Block 3-Antibiotics

Question 1

Antibiotics Cell wall synthesis inhibitors

Answer 1

• Beta-lactam ring common to all penicillins, Cephalosporins/Cephamycins, Carbapenems, Beta lactamase inhibitors
• Action of Betalactamases:
• Secreted by bacteria to provide resistance to beta-lactam antibiotics (penicillin)-Ex ESBL ^{<strong>(EXTENDED-SPECTRUM BATALACTASMASES)</strong>}
• Break down the beta-lactam ring=^{<u><strong>NON-toxic to bacteria</strong></u>}
• Genes are carried in plasmid, which carries other resistances

Question 2

Penicilins Cell wall synthesis inhibitors

Answer 2

• Nucleus: 6-aminopenicillanic acid-Beta lactam ring, Thiazolidine ring
• R-group: Semisynthetic penicillins
• Naturally occuring = Penicillin G & V ^{<u><strong>(Given only through INJECTION) </strong></u>}
• Narrow spectrum
• Works against gram (+) bacilli, cocci
• Against Gram (-) cocci & spirochetes
• Poor against gram (-) rods
• Semi-synthetic = Ampicillin, Amoxicillin, Methicillin ^{<u><strong>(can be GIVEN ORALLY)</strong></u>}
• R-groups allow for:
• Increases resistance to stomach acids
• Increases absorption in GI
• Resistance to Beta-lactamases
• Increases spectrum
• Work better against Gram (-) rods

Question 3

Penicilins Cell wall synthesis inhibitors (MOA)

Answer 3

• Interferes w/peptidoglycan synthesis:
• PBP (penicillin binding proteins)
• Transpeptidases
• Transcarboxypeptidases
• Carboxypeptidases
• Results in the interuption of polymerization
• Accumulation of peptidoglycan monomers LEADS to activation of autolytic enzymes (^{<u><strong>murein hydrolases</strong></u>}) = Lysis & bacteriocidal
• Staph aureus Murein hydrolases are NOT activated = Bacteriostatic ^{<strong>(INHIBIT GROWTH OF PATHOGEN, REVERSIBLE)</strong>}

Question 4

Cephalosporins Cell wall synthesis inhibitors

Answer 4

• Structure: 7-aminocephalosporanic acid, Betalactam ring + Dihydrothiazine ring
• Change in R-group through generations
• 1-4 generation go from narrow TO wide spectrum & 4th gen primarly against Pseudomonas aeruginosa (Gram -)
• Mode of action very similar to Penicillin

Question 5

Carbapenems Cell wall synthesis inhibitors

Answer 5

• ImiPENEM & meroPENEM
• Bactericidal-Broad spectrum compared to penicillins & cephalosporins ^{<u><strong>(GRAM - &amp; + and Obligate anaerobes-NO O2)</strong></u>}
• Work against MOST beta-lactamases including ESBLs
• Used only ICU when treatment of appropriate Antibiotic is unknown
• Named “carba” due to sulfur group on bectalam replaced by carbon
• Resistance by bacteria:
• Gram (-) rods have developed carbapenemase to inactivate
• Multi-drug resistant

Question 6

Vanomycin Cell wall synthesis inhibitors

Answer 6

• Structure: Large glycopeptide
• MOA: inhibits cross linking of peptidoglycan by binding to terminal D alanine ^{<u><strong>(NAM)</strong></u>}
• Pharm: BacteroCIDAL, Narrow, Gram (+)
• Bacteria resistance:
• Van A/B genes replace last D alanine w/Lactic Acid
• Gene carried on plasmids & transposon
• Strains of Enterococcus Spp & Staph aureus resistant

Question 7

Cell wall synthesis inhibitors

Answer 7

• Bacitracin-Large cyclic peptide
• MOA:
• binds to bactrophenol = inhibits transportation of Peptidoglycan precursors
• BecteroCIDAL
• Pharm: Narrow, Gram (+), Nephrotoxic, Topical
• Mycobacterial infections (acid fast):
• Cyclserine-Analog of D-alanin-Inhibit peptidoglycan synthesis
• Isoniazind (INH)-Inhibit mycolic acid synthesis (^{<u><strong>Mycobacterium tuberculosis)</strong></u>}
• Ethambutol: Intereferes w/synthesis of arabinogalactan

Question 8

Bata Lactamase inhibitors

Answer 8

• Structural analogue of penicillin
• Given together w/penicillin have little to no antibacterial properties JUST HELP penicillin fight against bacteria
• Calvulanic acid:
• Augmentin = Calvulanic + amoxycillin
• Sulbactam:
• Unasym = Sulbactam + Ampicillin
• Tazobactam:
• Zosyn = tazobactam + piperacillian
• Activity of all: Improved resistance against betalactamase bacteria

Question 9

Cell wall inhibitors-Bacerial resistance

Answer 9

• Mechanism:
• Intrinsic resistance-Bacteria lacking peptidoglycan (Chlamydia, Chlamydophila, Mycoplasma, Ureaplasma, Orientia, Ehrlichia and, Anaplasma)
• Mutation of porin proteins-Decrease perm among gram (-)
• Inactivating enzymes:
• Beta-lactamase-Have extended spectrum (ESBL)-^{<u><strong>Ineffective against carbapenems</strong></u>}
• Gene carried on plasmid-Could carry genes for other drug resistance (multidrug R-plasmids)
• Mutation of penicillin binding proteins (PBP)-Ex. Methichillin resistant Staph ^{<u><strong>(MRSA)</strong></u>}

Question 10

Antibiotics inhibit protein synthesis (30s)

Answer 10

• Aminoglycosides: Amino-sugar linked by glycosidic bonds to other sugars
• Natural-
• Streptomycin
• Neomycin
• Gentamicin
• Synthetic:
• Amikacin
• NetilMICIN
• MOA:
• Inhibit protein synthesis by interfering w/Function of 30S ribosome
• Inhibit initiation complex & misreading mRNA
• O2 dependent uptake into bacteria
• Ineffective against abscess & gram (+)

Question 11

Antibiotics inhibit protein synthesis (30s)

Answer 11

• Aminoglycosides
• Pharmacology:
• BacteriCIDAL-Narrow
• Effective against Aerobes (o2 dependent)
• Gram (-)
• Streptomycin - Mycobacterium (acid fast)
• Poorly absorbed in GI
• SE:
• 8th Cranial nerve damage = Hearing loss & or loss of balance (vestibulocochlear)
• Nephrotoxic
• Mech of resistance by bacteria:
• Enzymatic mod
• Transport interference=Decreased uptake
• Mutatation to Ribosomal binding site
• Accerlerated EXPORT out

Question 12

Antibiotics inhibit protein synthesis (30s)

Answer 12

• Tetracyclins:
• Structure-4 joined cyclic rings
• Mech-Reversible binding to 30S=Prevents binding of tRNA to mRNA
• Pharm: BacteroSTATIC, Broad-Mycoplasma ^{<u><strong>(CELLWALL LESS)</strong></u>}, Rickettisia ^{<u><strong>(PLEOMORPHIC)</strong></u>}, Chlaymidia
• Meds are photosensitive not as effective
• SE:
• Discoloration of teeth
• Ca+2 & Fe+3 Chelator (bind to)
• Suppress normal flora-GI/Vaginal
• Mech of Bacterial resistance:
• Decrease perm
• Active efflux
• Alteration to ribosomal bind site
• Enzymatic mods

Question 13

Antibiotics inhibit protein synthesis (50S)

Answer 13

• Macrolides
• Structure-Large lactone ring w/2 sugars
• Erythromycin, Azithromycin, Clarithromycin
• MOA: Binds to 50S=Prevents release of tRNA after formation of peptide bond
• Pharm=BacteroSTATIC, Broad, Gram (+)&(-), Chlamydia & mycoplasma ^{<u><strong>(cellwall less)</strong></u>}
• Drug of choice for pts w/penicillin allergy
• Mech of bacterial resistance:
• Alteration of 50s
• Enzymatic Mods
• SE:
• GI disturbance due to supression of flora

Question 14

Antibiotics inhibit protein synthesis (50S)

Answer 14

• _Chloramphenoicol-Nitrobenzine _
• MOA: binds reverisbly to 50S-inhibits protein synthesis @ peptidyl transferase or ELONGATION stage
• Pharm:
• BacterioSTATIC
• Broad-Includes Anaerobes (Abscess effective)
• SE:
• Bone marrow toxicity-Aplastic anemia (autoimmune)
• Acts as Hapten illicits Immune reponse once bound to LARGER mols
• Mech of bacterial resistance:
• Enzymatic resitance
• Decreased perm

Question 15

Antibiotics inhibit protein synthesis (50S)

Answer 15

• Lincosamides-Clindamycin & Linomycin
• MOA: Binding to 50s prevent peptide bond formation
• Pharm: BacterioSTATIC (Gram + & anaerobes) Ineffective against GRAM-
• Narrow spectrum
• Mech of bacterial resistance:
• Methylation of 23s rRNA
• SE: Supression of GI flora

Question 16

Antibiotics inhibit protein synthesis (50S)

Answer 16

• Streptogramins-Quinupristin & Dalfopristin
• MOA:
• Both derivatives given @ same time(^{<u><strong>synergistic)</strong></u>}
• Inhibits protein synthesis-
• Dalfo: Binds to 50s prevents peptide chain ELONGATION
• Quinu: Premature release of peptide
• Pharm: BacteriCIDAL-Gram +
• Recommended for Vancomycin^{<u>(inhibits corss-linking or D on NAM)</u>} resistant staph & enterococcus

Question 17

Antibiotics inhibit protein synthesis (50S)

Answer 17

• Oxazolidinones-Linezolid
• MOA: Binds to 50s interfere w/formation of initiation complex
• Pharm:
• Vancomycin resistant-Enterococcus (VREF)
• Methicillin resistant-Staph aureus (MRSA)
• BacterioSTATIC

Question 18

Antimetabolites inhibition of Folic

Answer 18

• Sulfonamide & Trimethoprim
• MOA:
• Sulfo - are structural analogue of PABA (p-aminobezoic acid)=Compete in binding
• Trimeth-prevents folic acid synthesis DIRECTLY acting on ^{<u><strong>DIHYDROFOLATE REDUCTASE</strong></u>}
• Stopping folic acid production eventually interferes w/production of purines & DNA
• These drugs DO not interfere w/Human cells due to folic acid is external
• Pharm:Used synergysticaly
• Broad spectrum
• BacterioSTATIC
• UTI & GI treatment
• Resp infections

Question 19

Antimetabolites-Sulfonamide & Trimethoprim

Answer 19

• Mech of bacterial resistance:
• Overproduction of PABA/Dihydrofolic acid
• Alteration of enzymes-_^{<strong>Tetrahydropteroic acid synthetase & Dihydrofolate reductase</strong>}_
• Folic acid dependency ^{<u><strong>(change from internal to external source w/in bacteria)</strong></u>}
• Decreased perm
• Dapsone & Paraaminosalicyclic:
• Similar structure, MOA, & Bacterial resistance to sulfonamides
• Pharm: Narrow-Mycobacterium (TB)

Question 20

Antibiotics inhibit nucleic acid synthesis

Answer 20

• DNA
• Metronidazole
• MOA: Nitro group reduced in vivo to make active drug that disrupts DNA under anaerobic conditions (w/o O2)
• Pharm:
• Initially anti-protozoan-_^{<strong>Trichomonas</strong>}_
• Bactericidal-Narrow (Anaerobic bacteria NOT aerobes)

Question 21

Antibiotics inhibit nucleic acid synthesis

Answer 21

• DNA
• Quinolones/Fluoroquinolones
• Nalidixic acid-Prototype drug
• Ciprofloxacin, Ofloxacin, Norfloxacin
• MOA: Inhibits bacterial DNA topoisomerases 2 (gyrase) & Topo 4
• Pharm: Bactericidal-Broad & Oral only
• Bacterial Mech of resistance:
• Alteration of Bacterial DNA gyrase/Topoisomerase
• Alteration of outer membrane proteins
• Efflux
• SE:
• Not in use for children & pregers affects Bone & cartilage

Question 22

Antibiotics inhibit nucleic acid synthesis

Answer 22

• RNA
• Rifamycin-Rifampin, Rifampicin, Rifabutin
• MOA:
• Inhibits DNA-Dependent RNA-poly=Prevents RNA synthesis
• _Pharm: _
• BacteriCIDAL, Broad
• Mycobacterium TB
• Gram + BUT NOT all Gram (-)
• Mech of bacterial resistance: Alteration of RNA polymerase

Question 23

Antibiotics Cell membrane Fnx

Answer 23

• Polymyxin B & E (COLISTIN) antibiotic
• Structure-Basic polypeptide
• MOA:
• Cationic detergent-^{<u><strong>DISRUPTS</strong></u>} cell membrane (GRAM -)
• Pharm:
• BacteriCIDAL, Narrow
• Gram (-)(due to bi-phosolipid bilayer)
• Use for last resort against multi-drug resistant ^{<u><strong>Pseudomonas aeruginosa</strong></u>}, ^{<u><strong>Klebsiella pneumoniae,</strong></u>}

Question 24

Antiparasitic Drugs (Anti-Proozoal)

Answer 24

• Heavy Metals: Asenical & Antimonials
  
  • ^{<em><strong>Melarsoprol</strong></em>=<strong>Inactivates enzymes</strong>}
• DNA replication:
• Quinoline derivatives=Chloroquine
  
  • ^{<strong>Interfere w/DNA replication & Hb digestion</strong>}
• Diamidines=Pentamidine
  
  • ^{<strong>Bind to DNA</strong>}
• Nitroimidazoles-Metronoidazole
  
  • ^{<strong>Breaks DNA</strong>}
• Folic Acid Biosynthesis: inhibition
• Pyrimethamine
• Sulfonamides/Trimethoprim ^{<strong>(inhibit protein synthesis)</strong>}
• Paramomycins
• Tetracyline, Clindamycin, Spiramycin
• ^{(<strong>treat malaria, babesisis, amebiasis, cryptosporidiosis)</strong>}

Question 25

Antiparasitic Drugs (Anti-Helmintic)

Answer 25

• Transport disruption
• Benzimidazole-Mebendazole
  
  • ^{<strong>Broad spectrum</strong>}
  • ^{<strong>Multiple paths-inhibit glucose transport & fumurate reductase <u>(anaerobic)</u>=Disrupts microtubules</strong>}
• Inhibition of Neuromuscular Action
• Pyrazinoisoquinoline-Paraziqautel
  
  • ^{<strong>Ca+2 agonist=Muscular contraction</strong>}
• Piperazines-Piperazine
  
  • ^{<strong>Muscular paralysis=stim phagocytic cells</strong>}
• Avermectins_-_Ivermectin
  
  • ^{<strong>Block neuromuscular action</strong>}

Question 26

Anti-viral drugs & mech

Answer 26

• Attachment/penetration:
• Adhesion inhibitors-Maravioc (blocks CCR-5 binding HIV)
• Fusion inhibitors-Enfuviritide (interfere w/Gp41 HIV)
• Nucleic acid synthesis:
• DNA polymerase inhibitors
• Nucleoside analogues=Acyclovir, Ganciclovir
• Protein synthesis-Interferons (recomb interferons)
• IFN a & b are produced in virally infected cells
• Viral drugs are hard to make due to their interference w/our own cells (selective toxicity is MANDATORY)
• Viruses HIGH mutation rate