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54 Cards in this Set
- Front
- Back
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BETA-LACTAM ABX
CATEGORIES |
1. Penicillin (-cillin's)
G = IV V = ORAL 2. Cephalosporins 1st, 2nd, 3rd gen - increasing gram neg activity - decreasing gram + activity 3. Carbapenems: Imipenem: decerebrate abx - high seizure potential 4. Monobactam (Aztreonam) BETA-LACTAM ABX - poor intracellular penetration - least toxic abx - bacteriocidal - time dependent |
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BETA LACTAM ABX
MECHANISM OF AXN |
Bind & competitively inhibits Transpeptidase = Penicillin Binding Protein
Bactericidal = kills bacteria *Gram-neg bugs: pass through PORINS in outer membrane to reach cell wall |
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BETA LACTAM ABX
- RESISTANCE |
SIX Ps: Penetration, porins, pumps, penicillinases, PBPs, Peptidoglycan
1. Alter the drug = drug inactivation Beta-lactamases: Cleave C-N bond ex// ESBL, penicillinase, cephalosporinase *Gram+ bugs secrete penicillinase *Gram- bugs have it bound to cytoplasmic membrane 2. Alter drug target: Change PBPs ex// MRSA 3. Can't reach/touch target - porin pore mtt (gram-neg) - Efflux pumps |
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six P's of Penicillin inactivity
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1. Penetration ( intracellular )
2. Porins (gram-neg) 3. Pumps (efflux) - decrease [ ] @ target site 4. PBPs: mtts 5. Peptidoglycan: absent in mycoplasma 6. Penicillinases: beta lactamases - MAJOR |
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BETA LACTAM ABX
- Elimination |
MOSTLY RENAL
Major exception: CEFTRIAXONE (3rd gen ceph) - biliary & renal elimination: intern's drug |
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beta lactam abx
TOXICITY |
REALLY NONTOXIC,
BUT MCC OF ABX ALLERGIC RXN HYPERSENSITIVITY 1. IgE - angioedema, laryngeal edema, anaphylaxis 2. IgG: hematologic, nephritis 3. IgG & C' = immune complex - serum sickness & vasculitis 4. T cell: delayed rash = VERY COMMON (esp when you give amox to pt w/ a virus OTHERS: - Seizures - disulfiram like rxn w/ cefotetan - Bone marrow suppression - Diarrhea (abx- associated colitis 2' C. dif) **pregnancy category B** **Except Imipenem = Category C** |
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PENICILLIN
- types |
4 TYPES:
1. Penicillin G / V 2. Penicillinase-R - methicillin, nafcillin, dicloxacillin, clox (oral "clocks" & i MET a NAsty OX) 3. Anti-Pseudomonal - James Bond: Car, Tic, Pipe Carbenicillin, ticarcillin, Piperacillin & mezlocillin 4. Aminopenicillins: - broader spectrum ("AMPed" up Pen) - more gram-neg (enterics - HELPS) **one of few 2 kill gram+ enterococcus** |
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PENICILLIN
- clinical use/DOC - used with? |
1. Strep Pneumo Pneumonia or N. meningitidis/S. pneumo meningitis
- Pen G or amp 2. GAS pharyngitis: Pen V 3. Listeria infxn: oral amp 4. non-MRSA Staph aureus: Penicillinase-R *use NAF for STAPH* 5. Pseudomonase: TCP - takes care of pseudomonas - other select gram- rod 6. Cat bite: Pasturella multocida & anaerobes 7. Gram+: B. anthracis, C. perfringens. Listeria 8. Spirochetes - Treponema pallidum: depot PCN G 9. Acute OM & Sinusitis: Amox 10. Select mixed abd infxns: Pip/Tazo 11. Enterococcal endocarditis: give w/ aminoglycoside 12. Clostridial myonecrosis **Used w/ CAST = B-lactamase inhibitors |
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PENICILLIN
- Distribution - toxicity (mechanisms) |
Wide distribution
- except eye, prostate, CSF, brain, phagocytes *CSF penetration ^ w/ inflamm Short 1/2 lives Pen & degradation products = HAPTENS - induce Ab formation - IgE mediated skin tests - Cross allergy w/ ceph & carbapenems (5-10%) *Use Monobactam if penicillin allergy *Use ceph if non-IgE rxn 2 pen Naf: Bone marrow depression w/ LT use Amp/Amox: in EBV = RASH |
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beta-lactamase inhibitors
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CAST
- Clavulanic acid - sulbactam - tazobactam *given as an adjunct w/ penicillin abx* |
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Penicillin resistant
- mechanisms - common organisms |
1. drug inactivation w/ b-lactamases
- S. aureua, N. gonorrhea, Aerobic & anaerobic gram-neg 2. Target alteration a.) MRSA - changed transpeptidase (D-ala terminus) - tx w/ vanco *VRSA: treated with daptomycin b.) S. pneumo c.) Enterococcus faecium - pcns are only bacteriostatic here |
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CEPHALOSPORINS
- general advantages - general classifications *1st and 2nd gen = narrowest (gram+ mostly) *3rd & 4th gen = extended spectrum (also gram-) |
pros:
1. new "basement" = more resistant to penicillinases 2. new R group side chain 1st gen: PH.D + CeFAZolin - PEcK + gram+cocci 2nd gen: Fam, Fa, Fur, Fox, Tea - HEN PEcKS 3rd gen: T's (for TRI) *major resistant gram-negs* - Ceftriaxone: meningitis & gonorrhea - Ceftazidime: Pseudomonas 4th gen: Cefepime - Pseudomonas & more gram+ |
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CEPHALOSPORINS
- DOC |
1. 3rd & 4th gen = meningitis
- good CSF penetration w/ inflamm 2. Sx prophylaxis: 1st gen 3. Skin infxns (MSSA or strep): 1st gen 4. N. Gonorrhea: 3rd gen **Ceftriaxone: meningitis & gonorrhea** 5. Pseudomonas sepsis: Ceftazidime, Cefoperazone cefepime (Give it TAZ, FOP, FEP) 6. CA-bacterial pneumonia (H. flu or S. pneumo) - 2nd gen: Cefuroxime 7. Anaerobic Coverage: 2nd gen - Cefotetan, Cefoxitin, Cefmetazole** (FOX Met an anaerobic bug for TEA) |
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CEPHALOSPORINS
- unique toxicity & elimination - resistance |
CEFTRIAXONE
- Biliary/gallbladder sludge - renal & biliary excretion Beta-lactamase production by gram-neg rods can be INDUCED by giving 3rd & 4th gen cephs does NOT work against Listeria or Enterococcus or MRSA **cross allergy 10-15% w/ PCN - don't use if IgE rxn in PCN |
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CARBAPENEMS
- special traits |
BROADEST COVERAGE: esp imipenem
(decerebrate abx - covers all) - smallest b-lactam - resistant to b-lactamases (including ESBLs) *cross-reactive w/ PCN (allergy)* |
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CARBAPENEMS
- USE/ types - toxicity |
Imipenem/Cilastatin
- kills all, except MRSA, some Pseudomona - limited use 2' SEs - SEIZURES **Cilastatin: Renal Dihydropeptidase Inhibitor MEROPENEM: better version of imipenem Ertapenem: DOC for severe diabetic foot infxns - does NOT cover Pseudomonas or enterococcus |
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AZTREONAM
(monobactam) - mech - use/DOC |
beta-lactamase resistant
USE: GRAM-NEG AEROBIC RODS - does NOT bind 2 transpeptidase of gram+ bacteria - also use in pts w/ PCN allergy - used in combo w/ gram+ killer usually MECH: "A TREe fell on the house" --> negative experience |
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Beta-lactamase resistant beta-lactams
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1. Penicillinase-R Beta Lactams
- met, naf, ox 2. Aztreonam (monobactam) 3. Carbapenems |
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ABX THAT COVER PSEUDOMONAS
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1. Anti-pseudomonal PCN
- Car, tic, Pipe - Zosyn 2. 3rd gen & 4th gen ceph - TAZ, FOP, FEP 3. Imipenem 4. Aztreonam 5. Quinolones - Ciprofloxacin 6. Aminoglycosides - gent - tobra - amikacin |
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ABX THAT COVER ANAEROBES
(including Bacteroides fragilis) |
1. PCN + B-lactamase Inhibitor
(CAST) 2. 2nd gen ceph: - fam, fa, fox, fur, te 3. Carbapenems 4. Chloramphenicol 5. Clinda 6. Metronidazole 7. Moxi Floxacin 8. Tigecycline |
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ABX THAT KILL HARD-TO-KILL GRAM+ BUGS
- MRSA - VRE |
MRSA
- Vanco - Linezolid - Daptomycin - Quinupristin/dalfopristin - Tigecycline 2. VRE: - Linezolid - Daptomycin |
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bacteriostatic vs bactericidal abx
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ECSTaTiC abt bacteriostatics
1. Erythro 2. Clinda 3. Sulfamethoxazole 4. TMP 5. Tetracyclines 6. Chloramphenicol BACTERICIDAL "Very Finely Proficient At Cell Murder" 1. Vanco 2. Fluoroquinolones 3. Penicillin 4. Aminoglycosides 5. Cephalosporins 6. Metronidazole |
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SULFONAMIDES
(folic acid antagonists) mech - tox |
PABA analogue
- competitive inhibition of dihydropteroate SYNTHETASE - bound to albumin *Bacteriostatic only - affects INTRACELLULAR organisms too TOXICITY: - G6PD --> hemolysis - Hypersensitivty - Crystalluria (esp V-depleted) - Pancytopenia - Tubulointerstitial nephritis - Photosensitive (Sulfas & Tetracyclines) - KERNICTERUS in infants - displace drugs from albumin (WARFARIN!!) |
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why don't sulfas or TMP hurt people?
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humans don't have Dihydropteroate synthetase
- they can't make folic acid (TH4), they have to EAT IT Folate --> PURINE SYNTHESIS |
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SULFA ABX
- types - use - distribution |
Types: systemic, GI Tract only, Topical (silver - buns)
Use in UTIs (sulfur & urine both smell) Use in CNS toxoplasma & nocardia - good csf penetration Use vs. intracellulars - PCP, plasmodia, listeria, etc. BROAD SPECTRUM |
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CLINCAL USES OF TMP/SMX
TMP Smx |
1. respiratory Tree
- Strep pneumo & H. flu 2. Mouth: GI tract - gram- 3. Pee: GU tract - UTI, prostatitis (TMP concentrates in prostate) 4. Syndrome (AIDS) - PCP prophylaxis (and other protozoans like toxo) |
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TRIMETHOPRIM
- mech - ADME - toxicity |
MECH: inhibits Dihydrofolate REDUCTASE
- prevents purine synthesis (anti folate) Bacteriostatic; used in combo w/ Sulfamethoxazole (synergism) CONCENTRATES IN PROSTATE TMP = Treats Marrow Poorly - megaloblastic anemia - eukopenia - granuloyctopenia **Leucovorin rescue = folinic acid supp** treats lots of stuff, inc outpt MRSA - alternative to pCN in Listeria tx |
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DAPSONE
- mech - uses |
aka A sulfone
Tx's: Hansen's Disease/Leprosy - Also PCP (allergy 2 TMP/SMX) - Toxo MECH: sulfa abx ADME: - hepatic & renal elim |
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DAPSONE
- toxicity |
1. Hemolysis: Hb oxidant
- G6PD - Methemoglobinemia - Rash - sulfone syndrome: like infectious mono - erythema nodosum leprosum |
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Aztreonam, Vanco, Dapto
- what bugs do they kill? - how? - tox of dapto & vanco |
Aztreonam: GRAM NEGATIVE ONLY
(b-lactam; transpeptidase) VANCO & DAPTO: ALL GRAM+ ONLY - vanco: blocks peptidoglycan SYNTHESIS (also bacitracin) - Daptomycin: Eliminates charge on cell membrane (cyclic lipopeptide) **Dapto = myopathy w/ cpk ELEVATION **Vanco = red man syndrome - rapid infusion--> histamine release **Vanco synergist w/ aminoglycosides **Vanco NOT absorbed orally - use in C. dif colitis |
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ABX that inhibit DNA fxn or structure
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1. Fluroquinolones - DNA gyrase
2. Rifampin - DNA-dept RNA pol mRNA synthesis 3. Metronidazole - toxic free radicals 3. Nitrofurantoin |
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VANCOMYCIN
- mech - use - ADME |
Binds @ peptidoglycan terminus (D-ala)
- inhibits cell wall cross linking by inhibiting peptidoglycan synthesis - bactericidal - time dept USE: - C. dif - MRSA - Gram+ - Enterococcus: only alt 2 PCN *synergist w/ aminoglycosides ADME: - POOR oral absorption = c.dif - Renal elim only |
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VANCO
- TOX - RESISTANCE |
RED MAN SYN: rapid infusion <1hr
- histamine - hypotension Pregnancy - baby oto & nephrotoxicity RESISTANCE: - Target alteration: enterococcus can give vanA resistance gene 2 staph - Target access: thickened cell wall |
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BACITRACIN
- use - mech |
inhibits peptidoglycan synthesis (and cell wall)
- bactericidal **nephrotoxic - used topically ONLY against GRAM+ |
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daptomycin
- where DON'T u use it? |
DON'T use it in pneumonia
- doesn't acheive adequate levels in the lung |
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FLUOROQUINOLONES
- mech - ADME - absorption factors |
Inhibits DNA gyrase (topoisomerase)
- bactericidal ADME: - Great oral - Don't take w/ Antacids, milk products, Al, Mg, Zn, Fe, Ca - Wide dist; also bone, CSF **[]s in prostate, lung, kidney - AFFECTS INTRACELLULAR BUGS Elim: stool & renal & liver |
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drugs that concentrate in the prostate
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1. Quinolones (also bone, lung, kidney)
2. TMP 3. Tetracyclines (P-QTT) |
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FLUOROQUINOLONES
- CATEGORIES |
"-floxacin"
- flocks of sinners gyrating - need to pee (UTI) - vomit if too much 1. Std: Ciprofloxacin 2. Respiratory: Levo, Moxi |
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FLUOROQUINOLONES
- tox |
1. Cns: elderly seizures, vertigo, etc
2. Cardiac: LONG QT 3. tENDONITIS/aCHILLES RUPTURE - athletes! 4. Arthropathy in babies - fluoroquinoLONES hurt the attchs to your BONE **resistance: chromosome encoded mtt in DNA gyrase - also efflux pumps & porins |
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FLUOROQUINOLONES
USE **poor gram+ coverage & NO anaerobe coverage** - DOES kill staph aureus & anthrax |
best for gram NEGATIVE bugs in UTI/GU infxns
1. UTIs, 2. Prostatis 3. Traveller's diarrhea (stool elimn) 4. Osteomyelitis (gets to bone) 5. CA pneumonia - intracellular bugs - use in Pseudomonas - Cipro 6. ANthrax proph |
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METRONIDAZOLE
- MECH - USE |
MECH:
Reductive process creates anion metabolites - damages bacterial DNA - requires lowredox potential (NOT active in aerobic) USE: ANAEROBES UNDER THE BELT (& MICROAEROPHILES) GET GAP on the Metro - intestinal parasites 1. Giardia 2. Entamoeba 3. Trichomonas 4. Gardnerella vaginalis (BV) 5. Anaerobes 6. H. Pylori (microaerophile) *also "M-I-L" drug 4 C. dif colitis bc vanco is better ADME: - GOOD CSF penetration; even into abscesses - FECAL, renal, hepatic elim |
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METRONIDAZOLE
- TOXICITY |
1. DISULFIRAM LIKE RXN
(Antabuse) - don't take w/ alcohol! - flushing, cramps, shock, seizure 2. seizures; other CNS 3. Metallic taste 4. headache *pregnancy category B |
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tYPES OF TUBERCULOSIS
- latent vs localized vs disseminated vs atypical |
ALL PPD+
latent: +infxn; no disease localized: focal in lungs; not disseminated Disseminated: extrapulmonary - M. tb esp meninges, bone, GU tract Atypical: M. avium complex - chronic pneumonia or disseminated - esp in AIDS/HIV+ - Tx w/ -mycin (rifabutin or clarithromycin). |
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GENERAL PRINCIPLES OF M. TUBERCULOSIS TX
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1. NUMBERS
- few organisms (Latent): few drugs - Many orgs (active infxn): many drugs 2. Prevent activation of disease - prophylaxis 3. Prevent emergence of resistance - TB is slow-growing, dormant, intracelular, mycolic acid (lipid) cell wall ***4 for 2, 2 for 4*** -DOT * Give B6 w/ INH * Make sure it's M. tb and not MAC - acid fast bacilli are M. tb until proven otherwise |
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TB FIRST LINE DRUGS
INH-SPIRE |
PERIS; I Saw a Red Pyre (burning the liver)
INH, PZA, RIF, ETB, = HEPATOTOXIC Streptomycin **second line drugs are used if resistance present; very bad SEs |
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TREATMENT OF MAC
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first line: take CARE it's not MAC
- Clazithromycin or Azithromycin - Rifabutin - Ethambutol 2nd line: Quinolones, streptomycin, Clofazamine |
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ISONIAZID
- mech - activity - Tox |
Prodrug ~ pyridoxine
- bacteria catalase-peroxidase needed to make active - inhibits mycolic acid synthesis MUST USE IN TB - not good against MAC TOX: 1. Hepatotoxic 2. Peripheral neuropathy: ^ renal excretion of B6 - give supp B6 always 3. Drug induced SLE - ANA vasculitis fast vs. slow acetylators based on genetics |
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tx of TB
- osteomyelitis TB - latent TB |
12 mo+ for sequestered sites
- cns or bone 9+ mo latent TB |
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RIFAMPIN & RIFAMYCINS (rifabutin)
- mech - activity - tox - unique |
4 R's of RIF
1. (DNA-dep) RNA POL inhibitor 2. Revs up P450 (inducer) 3. RED/orange body fluids 4. Rapid resistance if used alone - delays resistance 2 dapsone in leprosy *also used in Meningococcal prophylaxis & H.ib **Rifabutin used in MAC (can be found in lymph nodes, where M. tb isn't) & it's a weaker inducer of P450 =) |
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FAMOUS P450 INDUCERS
must know |
1. RIF
2. Ethanol (alcoholics) 3. Non-nucleoside ART 4. Anticonvulsants - Phenytoin - Carbamazepine - Phenobarbital **all are obviously metabolized by the liver** |
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PYRAZINAMIDE (PZA)
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prodrug activated by acidic pH of phagolysosome (where m. tb is)
- probably inhibits mycolic acid synthesis TOX: - Hepatotoxic - Hyperuricemia/gout |
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ETHAMBUTOL (ETM)
- mech - activity - toxic |
Decreases carb polymerization of cell wall
- blocks arabinosyltransferase BACTERIOSTATIC*** - only one in 1st line TB tx Hits M. tb & M. kansasii like INH ETHANE/BUTANE TORCHES EYE - Central scotoma - loss of color vision - gout |
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HANSEN'S DISEASE/LEPROSY TX
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1. RIF
- most active leprosy drug - 4R's of RIF 2. DAPSONE: A sulfone - sulfa: inhibits dihydropteroate synthase - also in PCP - TOX: G6PD: oxidant --> hemolysis 3. Clofazamine: - red-black clown climbing DNA helix - inhibits DNA replication - accumulates in tissues - can turn skin red-black |
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Classes of ANTIFUNGALS
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1. Polyenes: punch holes in membrane
- Amphotericin B 2. Anti-metabolites: - flucytosine 3. Azoles: - Inhibit Lanosterol --> ergosterol 4. Glucan synthesis inhibitors - echinocandins (ex//caspofungin, micafungin) inhibit 1,3 D-glucan synthase 5. Allylasmines: topical - terbinafine - inhibit squalene oxidase (inhibit ergosterol synthesis) 6. OTHERS: - Griseofulvin: disrupts mitotic spindles |
