Antibiotics that inhibit protein synthesisStreptomycin was the first aminoglycoside discovered in 1947.
All aminoglycosides are resemble in their mode of action and in their pharmacokinetics, therapeutic and toxic properties. The main difference in their range of antibacterial activity, cross resistance is variable.
Mode of actionBinding to ribosome in such a way wrong amino acid sequences enter into peptide chains. The resulting abnormal proteins are fatal to the microbe. So it bactericidal and exhibit concentration-dependent bacterial killing.
PharmacokineticAminoglycoside water soluble, not cross readly cell membrane or absorbed by intestine. So it is given iv or im. and they are distributed mainly to extracellular compartment , the transfer into the CSF is poor even when the meninges are inflamed . The t½range from2-5h.and they are eliminated unchanged mainly by GF and attain high conc.in urine.dose reduction is necessary in renal impairment,including that of normal ageing,so it give as high conc. Once daily.Aminoglycoside are active against staphylococcus aureus, aerobic G- organisms including almost all of the enterobacteriaceas
Note aminoglycoside has no activity against anaerobics because they lack the pump that depend on O2.
Clinical usesG- bacllary infection, particularlly septicemia Tobramycin is effective in pseudomonas aeruginosa.
Bacterial endocarditis (enterococcal, streptococcal, staphylococcal).
Tuberculosis, brucellosis, tulareamia, and plaque.
Topical uses neomycin, framycetin (because they are very toxic, and Tobramycin for cystic fibrosis as inhilation.
Adverse effectsLong duration or dose high and renal clearance are inefficient (because of disease or age) and the patient is dehydrated and drug inter action.
Nephrotoxicity low BP,loop diuretics and advanced age are risk factor.
Ototoxicity both vestibular and auditory cause hearing loss,vertigo,tinnitus.
Neuromuscular blockade may aggraviate myasthenia gravis or cause transient mysthenic syndrome.
Rash allergic reaction,blood disorder.
Individual aminoglycosideGentamicin is active against aerobic G- bacilli including. E coli, enterobacter, Klebsiella, proteus and pseudomonas. In streptococcal and enterococcal endocarditis, gentamicin is combined with benzylpencillin and in enterococcal endocarditis with amipicillin.
in septicemia use combination metronidazole, gentamycin,and penicillines.
Tobramycin is similar to gentamicin; it is more active against most strains of Pseudomonas aeruginosa and may less nephrotoxic.
Amikacin is expensive and is of value mainly because it is more resistant to aminoglycoside-inactivating bacterial enzymes than gentamicin therefore it is used with gentamicin resistant organism.
Netilmicin less ototoxic and nephrotoxic.
Neomycin topically only because is too toxic to be given systemically,used for skin,eye,ear infection,enough topical absorption cause 8 cranial nerve damage , orally for bowel preparation prior to colorectal surgery.
Streptomycin antituberculous activity brucellosis with doxycycline, have sever ototoxic
Spectinomycin is used as second line for treatment of gonorrhea.
have a broad range of antibacterial activity. New tetracyclines and relatives have wider spectrum of activity that includes bacteria with acquired resistance to other classes of antibiotics.
Mechanism of actionTetracycline interfere with protein synthesis by interfere with ribosome it bacteriostatic.
Partially absorbed from elementary tract, it alter the flora of intestine and cause diarrhea, it distributed throughout the body and cross the placenta, it excreted unchanged in urine except doxycycline and minocycline are eliminated by non-renal route so used in impaired renal function
Act of most G+ and G- pathogenic bacteria but increasing bacterial resistance and low innate activity limit clinical use.
Tetracycline remain the first choice for infection with chlamydia (psittacosis, trachoma, pelvic inflammatory disease, lymphogranuloma, venerum), mycoplasma (pneumonia), rickettsiae (Q fever, typhus) Vartonella spp,and borrelias (lyme disease, relapsing fever), vibrio cholera, brucella,in acne.
Clinical usesIn addition to doxycycline therapeutic and prophylactic regimens for malaria and is active against amoebae and variety of other protozoa. Skin infection in acne vulgaris.
An unexpected use for tetracycline in (SIDAH) treatment of hyponatremia due to syndrome of inappropriate ADH secretion for which demeclocycline is effective when water restriction has failed.
Adverse effectsHeart burn, nausea and vomiting due to gastric irritation are common, and attempts to reduce this with, diarrhea and opportunistic infection.
Disorder of epithelial surfaces, perhaps due partly to vitamin B complex deficiency and partly to mild oppurtunistic infection with yeast and molds, lead to sore mouth and throat, black hairy tongue, dysphagia and perianal soreness, so give vitamine B preperation. Tetracycline selectively enter teeth and growing bone of the fetus and of children.This cause dental enamel hypoplasia with pitting, yellow or brown pigmentation and caries, so avoid tetracycline last 2 months of pregnancy to 12 years of age.
It has anti anabolic effect(inhibit protein synthesis) so increase blood urea.
Dairy products reduce absorption to a degree, but antacid and iron preparation do so much more, by chelation to calcium, aluminum and iron.
Photo sensitivity and skin rash.
Vestibular problem with minocycline,dizziness,vertigo.
Prolonged therapy can also stain the fingernails
upto 10 years
Only doxycyclineIndividual tetracyclines
Doxycycline: is well absorbed from gut even after food, execreted in bile.
Minocycline: its antibacterial to Neisseria meningiditis, its well absorbed even after meal.
Tetracycline: its used for skin infection in acne for 3 months, used before meal bec. It chelating calcium from milk.
Tigecycline: in treatment ofcomplicated skin and intra-abdominal infection.
Mechanism of actionbind to ribosome, so interfere with protein synthesis, (bacteriostatic) is effective mostly with G+ and less in G-
Absorption after oral administration is best with erythromycin estolate even with food in stomach, the estolate hydrolyzed to active erythromycin which diffuse in most the tissue except brain and CSF ,half-life 2-4h, is bactericidal at higher dose, excretion in bile and feces, it has a prokinetic effect on gut.it time dependent killing bacteria.
Erthromycin (Clinical uses)Mycoplasma pneumonia in children
Legionella spp (including legionnair’s disease) with or without rifampicin
Diphtheria (including carriers) pertussis and some chlamydial infections
Erthomycin is an effective alternative to pencilline allergic patients infected with staphylococcus aureus, streptococcus pyogens, streptococcus pneumonia or treponema pallidum, it used in acne.
Erthromycin (adverse effects)Is remarkably non toxic but the estolate can cause cholestatic jaundice, GIT disturbances (28%) diarrhea and nausea, but opportunistic infection is uncommon. Its ototoxic at high dose reversiblly , its enzyme inhibitor,interfer
With the metabolic inactivation of some drugs,
Warfarin,carbamazepine,increasing their effect.
ClarithromycinHalf-life 3hrs after 250mg, 9hrs after 1200mg
And the remainder is eliminated in urine. Its saturable kinetic.
Respiratory tract infections (atypical pneumonias and soft tissue infections
Myocbacterium avium intracellulare in patients with AIDS,also Azithromycin.Clarithromycin effective against Helicobacter pylori.
Gastrointestinal tract are uncommon (7%)
Is effective against a number of important G- including Haemophilus influenzae and Neisseria gonorrhea, and against Chlamydia, but is a little less effective than erythromycin against G+ organisms,high conc.in tissue relative to those in plasma.
Half-life 50 hrs, excreted in bile and feces, hepatic excretion so in liver disease should be avoided.
Azithromycin (clinical uses)Respiratory tract infections
Soft tissue infections
sexually transmitted diseases. Especially genital Chlamydia infections
GIT disorders 9%.,not have enzyme inhibitor.
MacrolidesIs the first of the ketolides which related to macrolides. It act against most erthromycin-resistant strains of streptococcus pneumoniae but its not active against erythromycin- resistant Staphylococci , including most MRSA.
Diarrhoea more than macrolides,and some patients experience transient visual disturbance. Given in liver diseases but not in renal diseases.
Structurally a lincosamide rather than a macrolide, is the same as macrolide but it have efficacy against anaerobes such as Bacteroides fragilis.
Staphylococcal bone and joint infections
Serious intra-abdominal sepsis+gentamycin.
Severe acne and non sexually transmitted infection of genital tract.
Pseudomembranous colitis caused by c.difficile
We stop the drug if any diarrhea occur.
clindamycinHas a broad spectrum of activity and is primarily bacteriostatic, but may be bactericidal against H.influenzae, N.meningitides & Strept.pneumonia also against anaerobic, bec. Of its toxicity so only used in life-threatening infection, it penetrate all tissues including CSF and brain, preparation oral, IV, IM.
Meningistis and brain abscess
Haemophilus epiglottistis in children.
Typhoid fever,salmonella septicemia.
Topical administration is effective for bacterial conjunctivitis
Adverse effectsBone marrow toxicity (adose-dependent reversible depression of erythocyte, platelet and leucocyte formation, or idiosyncratic probably genetically determined which is not dose related and usually fatal aplastic anemia.
Optic and peripheral neuritis occur with prolonged use but are uncommon
Grey baby syndrome occurs in neonates as circulatory collapse in which the skin grey and cyanotic colour,it is caused by failure of the liver to conjugate,and kidney to excreate the drug.
Bone marrow damage .Is a steroid antimicrobial that finds use almost exclusively against B-lactamase producing staphylococci,because staphylococci may rapidly become resistant via a one –step genetic mutation , the drug is combined with another antistaphylococcal agent E.G. flucloxacillin.
Its readily absorbed and distributed widely in body tissues including bone.
Preparation as ointment or gel used for staphylococcal infection and as cream to eradicate staphylococcal nasal carrier state.
Clinical usesTreating severe staphylococcal infections, inccluding osteomyelitis.
Mild gastrointestinal upset is frequent
Jaundice may develop, particularly with high doses given intravenously.
Mech. Of action
Is a bactericidal, it act only against G+ bacteria which resist vancomycin (enterococcus faecium, legionella pneumophila, Moraxella catarrhalis and mycoplasma
Veins phlebitis, arthralgia, myalgia and its an enzyme inhibitor of cytochrome P450.
Resistance to antimicrobials: Quinupristin-dalfopristin and linezolid
Mechanism of actionA synthetic oxazolidinone is the first member of this new class, inhibiting formation of initiation complex between transfer RNA, mRNA & ribosomal subunits at the first stage of protein synthesis.
Bacteriostatic against most G+ve bacteria including staphylococci,Streptococci and enterococci resistant to other anti microbial agent but its bactericidal against pneumococci.
Nausea, vomiting, headache, irreversible peripheral neuropathy, bone marrow suppression, may inhibit MAO and cause hypertension.