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Pharmacology - Block 3 - Part 4

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davidwurbel7's version from 2016-08-14 07:07

Inhibitors of Nucleic Acid Synthesis

Question Answer
Bacteria synthesise their own folate from precursors this precursureP-Aminobenzoic Acid (PABA)
The enzyme bacteria use to synthesize folateDihydropteroate Synthase
This antibiotic competes with p-aminobenzoic acid (PABA) and inhibits dihydropteroate synthaseSulfonamides
Synthesis of tetrahydrofolate requires an this enzyme calledDihydrofolate Reductase
The antibiotic inhibits the dihydrofolate reductase enzyme (DHFR) and provides a sequential blockade of synthesis of tetrahydrofolateTrimethoprim
A fixed dose combination. Dose ratio of 5:1. Causes sequential block of folate metabolism individually are bacteriostatic. Together they are Bactericidal & Synergistic. Less resistance to combination than with either drug administered alone. 50,000times more selective for bacterial enzymesTrimethoprim – Sulfamethaxazole(TMP-SMX)
Mechanism of resistance to this drug is a mutation in the bacteria leading to overproduction of PABA, enzyme’s less affinity for drug, decreased permeability to drugTrimethoprim – Sulfamethaxazole(TMP-SMX)
This mechanism of resistance enzyme undergoes mutation resulting in decreased affinity for the sulfonamidesAlternated Dihydropteroate Synthetase
Generalized eruption of lesions that initially had a target-like appearance but then became confluent, brightly erythematous, showed a crinkled surface and became bullous. If these lesions are touched, the epidermis will be dislodged and erosions will appear (Nikolsky sign)Stevens-Johnson Syndrome
Adverse reactions include crystalluria (Nephrotoxic due to crystal formation in kidney) ….(Rx by NaHCO3 ) - form crystal in urine - patients will have white urine, nausea, vomiting, gastritis, hemolysis in G-6-PD deficiency and hypersensitive reactionsSulfonamides
Adverse reaction with sulfonamides in patients with G-6-PD deficiencyHemolysis
Mechanism of action of this class of drugs is inhibiting bacterial Topoisomerase II (DNA gyrase) and topoisomerase IV- which are responsible for separation of replicated DNA during cell divisionFluoroquinolones
Adverse effects of this drug is arthropathy in children (avoid in pregnancy and children below 18 years). Tendon rupture due to deposition in cartilage & disruption of matrixFlouroquinolones
Drug interactions prolonged QT interval- with Sparfloxacin, Gatifloxacin- especially in patients taking theseCYP Inhibitors
These reduce the absorption Flouroquinolones as well as TetracyclinesAntacids
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Question Answer
Urinary Tract InfectionsNorfloxacin-2nd
Typhoid (enteric fever)Ciprofloxacin-1st
Gonorrhoea(ciprofloxacin, ofloxacin for gonorrhea – single dose - 2nd, but ceftriaxone is first line drug)
ChlamydiaOfloxacin
Pseudomonas infectionsCiprofloxacin
Drug Resistant pneumococciLevofloxacin, Sparfloxacin
AnthraxCiprofloxacin
Topical sulfonamide for treatment of burnSilver Sulfadiazine
Urinary tract infections –uncomplicated mildTMP-SMX
Ulcerative colitis, rheumatoid arthritisSulfasalazine
ConjunctivitisSulfacetamide eye drops
MalariaSulfadoxine + pyrimethamine
ToxoplasmosisSulfadiazine + pyrimethamine
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Drugs of Choice

Question Answer
DOC for syphilisBenzathine/Procaine Penicillin G
DOC for actinomycosisPenicillin G
DOC for Staph aureusMethacillin Group
DOC for ListeriaAmpicillin
DOC for endocarditis and H. pylori infectionAmoxicillin
DOC for Pseudomonas infectionPiperacillin
DOC for Rheumatic feverBenzathine Penicillin G
DOC for Listeria meningitis and Enterococcal infectionsAminopenicillins (Amoxicillin and Ampicillin)
DOC for prophylactic gonorrhea and syphilisBenzathine/Procaine Penicillin G
DOC for prophylactic bacterial endocarditisAmoxicillin
DOC for Staph aureus skin infections and abcessesCloxacillin
DOC for MRSAVancomycin
DOC for empiric treatment in adults against bacteria meningitisCeftriaxone
DOC for empiric treatment in pediatrics against bacteria meningitisCefotaxime
DOC for gonorrhoeaCeftriaxone
DOC for empirical treatment of nosocomial infections by suspected beta-lactamase-producing bacteriaCefepime
DOC Cephalosporin for PseudomonasCeftazidime
DOC for Enteric fever or salmnellosisCiprofloxacin, Ceftriaxone/Cefotaxime
DOC for Mycoplasma pneumonae, C.diphtheriae, Campylobacter jejuni, Chlamydia, Legionella, Bordetella pertussis, Streptococcus pyogenesEythromycin
DOC for Chlamydia, Mycobacterium avium, Toxoplasma gondii, Helicobacter pyloriClarithromycin
DOC for Chlamydia, M. avium, H influenza, NeisseriaAzithromycin
DOC for NocardiosisTrimethoprim – Sulfamethaxazole(TMP-SMX)
DOC for Pneumocystis jirovecii in AIDSTrimethoprim – Sulfamethaxazole(TMP-SMX)
DOC for Pneumocystis jirovecii prophylaxisTrimethoprim – Sulfamethaxazole(TMP-SMX)
DOC for Rocky Mountain Spotted FeverTetracyclines
DOC for typhusTetracyclines
DOC for Q feverTetracyclines
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(insert 2.27)
Question Answer
DOC for pertussisErythromycin
DOC for mycoplasma pneumoniaeErythromycin
DOC for typhoidCiprofloxacin
DOC for bacteroidesMetronidazole
DOC for CoccidioidesFluconazole
DOC for topical dermatophytesTerbinafine
DOC for esophageal and oropharyngeal candidiasisFluconazole
DOC for crytococcal meningitisFluconazole
DOC for vaginal candidiasisFluconazole
DOC for P. falciparum and P. malariaeChloroquine
DOC for vivax and ovaleChloroquine and Primaquine
DOC for chloroquine resistant P. falciparumQuinine
DOC for tissue amebiasisMetronidazole
DOC for luminal amebiasisDiloxanide Furoate
DOC for amoebic colitisMetronidazole + Diloxanide furoate
DOC for asymptomatic amebiasisDiloxanide furoate
DOC for hepatic amebiasisMetronidazole + Chloroquine + Diloxanide furoate
DOC of giardiasisMetronidazole/tinidazole
DOC of toxoplasmosisPyrimethamine + Sulfadiazine or TMP-SMX
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DOC for leishmaniasis : Sodium stibogluconate
Question Answer
DOC African sleeping sickness(late CNS stage of trypanosomiasis)Melarsopral
DOC Haemolymphatic stage of trypanosomiasisSuramin, Pentamidine
DOC Trypanosoma Cruzi (Chagas’ disease)Nifurtimox
DOC Intestinal nematodesMebendazole or albendazole or Pyrantel palmoate
DOC W.bancrofti, Loa Loa, Toxocara canisDiethylcarmazine
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DOC Onchocerca Volvulus: Ivermectin
Question Answer
DOC Drancuncula medinensisNiridazole
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General Principles and Clinical Use of Antimicrobials

(Insert table 2-3)
Question Answer
Lowest concentration of antibiotic which prevents visible growth of bacterium in cultured plates is thisMinimum inhibitory concentration
Antimicrobial action depends on length of time plasma concentration is above MICTime-Dependent Killing
Maximizing peak plasma levels increasing rate and extent of killing, single large dose administrationConcentration-Dependent Killing
This antibiotic class shows concentration-dependent killing effectAminoglycoside
Persistent suppression of bacterial growth after limited time exposure to an antimicrobial agent is known as thisPostantibiotic Effect
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(Insert 8)
Ototoxicity/nephrotoxicity-
AGs- never use with furosemide
Disulfiram like reaction with alcohol
Metroonidazole, Cephalosporins--??
CYP enzyme inhibitor like
Erythromycin, azole antifungal, HIV protease inhibitors
CYP enzyme inducer- rifampin
Question Answer
Appearance of a new infection with antimicrobial therapy. Suppression of normal microbial floraSuperinfection
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(Insert 11-16)
Question Answer
Endocarditis prophylaxis in patients with valvular heart diseases undergoing dental extraction, upper respiratory proceduresAmoxicillin/Clindamycin
Genitourinary/gastrointestinal proceduresAmpicillin/Vancomycin+Gentamycin
Surgical prophylaxisCefazolin
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Antifungal

Question Answer
Inhibitors of Fungal Membrane StabilityAmphotericin B, Nystatin
Inhibitors of Ergosterol SynthesisKetoconazole, Fluconazole, Itraconazole, Miconazole, clotrimazole and Terbinafine
Inhibitors of Fungal Cell Wall SynthesisCaspofungin, Micafungin
Inhibitors of Fungal DNA sunthesisFlucytosine
Inhibitors of Fungal mitosisGriseofulvin
The mechanism of action binds to ergosterol in fungal cell membranes change in membrane permeability allowing leakage of intracellular componentsAmphotericin B
Broad spectrum of action - Aspergillus, candidia, cryptococcus, histoplasma, mucor, sporothrix. Remains drug of choice for nearly all life threatening fungal infectionsAmphotericin B
Adverse effects include infusion related fever chills, muscle rigor, hypotension and dose dependent nephrotoxicity - reduced GFR, tubular acidosis, Hypokalemia, anemia by decreased erythropoietinAmphotericin B
This form of amphotericin B is better tolerated and has reduced nephrotoxicityLiposomal Amphotericin B
Drug used in combination with amphotericin B that can reduce the adverse effects of amphotericin BFlucytosine
The mechanism of action acts by disrupting fungal membrane by binding to ergosterolNystatin
Used as a topical cream used to vaginal candidiasis. Orally to treat oropharyngeal candidiasisNystatin
The mechanism of action inhibits fungal CYP3A (lanosterol 14-demethylase) enzyme which is responsible for converting lanosterol to ergosterol. Specifically inhibits at the step of 14-alpha-demethylation of lanosterolAzoles
Clotrimazole, econazole and miconazole are examples of these type of antifungalsTopical Azoles
This drug requires an acid environment is needed to dissolve drug. Does not enter the CNS wellKetoconazole
Adverse effects of this drug include gynaecomastia, loss of hair and libido, oligospermiaKetoconazole
This drug has low CNS effects and is not effective against fungal meningitisKetoconazole
A CYP3A4 inhibitor inhibits metabolism of warfarin, sulfonylureas, cyclosporine, terfenadineKetoconazole
Use as a systemic drug has fallen out of clinical use in the USA. However it is currently used as a topical antifungal in creams for treating dermatophytosis & candidiasis, and as a shampoo for the treatment of seborrheic dermatitisKetoconazole
Disadvantage of this drug is that it has a greater propensity to inhibit mammalian CYP-450 compared to other “azoles”Ketoconazole
Well absorbed orally, enters CNS. Least effect on liver enzymes. Used orally, i.v, eye dropFluconazole
Drug of choice in esophageal and oropharyngeal candidiasis. DOC for infections caused by Coccidioides. For vaginal candidiasis. Used for treatment of cryptococcal meningitisFluconazole
It is a CYP inhibitor - Drug-drug interactions, similar to ketoconazole but to lesser degreeItraconazole
Use as a broad spectrum antifungal indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients - Blastomycosis, pulmonary and extrapulmonary. Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis. Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapyItraconazole
Prevents ergosterol synthesis by inhibiting squalene epoxidase. This leads to squalene accumulation which causes membrane disruption and cell deathTerbinafine
This drug inhibits squalene epoxidaseTerbinafine
Terbinafine inhibits this enzymeSqualene Epoxidase
First line of therapy for Dermatophyte infections tinea pedis/ corporis/cruris/capitis and pityriasis versicolorTerbinafine
Used to treat fungal infections of the nails (Onychomycosis). For fungal infection of the nail, is given for a long time (6-12 weeks). It is given orally and also is available for topical administrationTerbinafine
The mechanism of action binds to microtubules comprising the spindles and inhibits fungal mitosisGriseofulvin
Used in infections of skin, hair, nails - needs prolonged therapy (2-6 weeks) for resultsGriseofulvin
A CYP Enzyme inducer- Induces metabolism of drugs (eg warfarin, oral contraceptives). Adverse effects includes disulfiram like reaction with alcoholGriseofulvin
A prodrug that is converted to 5-fluorouracil by cytosine deaminase and in turn inhibits thymidylate synthaseFlucytosine
5-flucytosine is converted to 5-fluorouracil by this enzymeCytosine Deaminase
This drug is usually combined with fluconazole and sometimes amphotericin BFlucytosine
Indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or CryptococcusFlucytosine
Adverse effects include bone marrow suppression (anemia, leukopenia & thrombocytopenia)Flucytosine
Capsofungin and Micafungin are examples of this type of antifungalCell Wall Inhibitor
The mechanism of action is to inhibit Fungal cell wall by inhibiting synthesis of beta-glucanCapsofungin, Micafungin
Uses include treatment of invasive Aspergillus in patients who cannot tolerate, or have failed therapy with amphotericin B. Oral & esophageal Candidiasis refractory to azoles & amphotericin BCapsofungin, Micafungin
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