Tetracyclines, Aminoglycosides Flashcards
Tetracyclines
Chemistry
Mechanism of Action
Mechanisms of Resistance
Contain 4 condensed rings with substituents
Is a basic compound–> form water soluble salts with acid
Amphiphilic
Form chelates with Ca,Mg,Fe,Al (inorgnic cations)
Light exposure–> oxidised to quinones
(= nephro- and phototoxic)
MoA
Enter bacteria: diffusion and carrier mediated transport
Inhibit 30S ribosomal subunit
Inhibit binding: aminoacyl tRNA–> ribosome mRNA
complex–> elongation of peptide chain stops–>
BACTERIOSTATIC
MoR; resistance rare
Plasmid mediated
Expression of TC efflux pumps (ex staph aur)
Expression of protection proteins-> displace TC from
ribosomal binding site (Ex. E. Coli)
Expression of FMO-> hydrolyses and inactivates TCs
Tetracyclines
Spectrum
Pharmacokinetics
BROAD spectrum
G+: staphy aur, strepto, listeria, bac anthraxis
G-: neisseria, H. influenza, H. Pylori, yersinia
Spirochetes: borellia burg, treponema pallidum
Obligate IC parasites: rickettsiae, mycoplasma, chlamydia
GI absorption depends on lipid solubility
6 Hydroxy TCs: rel. hydrophilic
incompletely absorbed
6 Dehydroxy TCs: rel lipophilic
completely absorbed–> lower dose enough
DO NOT take with Ca, Mg, Fe, preps…
Vd= 1-2kg/l–> some minute accumulations; distribute
pretty evenly
Mainly renal elimination
Doxycycline: biliary elimination
Minocycline: biotransformation
Tetracyclines
SE
GIT irritation Pseudomembranous colitis Phototoxicity Liver injury: steatosis in preggos Allergic reactions: rare Depo in growing bones: CI in kiddies under 8 complexes with Ca apatite reversible inhibition of growth irreversible discolouration
Tetracyclines
Drug Groups
6 Hydroxy TCs
6 Dehydroxy TCs
6 Hydroxytetracyclines
Oxtytetracycline
incomplete GIT absorption; mainly renal elim
Tetracycline
incomplete GIT absorption; elim: bile and urine
Limecycline
completely absorbed via carrier mediated transport
eliminated mainly renally
6 Dehydroxytetracyclines
Doxycycline
completely absorbed
mainly fecal elimination
Tetracyclines
Indications: 2 Groups
Bacterial Acne H. Pylori Eradication (or a Macrolide) Cholecystitis Lyme Disease
Cholera
Plague
Anthrax
IC Parasite
Rickettsial
Mycoplasma
Chlamydia
Aminoglycosides
Chemistry
Mechanism of Action
Mechanisms of Resistance
3 aminosugars linked by glycosidic bond
Polycations–> water soluble not lipid soluble
MoA
Uptake into bacteria: diffusion through aquaporin or
uptake via 2ary active transport (via negative charge
inside; maintained by oxidative phosphorylation)
Bind to 30S ribosomal subunit--> inhibits initiation; finally leading to misreading--> mutated membrane protein--> leaky membrane--> BACTERIOCIDAL
MoR
AG can’t enter bacteria (ex anaerobes)
AG can’t bind to 30S (ribosomal resistance)
AG converted–> inactive metabolites via
adenylation of OH
phosphorylation of OH
acetylation of OH or NH2 groups
Aminoglycosides
Spectrum
Pharmacokinetics
Narrow Spectrum; mainly G-s
Enterobacteriacae (E Coli, Klebsiella, Enterobacter)
Pseudomonas
Some G+
Some enterococci
Staphyl
Poor GIT absoprtion–> IV
Largely extracellular distribution (Vd=0.25l/kg)
Accumulate in inner ear and kidney-> toxic SE
Low PPB
Elimination: mainly urinary excretion unchanged
AGs
Toxic Effects
Ototoxic and Nephrotoxic; depend on cumulative dose
Ototoxicity is irreversible
Nephrotoxicity is reversible
–> hearing impairment, disturbed equilibrium
Give AGs in !!!single dose!!! to minimise nephrotoxicity
Decrease dose proportionally to decrease in GFR
Impaired NM transmission: due to Ca antagonism
Manifested only if there are other causes for NMJ impaired transmission ex Myasthenia Gravis
Classification of AGs
For severe G- infections For resistance G- infections For topical use For specific infections For gonorrhoea
AGs
For severe G- Infections
Gentamycin
Tobramycin
Klebsiella/ E Coli, pseudomonas, enterobacter
Sepsis, severe pyelonephritis, G- pneumonia, meningitis
Recommended Combos
E.Coli: Ampicillin or caphalosporins
NEVER mix AGs (cations) with B Lactam (anion) in one solution–> form salt. Inject separately
Gentamycin:
Osteomyelitis: locally implanted gentamycin minichip
AGs
For resistant G- Infections
Amikacin
When resistance to genta- and tobramycin +
AGs
For Topical Use
Neomycin
Kanamycin
Topically due to nephrotoxicity
Bladder irrigation
Outer ear infections
AGs
For Specific Infections
Streptomycin
Narrow spectrum due to resistance
Tularemia
Brucelliosis
Plague
TBC
AGs
For Gonorrhoea
Spectinomycin
Is not an AG but an aminocyclitol
Not bactericidal but bacteriostatic
No oto- and nephrotoxicity
2nd choice for gonorrhoea.
First choice: ceftriaxone
