Drugs Flashcards
Amytal
barbituate, blocks complex I (NADH dehydrogenase) in ETC
Rotenone
pesticide, blocks complex I (NADH dehydrogenase) in ETC
Antimycin A
antibiotic, blocks complex III (cytochrome b-c1 complex)
Cyanide
smoke, industrial chemical; blocks complex IV (cytrochrome c oxidase)
Carbon monoxide
combustion product, blocks complex IV (cytrochrome c oxidase)
Azide
antimicrobial agent, AZT; blocks complex IV (cytrochrome c oxidase)
Oligomycin
antibiotic, blocks complex V (ATP synthase)
AZT (zidovudine)
anti-retroviral drug, blocks DNA pol-gamma which is the mitochondrial DNA replication enzyme
Dinitrophenol
explosive, chemical uncoupler
Salicylate
product of aspirin metabolism, chemical uncoupler
Tetracycline
antibiotic, blocks binding of aminoacyl-tRNA to A-site of ribosome; acts only on bacteria
Streptomycin
antibiotic, prevents the transition from translation initiation to chain elongation and also causes miscoding; acts only on bacteria
Chloramphenicol
antibiotic, blocks the peptidyl transferase reaction on ribosomes; acts only on bacteria
Erythromycin
antibiotic, binds in the exit channel of the ribosome and thereby inhibits elongation of the peptide chain; acts only on bacteria
Rifamycin
antibiotic, blocks initiation of RNA chains by binding to RNA polymerase (prevents RNA synthesis); acts only on bacteria
Puromycin
antibiotic, causes premature release of nascent polypeptide chains by its addition to the growing chain end; acts on bacteria and eukaryotes
Actinomycin D
antibiotic, binds to DNA and blocks the movement of RNA polymerase (prevents RNA synthesis); acts on bacteria and eukaryotes
Cycloheximide
antibiotic, blocks the translocation reaction on ribosomes; acts only on eukaryotes
Anisomycin
antibiotic, blocks the peptidyl transferase reaction on ribosomes; acts only on eukaryotes
a-Amanitin
antibiotic, blocks mRNA synthesis by binding preferentially to RNA polymerase II; acts only on eukaryotes
Penicillin
acts against gram + organisms, has short half-life due to renal excretion
Paired with probenecid which impairs renal secretion
Penicillin V
oral form of penicillin
penicillin targets penicillin binding proteins in cell membrane of bacteria and prevents the cross-linking of peptidoglycan to cell membrane
Penicillin G
IV form of penicillin
Targets the penicillin binding proteins involved in cross-linking peptidoglycan to the cell membrane
Benzathine
IM form of penicillin, longer lasting
associated with irritation and local pain
Aztreonam
cell wall inhibitor that binds to penicillin binding protein
only works on gram-negative bacteria!
use if have an allergy to penicillin
What are the three antibiotics that inhibit penicillinases?
Clavulanate, Sulbactam, and Tazobactam
What are the two antistaphlococcal penicillins and what makes them different than penicillin?
Naficillin and dicloxacillin
have same mechanism as penicillin but have larger R group so resistant to penicillinases
have a narrower spectrum
What are the two aminopenicillins?
Ampicillin and amoxicillin
What is the spectrum, mechanism, and combination drugs that are associated with ampicillin and amoxicillin?
Spectrum: gram-negative bacteria
Mechanism: inhibit cross-linking of peptidoglycans to cell membrane by binding to penicillin binding proteins
Ampicillin - Sulbactam
Amoxicillin - Clavulanate
What are the antipseudomonal penicillins?
Ticarcillin and Piperacillin
What is the spectrum, mechanism and combo drugs associated with Tircacillin and Piperacillin?
Spectrum: broad, gram-negative bacilli (including Pseudomonas!)
Mechanism: same as penicillin, ineffective against penicillinases
Ticarcillin - Clavulanate
Piperacillin - Tazobactam
Cephalosporins are a subclass of penicillin. What is the mechanism, bactericial/static, and where are they processed?
Mechanism: same as penicillin, bind to penicillin binding proteins which inhibit cell wall synthesis
Bactericidal
Cephalosporins are primarily excreted by the kidneys. Alter dosage for renal insufficiency.
Cephalosporins have multiple generations. What are some features of he first generation (cefazolin)?
Spectrum: gram+
Does not cross blood-brain barrier (BBB)
What are some features of the 2nd generation of cephalosporins (cetoxitin, cefuroxime)?
Spectrum: more gram-negative activity, weaker gram-positive activity
Doesn’t cross BBB
used for prophylasis treatment; can inhibit vitamin K production (prolongs bleeding); causes a disulfiram-like reaction
What are some features of the 3rd generation of cephalosporins (ceftriaxone, cefotaxime)?
Spectrum: streptococci and more serious gram-negative infections
Can cross BBB
Ceftriaxone interacts with calcium to form crytsals that precipitate in the lungs and kidneys
What are some features of the 4th generation of cephalosporins (cefepime)?
Cefepime = 1st (cefazolin) + 3rd (ceftazidime)
Spectrum: broadest, gram+/- including Pseudomonas
What are some features of 5th generation cephalosporins (ceftaroline)?
Engineered to bind penicillin-binding protein 2a in MRSA (Staph. aureus)
Carbapenems are a subclass of penicillin. What are the carbapenem drugs and what is the spectrum, mechanism, and combo drugs associated?
Drugs: Imipenem and meropenem
Spectrum: broad, but MRSA resistant
Mechanism: binds to penicillin-binding proteins, low susceptibility to bate-lactamases
Imipenem - Cilastatin – if treat without, there will be renal affects
What is the spectrum, mechanism, and side effects of Vancomycin?
Spectrum: gram-positive, esp MRSA, C. difficile
Mechanism: inhibits release of bactoprenol carrier – prevents peptidoglycan synthesis
Side effects: excreted by kidneys, nephrotoxic
What is the mechanism and side effects of Bacitracin?
Mechanism: inhibits dephosphorylation of bactoprenol carrier; inhibits peptidoglycan cell wall synthesis
Side effects: nephrotoxic, rarely used except for opthalmic and dermatologic preparations
Polymyxin B is used in triple antibiotic ointment. What is the spectrum, mechanism, side effects, and bactericial/static status of polymyxin B?
Spectrum: treats MDR gram-negative, including Pseudomonas
Mechanism: binds to phosphatidylethanolamine creating holes in cell membrane and release of cellular contents
Side effects: nephrotoxicity
Bactericidal
What is the spectrum, mechanism, bactericidal/static status of daptomycin?
Spectrum: gram-positive
Mechanism: binds to cell membrane leading to depolarization of membrane –> cell death
Bactericidal
When lysine added to cell membrane, daptomycin is repelled due to positive charge
Rifampin: mechanism, spectrum, resistance, adverse effects, bactericidal/static
Mechanism: binds to RNA polymerase at active site, blocks mRNA elongation
Spectrum: gram+/- , mycobacteria tuberculosis
Resistance: intrinsic - drug unable to bind; acquired - mutation in RNA pol preventing binding
Adverse effects: GI tract effects, hepatotoxic due to cytochrome P450
Note: body fluids turn orange-red!!!
Fixaxomicin: bactericidal/static, mechanism, spectrum, adverse effects
Bactericidal
Mechanism: inhibits RNA polymerase by binding to sigma factor subunit
Spectrum: narrow, used to treat recurrent C. diff infections
Adverse effects: low absorption, nausea, vomiting
Fluoroquinolones inhibit _____ ______________?
DNA replication
What are the drugs within the fluoroquinolone class of drugs?
Ciprofloxacin, levofloxacin, and moxifloxacin
Ciprofloxacin, levofloxacin, and moxifloxacin: bactericidal/static, mechanism, spectrum, resistance, adverse effects
Bactericidal
Mechanism: binds to bacterial topo II and IV
topo II – prevents relaxation of + supercoiling, gram-
topo IV – interferes with DNA separation, gram+
Spectrum: broad, gram+/- and mycoplasma
Resistance: efflux of drug through transporters, gram-
Adverse effects: GI, tendon rupture, prolonged QT interval
Notes: chelate cations from Ca2+, Fe, Al; renal dysfunction, levofloxacin good for UTIs
Sulfamethoxazole: bactericidal/static, mechanism, spectrum, resistance, adverse effects
Bacteristatic
Mechanism: competitive inhibitor of dihydropteroate synthetase with PABA
Spectrum: don’t act against bacteria, but folate pathway
Resistance: increased product of PABA, increased efflux
Adverse effects: crystalluria, hemolysis (G6PDH), kernitcterus (albumin-bilirubin)
Trimethoprim: bactericidal/static, mechanism, adverse effects, disease treatment
Bacteristatic
Mechanism: sequential block of folate pathway, DHFR
Adverse effects: bone marrow suppression, hyperkalemia (increased K– heart arrythmia)
Diseases treated: UTIs, Shigella, Salmonella, Pneumocystis (fungi)
Bactrin
combo of sulfamethoxazole and trimethoprim (TMP-SMX)
sequential block of folate pathway causes these two drugs to become bactericidal
Metronidazole: bactericidal/static, mechanism, spectrum, adverse effects
Bactericidal
Mechanism: becomes reduced (electron sink), generates free radicals to break DNA
uses ferredoxin in reduced form (aerobes would have oxidized ferredoxin)
Spectrum: protozoa, anaerobic bacteria including C. difficile
Adverse effects: nausea, diarrhea, headache, metallic taste
Note: involved in disulfiram reaction –> hangover
Nitofurantoin: bactericidal/static, mechanism, spectrum, adverse effects
Bactericidal
Mechanism: reduce flavoproteins to reactive intermediates –> inhibits DNA, RNA synthesis
Spectrum: broad
Adverse effects: vomiting and pulmonary toxicity
Note: ineffective outside of lower urinary tract
What is the disulfiram reaction?
Ethanol –ADH–> Acetaldehyde –ALDH-> Acetate
Metronidazole inhibits ALDH causing an accumulation of acetaldehyde causing a hangover
2nd generation cephalosporins involved too…?
Linezolid
Bacteriostatic
Mechanism: binds to 23S on 50S subunit
Spectrum: gram-positive, including MRSA and VRE
Adverse Effects: bone marrow suppression, Serotonin syndrome
Note: excellent bioavailability!
Aminoglycosides - GNATS
Gentamicin, neomycin, amikacin, tobramycin, streptomycin
Bactericidal
Mechanism: prevents formation of initiation complex, misreads mRNA, induces early termination; acts on 30S subunit
Spectrum: gram-negative aerobes! - need energy to enter cell
Adverse Effects: Nephrotoxicity, Ototoxicity, Teratogenic (not for use by pregnant women!)
Notes: large single dose more effective
Tetracyclines - TDM
Bacteriostatic Mechanism: binds to 30S subunit, preventing tRNA attachment in A-site Spectrum: broad, less now due to widespread resistance Adverse Effects: form stable chelates, GI irritation, pregnancy class D drug
Macrolides - EAC
Bacteriostatic
Mechanism: inhibits translocation, binds to 23S on 50S subunit
Spectrum: broad coverage of respiratory pathogens
Adverse effects: GI discomfort, hepatic failure, inhibitor of cytochrome P450s
Note: Clarithromycin not safe during pregnancy!
Chloramphenicol
Bacteriostatic
Mechanism: binds to 50S, prevents peptide bond formation - peptidyltransferase
Spectrum: extended, limited due to severe side effects
Adverse Effects: bone marrow suppression, TOXIC, aplastic anemia, gray baby syndrome (low activity of glucuronyl transferase)
Clindamycin
Bacteriostatic
Mechanism: blocks translocation at 50S subunit
Spectrum: gram-positive, includes anaerobes
Resistance: has cross-resistance with macrolides and streptogramins (Q/D)
Adverse Effects: diarrhea, hypersensitivity, superinfection with C. difficile, ab pain
Quinupristin/Dalfopristin (Streptogramins)
Bacteriostatic (self); Bactericidal (combined)
Mechanism: binds to 50S to inhibit translocation
Spectrum: reserved for infections caused by MDR gram-positive bacteria
Adverse Effects: inhibits cytochrome P450s
