بسم هللا الرحمن الرحيم

Transcription

1 بسم هللا الرحمن الرحيم 1.lincomycin and clindamycin: Continuously with those agents which usually act by inhibiting microbial protein synthesis which step is involved it is not at this level offered and lincomycin and clindamycin the last two under protein synthesis inhibitor,they are static and they have a good activity against Gram positive and Gram negative microorganisms. You need the property of such substances that they are concentrated in bone and teeth and they are widely used by dentist along with cephalosporins. Many antibiotics but these particularly effective against bone and teeth soft tissues infection etc major side effect is pseudomembranous colitis. The most important things in lincomycin and clindamycin that they are considered broad spectrum but the leaky property is that they are very toxic specially with unique property with pseudomembranous colitis. tetracyclin and lincomycin are the major 2 antibiotics associated with pseudomembranous colitis. treatment is to stop the drug and give the drug of choice in this case which is the cell wall inhibitor antibiotic : vancomycin. 1 P a g e

2 there is contraindication in the uses of these to drugs mainly the hepatic impairment and to the previous pseudomembranous colitis. Finally, it doesn t act on protein synthesis in fact but they act by interfering with the permeability of the plasma membrane of susceptible microorganism, they are very toxic particularly to the kidneys. 2.Polymyxins : Paramixin P or E they are effective against Gram negative microorganisms and even they say that they produce nephrotoxicity (as compare with aminoglycosides) for this reason they are used locally. likewise bacitracin but bacitracin act on cell wall,it is one of the vancomycins,it s very nephrotoxic and only used topically. Antimotabolites(Sulfodugs) Are widely used until now whether they are used locally or systemically, they are static and broad spectrum. Chemotherapeutic agents synthetic drugs they are structural analogs to parabenzoic acid (please return to the slide to see the structure of para-aminobenzoic acid) they has some sot in the similarity in the structure to the interfere nearly with the synthesis of Faricacid from para-aminobenzoic acid. They are broad spectrum which is the case with many Gram positive and Gram negative microorganisms and even against atypical infections. Broad spectrum mechanism means any infection is caused by such microorganism and be treated of sulfodrugs with the infected with 2 P a g e

3 the management of upper respiratory tract, toxoplasmosis and clamidia infection locally applied sulfa could be used to sterilize the bowel before the surgery like Sulfadiazen which is no absorb and salfasalazin as too major active ingredient one of them belong to the sulfa and has an antimicrobial activity and the second ant inflammatory effect. So the unique properties of this drug that it is effective in bacterial infection as well as in certain inflammatory diseases particularly ulcerative colitis diease and many inflammatory conditions it is hydrolysis orally in the intestine to the two components : sulfapyridine and sulfasalazine these are the preparation sulfa(sulpha in British) drugs. Sulfa preparations are orally effective and they are well absorb like sulfa merazine, sulfa methazine and sulfisoazol, they have short half life and well absorb. Some others they well not absorbed and used locally like sulfa diazine and sulfa acetamide and tey have short half life. The most likely use sulfa drug it has an intermediate action know as sulfa methoxazole, is the most widely used sulfa antimicrobial agent, it is well absorb and has an intermediate duration of action. Some of sulfa salazine is used as an antibacterial and in cases of inflammatory conditions it is well absorb and has long half life. How salfa acts? They act by inhibiting dihydrofolic acid wath ever synthase enzyme. 3 P a g e

4 Parabenzoic acid is essential for the bacteria, you have some sort of selectivity to the sulfa drug in order to fall folic acid which are important for nucleic acid synthesis in the bacteria. slide 23 2 drugs ( trimethoprim + sulfa )act on consigative steps in nucleic acid synthesis,combination of both more cidal and the advantige is make aprodact that the spectrum of activity going to be little bit broad. slide 24 - if bacteria take folate from enviroment no effect of drug. - mutation in such gene that produce protein products. slide 25 -sulfa compete bilirubin in its site so displace bilirubin and increase free bilirubinand enter CNS => neurotoxic, the condition called kernicterus, more common in children. slide 26 - pharmacokinetics :slow and rapid metaboliser( acetylators) -unique property: precipitate in urine and make renal stones or drug crystals so to overcome this problem 3 ways : 4 P a g e

5 1- goog fluid intake. 2-take sulfaisoxazole (best urine solubility ), most used the sulfamethoxazolebut in this problem we replace it. 3-combine sulfa drug but when decrease the dose we decrease also the theraptic level so yoy have to give something else to elevate blood level. slide27 -trimethoprim : has sub-similtary in its structer to folic acid, could be use alone (available in oral form ) slide 28 -trimethoprim has sub similarity in its )structer to folic acid, also could be use alone (orally). -among sulfa drugs only sulfamethoxazole can combine with it ( same half life). -not metabolise by liver. slide 29 -cotrimoxazol its a generic name. -act on 2 stepsof nucleic acid synthesis( in susceptible bacteria ) -it compine ststic drug + ststic drug = the product is cidal. slide 30 5 P a g e

6 - kernicterus =>dueto sulfa drugs compete with bilirubin on its site. -very imortant major drugs have contraindicatore wihe(g-6-p deficiency )they are tetracycline,sulfa, nitrofurantion make sever hemolysis. -steven-johnson syndrome unique for sulfa drugs(or it combinations). -mm's = mean muocus membrane. slide 31 - quinolones have very broad spectum, it inhibit gyrase enzyme + topoisomerase( for DNA synthesis )so in general it inhibit DNA synthesis Flouroquinolones simply inhibit the DNA synthesis in the bacteria, which leads to no protein thus the effect is cidal and they are widely used when they were discovered and then there were generations were synthesized and they were divided according to the historical years and the spectrum of activity, especially they found that these drugs are highly effective in pseudomonas. Many were withdrawn from the market, others had their use being restricted even in certain middle east countries not only USA, due to severe toxicity especially concerning the heart ( cardiotoxicity) not only that but also a lot of them were discovered to produce carcinogenicity ( discovered in post marketing studies). If you look at them, some of them are obscure and no longer used although they are newly synthesized and introduced into the market, others were restricted and some are still used widely used, most widely used quinolones nowadays. 6 P a g e

7 Their use has been recently reduced also because the resistance to such drugs is very easy, bacteria could accommodate to such drugs and they could even have some sort of mutation in either in gyrase or tropoisomerase enzymes (resistance is common) 1 st generation: nalidixic acid (you don t have to know the rest.) Nalidixic acid is only effective in urinary tract infections because it is active only in acidic PH (at PH=5), it is also known as urinary tract antiseptic, so it s a characteristic of it to be only used in the management of urinary tract infection that may be caused by whatever susceptibly microorganism, more effect against gram positive but it may have some gram negative activity, such as shigella and E. coli but NO activity against pseudomonas, which may cause frequent urinary tract infection, but nalidixic acid isn t that much active against it. 2 nd generation :exhibit more activity against gram negative including pseaudomonal microorganisms, the case is the same with the 3 rd and 4 th generations. ciprofloxacin is the #1 most widely used nowadays all over the world among all flouroquinolones, and highly effective, side effects incidents are less frequent compared to others. Olfloxacin, not that much used. 3 rd generation : levofloxacin. 4 th generation : moxifloxacin. The rest either have restricted use or are even withdrawn. A question was asked and the dr. answered Nalidixic acid has GIT irritation as a side effect, active only at ph=5, so in the GIT its 7 P a g e

8 completely inactive, it goes to the kidney and there it is activated. That s good because it adds to its selectivity( that s why it was called urinary tract antiseptic) likewise, nitrofurantoin which we ll take later on, is specific only for UTI. UTI is one of the most difficult infections that could face an infection specialist, even with the identification of the bacteria and the bacteria is sensitive to a specific antibiotic, unfortunately the treatment is not that much successful with that antibiotic,so they switch to another one. Infection could lead to complications and renal damage and failure, so kidney infection are hard to find a specific antibiotic or chemotherapeutic agent effective in the management of such infection. Quinolones are orally effective and well absorbed but affected by food containing Ca ++ and iron so don t take food containing Ca ++ and iron or don t take food at all, like tetracyclins, so take them on an empty stomach. Mainly (particularly Ciprofloxacin & levofloxacin) used in complicated UTI s, respiratory infections invasive external otitis, bacterial prostatitis and cervicitis, bacterial diarrhoea caused by shigella, salmonella and E. coli Resistance: Simply mutations in enzymes they inhibit or production of certain proteins that could bind to DNA gyrase and protect it from the action of such quinolones, increased efflux by pumps, mutations in DNA gyrase or tropoisomerase enzymes. 8 P a g e

9 Side effects: GIT irritation; photosensitivity - Cardiac toxicity which is a unique side effect that wasn t mentioned earlier Most characteristic side effect to quinilones which represented a problem since they were discovered that many may be associated with prolongation of QT interval which is detected by performing an ECG for the patient. so they screened the drugs to see which caused it or not and many were withdrawn because of this side effect and others were used with restrictions especially in the USA. rememeber the unique side effects of chloramphenicol are aplastic anemia and grey baby syndrome, and of Penicillin is allergy, although it is common in all ***** drugs with their side effects will be included in the exam as a matching question (Godwilling)***** - Some are not recommended in children or during pregnancy because they may interfere cartilage development - Some have been reported to be carcinogens Photosensitivity is ranges a little sensitivity in the eye and that means intolerence to the light, some sort of an allergy to the light a lot of drugs produce this side effect in which the patient feels that he is not comfortable to the light when he go out he can not open his/her eyes 9 P a g e

10 so the doctor advices him to wear dark glasses ( There are persons have allergy to the sun or light without taking drug). This side effect is not going to be exhibited by 100% of patients receiving such drugs it is more. it acts of many sites on DNA,RNA, protein plasma membrane on all thing this is the unique property of it. ** Note :Tachycardia and bradycardia a rare sort of cardia arrythma in the heart. Nitrofurantoin Synthetic bacteriacidal effective antibiotic against Gram positive and Gram negative microorganisms as good activity against Gram negative bacteria especially E.coli, very high effective in urinary tract infection and even it is considered or destined under urinary tract antiseptic. Why the doctor mention it at the end of antibiotic lectures?because he just wants to give you idea that it acts by certain reactive intermediate that could act by different mechanisms active of DNA, on the structure of RNA, on protein synthesis also found to be interfering with many metabolic process in the bacteria. Resistance of it is very very rare because there is no effect on the cell wall even up to the extent that once we discover that a certain microorganisms sensitive to Nitrofurantoin the microorganism remains ever sensitive. 10 P a g e

11 It produces active intermediates that could help the DNA, the RNA, the protein of the microorganisms and even interfere with many metabolic process which important to survival the bacteria. Making resistance development of resistance to such drugs infrequent or even zero resistance develops by sensitive microorganisms and finally pulmonary fibrosis is the major side effect to this antibiotic and it is contraindicated to be given to patient with G- 6-PD dificency. Note: The doctor said that there will be no equations in the final exam. This is my first sheet and I tried my best sorry if there is any mistake or shortage.finally, I want to thank Alaa Jumaa and every one help me in this sheet Done by: Shaima Al-Haj 11 P a g e