Antibiotics Lecture Notes 2024-2025 PDF

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation...

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation Abbreviation Key information Book >> >> Abdulhamid Eithar zaki Al-Abadi 221-222-223 notes References Student explaintion Deleted Title: common drugs in treating bacterial infection CRN No: 15569(Male), 15581 (Female) Block: 1.2 (Infection and Immunity) Subject / Discipline: pharmacology Expert: Dr. Shereen Refaie Block Coordinator: Dr. Sayed. A. Quadri  The human cell different from We will talk about the cell wall bacterial cell in two main because we have very good group things, first there is no nucleus of antibiotics act mainly to in bacterial cells(DNA strand in destroyed the cell wall of the the cytoplasm), the second Bactria. important structure that present in bactria and not in human cells is the cell wall. The cell wall is: the outer layer cover the cell membrane. the function is to protect the Bactria. This picture was explained in. bacterial structure and If the cell wall is destroyed the bactria can die. function lecture. 12/7/21 Dr. Shereen Refaie  1 2 The place of the cell 1wall is different in the negative gram Bactria and the positive. In the positive it is outside the cell membrane Thick (many layers). The cell wall consists of layers of polymer of alternative molecules (NAM & NAG). Between the layers there is link called crosslink they are very important for the integrity of the cell wall. In the gram negative the cell wall is between two membranes(outer membrane, cell membrane) thinner. Gram-negative bacteria have more resistance due to the outer membrane and thinner peptidoglycan layer Peptidoglycan: This is a polymer of alternating N -acetylmuramic acid (NAM)&N-acetylglucosamine (NAG). 12/7/21  The NAM&NAG are produced inside the cell then they go out to make the cell wall. Transglycosylases enzyme connect the NAM&NAG together The enzyme that responsible for cross linking is (Transpeptidase) it is very important because It is involved in the terminal stages of assembling the cell wall by crosslinking the peptidoglycan layer and reshaping the cell wall during growth and The antibiotics the target the cell wall will division. inhibit the transpeptidases enzyme. 12/7/21 Dr. Shereen Refaie First classification: according to what they do to bacteria Classification of antimicrobials Bacteriostatic Bactericidal Bacteriostatic or Bactericidal (according to concentration) Erythromycin Isoniazid Explaination in the next slide. Explanation in next slide 12/7/21 Dr.Shereen Refaie 6  1-Bacteriostatic: (static = stop)(It is just used with mild infection, not with severe infections.) Bacteriostatic will help immune system to kill bacteria by stopping the growth and multiplication of bacteria. For example, You have a bacterial infection Doctor Mohammed give you Antibiotic(Bacteriostatic) This drug will stop the growth and multiplication of bacteria and immune system will complete the mission. RememberThe killing of bacteria will be by immune system. bacteriostatic will just make the bacteria weak Students explanation by stooping their multiplication and growth. It just used with mild infection Note: we don’t give patients with immunecomprissed diseases this drug why? Because we stop the multiplication not kill the bacteria. 2-Bactericidal(Cidal=killing) We use these drugs to kill the bacteria directly. 3-(Some act like Bacteriostatic and Bactericidal) Depends in the dose. If we give a patient a high dose it will be Bactericidal, a low dose will be Bacteriostatic. e.g.Erythromycin Isoniazid The PIC just to understand  Classification of antimicrobials Broad spectrum Narrow spectrum Second classification: according to Which are active against both gram- which type of bacteria they react. Which are active only against gram-positive or positive and gram-negative bacteria e.g., gram-negative bacteria e.g., Penicillin G, cephalosporins (2nd, 3rd, 4thgeneration), Sulphonamides Broad spectrum: this type of drugs work against both(positive and negative)type of bacteria. It is not very effective against resistant organisms like pseudomonas. Narrow spectrum: it work only against one type either(positive or negative). Extended-spectrum: It is Broad spectrum, but it can work against resistant organism. Extended-spectrum: Which affect bacterial strains commonly resistant to other antibacterial agents as Pseudomonas aeruginosa 12/7/21 Dr. Shereen Refaie  Third classification according to their target in the bacteria. In summary: every drugs gave a specific target to work on. for example, Amoxicillin(bactericidal ,Broad spectrum and Cell wall inhibitor) (Name of the target + inhibitor) Example: Translation(target)+inhibitor = Translation inhibitor No need to memorise all the examples. Only what we will take with details. 12/7/21 Dr. Shereen Refaie  Beta-Lacten antibiotics + Vancomycin they inhibit the cell wall synthesis Inhibitors of cell wall synthesis A-β-Lactam antibiotics They called β-Lactam because they have a common 1-Penicillin chemical structure In beta ring. these ring is responsible for efficacy of the drug. It should be intact to work. the most common are the first two 2-Cephalosporins If it’s broken will lose the efficiency. 3-Monobactams 4- Carbapenems B-Vancomycin Vancomycin Is only for the sever resistant infections, for short period of time(because it is a toxic drug) as injection. 12/7/21 Dr. Shereen Refaie  Penicillin The doctor didn't explain Pharmacokinetics: anything in this slide. ü After absorption, they are distributed all over the body ü Very little passage across normal Blood Brain Barriar(BBB) but PASS EASILY with INFLAMMEDMENINGES Why is it widely used/? Safe ü Pass placental barrier but NOT teratogenic that’s mean it will not cause fetus malformation for all ages and it has ü They are bound to plasma proteins 1\Very good absorption and distribution. ü Excreted by renal active tubular secretion. This secretion is inhibited by Probenecid(this drugwill keepPenicillin inside our body) 2\It is naturally from Bread molds. Mechanism of action: Bind to specific Penicillin-Binding Protein (PBP): Inhibit cross linking of peptidoglycan, a final step in cell wall synthesis(i.e., inhibit cell wall synthesis) Activate autolytic enzymes (autolysins) leads to lysis of cell wall 12/7/21 11  1\Against gram positive it will directly go to cell wall, but in gram negative they have additional outer membrane it will enter through the pores. 2\After entering the cell it bind with a receptor called(Penicillin-Binding Protein “PBP” to be activated). 3\Then it will inhibit (Transpeptidase enzyme ). As a result, there will not be a cross linking between peptidoglycan layers. https://youtu.be/a81nHSqQuvI Link for the video How bacteria resist? 1\By producing enzyme called( beta lactamase) which is responsible to inhibit beta lactamase ring(which is for responsible for efficacy of the drug). 2\ by change the shape of (PBP) so Penicillin will not bind to the receptor. As a result, the Penicillin will not be activated. 3\ (only for gram negative)the bacteria will Close the pores so Penicillin will not be able to enter the bacteria. 12/7/21 video Dr. Shereen Refaie  β-Lactam Antibiotics Penicillin First penicillin that discovered Preparations: (‫)عيوبه كثيره‬ 1-Penicillin G: Natural form of penicillin ØShort duration of action(6 hours) ØAcid sensitive (destroyed by gastric acidity, not effective orally) ‫حساسه للحمض اللي في المعده ف‬ injection ‫ناخذها‬ Øβ-lactamase (penicillinase) sensitive. ØNarrow spectrum (not effective against Gram –vebacilli) 12/7/21 Dr. Shereen Refaie  Penicillin Here we modified its composition with the 2-β-lactamaseresistant penicillin: addition of materials to improve it in some ways, such as making it suitable for the two Effective orally in treatment of staph infection types of Bacteria. e.g., Oxacillin, Cloxacillin, Temocillin 3- Broadspectrumpenicillin: Β-lactamase sensitive but acid resistant (effective orally) Ampicillin: incompletely absorbed orally ,affected by food +no longer duration Amoxicillin: similar to Ampicillin but has Better oral absorption,Not affected by food, and Long erduration of action 12/7/21 Dr. Shereen Refaie  Penicillin 4-Extended spectrum (Anti-pseudomonal) penicillin: qPiperacillin qTicarcillin üBroad spectrum & effective against pseudomonas aeruginosa, Proteus & Klebsiella Pseudomonas= symbol for resistant bacteria üThey are β-lactamase sensitive Note: All penicillin are B lactamase sensitive Except Oxacillin, Cloxacillin, Temocillin (They are B lactamase resistance) 12/7/21 Dr. Shereen Refaie  Indications of Penicillin 1.Treatment:They are1st choicefor many infections 2-Prophylaxis of Ex. If the patient has an artificial valve in his heart or the patient Sub-acute bacterial endocarditis: for preventing has rheumatoid diseases and he is bacteria that are always present on the surface of tissues around doing an dental procedure the doctor must give him penicillin teeth from spreading into the blood. This is especially important in before starting to prevent The bacteria in the oral cavity from patientswithsometypesofdefective(rheumaticheartdisease) spreading to the blood and then settle on the valve and cause orartificialheartvalvessinceblood-bornbacteriahaveatendency infection to settle on the valves and cause serious infections. The antibiotics (Sub-acute bacterial endocarditis) may be given orally, intramuscularly, or even intravenously. They usually aregivenimmediately beforethedental surgery 12/7/21 Dr.Shereen Refaie 16  From mild allergy to severe allergy(Anaphylactic shock) Which is sever Side effects of penicillin: edema and sever 1-Allergy: urticaria, angioedema& ANAPHYLACTIC SHOCK inflammation ( the patient may die) Avoided by: üCareful patient history Sensitivity test: we take very diluted penicillin and inject it intradermal in a üPenicillin sensitivity test marked small area of the skin and wait for few minutes If the patient is allergic we can see signs of inflammation and allergy(redness and etching). **If the patient is allergic to penicillin: qNever re-use penicillin Being allergic to penicillin means that 20- qCross allergy between penicillin & other β-lactams 30% you are allergic to other B lactamase. ( we don’t use the same group or family). it called cross allergy 2-Diarrhea: due to super-infection specially with broad spectrum penicillin Because the antibiotic doesn’t differentiate between good and harmful bacteriaSo, penicillin will kill the intestinal flora which is responsible for cleaning the bowels from any toxins and cause 12/7/21 Dr. Shereen Refaie diarrhea.  Resistance to penicillin is made by: 1- Beta lactamase (most bacteria do) qResistance develop in bacterial strains 2- changing penicillin producing β-lactamase enzyme binding protien. qAugmentin ®: A combination 3- close the pores in gram negative bacteria of Clavulanic acid (β-lactamase inhibitor) only. with Amoxicillin. qIt is effective against β-lactamase producing bacteria Amoxicillin (broad spectrum penicillin) + Clavulanic acid (β- lactamase inhibitor) = Augmentin 12/7/21 Dr. Shereen Refaie  β-Lactam Antibiotics Cephalosporins More active than penicillin against gram negative Similar to penicillin but more resistant to β-Lactamase enzyme bacteria Like in respiratory and urinary track infection Mechanism of action: as penicillin, bactericidal antibiotics by More generation = more inhibiting bacterial cell wall synthesis resistant to beta lactenase and more active against grame negative. Classification: 1stgeneration: e.g. Cefradine Broad spectrum active against mainly Gram +ve organisms NOT pass BBB not effective in meningitis The doctor said that 1st and 2nd are not very important and she started from the third. 12/7/21 Dr. Shereen Refaie  Cephalosporins 2nd generation: e.g. Cefuroxime Broad spectrum similar 1st generation but less active against Gram +ve & more active against Gram –ve Do NOT pass BBB EXCEPT cefuroxime All Start with cef 3rd generation: e.g., Cefotaxime Similar to 2nd generation but less active against Gram +ve & more active against Gram –ve PassBBB usefulinmeningitis BBB= Blood-brain barrier 12/7/21 Dr. Shereen Refaie  Cephalosporins 4thgeneration: e.g. Cefepime Similar to 3rdgeneration (more against Gram –ve) More resistant to βlactamase Pass BBB & useful in meningitis The most advanced generation 5thGeneration: Ceftaroline,the only fifth-or advanced-generation cephalosporin. qis a potent antibiotic that should be reserved for serious infection. specifically, against multidrug-resistant infections like MRSA (methicillin-resistantS. aureus) and VRSA (vancomycin-resistantS. aureus). 12/7/21 Dr. Shereen Refaie  Cephalosporins Uses : 1-Infections resistant to penicillin: e.g staph, gonorrhea 2-Anaerobic infections Gram negative infections 3-Respiratory tract infection 4-Urinary tract infection especially Gram –ve 5- Meningitis 12/7/21 Dr. Shereen Refaie  Disadvantge that it is only can taken as injection Cephalosporins 1-2 same as penicillin Side effects: 1- Allergy & cross allergy with penicillin ( in 10% of patients allergic of penicillin) 2- GIT upsets & Diarrhea (due to superinfection) I.M: intramuscular = painful 3- irritant: if given I.V: intravenous = inflammation in the vain and thrombosis (thrombophlebitis) I.M painful I.V. Thrombophlebitis 4- Dose-related and reversible nephrotoxicity especially if concurrently used with loop diuretics, NSAIDs or gentamicin Higher dose = higher chance of nephrotoxicity (Especially given with other nephrotoxin drug) Because it is dose related. 12/7/21 Dr. Shereen Refaie  Flouroquinolones remember they all end with FLOXACIN Norfloxacin-Ciprofloxacin, gatifloxacin Broad spectrum: Effective against: ØGram -ve organisms including Pseudomonas ØGram +ve organisms including strep pneumoniae , Chlamydia and mycobacteria 12/7/21 Dr. Shereen Refaie  Quinolones Mechanism of action: antibiotics Bactericidal - Block bacteria DNA synthesis by inhibiting bacterial DNA gyrase (topoisomerase II) - Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription & replication It inhibits the DNA gyrase, so we can’t separate the supercoiled 2 strands from each other and there will be no DNA synthesis (no transcription) =No growth of the bacteria 12/7/21 Dr. Shereen Refaie  Quinolones Mainly in gram negative inections Uses 1-Urinary tract infection & prostatitis 2-Sexually transmitted diseases as gonorrhea & chlamydia 3-Respiratory tract infections 4-Typhoid fever & intra-abdominal infections 5- Osteomyelitis 6- Septicemia 12/7/21 Dr. Shereen Refaie Side effects: Arthropathy = inflammation of the joint because of degradation 1-Hypersensitivity reactions & Photosensitivity of the cartilage. 2-Nephrotoxicity 3-Chondrolytic & reversible arthropathy: joint swelling & You can’t give it in conditions of damage of growing cartilages so they are contraindicated in pregnancy or lactation because it can pregnancy, lactation & pre-pubertal children affect the baby’s growth Or children until 15 or 18 4-Confusion, headache & dizziness 5-Drug-interactions: inhibit metabolism of theophylline, warfarin & sulfonylureas 12/7/21 Dr. Shereen Refaie  All question are from mid exams 23-17 1) Which type of antibiotic primarily works 2) Which class of antibiotics works by by inhibiting cell wall synthesis in bacteria? inhibiting bacterial DNA synthesis? A) Tetracycline A) Macrolides B) Quinolones B) Tetracyclines C) Penicillin C) Quinolones D) Macrolides D) Penicillins 3) What is the primary mechanism of 4) Which generation of cephalosporins is resistance to penicillin in some bacterial primarily effective against Gram-negative strains? bacteria and can cross the blood-brain barrier, making it useful in treating A) Mutation in ribosomal RNA meningitis? B) Production of beta-lactamase enzyme C) Inhibition of DNA synthesis A) First generation D) Increased efflux pump activity B) Second generation C) Third generation D) Fourth generation 5) What is the difference between bactericidal and bacteriostatic antibiotics? A) Bactericidal antibiotics stop bacterial growth, while bacteriostatic antibiotics kill bacteria directly B) Bactericidal antibiotics kill bacteria directly, while bacteriostatic antibiotics stop bacterial growth C) Both bactericidal and bacteriostatic antibiotics kill bacteria directly D) Both bactericidal and bacteriostatic antibiotics only stop bacterial growth 1)C - 2)C - 3)B - 4)C - 5)B  [email protected] Ext: 7874 7 December 2021 Dr Shereen Refaie  team Wishes you the best