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Pharmacology book -8-toxicities

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medmaestro's version from 2015-11-03 05:35

Section

8. most important mechanism of drug resistance
Question Answer
Beta lactamsinactivating enzyme beta lactamase
Tetracyclinesefflux pump (decreased concentration in the cell)
Chloramphenicolinactivating enzyme (acetyl transferase)
Aminoglycosidesinactivating enzyme
Macrolidesdecreased permeability or efflux pumps
Sulphonamidesform large amount of PABA ;decreased activity of Folate Synthase
Fluoroquinolonesaltered DNA Gyrase with reduced affinity
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TRANSFER OF RESISTANCE against all antibiotics is PLASMID MEDIATED EXCEPT Fluoroquinolones for which transfer of resistance is mediated by chromosomal mutation .
9.Drug of choice for suspected or proved microbial pathogens

 

Suspected / proved etiologic agentDrug(s) of First choice
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Gram Negative Cocci
Question Answer
Moraxella catarrhalisCefuroxime,a fluoroquinolone
Neisseria gonorrhoeae (gonococcus )Cefexime,Ceftriaxone
Neisseria meningitides (meningococcus)Penicillin G
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Gram-Positive cocci
Question Answer
Streptococcus pneumonia (pneumococcus)Penicillin G
Streptococcus , haemolytic,groups A,B,C,GPenicillin G
Viridans StreptococciPenicillin G +/- Gentamicin
Staphylococcus,methicillin resistant(MRSA)Vancomycin
Staphylococcus,non-Penicillinase producingPenicillin G
Staphylococcus,Penicillinase producingPenicillinase –Resistant penicillin (Oxacillin,Cloxacillin,Naficilline)
Enterococcus faecalisampicillin +/- gentamicin
Enterococcus faeciumVancomycin +/- gentamicin
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Gram-Negative Rods
Question Answer
AcinetobacterImipenem or Meropenem
Prevotella,oropharyngeal strainsClindamycin
Bacteroides,gastrointestinal strainsMetronidazole
BrucellaDoxycycline+Rifampicin
Campylobacter jejuniErythromycin or Azithromycin
EnterobacterErtapenem,Imipenem,Meropenem,Cefepime
Escherichia coli (sepsis)Cefotaxime,Ceftriaxone
Escherichia coli (uncomplicated urinary tract infection)Fluoroquinolones.Nitrofurantoin
Hemophilus (Meningitis and other serious infections)Cefotaxime,Ceftriaxone
Hemophilus(Respiratory inf, Otitis)TMP-SMZ
Helicobacter pyloriAmoxicillin+Clarithromycin+Proton pump inhibitor(PPI)
Klebsiella (ESBL-Extended Spectrum Beta Lactamase –producing)Carbapenems
Klebsiella (Not producing ESBL)Cephalosporins
Legionella speciesazithromycin,or fluoroquinolones +/- rifampicin
Proteus mirabilisampicillin
Proteus vulgaris & other species(Morganella,Providencia)Cefotaxime,ceftriaxone
Pseudomonas aeruginosaAminoglycoside + antipseudomonal penicillin
Burkholderia pseudomallei (MELIOIDOSIS)Ceftazidime
Burkholderia mallei (GLANDERS)Streptomycin + tetracycline
Salmonella (Bacteremia)Ceftriaxone
SerratiaCarbapenem
ShigellaFluoroquinolone
Vibrio (cholera,sepsis)Tetracycline
Yersinia pestis (plague)Streptomycin +/- Tetracycline
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Gram-Positive Rods
Question Answer
ActinomycesPenicillin G
Bacillus (EXCLUDING ANTHRAX)Penicillin G
AnthraxCiprofloxacin or Doxycycline
Clostridium (Eg. Gas gangrene,sepsis)Penicillin G
Clostridium tetani (Tetanus)Metronidazole
Corynebacterium diphtheriaeerythromycin
Corynebacterium jeikiumVancomycin
ListeriaAmpicillin +/- aminoglycoside
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Acid Fast Rods
Question Answer
Mycobacterium tuberculosisIsoniazid (INH) +Rifampicin+Pyrazinamide+/- Ethambutol (HRZE)
Mycobacterium lepraedapsone + rifampicin +/- clofazimine
Mycobacterium kansasiiINH + Rifampicin+/-Ethambutol
Mycobacterium avium complexclarithromycin or azithromycin
Mycobacterium chelonei,fortuitumAmikacin+Clarithromycin
NocardiaTMP-SMZ
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SPIROCHETES
Question Answer
Borrelia burgdorferi (Lyme disease)Doxycycline,Amoxicillin,Cefuroxime axetil
Borrelia recurrentis (Relapsing fever)Doxycycline
LeptospiraPenicillin G
Treponema pallidum(Syphilis)Penicillin G
Treponma pertunae (yaws)Penicillin G
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Others
Question Answer
Mycoplasmaserythromycin or doxycycline
Chlamydiae psittacidoxycline
Chlamydia trachomatis(urethritis or pelvic inflammatory disease)doxycline
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Or azithromycin
Question Answer
Chlamydia pneumoniaDoxycycline
Rickettsiaedoxycline
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10.Non tuberculous Mycobacterium
Question Answer
Photochromogens(Develop pigments in or after exposure to light)-grows at 25oC M.kansasii,M.marinum,M.simiae (KaMaSi)
Scotochromogens(develop pigments in dark)-grows at 37oCM.scrofulaceum,M.gordonae,M.szulgai (ScroSzuGord)
NonChromogens –Oppurtunistic pathogensMycobacterium avium complex (MAC)=Myc.intracellulare(aka Battey bacillus)+Myc.avium(M.avium is the MOST COMMON opppurtunistic pathogen of humans),Others are M.xenopi,M.ulcerans,M.malmoense,M.hemophilum,M.genavense;These two-M.smegmatis & M.flavescens rarely cause disease
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11.Optimum temperature for growth:
Question Answer
M.xenopi & M.avium(NonChromogens) 45oC-Thermophiles
Scotochromogens37 oC
Photochromogens25 oC
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12.CELL CYCLE EFFECTS OF ANTICANCER DRUGS(CCS are drugs effective when cells are proliferating;CCNS are drugs effective whether the cells are dividing or are in resting phase.)
Step of cell cycle affectedCCS-Cell Cycle Specific drugsCCNS-Cell cycle non specific drugs
G1-SEtoposidePlatinum compounds
SAntimetabolitesAlkylating agents
G2-MBleomycin,EtoposideAnthracyclines,Dactinomycin
MVinca alkaloids,Taxanes,Ixabepilone(NEW DRUG),EstramustineMitomycin,Camptothecins
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13.CLASSIFICATION OF ANTI CANCER/NEOPLASTIC DRUGS
ALKYLATING AGENTS
Question Answer
Nitrogen mustardsmechlorethamine , cyclophosphamide,ifosfomide,melphalan,chlorambucil
EthyleniminesThio-TEPA ,Hexamethylmelamine(Altretamine)
Alkyl sulphonatesbusulfan
Nitrosoureascarmustine ,Lomustine,Streptozocin
Triazinesprocarbazine,dacarbazine,temozolamide
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PLATINUM COMPOUNDS
Cisplatin,Carboplatin,Oxaliplatin
ANTIMETABOLITES
Question Answer
Purine analogues5 FU,Cytarabine,Gemcitabine
Purine analogues6MP, Thioguanine,Pentostatin,Cladribine
Folic acid analoguesMethotrexate ,Pemetrexed
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NATURAL PRODUCTS
Question Answer
Vinca alkaloidsVincristine,Vinblastine,Vinorelbine
TaxanesPaclitaxel ,Docetaxel
Epipodophyllotoxins(Topoisomerase II inhibitor)Etoposide,Teniposide
Camptothecins(Topoisomerase I inhibitor)Topotecan,Irinotecan
Antitumour antibioticsAnthracyclines(Daunorubicin,doxorubicin,Epirubicin,Idarubicin,Mitoxantrone),Bleomycin,Dactinomycin,Mitomycin C
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Enzymes: L-Asparaginase
HORMONES AND RELATED AGENTS
Question Answer
CorticosteroidsPrednisolone,Prednisone
AntiestrogensSERMS(Tamoxifen,Doloxifen),Aromatase inhibitors(Aminoglutethamide,Formestane,Exemestane,Anastrozole,Vorozole,letrozole
ProgestinsMedroxyprogesterone acetate
EstrogensDiethylstilbesterol,Ethinyl estradiol
AndrogensTestosterone
AntiandrogensFlutamide
GnRH AnaloguesLeuprolide,Goserelin,Naferelin,Buserelin,Histerelin
GnRH AntagonistsCetorelix,Ganirelix,Abarelix
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MISCELLANEOUS
Question Answer
BIOLOGICAL RESPONSE MODIFIERSRecombinant IL-2(Aldesleukin),GM-CSF(Sargramostim),G-CSF(Filgrastim),Monoclonal antibodies (Rituximab,Transtuzumab etc)
Substituted ureaHydroxy urea
Adrenal cortex suppressantMitotane
Tyrosinase kinase inhibitorsImatinib,Geftinib,Erlotinib
RetinoidsIsotretinoin
Arsenic compoundsAs2 O 3
Adenosine deaminase inhibitorPentostatin
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DISTINCTIVE TOXICITIES OF ALKYLATING AGENTS

DrugToxicity
CyclophosphamideAlopecia,Hemorrhagic cystitis ,SIADH
IfosfamideHemorrhagic cystitis,SIADH
Busulfan Pulmonary fibrosis,Hyperpigmentation , Adrenal insufficiency
ProcarbazineSecondary leukemias,Disulfiram like reaction,Behavioural changes,CNS depression
CisplatinEmesis,nephrotoxicity,peripheral sensory neuropathy,Ototoxicity
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DISTINCTIVE TOXICITIES OF ANTIMETABOLITES

Question Answer
6-MP & 6-TGHepatotoxicity
MethotrexateMucositis,Hepatotoxicity
5-FUHand and Foot syndrome,Neurotoxicity
CapecitabineHand and foot syndrome,hyperbilirubinemia
Cytarabinecerebellar ataxia
FludarabineArthralgia
GemcitabineDiarrhoea
All antineoplastic antimetabolites causebone marrow suspension
Alkylating agents are used forChronic leukemias
Antimetabolites are used forAcute leukemias
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DISTINCTIVE TOXICITIES OF NATURAL ANTICANCER DRUGS

Question Answer
BleomycinPulmonary Fibrosis
AnthracyclinesCardiotoxicity
PaclitaxelPeripheral Neuropathy,Hypersensitivity
DocetaxelPeripheral Neuropathy,Fluid Retention
IrinotecanDiarrhoea
TopotecanNeutropenia
VincristinePeripheral Neuropathy(MARROW SPARING ),SIADH
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SELECTED TOXICITIES OF HORMONAL AGENTS

drugtoxicity
Flutamidehot flushes,liver dysfunction
SERMsMenopausal symptoms,fluid retention,thromboembolism,increased incidence of endometrial ca
Progestinsfluid retention
Corticosteroidsfluid retention , hypertension,diabetes,increased susceptibility to infections
GnRH agaoniststransient flare upreaction,hot flushes,impotence,gynaecomastia,osteoporosis
Aminoglutethamideadrenal insufficiency,myelosuppression,rash
Aromatase inhuibitorsfatigue,hot flushes,arthralgia
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TOXICITIES BY ATRA(ALLTRANS RETINOIC ACID)-used in acute promyelocytic leukemia

Question Answer
Vitamin A toxicityheadache, fever ,dryness ,skin rash ,pruritis,conjunctivitis
Retinoic acid syndromefever ,leucocytosis,dyspnoea,weight gain,pulmonary infiltrates,pleural or pericardial effusion
CNS toxicitydizziness,anxiety,depression,confusion,agitation
OthersHypercholesterolemia,Hypertriglyceridemia,Abdominal pain and diarrhoea
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