Pharmaceutical Classes

darodri6's version from 2016-04-03 00:12

Protein Synthesis Inhibitors

Drug Class (specific drugs)MOASpectrumAdverse EffectsOther High-Yield Points
Aminoglycosides (Gentamycin, Amikacin, Tobramycin)-Inhibits formation of initiation complex --> causes misreading of mRNA
-Active transport across bacterial cell membrane into cytoplasm via an OXYGEN-DEPENDENT process
-passive diffusion via PORIN CHANNELS across the outer membrane
-Bactericidal due to irreversible binding to 30S subunit and formation of abnormal proteins
Aerobic G- (inc. PSEUDOMONAS)-Toxic to Nephrons & Ears (builds up in renal cortex & lymph of the inner ear) due to prolonged high trough levels
-Neuromuscular blockade
-Causes Contact Dermatitis in topical applications
Tetracycline (Tetracycline & Doxycycline)-Reversibly binds to 30S subunit blocking access of tRNA to mRNA at the A (acceptor) site
-Prevents attachment of aminoacyl-tRNA to acceptor site (A site)
-Broad Spectrum
-Many gram + including Community Acquired MRSA
-Gram - (but many resistant strains)
-Toxin secreters (cholera), rickettsiae, spirochetes, mycoplasma, and chlamydia (intracellulars!)
-Chelation (readily bound to calcium deposited in newly formed bone or teeth in young children. Do not give in children < 8 years old)
-Gastric Discomfort (take with food but NOT DAIRY)
-Nephrotoxic (renal tubular acidosis due to expired meds)
-worse if taken with dairy, magnesium and alumnium antacids, and iron preparation due to formation of non-absorbable chelates
-Concentrates in tissues with high CALCIUM content (bad in pregnany and crosses the placenta)

-Passive diffusion & energy-dependent protein mechanism
-General 1st line: COPD Exacerbations, Rocky Mountain Spotted Fever, Borrelia, alternate for mycoplasma, chlamydia; minocycline for acne (Propionobacteriu, acnes); brucellosis, erlichiosis, granuloma inguinale, H pylori, Vibrio spp
Tigecycline-Reversibly binds to the 30S ribosome, interfering with tRNA binding-broad spectrum
-including MRSA and Acinetobacter, gram negs but NOT Pseudomonas, Proteus, Providencia
:-Distributed RAPIDLY into tissue cells, therefore generally not effective against BACTEREMIA
Macrolides (Erythromycin, Clarithromycin, Azithromycin)-Bind irreversibly to a site on the 50S subunit
-Binding site is near the peptidyltransferase center and transpeptidation is prevented via blocking the polypeptide exit tunnel
-tRNA is dissociated from the robosome
-delivered to site of infection via hitching a ride along the LEUKOCYTES
-H. pylori
-Agonists at motilin receptor: profund diarrhea, cramping (sometimes used to increase GI motility)
-Phlebitic (IV) = inflammation of vein & thrombosus
-Metallic Taste- Clarithromycin
-Erythromycin, clarithromycin - Prolonged QT interval (ventricular depolarization & repolarization)
-Uses = skin, respiratory tract including atypical pneumonia
(Community Acquired Pneumonia (with 3rd generation cephalosporin), Upper respiratory infection, Acute Otitis Media)

KINETICS = potential for drug interactions via CYP450 3A4. Erythromycin & Clarithromycin inhibit cytochrome P450 (but Azithromycin does not) --> increased serum levels of other drugs.
Chloramphenicol-Protein Synthesis Inhibitor (50S)
-Binds reversibly to 50S subunit and inhibits peptide bond formation (inhibits peptidyl transferase), thereby preventing addition of a new A.A. to the growing peptide strand
-Broad spectrum
-may be used for serious rickettsial infections & Rocky Mountain Spotted Fever
-Gray Baby Syndrome: babies lack glucuronidine transferase (needed to metabolize chloramphenicol) --> chloramphenicol accumulates and affects mitochondira, leading to acidosis, gray color, death
Clindamycin-Protein Synthesis Inhibitor (50S)
-Binds to 50S and prevents aminoacyl-tRNA translocation step
-some G-
-Anaerboes, but NOT C. diff (causes C. diff)
-CA (community-acquired) MRSA
-USE: anaerobic infections, skin/soft tissue in penicillin allergy; abscesses
(used for anaerobic infections "Above the Belt"
:-Hepatically cleared
-High risk of C. diff!!!
Linezolid-Protein Synthesis Inhibitor (50S)
-Binds to 50S subunit to prevent formation of 70S initiation complex
-G+ (includind MRSA, VRE, and Listeria)
Mild Side affects:
-Thrombocytopenia (deficient platelets in the blood; particularly when administered > 2 weeks)
-Irreversible peripheral neuropathy and optic neuritis with > 28 day use

Inhibits monoamine oxidase activity; can precipitate serotonin syndrome in patients taking SSRIs
-Drug interactions with sympathomimetics and serotinergics
-Bacteriostatic but -cidal against streptococci & Clostridium perfringens

DNA & Antimetabolites

Drug Class (specific drugs)MOASpectrumAdverse EffectsKinetics or ResistanceOther High-Yield Points
Quinolones & Fluoroquinolones-Generally: inhibit DNA gyrase and topisomerase IV --> Death to Prokaryotes via inability to relieve supercoiling of their DNA and unlinking of interlinked chromosomes:-CHELATION (generally not used for children or pregnant women; food/drug)
-QTc PROLONGATION (delayed de/re-polarization of ventricles)
-Resistance also via mutations in topoisomerase, efflux pumps, or altered porin channels

Ciprofloxacin (2nd gen Fluoroquinolone)-Inhibition of topoisomerase -->CLEAVAGE of DNA and CELL DEATH
-Concentration-dependent killers
-G- Aerobes (inc. PSEUDOMONAS)
-good vs intracellular
:-generally used for G- only (complicated UTI's, prostatitis, anthrax, G- osteomyelitis, PSEUDOMONAS
Gemifloxacin & Levofloxacin (3rd gen Fluroquinolones):-aka "respiratory" FQ (coveres S. pneumoniae, M. pneumoniae, C. pneumoniae & L. pneumophilia)
-some PSEUDOMONAS coverage
-no anaerobic coverage
::-can be used empirically as monotherapy for CA Pneumonia, skin and soft tissue infections, or UTI's
Moxifloxacin (4th gen Fluroquinolone):-aka "respiratory" FQ (same coverage as 3rd gen FQs)
-also covers some anaerboes (Bacteroides --> below the belt)
-can be used empirically as monotherapy for CA Pneumonia, skin and soft tissue infections (but NOT UTI's)
-also covers Bacteroides ("below the belt" anaerobe)
Bacterial Folate Disrupters
(Sulfonamides & Sulfones, and Trimethoprim & Pyrimethamine)
-Each act to inhibit folic acid synthesis -->disruption of DNA synthesis -->inhibition of bacterial growth-Pneumocystis jiroveci (fungus that is aka protozoa)
::-combination = synergy (SMX-TMP = Sulfamethoxazole/Trimethoprim combo)

USES: UTIs', pneumonia in immunocompromised, burns, leprosy, conjunctivitis, malaria
Sulfamethoxazole (Sulfonamide)-PABA analog
-PABA is a precursor for dihydrofolic acid -->eventually forms folic acid for DNA
-high levels of PABA analog work to competitively inhibit dihydropteroate synthase
:-Hypersensitivities (Steven-Johnson or Rash)
-Crystalluria (drink lots of fluids!)
-Kernicterus in newborns
-Hemolytic Anemia in G6PD deficiency
-increased production of PABA
-alteration in dihydropteroate synthetase
-lowered cellular permeability
Trimethoprim-Dihydrofolate reductase inhibitor
-prevents conversion of dihydrofolic acid into tetrahydrofolic acid
-renal failure
-macrocytic anemia
-altered bacterial DHFR
-increased bacterial expression of DHFR
Rifampin (type of Rifamycin)-form very stable complex with RNA polymerase in order to prevent elongation (low affinity for human RNA poly)-kills bacteria in the phagosome
-very broad spectrum (inc. MYCOBACTERIA)
-not for Enterobacteraceae
*Stains bodily fluids red/orange
*powerful enzyme inducer (MANY drug interactions -->will decrease effect of other drugs)
*Hepatitis (hepatoxic)
*Flu-like hypersensitivity
RESISTANCE: spontaneous mutation of rpoB gene (RAPID & PREDICTABLE)USES:
-monotherapy use for prophylaxis of N. meningitides or H. influenzae meningitis only
-part of combination therapy for TUBERCULOSIS, leprosy, bone infections
Rifamixin (type of Rifamycin)-Inhibits DNA-dependent RNA polymerase -->reduced RNA synthesis (just like Rifampin)-E. coli
-possibly C. diff
*uncomplicated travelers diarrhea (does not achieve therapeutic levels systemically)
Drugs that generate ROS: anaerobic and/or antiprotozoal::::
Metronidazole-activated by pyruvate-ferredoxin oxureductase (PFOR) to its active form -->active form binds DNA & proteins -->leads to microbial death*Protozoa (Giardia spp, Trichomonis vaginalis)
*H. pylori
*Inhibition of aldehyde dehydrogenase (alcohol breakdown) -->disulfiram reaction
-Neurotoxic effects
-Food/drug interaction can also inhibit warfarin metabolism
*C. diff (1st line)
-"below the belt" anaerboes
Nitazoxanide-activation by pyruvate ferredoxin oxireductase -->formation of free radicals & ROS*Giardia in kids
-adjunct to antiretroviral therapy (ART) in cryptosporidium
Urinary Tract Drugs::::
Phenazopyridine-acts as a urinary tract antispetic (antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction):*contraindicated in pateints with CrCl < 50 (limited creatinine clearance = limited renal function)
*Changes urine color to orange/red
Nitrofuratonin-reduced form damages bacterial DNA*E. coli
*Urinary tract only - acidic urine better effective treatment and prophylaxis of uncomplicated UTI