antibiotics quick review

ANTIBIOTICS QUICK REVIEW

Agents That Inhibit Peptidoglycan Synthesis

Drug Structure Mech. of Action Pharmacology Side Effects ResistancePenicillinsNatural

Nucleus6-aminopenicillanic acid

beta lactam ring thiazolidine ring-side chain radicals determine properties of different penicillian types

blocks peptidoglycan synthesis

blocks Transpeptidases and Carboxypeptidases involved in cell wall synthesis

active autolytic enzymes Bactericidal against growing

bacteria

Natural Penicillins Penicillin G

acid labile narrow spectrum high potency

Penicillin V same but low potency

Hypersensitivity penicilloyl can act as

hapten

Beta Lactamase- breaks lactam ring

Altered cell wall formation

Tolerance sometimes autolytic

enzymes not activated by Penicillin

results in: Low MIC High MBC

Semisynthetic various side chains added to nucleus to create various effects

stable in stomach acid wider spectrum Beta lactamase

resistance

CephalosporinsNote:Semisynthetic cephalosporins similar to Penicillin’s

like Penecillin except: Dihydrothiazine ring

same as Penicillin above Broad spectrum (gram+ -)

Bactericidal Parenterally admin. orally admin.

Hypersensitivity same as Penicillin

Beta Lactamase Inhibitor

Little antimicrobial activity given in combination with beta lactam sensitive drugs

Examples: Augmentin = Clavulanic Acid + Amoxycillin Timentin = Clavulanic Acid + Ticarcillin Unasym = Sulbactam + Ampicilin Zosyn = Tazobactam + Piperacillin

Vancomycin Blocks transfer of Amino Sugars onto growing peptidoglycan

Narrow spectrum Bactericidal

Neurotoxic Nephrotoxic

alteration of cell wall Tolerant organisms

Bacitracin same as above Topical application Oral administration

Nephrotoxic

Cycloserine Blocks D-alanine incorporation into Peptidoglycan

Narrow Spectrum: Mycobacterium tuberculosis

CNS toxicity

Agents That Block Protein Synthesis by Binding Ribosomal SubunitsDrug Category Specific MOA Bugs Side Effects Resistance

Aminoglcosides Gentamicin Streptomycin Tobramycin Amikacin

Bactericidal Blocks formation of initiation complex

mRNA misreading

Narrow spectrum

- gram (-) rods Ototoxicity

- especially in combo with loop diuretics

Nephrotoxicity

Enzymatic modification - Acetyltransferase Blocks transport into cell Alteration of biding site

TetracyclinesDoxycycline and Minicycline (cleared in feces.. use in renal failure)Mini dox feces

Bacteriostatic Prevents attachement of charged tRNA

Renal clearance except for mini dox

Broad SpectrumChlamydiaBorrelia burgdorferiRickettsiae (Board Question!)AcneTularemiaCholeraUreaplasmaMycoplasma

CB RAT CUM

Discoloration of kids teeth

Bone growth block in kids

GI Fanconi’s Syndrome Photosensitivity

Plasmid less Permeable bacteria Resistant to All if resistant

to one

Chloramphenical Bacteriostatic Blocks peptidyl transferase

Meningitis bugsH influenzaN meningitidisStrep Pneumonia

Marrow depression Aplastic Anemia Gray baby

(premies with low liver UDP-glucuronyl transferase)

Acetyltransferase altered cell wall decreasing

permeability

Erythromycin Bacteriostatic Blocks

TranslocationGram (+) CocciLegionellaMycoplasmaNeisseriaChlamydia LMN C+(C+ is as easy as LMN) (not ABC)

Hepatotoxic GI

altered cell wall decreasing permeabilty

alteration of 50S binding site

Cross resistance between macrolides & lincosamides

Lincosamides Lincomycin

Bacteriostatic

Clindomycin

Agents Inhibiting Nucleic Acid FunctionDrug Category Specific MOA Bugs Side Effects Other

Metronidazole Bactericidal Steps1. Passive Diffusion into cell2. Reduction of drug produces toxic intermediates3. breaks bacterial DNA

Narrow spectrum- Anaerobic bacteria/protazoa- Amebiasis - Giardia- Gardenella- Trichomoniasis

vAGinA and GuT

Disulfiram – like rxnVestibular dysfunction

I took the Metro and got dizzy and vommitted (disulfarim-like)

Rifampin Blocks RNA Polymerase

Anti-TB broad spectrum, but

resistancedevelopes quickly so must be

used in Combination with others

The 4 R’s for R ifampin - RNA Polymerase- Revs up P450- Red/orange body

fluid- Resistance is rapid

Nalidixic Acid Bactericidal Blocks DNA Gyrase

UTI Cartilage and Tendon damage in animal studiesCI- Pregnancy- Kids

Quinolones “ “ “

Mechanism of action not exactly clear:

Drug Structure Mech. of Action Pharmacology Side Effects ResistanceIsoniazid (INH) Pyridoxine

(B6) Analog ? Antagonizes

Pyridoxine catalyzed reactions

Anti-TB quick resistance so combine with

other anti-TB drugs Narrow spectrum

NitrofuransNitrofurantoin

? oxidation of Pyruvic Acid

Bacteriostatic Broad Spectrum

Ethambutol ? Anti-TB quick resistance so combine with

rare retinal damage

other anti-TB drugs

Agents Blocking Folic Acid Synthesis

Drug Structure Mech. of Action Pharmacology Side Effects ResistanceSulfonimidesSulfanilamideSulfamethoxazole

various side chains

PABA Analogs tie up

Tetrahydropteroic acid synthetase

Purine synthesis inhibited

Urinary tract infections Bacteriostatic Broad Spectrum

Hypersensitivity PABA Overproduction Structural alteration of

Tetrahydropteroic acid Folic Acid dependency Decreased permeability

SulfonesDDS

unknown, but probably like above

Leprosy treatment Narrow Spectrum

unknown mechanism

Trimethoprim Blocks dihydrofolate reductase

prevents folic acid synthesis

Purine synthesis inhibited

mixture of Trimethoprim and Sulfamethoxazole will inhibit 2 steps in folic acid synthesis thereby increasing spectrum of activity

same as sulfonimides

same as sulfonimides but based on Dihydrofolate reductase

Agents that Damage Cell Membrane

Drug Structure Mech. of Action Pharmacology Side Effects ResistancePolymixinPolymixin BPolymixin E (Colistin)

Polypeptide Cationic Detergent Bactericidal against Resting and Dividing bacteria

Narrow Spectrum Topical Ointments

Neurotoxic- dose related / reversible

Nephrotoxic- dose related

Altered cell wall to protect inner membrane

Agents with Unknown Mechanisms of Inhibition

Drug Structure Mech. of Action Pharmacology Side Effects ResistanceIsoniazid (INH) Pyridoxine

(B6) Analog ? Antagonizes

Pyridoxine catalyzed reactions

Anti-TB quick resistance so combine with

other anti-TB drugs Narrow spectrum

NitrofuransNitrofurantoin

? oxidation of Pyruvic Acid

Bacteriostatic Broad Spectrum

Ethambutol ? Anti-TB quick resistance so combine with

other anti-TB drugs

rare retinal damage