First Aid Pharmacology Antimicrobials

8/12/2019 First Aid Pharmacology Antimicrobials

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Flash cards by Seetal K. Dhaliwal H. SSection V

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Antimicrobial therapy:Mechanism of Action Drugs

Block cell wall synthesis by inhibition of

peptidoglycan cross-linking

Penicillin, ampicillin, ticarcillin, piperacillin, imipenam,

aztreonam, cephalosporins.

Block peptidoglycan synthesis Bacitracin, vancomycin

Disrupt bacterial cell membrane Polymyxins

Block nucleotides synthesis Sulfonamides, trimethoprim

Block DNA topoisomerase FluoroquinolonesBlock mRNA synthesis Rifampin

Block protein synthesis at 50S ribosomal Chloramphenicol, Macrolides, Clindamycin, Linezolid,

Streptogamins (quinupristin, dalfopristin)

Block protein synthesis at 30S ribosomal Aminoglycosides, Tetracyclines

Bacteriostatic Erythromycin, Clindamycin, Sulfamethoxazole,

Trimethoprim, Tetracyclines, Chloramphenicol.

Bactericidal Vancomycin, Fluoroquinolones, Penicillin,

Aminoglycosides, Cephalosporins, Metronidazole.

ECSTaTiCbacteriostatics.

Very Finely Proficient

At Cell Murder

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Penicillins: Penicillin G (IV) and Penicillin V (oral):

Binds PBP, blocks transpeptidase of cell wall cross-linking, activate autolytic enzymes.

Bactericidal for gram postive cocci and rods & gram negative cocci and spirochetes. -lactamase sensitive. May cause hypersensitivity reactions & Hemolytic anemia.

Methicillin, Nafcillin, Dicloxacillin (penicillinase-resistant penicillins):

Narrow spectrum. -lactamase resistant due to heavier R group.

Used forS. aureus (except MRSA due to altered PBP site); Use Naf for Staph

May cause hypersensitivity reactions; methicillin interstitial nephritis. Ampicillin, Amoxicillin (aminopenicillins):

Broad spectrum (-lactamase sensitive); Clavulanic acid/Sulbactam (penicillinase inhibitor)

enhances spectrum. AmOxicillin has greater Oral bioavailability than ampicillin.

Used in some gram positive bacteria & gram neg rodsH. pylori (amoxicillin),H. influenzae, E.coli, Listeria monocytogenes (ampicillin),Proteus mirabilis,Salmonella, enterococci & Borrelia

(amoxicillin); Ampicillin/Amoxicillin HHELPS kill enterococci & Borrelia

May cause hypersensitivity reactions, rash or pseudomembranous colitis.

Ticarcillin, carbenicillin, piperacillin (antipseudomonals):

Extended spectrum; TCP takes care ofPseudomonas; Used to kill Pseudomonas spp., and gram

neg rods; -lactamase sensitiveuse with clavulanic acid. Synergistic with aminoglycosides.

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Cephalosporins:

1st generation (cefazolin, cephalexin) PEcK:

Gram positive cocci,Proteus mirabillis, E. coli, Klebsiella pneumoniae.

2nd generation (cefoxitin, cefaclor, cefuroxime) HEN PEcKS:

Gram positive cocci,H. influenzae, Enterobacter aerogenes, Neisseria spp.,Proteus

mirabillis, E. coli, Klebsiella pneumoniae,Serratia marcescens. 3rd generation (ceftriaxone, cefotaxime, ceftazidime):

Serious gram neg infections; meningitis (penetrates BBB); ceftazidinepseudomonas;

ceftriaxone gonorrhea.

:

Activity against organisms.

Toxicity:

Hypersensitivity reactions. Cross hypersensitivity with penicillins (in 510%).

nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (incephalosporins with a methylthiotetrazole groupi.e. cefamandole)

-lactam drugs that inhibit cell wall

synthesis but are less susceptible to

penicillinase. Bactericidal.

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Aztreonam:

MOA: same as penicillin &

cephalosporins.

Resistant to -lactamase. No cross

allergenicity with penicillins.

Used for gram neg rodsKlebsiellaspp., Pseudomonas spp., Seratia spp.

No activity against gram positive or

anaerobes.

For penicillin-allergic patients & those

with renal insufficiency who cannot

tolerate aminoglycosides.

Toxicity:

Usually nontoxic; occasionally GI

upset. No cross sensitivity withpenicillins or cephalosporins.

Imipenem/cilastin, meropenem:

MOA: same as penicillin &cephalosporins.

Resistant to -lactamase (carbapenem).Imipenem is broad spectrum:

Administered with ciLASTIN to

inactivation in renal tubules. Used for gram positive cocci, gram ned

rods, & anaerobes. DOC forEnterobacter.

The significant side effects limit use to

life threatening infections, or after drugshave failed. Meropenem, however, hasreduced risk of seizures & is stable todihydropeptidase I.

Toxicity:

GI distress, skin rash, & CNS toxicity

(seizures) at high plasma levels.

With Imipenem, the kill is LASTIN with ciLASTIN.

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Vancomycin:

MOA: inhibits cell wall mucopeptide

formation by binding D-ala D-ala.

Resistance occurs when aa change from

D-ala D-ala to D-ala D-lac.

Used for serious, gram-positive multi-

drug resistant organisms;

S. aureus, C. difficile -

pseudomembranous colitis.

Toxicity:

Nephrotoxicity, Ototoxicity,Thrombophlebitis, diffuse flushing

red man syndrome (can large

prevent by pretreatment with

antihistamines and slow infusion rate).

Well tolerated in generaldoes NOT

have many problems.

Protein synthesisinhibitors:

Buy AT 30, CCELL (sell) at 50

30S inhibitors:

Aminoglycosides (bactericidal)

Tetracycline (bacteriostatic)

50S inhibitors:

Chloramphenicol, Clindamycin

(bacteriostatic)

Erythromycin & other macrolides

(bacteriostatic)

Lincomycin (bacteriostatic)

Linezolid (variable)

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Aminoglycosides: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycinbactericical.

Inhibits formation of initiation complex & cause misreading of mRNA. Require O2

for uptakecannot kill anaerobes

Mean GNATS canNOT kill anaerobes Used for severe gram neg rod infections. Synergistic with -lactam antibiotics.

Neomycin for bowel surgery.

Nephrotoxicity (especially when used with cephalosporins). Ototoxicity (especially

when used with loop diuretics). Terotogen.

Macrolides: Erythromycin, Azithromycin, Clarithromycinbacteriostatic.

Inhibits protein synthesis by blocking translocation; bind to the 23 rRNA of the

50S ribosomal subunit. Used for URIs, pneumonias, STDsgram positive cocci, Mycoplasma, Legionella,

Chlamydia, Neisseria.

Prolonged QT interval (especially erythromycin), GI discomfort (most common

cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes.

Increases serum concentration of theophyllines, oral anticoagulants.

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Tetracyclines:

Tetracycline, doxycycline, democlocycline, minocycline.

Binds 30S & prevents attachment of aminoacyl-tRNA; limited CNS

penetration. Doxycycline is fecally eliminated & is safe in renal failure

patients. Must NOT take with milk, antacids, or iron-containing preparations

because divalent cations inhibit absorption in gut. Used in Vibrio cholerae, Acne, Chlamydia, Ureaplasma Urealyticum,

Mycoplasma pneumoniae, Tularemia,H. pylori, Borrelia burdorferi (Lyme

disease) & Ricketssia.

Toxicity:

GI distress, dicoloration of teeth & inhibition of bone growth in children,photosensitivity.

Contraindicated in pregnancy.

VACUUM The BedRoom.

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Chloramphenicol:

Inhibits 50S

peptidlytransferase.

Used in meningitis (H.

influenzae, N. meningitidis, S.

pneumoniae).

Conservative owing to toxicities.

Toxicity:

Anemia (dose dependent), aplastic

anemia (dose dependent), graybaby syndrome (in preemies due to

lack of liver UDP-glucuronyl

transferase)

Clindamycin:

Blocks peptide bond

formation at 50S subunit.

Treats anaerobes above the

diaphragmBacteroides

fragilis, Clostridium

perfringens.

Toxicity:

Pseudomembranous colitis (C.

difficile overgrowth), fever,

diarrhea.

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Sulfonamides:

Sulfamethoxazole (SMX),

sulfisoxazole, sulfadiazine.

PABA antimetabolites inhibit

dihydropteroate synthetase.

Used in gram positive, gram neg,Nocardia, Chlamydia. Triple Sulfas

or SMX for simple UTI.

Toxicity:

Hypersensitive reactions, hemolysis if

G6PD deficiency, nephrotoxicity(tubointerstitial nephritis),

photosensitivity, kernicterus, displace

other drugs from albumin (i.e.

warfarin)

Trimethoprim:

Inhibits bacterial dihydrofolate

reductase.

Used with sulfonamides (TMP-

SMX), causing sequential block of

folate synthesis. Combination used for recurrent

UTIs, Shigella, Salmonella,

Pneumocystis jiroveci pneumonia.

TMP Treats Marrow Poorly

Toxicity:

Megaloblastic anemia,

leukopenia, granulocytopenia.

May alleviate with supplemental

folinic acid.

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Fluoroquinolones:

Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin,enoxacin & nalidic acid (a quinolone).

Used for gram neg rods of urinary and GI tracts (including Pseudomonas),

Neisseria, & some gram positive organisms.

Toxicity:

GI upset, superinfections, skin rashes, headache, dizziness. Contraindicated in

pregnancy & children damages cartilage. Tendonitis & tendon rupture in adults, leg

cramps & myalgia in kids.

Inhibit DNA gyrase

(topoisimerase II). Must not be

taken with antacids. Bactericidal.FluoroquinoLONES hurt your BONES

Metronidazol: Treats Giardia, Entamoeba, Trichomonas, Gardenella vaginalis, Anaerobes

(Bacteriodes, Clostridium). Used with bismuth & amoxicillin (or tetracycline) for

triple therapy of H. Pylori.

Toxicity:

Disulfiram-like reaction with alcohol; headache, metallic taste.

Forms toxic metabolites in bacterial cell that damage DNA.

Bactericidal & antiprotozoal.

GAP METRO

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Polymixins:

Bind to cell membrane of bacteria & disrupt their osmotic properties. Polymyxins

are cationic, basic proteins that act like detergents.

Used for resistant gram negative infections.

Toxicity:

Neurotoxicity, acute renal tubular necrosis.

Polymyxin B, polymyxin E.

MYXins MIX up membranes.

Antimicrobial drugs:Bacterium Prophylaxis Treatment

M. tuberculosis Isoniazid ifampin, soniazid, yrazinamide,thambutol ( for treatment)

M. avium-intracellulare Azithromycin Azithromycin, rifampin, ethambutol,

streptomycin

M. leprae NA Dapsone, rifampin, clofazimine

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Anti-TB drugs

INH-SPIRE (inspire):

Isoniazid (INH), Streptomycin, Pyrazinamide, Rifampin, Ethambutol.

Cycloserine (2nd line therapy)

Ethambutol optic neuropathy (red-green color blindness). For other drugshepatotoxicity.

Isoniazid (INH): Injures Neurons & Hepatocytes

Synthesis of mycolic acids.

Causes neurotoxicity & hepatotoxicity. Pyridoxine (Vit B6) prevents neurotoxicity.

Rifampin:

Inhibits DNA-dependent RNA polymerase.

Delays resistant to dapsone when used for leprosy. Used for meningococcal

prophylaxis & chemoprophylaxis in contacts of children with Haemophilus influenzae

type B.

Minor hepatotoxicity & drug interactions ( CYP450); orange body fluids(nonhazardous side effect).

Rifampins 4 Rs:RNA polymerase inhibitor

Revs up microsomal P-450

Red/Orange body fluids

Rapid resistance if used alone13


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Antifungal therapy:14


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Amphotericin B: Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of

electrolytes.

Used for Cryptococcus, Blactomyces, Coccidioides, Aspergillus, Histoplasma,

Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not

cross BBB.

May cause fever/chills (shake & bake), hypotension, nephrotoxicity,

arrhythymias, anemia, IV phlebitis (amphoterrible). Hydration reduces

nephrotoxicity. Liposomal amphotericin reduces toxicity.

Nystatin: Binds ergosterol disrupting fungal membranes. Too toxic for systemic use.

Swish and swallow for oral Candidiasis (thrush); topical for diaper rash or

vaginal candidiasis.

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Azoles:

Inhibits fungal sterol (ergosterol) synthesis.

Used for systemic mycoses. Fluconazole for Cryptococcal meningitis in AIDS

(can cross BBB), & candidal infections of all types (i.e. yeast infections).

Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans;

hypercortisolisms. Clotrimoxazole & miconazole for topical fungal infections.

Toxicity causes hormone synthesis inhibition (gynecomastia), liver dysfunction

(inhibits CYP450), fever, chills.

Flucytosine:

Inhibits DNA synthesis by conversion to 5-fluorouracil.

Used in systemic fungal infections (candidiasis, cryptococcus) in combination with

amphotericin B.

Causes nausea, vomiting, diarrhea and bone marrow suppresion.

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Terbinafine: Inhibits fungal enzyme squalene epoxidase.

Used to treat dermatophytoses (especially onychomycosis).

Caspofungin: Inhibits cell wall synthesis by inhibiting synthesis of -glucan.

Used to treat invasive aspergillosis.

Causes GI upset, flushing.

Griseofulvin: Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing

tissues (nails).

Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea,ringworm).

Teratogenic, carcinogenic, confusion, headaches, CYP450 & warfarin metabolism.

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Antiviral Chemotherapy:

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Amantadine:

Blocks viral penetration/uncoating (M2 protein); may buffer pH of endosome. Alsocauses the release of DA from intact nerve terminals.

Prophylaxis & treatment of Influenza A; Parkinsons disease.

Toxicity ataxia, dizziness, slurred speech.

Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine, sonot used.

Amantadine blocks influenza A & rubellA & causes problems with the cerebellA.

Rimantidine is a derivative with fewer side effects. Does not cross BBB.

Zanamivir, oseltamivir: Inhibits Influenza neuraminidase, decreasing the release of progeny virus.

Treatment of both Influenza A and B.

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Acyclovir:

Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog.Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA

polymerase by chain termination.

Used for HSV, VZV, EBV, HSV-induced mucocutaneous & genital lesions as well as

for encephalitis. Prophylaxis in immunocompromised patients. For herpes zoster,

use famciclovir. No effects on latent forms of HSV and VZV.

Generally well tolerated. Resistance develops when lack thymidine kinase.

Ribavirin: Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP

dehydrogenase.

Used for RSV & chronic Hepatitis C.

Causes hemolytic anemia. Severe teratogen.

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Ganciclovir:

5-monophosphate formed by a CMV viral kinase of HSV/VZV thymidine kinase.Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits

viral DNA polymerase.

Used for CMV, especially in immunocompromised patients.

Toxicity leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to

host enzymes than acyclovir.

Resistance develops if mutated CMV DNA polymerase of lack viral kinase.

Foscarnet: Viral DNA polymerase inhibitor that binds pyrophosphate-bindinig site of the

enzyme. Does not require activation by viral kinase.

Used for CMV retinitis in immunocompromised patients when Ganciclovir fails &for acyclovir-resistant HSV.

Causes nephrotoxicity.

Resistance develops with mutated DNA polymerase.

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HIV therapy: Protease Inhibitors:

Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir.

Toxicity GI intolerance (nausea, diarrhea), hyperglycemia, lipodystrophy, thromocytopenia

(indinavir).

Reverse transcriptase inhibitors:

Nucleosides (Zidovudine [ZDV/AZT], didanosine [ddI], zalcitabine [ddC], stavudine [d4T],

lamivudine [3TC], abacavir): Have you dined (vudine) with my nuclear (nucleosides) family?

Non-nucleosides (Nevirapine, Efavirenz, Delavirdine): Never Ever Deliver nucleosides.

Toxicity: bone marrow suppression (neutropenia, anemia), peripheral neuropathy, lactic acidosis

(nucleosides), rash (non-nucleosides), megaloblastic anemia (ZDV), pancreatitis (ddI). GM-CSF &erythropoietin can be used to reduce bone marrow suppression.

Part of HAART. Used when CD4


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Interferons: Glycoproteins from human leukocytes that block various stages of viral RNA & DNA

synthesis. Induce ribonuclease that degrades viral mRNA.

IFN- chronic Hepatis B & C, and Kaposis sarcoma;

IFN- MS;

IFN- NADPH oxidase deficiency.

Toxicity: Neutropenia

Antibiotics to avoid in pregnancy: Sulfonamideskernicterus

Aminoglycosidesototoxicity

Fluoroquinolonescartilage damage

Erythromycinacute cholestatic hepatitis in moms (and

clarithromycinembryotoxic) Metronidazolemutagenesis

Tetracyclinediscolored teeth & inhibition of bone growth

Ribavirinteratogenic

Griseofulvinteratogenic

Chloramphenicol gray baby

SAFE Moms Take

Really Good Care

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First Aid Pharmacology Antimicrobials

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