomes frozen in place (polysomes). Abdominal distention. usually delayed in onset. Binds to mammalian cell ribosomes. Broad-spectrum. Use for RMSF of young children and pregnant women (tetracycline toxic). Irreversible type wipes out bone marrow  aplastic anemia. stop if you see leucopenia. cyanosis. Gets to brain and CSF. Antagonist with macrolides. irregular resp. Toxicity: Thrombocytopenia. Try not to use that much. May be genetically linked. vomiting. Glucoronide conjugate and hydrolysis products excreted via tubular secretion. anemia. G-. Binds 50S  block initiation via blocking ribosomal assembly. Good for Gram+. Metabolized via conjugation with glucoronic acid in liver (not toxic but inactive). anaerobes. Hepatic insufficiency  increased half-life. Parent compound cleared by glomerular filtration (10%). Aplastic anemia: 70% of dyscrasias. vasomotor collapse (can be fatal). VRE. Sometimes reduce cell permeability or affinity of 50S binding site. . High oral bioavailability  good for outpatient use. Blurred vision. Binds 50S  can’t form peptide bonds. Toxicity (rare but severe): Bone marrow depression: due to mitochondrial protein inhibition. aerobes. neutropenia. Good for G+. Resistance: Mostly enzymatic acetylation. digital parasthesias. Heaches. Reversible type is dose-related. Well-absorbed from GI. erythropoietic cells very sensitive. Can also give via IV. Gray baby syndrome: insufficient glucuronyl transferase  don’t clear. Only for hospitalized patients. typhus. Inhibits P450.

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intra-abdominal infections. PeptoBismal. aerobes. . oxytetracycline. Proteus. Used in complicated skin and soft tissue infections. Block translocation of elongating peptide. minocycline. Superinfection due to broad-spec  oral thrush. Arthralgia/myalgia (40%). Used for Chlamydia. Permanent staining of growing teeth (pregnant women and children). Intermediate-acting: demeclocycline. Binds 50S. Can have induced bacterial degradation of tetracyclines. Mg. Used for MRSA. CSF. Al3+): chelation. Common GI upset.antacid. Pain at infusion site (40%). GI irritation from oral administration. chlortetracycline.S. Less from di. Usually adequately absorbed in GI. yeast infections. Group A: dalfopristin. acne. Upregulation of efflux pump TetA. Al-. not faecalis). G+ bacteria have lower MIC but develop resistance quicker. Broad-spectrum: gram+ cocci and gram.Tetracyclines Bacterial: Reversibly inhibit protein synthesis via 30S or 50S Streptogramins Bacteriostatic. Decreased access to ribosome: ribosome protection proteins. transport for uptake. Doxycycline chelates cations poorly  absorbed better with food. Methacycline not in U. Minocycline and doxycycline most active by weight. Rarely used.valent metals (Ca2+. Less from milk. Four fused rings with electron-negative O for chelating Ca. Toxicity (nasty drug—use only when necessary): Hyperbilirubinemia (3-35%). glycycline class. Gets to all tissues and fluids. pneumoniae. Mg2+. Genes for resistance carried on plasmid (inducible). Resistance frequent  usually don’t use for G+ cocci infections. Al. Fe. Rickettsia. Large polyunsaturated non-peptide ring. Can inhibit mammalian protein synthesis. placenta. Chlortetracycline: basis for deriving tetracycline. and/or downregulation of influx. but have selective toxicity: Bacterial ribosomes have higher affinity. Distort ribosome  no tRNA binding. Binds 30S (16s rRNA)  block tRNA binding to A site. Thrombophlebitis from IV administration. aeruginosa. walking M.or tri. Short-acting: tetracycline. Deposited in bones  40% depression of growth in premature infants. Liver dysfunction: lethargy. Resistance: P. VRE (faecium only. Ca. Cyclic peptides. glomerular filtration. Excreted via bile and feces (accumulates in liver).bacilli. methacycline. Decomposes in solution  dissolve just before use. Group B: quinipristin. Fe3+. Tigecycline: derivative of tetracycline. Brucella. Active against MRSA and VRE. iron supplements. jaundice from large doses. Long-acting: doxycycline. Toxicity: Fanconi syndrome: renal dysfunction due to outdated preparations. Photosensitivity: less time to develop sunburn. Administer as sodium or HCl salts: more water soluble. Good for Gram+.

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Clearance mostly by N-demethylation and conversion to sulfoxide. Most useful for M. Discontinue drugs and treat with metronidazole or vancomycin. clarithromycin. nausea. Clarithromycin: first-pass metabolism to active metabolite. Abdominal pain. Azithromycin: concentrated within cells (phagocytes). Erythromycin inhibits CYP450  inhibit metabolism of other drugs. 5x risk of cardiac death (long QT) if combined with another inhibitor of CYP3A.e. placenta. Can be lethal. clindamycin. Bacteriostatic. Toxicity (generally low): GI: erythromycin stimulates motility  cramps. but doesn’t penetrate mitochondria  fine. fragilis. Superior to macrolides for anaerobes. Don’t use for S. Unstable at acid pH. pneumoniae. Mostly excreted via bile and feces. Doesn’t get to CSF and CNS. Resistance: usually decreased binding affinity to 50S. 10% excreted unmetabolized.01-10%) from C. telithromycin (ketolide). Binds 50S (antagonist to macrolides. no pathogens. diarrhea. Erythromycin (prototype). Binds 50S (23S rRNA site. ester (ethylsuccinate). Resistance: cross-resistance with macrolides due to ribosomal methylation by erm. Tissue fibroblasts are reservoir  half-life increased to 40-68 . Toxicity: Diarrhea (2-20%). Esters inactive until hydrolyzed in blood. T. Allows for 6-8 peptide tRNA build-up before elongation is blocked. Good for gram+ cocci and bacilli (accumulates 100x more drug than Gram-). mucoid/bloody stools. L. fever. pneumophila. IM administration  severe and persistent pain. Lincomycin (no longer used). more common in children. Strains resistant to clindamycin often resistant to macrolides. Macrocyclic lactone ring of 12-16 atoms. Good for Gram+. Can be bactericidal in high concentrations. difficile toxin. Can relapse. Used as a substitute penicillin if allergic to β -lactams. vice versa. azithromycin. diarrhea. Coat or give as salt (stearate). Dose-related. puromycin. PMNs. septic abortions). estolate (lauryl sulfonate or propionyl ester). E tunnel)  inhibit translocation. Gets to everything except CNS.Lincosamides (Clindamycin) Bacterial: Reversibly inhibit protein synthesis via 30S or 50S Macrolides Bacteriostatic. Skin rashes (10%. Pseudomembranous colitis (0. Can detect using barium enema and air contrast enema. Gets to bone and fibrous CT  used for staph osteomyelitis. Can inhibit mitochondrial ribosome. gondii. Food delays absorption. B. Erythromycin has more side effects  not used as much as others. aureus: concern of resistance. vomiting. more common with HIV). Antagonistic binding to chloramphenicol. carini. White/yellow plaques on mucosa of colon: fibrinoid. CSF. chloramphenicol). anaerobes. unmetabolized. Also for Chlamydia pneumoniae. Opioids (and others that inhibit peristalsis) prolongs condition. Also use for infections of female genital tract (i. Cholestatic jaundice from extended treatment of estolate (reversible). P.

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Use IM or IV (no IV for streptomycin). Block postsynaptic nAChR (weaker effect. Irreversibly inhibit protein synthesis. isosthenuria. phosphorylation. Degeneration of hair cells. Clearance varies  monitor blood levels to prevent toxicity. Enterococci. Potency: neomycin > kanamycin > amikacin > gentamicin > tobramycin. tobramycin.Bacterial: Alter protein synthesis via 30S Aminoglycoside s Bactericidal (concentration-dependent). usually reversible. congeners. may have some 50S sites as well. reversible). Two+ amino sugars connected to hexose core via glycosidic linkage. perilymph of inner ear. or fusion into giant hairs. neomycin. reversible. Initially have excretion of brush border enzymes. drifting eyes at end of movement. kanamycin. Streptomycin  8th nerve toxicity. Possible mechanisms: Block initiation  streptomycin monosomes. sloughing. endolymph. Amikacin is least susceptible to enzymatic modification. Bacteria can have plasmids encoding different inactivating enzymes. Gentamicin. Decreased drug uptake from altering bacterial active transport system. Worse for patients with myasthenia gravis and Parkinson’s. . kanamycin. Good for aerobic G. Half-life 2-3 hours  50-100 hours in aphrenic patients. Popular for nosocomials: P. From streptomyces: streptomycin. Not in anaerobes: needs bacterial electron transport to move into cell. amikacin have milder toxicity. low GFR. imbalance. Ototoxicity: damage cochlear and vestibular hair cells. Several binding sites on 30S. Acute tubular necrosis. Acetylation. Aminoglycosides lose affinity to ribosomes. neomycin. Not in CNS. Treat via Ca2+ IV administration (calcium salt). Can get into CNS if the meninges is inflamed (meningitis). Mostly vestibular: streptomycin and gentamicin. Irreversible with longer and higher doses (>7 days). vacuolize  myeloid bodies. Cationic  don’t bind to serum proteins. aeruginosa. dizziness (mostly vestibular). Aminoglycosides are cationic  don’t use in IV solution with anions (penicillins). Excreted via glomerular filtration (unmetabolized). proteinuria. Synergy with penicillins: break open cell wall so aminoglycoside can enter. Neuromuscular block: Block presynaptic Ca2+ channels (reversible). Drug stays in extracellular space (VD). Misread codons: Block translation and prematurely terminate. Concentrated in renal cortex. Postantibiotic effect: residual bactericidal activity below MIC  oncedaily doses.bacteria (most widely used). Later get vertigo. disrupt cell function  cell death. Get high-pitched tinnitus and hearing loss. necrosis. High plasma creatinine and BUN. Synergistic with other neuromuscular blockers: d-tubocurarine. Don’t cross human cell membranes well  not orally absorbed. adenylation. Resistance: Usually via enzymatic modification and inactivation. Make nonfunctional proteins. Neomycin: cells swell. Mostly auditory: amikacin. Toxicity: Nephrotoxicity is saturable.

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Nalidixic acid: oldest. DNA gyrase targeted in G. Most excreted renally. GI. levofloxacin. Ciprofloxacin good against Anthrax. Rapidly degraded in plasma. GI upset (3-17%): nausea. Goes through enterohepatic circulation. E. sparfloxacin. Ciprofloxacin increases seizures via inhibiting GABA. Use topically for Staph. aeruginosa. vomiting. CNS: headache. for G+ and G-. E. P. Chlamydia. Lomefloxacin. Treat and prevent traveler’s diarrhea. Clinafloxacin. dizziness. Synergistic with sulfonamides. Respiratory. least active. coli. Monitor liver function tests. enoxacin. S. Mycobacterium. Gatifloxacin: hypo. aureus. Shiggella. S. gatifloxacin: better for G+. Strep. Folate reductase inhibitor (inhibit dihydrofolate reductase). P.000x higher affinity to bacterial than mammalian enzyme. moderate to good for G+. Excreted very rapidly  use for UTIs. GU. coli. extend spec to G+. Both excreted in urine.Bacterial: Nucleic acid metabolis m Fluoroquinolone s (Quinolones) Rifampin Mupirocin Bacterial: Intermediary metabolis m (Antifolate ) Trimethoprim Bactericidal. oflaxacin. Use 5x more sulfamethoxazole  eventually becomes 20:1 ratio (ideal). Moxifloxin. Very good against G-. Binds to A subunit (DNA strand cutting). . Inhibit bacterial growth at much lower concentration than for eukaryotes. 50. E. coli. DNA gyrase and topoisomerase inhibitor.bacteria. Salmonella. Broad-spec. UTI’s. Excreted non-renally  use for aphrenic patients. Good for Gram+ aerobes. Trovafloxacin: acute hepatitis and hepatic failure. Gets into bone  use for osteomyelitis from S. aureus. aeruginosa.B. anaerobes. Enterobacter. ciprofloxacin. Resistance: mutations in bacterial DNA gyrase subunits. section) Inhibits iso-leucyl-tRNA synthetase  can’t incorporate iso-leucyl into peptide. Paired together due to similar half-lives (9-11 hrs). Good for MRSA. Enhanced activity: Fluorine substitution at C6  increased against G. H. Salmonella. TMP lipid-soluble  goes everywhere. carinii. Potentiated by NSAIDs  seizures. Structural analog of pteridine of folic acid. SMX only in extracellular space. pefloxacin.glycemia. AIDS. delirium. trovafloxacin: better for G+. Less resistance. Bactrim: trimethoprim-sulfamethoxazole.and hyper. Tendonitis and tendon rupture (ciprofloxacin). Piperazine attached to C7  essential for P. May inhibit P450  drug interaction problems. influenzae. insomnia.bacteria. Topoisomerase IV targeted in G+ bacteria (separate DNA into daughter cells). Good for G+ and G-. (T. Most have very high oral bioavailability. Possible damage to growing cartilage + arthropathy  not for patients under 18. Toxicity: well-tolerated. pneumoniae. diarrhea. Sparfloxacin: half renal and half fecal excretion. Shigella.

sulfamethazine (“Triple Sulfa”) No longer available Sulfasalazine Sulfapyridine bonded to 5-ASA. Synergistic with sulfonamides. methionines. Sulfisoxazole.Pyrimethamine Folate reductase inhibitor (inhibit dihydrofolate reductase). Treat UTIs: highest water solubility and excreted unmetabolized. Sulfadiazine: crosses into CSF  bacterial meningitis. Splits via intestinal flora. Inhibit de novo synthesis of folic acid. Lose permeability to sulfonamides or active efflux Broad-spectrum: gram+ cocci and gram. Sulfisoxazole short-acting. erythema.A. Dihydropteroate synthase normally catalyzes reaction (not in mammals). Good for Actinomycetes. IBS. Hematopoietic acute hemolytic anemia. Resistance (rapidly develops): Increased intracellular PABA (less common). Toxicity: Crystalluria: acetylated metabolites of sulfamethoxazole and sulfadiazine precipitate in kidney tubules. Sulfadoxine: only long-acting still in use. sulfamerazine. Time to deplete folate stores Resemble PABA (p-aminobenzoic acid)—bound to pteridine and glutamate during folate biosynthesis  make fake analogs of folate. Selective toxicity: Mammals don’t make it—use dietary sources. aplastic anemia. Sulfonamides with folate reductase inhibitors: Bactrim: sulfamethoxazole + trimethoprim Fansidar: sulfadoxine + pyrimethamine (for chloroquine-resistant malaria) Sulfadiazine + pyrimethamine (for acute toxoplasmosis) Bacterial: Intermediary metabolis m (Antifolate ) Sulfonamides . Hypersensitivity: rashes. 5-ASA goes to colon  anti-inflammatory. External uses: Silvadine (silver sulfadiazine): pre vent and treat burns Sulfacetamide: eye or ear drops Sulfacetamide: lotion has drying agent for acne and other skin conditions Trisulfapyrimidines: sulfadiazine. drug eruption. sulfamethoxazole. A. Sulfapyridine can be toxic  Olsalazine is dimer of 5-ASA instead. Used for Chron’s disease. Effect delayed for several replication cycles after administration. Effects reversed by: High concentrations of PABA.’s  bacteriostatic. purine. purines.bacilli. Reduce via sodium bicarbonate. Enzymes have reduced affinity for sulfonamides (via R-factors). Folate needed as cofactor to make thymidine. agranulocytosis. sulfamethoxazole intermediate-acting. protozoal parasites. pruritis. serines (can be in pus). fever. Presence of thymidine. Mixed bactericidal/static. Clamydias. High affinity for plasmodial enzyme. enteritis. Bacteria don’t have transport system to uptake folic acid. malaise. Structural analog of pteridine of folic acid.

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Ethambutol. Clofazimine.B. . Unknown effect on fetus  don’t use in pregnancy.AntiTuberculosis Bacterial: AntiMycobacte r. Induces P450 system  decreased half-lives of others (i. Used primarily for MAI. Anti-Leprosy All cause hepatotoxicity: mild elevation of liver enzymes (15-20%). Cycloserine.: Para-aminosalicylic acid. Less hepatitis than INH. Alcohol increases metabolism of INH  more hepatotoxicity. Increases urinary excretion and depletion of Vitamin B6 (pyridoxine). Fixed-dose combinations: Rifamate: isoniazid and rifampin. Amikacin. Second-line drugs for resistant T. Less induction of P450. Anti-inflammatory. Kanamycin. oral contraceptives. Pyrazinamide. Interferes with biosynthesis of mycolic acid of cell wall. anti-convulsants. Rifampin. Avoid in pregnant women: congenital deafness. saliva. Rifater: isoniazid. Get into most tissues. coumadin. reversible ocular toxicity: decreased acuity and color vision. Not used in children: can’t report changes in vision. Dapsone. Rifampin. Binds to DNA. Resistance developing.e. Lesions will turn tan to black. Inhibits DNA-dependent RNA polymerase. pyrazinamide. Can color skin and conjunctiva red. tears. including center of caseous granulomas. Quinolones (levofloxacin). hypoglycemics and corticosteroids). sweat. Leads to peripheral neuropathy and anemia. feces. rifampin. Rifabutin similar in structure and activity. Ethionamide. Isoniazid (INH). Dose-depedent. Body fluids turn bright orange-red: urine. Capreomycin sulfate. Streptomycin (aminoglycoside). Absorbed orally. Bacteriocidal.

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Not well absorbed in GI tract  use for GI candidiasis. Too toxic for systemic use: use for skin or mucous membranes. 90% bound to serum proteins. Imidazoles: ketoconazole. Fluconazole water-soluble  can give via IV. Toxicity of targeting human P450: Elevation of serum transaminase. menstrual irregularities. Least for fluconazole (most selective toxicity). Used in induction therapy: replace with azole for maintenance therapy. muscle spasm. One side hydrophilic for aqueous pore. Inflammation of vein (phlebitis) at injection site. Well-absorbed from GI. Use sodium deoxycholate or lipid vehicle to make liposomes for delivery. Most selective: fluconazole > itraconazole > ketoconazole. use lower dose. decreased renal perfusion. Premedication with corticosteroids. meperidine. Delayed toxicity: nephrotoxicity. Safe for systemic use. Doesn’t cross GI epithelium  need IV admin. miconazole. vomiting. Metabolized by liver. Fluconazole excreted renally. Ketoconazole toxicity: GI: nausea. use test dose. damage of tubular cells. fever. but fluconazole gets to CSF. Broad-spec. ABLC: Ampho B + lipid complex. voriconazole. Other drugs not metabolized by P450  toxic. Ambisome: Ampho B + liposome. Water insoluble: large polyene ring with 36 atoms. headache. Can also slow infusion rate. azotemia. Doesn’t get to CNS: need intrathecal injection. Slow urinary excretion: half-life of 15 days. Fungicidal. hypotension after IV infusion. Higher affinity for fungal P450  selective toxicity. K+ and Mg2+ wasting. . Doesn’t get to CNS. Bind to ergosterol in cell membrane of fungi  pores  K+ leakage. mucosal. Prevent and treat vaginal. antihistamine will help. other side hydrophobic for membrane. gynecomastia.Polyenes (Amphotericin B) Fungal: Cell membrane function Nystatin Azoles Fungicidal. Related to amphotericin B. cutaneous candidaisis. Miconazole and clotrimazole older and less safe: restrict to topical use. Fungicidal. fluconazole. oral. antipyretics. Toxicity: Chills. esophageal. Renal: irreversible. Renal tubular acidosis. ravuconazole. Hepatotoxicity. Prerenal component: reversible. Decrease via adding lipids: Amphocil: Ampho B + cholesterol sulfate (colloidal dispersion: ABCD). clotrimazole. posaconazole. Reduced synthesis of adrenal and gonadal steroid hormones. Inhibit P450 for synthesis of ergosterol  leaky cell membranes  death. Triazoles: itraconazole. vomiting. unmetabolized  can use for UTI’s. anorexia. Hepatotoxicity and anemia from reduced erythropoietin (kidney damage). Infertility. Broad-spec.

Capsofungin. Nausea. 5-FC converted to 5-FU  F-dUMP. F-dUMP blocks thymidylate synthase (needed to convert dUMP to dTMP. Resistance: use as an adjuct to amphotericin B or azoles. vomiting. photosensitivity. Severe hepatotoxicity. Inhibits fungal growth via spindle disruption  prevent mitosis.3 D-glucan synthase. Well-absorbed by GI. nausea. Micafungin. Fungistatic. Limited to C. neoformans. Narrow spec. IV administration. vomiting. headache. dermatophyte infections (i. Toxicity (uncommon): headache. Inhibit fungal cell wall synthesis: inhibit 1.Fungal: Cell membrane function Allylamines (Terbinafine) Fungal: Nucleic Acid Metabolis m Flucytosine (5FC) Fungal: Cell Wall synthesis Fungal: Cell division Glucan Synthesis Inhibitors (Echinocandins) Griseofulvin Fungicidal. Toxicity (rare): GI upset. some Candida and Aspergillus.e. neutropenia). Inhibit non-P450 squalene oxidase  accumulate squalene  death. F-dUDP. Topical and oral for mucocutaneous. Toxicity: Bone marrow depression (anemia. bone marrow suppression (leucopenia. Human cells can’t deaminate 5-FC to F-FU  selective toxicity. thrombocytopenia). diarrhea (may damage DNA). Excreted via kidney. Doesn’t inhibit P450  avoids drug-drug interactions. Serum binding 20%. onchomycosis). leucopenia. mental confusion. mostly unmetabolized. gets everywhere (including CNS). . F-dUTP (inhibit DNA/RNA synthesis).

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4Aminoquinolines (Chloroquine) AntiMalarials Doxycycline (Tetracycline) Artemisinin 8Aminoquinolines (Primaquine) Good for asexual erythrocytic P. Contraindicated with psoriasis or porphyria. Good for exo-erythrocytic P. which is toxic and can’t be reduced when G6PD is low  cell is damaged. cyanosis. Blacks have A. Gets everywhere. R3: no response to initial therapy. Concentrated in liver. Gets everywhere. Large doses: cramps. Block polymerization of heme to hemozoin. enter plasmodial mt  swelling and vacuolization.vivax + all gametocytes. relapses even sooner. falciparum. which is made by G6PD. mild anemia. vivax or P. . GI upset. Chloroquine-ferriprotoporphyrin IX complex from digesting Hg  lyse membrane. Schizontocidal for all species. Test for G6PD deficiency before giving primaquine. Mediterranean and Asian B. Heme degradation by parasite releases Fe  reduces peroxide bond in artemisinin  high-valent iron-oxo species  free radicals of oxygen. ovale. Drug increases amount of oxidized glutathione (GSSG). Males more susceptible since G6PD is on X chromosome. Lichenoid skin eruptions with prolonged treatment. but relapse 2-4 weeks later. lung. Mechanism: 20X more concentrated in RBC than in plasma. unmetabolized. epigastric disease. Absorbed rapidly from GI. kidney. Reductase to get rid of GSSG needs NADPH. Fetuses are G6PD deficient  risk of hemolysis. Drug of choice for dormant liver forms of P. Inactive against liver-stage metabolites. Chinese herbal antimalarial. pruritis. Doxycycline inhibits protein synthesis in malaria. spleen. Excreted slowly: 70% renal. Hemolytic anemia with G6PD deficiency. Hemolytic anemia with G6PD deficiency.7). visual disturbances.S. Half-life 4 days  once-weekly prophylaxis.variant of gene  older erythrocytes hemolyzed. Protonated in food vacuole (pH 4. R2: initial improvement. Concentrate in lysosomes  inhibit acid hydrolases in plasmodial vacuoles. Amodiquine: related but toxic. Selective toxicity for parasitized erythrocytes. Has delay: targets apicoplast.variant  more erythrocytes destroyed. Rapidly absorbed and metabolized. Can’t cure P. leukocytosis. Toxicity: well-tolerated. completely cures P. Delay  good for prophylaxis but not treatment. Toxicities (reversible): Headache. Toxicity: potential neurotoxicity. Drug of choice for non-falciparum and sensitive falciparum malaria. Resistance: R1: initial therapy works. Induces or up-regulated P-gp for efflux. vivax and P. falciparum and P. Intercalate DNA  inhibit nucleic acid synthesis. Binds to DNA. Excreted in urine. ovale. Artemether-lumefantrine: now in U. vivax. declining in use. vivax + gametocytes of P.

Cardiac depressant. Fansidar half-life about 170 hours. Toxicity: well-tolerated. Short half-life  take ever 8 hours. Combination drugs: sequential inhibition. High doses: depresses respiration. fansidar. Some gametocytocidal against P. Drug of choice for resistant P. vivax and P. Good for erythrocytic forms of all. less resistance: Fansidar: pyrimethamine + sulfadoxine. dizziness. Toxicity: Cinchonism: tinnitus. Resistance: elevated DHFR or altered binding affinity. Fansidar very good for chloroquine-resistant falciparum. Fansidar  rare but severe cutaneous reactions. headache. uterine contractions in 3rd trimester. Selective toxicity: preferential binding to parasites. Inhibit DHFR (dihyrofolate reductase) in plasmodia.Quinoline methanols (Quinine) AntiMalarials Folate antagonists Suppressive: good for erythrocytic forms but not liver stages. . nausea. Orally effective: absorbed in upper GI. Quinidine also antiarrhythmic. proguanil (chloroguanide). Proguanil also good for hepatic forms. blurred vision. falciparum. long half-life. Erythema multiforms. Stevens-Johnson syndrome. No longer used for prophylaxis. flushing. Mefloquine good for chloroquine-resistant falciparum. Well-absorbed from GI. insulin release  hypoglycemia. malariae. toxic epidermal necrolysis. Excreted in urine: metabolized by hydroxylation. Maloprim: dapsone + pyrimethamine. hemolytic anemia (G6PD deficiency). Proguanil half-life about 16 hours  daily. Pyrimethamine. Pyrimethamine has long half-life (4 days)  once a week.

possibly from intake with meals. Administer orally for 20 days. . dry mouth. Common flatulence. Toxicity: Occasional abdominal distress and diarrhea. Aerobic cells of humans don’t do reductive activation. Can be luminal and tissue. Paromomycin sulfate (aminoglycoside). Not available in U. fever. Dehydroemetine: severe amebic dysentery. Dehydroemetine. pruritis. Metronidazole. Administer with a luminal amebicide. Hypersensitivity with intolerance to iodine. 10% is absorbed. Nitro group is reduced to products disrupting DNA helix. Accumulates in patients with renal insufficiency  renal toxicity. Possible iodine problems: Increase protein-bound serum iodine  less 131I  thyroid enlargement. Iodoquinol. Disulfiram-type interaction with ethanol. Selective toxicity: prodrug needs reductive activation of nitro group by anaerobic or microaerophilic pathogens  reactive radical anion kills DNA/membrane. Good for C. metallic taste in mouth. Active against tissue trophozoites. Nifurtimox: T.S. Split into diloxanide and furoic acid in GI tract: 90% diloxanide absorbed  covert to glucoronide  excrete. giardiasis. Alternative to diloxanide furoate for asymptomatic amebiases (not as safe). urticaria. amebiasis. Administer orally. Drug of choice for asymptomatic infections. Supplement with metronidazole for all other amebiases. 50% failure rate. cruzi. difficile (drug of choice). Usually don’t use unless others have failed. Iodine intoxication  dermatitis. Diloxanide furoate. Possible mechanism of futile redox cycling. but strongly absorbed from GI  more systemic.Luminal amebicides AntiProtozoals Systemic amebicides Mixed amebicides Not active against tissue trophozoites. Toxicity (not serious): nausea. chloroquine: for hepatic abscesses. 10% is active amebicide. Protozoa and anaerobic bacteria. Supplement with metronidazole for all other amebiases. Not absorbed by GI tract. no serious side-effects. headache. Infrequent GI toxicity.

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Drug of choice for Strongyloides and Onchocerciasis. vomiting. Piperazine: treatment for ascariasis lumbricoides. Concentrated in liver and fat and stored  4 doses per year. weakness. Wolbachia antigen is released with drug  immune response. albendazole. tropical eosinophilia. Broad spec. headache. drowsiness. Agonist of GABA-gated chloride channels on nematode muscle. vomiting. Mebendazole: poorly absorbed. not absorbed by GI tract. Praziquantel: single dose to treat Schistosomiasis. Administered orally (without food). . Single annual dose is effective to prevent blindness. Selective toxicity: human microtubules would need higher concentration. Drug of choice for nearly all nematodes. Inhibit microtubule polymerization via binding to β -tubulin. dizziness. nausea. Absorbed and metabolized in liver by P450  cross-reactivity with P450 drugs. Drug of choice for filariasis. mebendazole. nausea. malaise. Can have severe allergies to products of killed organisms (onchocerchiasis). nematodes Niclosamide: cestodes/tapeworms. Benzimidazoles: thiabendazole. Enhance susceptibility to immune response. Lack of toxicity to humans. Enhanced by lower pH. Praziquantal: drug of choice for nearly all trematodes (not Fasciola hepatica). Potential for cystocercosis after drug treatment: avoid with purges. Vegetarian diets have alkaline urine  toxicity if dose is too high.channels. Mechanisms: Rapid titanic contraction of worm musculature (spastic paralysis). Administer orally. Gets to all tissues except fat. unmetabolized or as N-oxide metabolite. Loa loa. Roundworms are paralyzed and expelled by rectum. Absorptions: Thiabendazole: GI tract after oral administration (higher toxicity). Worms detach and move to liver  immune system reacts. Inhibit egg production at low doses. Diethylcarbamazine. cestodes. Mechanisms: Immobilize microfilariae. Albendazole: variably absorbed. Inhibit oxidative phosphorylation and stimulates ATPase  kill cestode.AntiHeminths Antitrematodes. Rapid absorption. Ivermectin: single dose to prevent Onchocerca Volvulus.S. Tonic paralysis of parasite: activate GABA-gated Cl. Toxicity: Headache. Also used against cestodes. Low cost  used in developing countries. Increases calcium permeability. Vacuoles in apical tegument. Toxicities from thiabendazole: anorexia. Toxicity: nausea. epigastric pain. Mechanism: Inhibition of phosphorylation  biochemical changes. Ivermectin. Excreted in urine. Combine with anti-snail to prevent reinfection. dizziness. Not in U. Albendazole treats cystocercosis of pork tapeworm at larval stage.

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