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ß-Lactams: Mechanisms of Action and Resistance
 
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Developed and produced by http://www.MechanismsinMedicine.com Animation Description: This animation starts with the explanation of bacterial cell wall synthesis, the process targeted by ß-Lactams. Structurally, most bacteria consist of a cell membrane surrounded by a cell wall and, for some bacteria, an additional outer layer. Internal to the cell membrane is the cytoplasm which contains ribosomes, a nuclear region and in some cases granules and/or vesicles. Depending on the bacterial species, a number of different external structures may be found such as a capsule, flagella and pili. In gram negative bacteria, the gap between the cell membrane and the cell wall is known as the periplasmic space. Most gram positive bacteria do not possess a periplasmic space but have only periplasm where metabolic digestion occurs and new cell peptidoglycan is attached. Peptidoglycan, the most important component of the cell wall, is a polymer made of N-acetyl muramic acid alternating with N-acetyl glucosamine which are cross-linked by chains of four amino acids. The function of the bacterial cell wall is to maintain the characteristic shape of the organism and to prevent the bacterium from bursting when fluid flows into the organism by osmosis. Synthesis of peptidoglycan and ultimately the bacterial cell wall occurs in a number of stages. One of the first stages is the addition of 5 amino acids to N-acetyl muramic acid. Next, N-acetyl glucosamine is added to the N-acetyl muramic acid to form a precursor of peptidoglycan. This peptidoglycan precursor is then transported across the cell membrane to a cell wall acceptor in the periplasm. Once in the periplasm, the peptidoglycan precursors bind to cell wall acceptors, and undergo extensive crosslinking. Two major enzymes are involved in crosslinking: transpeptidase and D-alanyl carboxypeptidase. These enzymes are also known as penicillin binding proteins because of their ability to bind penicillins and cephalosporins. Eventually, several layers of peptidoglycan are formed all of which are crosslinked to create the cell wall. Gram positive bacteria have many more layers than gram negative bacteria and thus have a much thicker cell wall. Beta-lactam antibiotics include all penicillins and cephalosporins that contain a chemical structure called a beta-lactam ring. This structure is capable of binding to the enzymes that cross-link peptidoglycans. Beta-lactams interfere with cross-linking by binding to transpeptidase and D-alanyl carboxypeptidase enzymes, thus preventing bacterial cell wall synthesis. By inhibiting cell wall synthesis, the bacterial cell is damaged. Gram positive bacteria have a high internal osmotic pressure. Without a normal, rigid cell wall, these cells burst when subjected to the low osmotic pressure of their surrounding environment. As well, the antibiotic-penicillin binding protein complex stimulates the release of autolysins that are capable of digesting the existing cell wall. Beta-lactam antibiotics are therefore considered bactericidal agents. Bacterial resistance to beta-lactam antibiotics may be acquired by several routes. One of the most important mechanisms is through a process known as transformation. During transformation, chromosomal genes are transferred from one bacterium to another. When a bacterium containing a resistance gene dies, naked DNA is released into the surrounding environment. If a bacterium of sufficient similarity to the dead one is in the vicinity, it will be able to uptake the naked DNA containing the resistance gene. Once inside the bacterium, the resistance gene may be transferred from the naked DNA to the chromosome of the host bacteria by a process known as homologous transformation. Over time, the bacterium may acquire enough of these resistance genes to result in a remodelling of the segment of the host DNA. If this remodelled DNA segment codes for cross-linking enzymes (i.e. penicillin binding proteins), the result is the production of altered penicillin binding proteins. These altered penicillin binding proteins can still cross-link the peptidoglycan layers of the cell wall but have a reduced affinity for beta-lactam antibiotics thus rendering the bacterium resistant to the effects of penicillin and other beta-lactam agents. This transfer process has resulted in penicillin-resistant S. pneumoniae through the acquisition of genes from other naturally occurring penicillin-resistant Streptococcus species. A second important mechanism by which bacteria become resistant to beta-lactam antibiotics is by the production of enzymes capable of inactivating or modifying the drug before it has a chance to exert its effect on the bacteria. View animation to read more.
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Ampicillin capsules|Use|Side effects
 
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Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously.Like all antibiotics, it is not useful for the treatment of viral infections. Common side effects include rash, nausea, and diarrhea. It should not be used in people who are allergic to penicillin. Serious side effects may include Clostridium difficile colitis or anaphylaxis. While usable in those with kidney problems, the dose may need to be decreased.Its use during pregnancy and breastfeeding appears to be generally safe. Ampicillin was discovered in 1958 and came into commercial use in 1961.It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.Its wholesale cost in the developing world is between US$0.13 and 1.20 for a vial of the intravenous solution as of 2014.In the United States, it is available as a generic medication and 10 days of treatment cost about $13. Ampicillin is used to treat infections by many Gram-positive and Gram-negative bacteria. Ampicillin was the first 'broad spectrum' penicillin with activity against Gram-positive bacteria including Streptococcus pneumoniae, Streptococcus pyogenes, some isolates of Staphylococcus aureus (but not penicillin-resistant or methicillin-resistant strains), and some Enterococcus. Activity against Gram-negative bacteria includes Neisseria meningitidis, some Haemophilus influenzae, and some of the Enterobacteriaceae. Its spectrum of activity is enhanced by co-administration of sulbactam, a drug that inhibits beta lactamase, an enzyme produced by bacteria to inactivate ampicillin and related antibiotics. It is sometimes used in combination with other antibiotics that have different mechanisms of action, like vancomycin, linezolid, daptomycin, and tigecycline. Ampicillin can be administered by mouth, an intramuscular injection (shot) or by intravenous infusion. Indications : respiratory infections sinusitis bronchitis pharyngitis otitis media bacterial meningitis Salmonella, Shigella, and Listeria bacteria. gastrointestinal infections caused by contaminated water or food. healthcare-associated infections related to infection from urinary catheter use unresponsive to other medications. Haemophilus influenzae, Streptococcus pneumoniae infections. Genito-urinary tract infections prevent infection (prophylaxis) in those who previously had rheumatic heart disease or are undergoing dental procedures. Side effects: Ampicillin is comparatively less toxic than other antibiotics. In very rare cases, it causes severe side effects such as angioedema, anaphylaxis, and C. difficile infection. Some develop black 'furry' tongue'. The most serious adverse effects are seizures, serum sickness, anaphylaxis, pseudomembranous colitis. The most common side effects to be expected in ten percent of users are diarrhea and rash. Less common side effects can be nausea, vomiting, itching, blood dyscrasias, and mild allergic reactions. Other conditions may develop up several weeks after treatment.
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Drug of choice For AIIMS DSSSB GMCH EXAM - Nurses hub
 
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Subscribe this CHANNEL Drugs Of Choice List (1)Penicillin G Streptococcus pneumoniae, S.Viridans, Hemolytic Streptococci group A, B, C, G, Staphylococcus (Non-Penicillinase producing) Neisseria meningitidis,Clostridium(ABC)Bacillus Cereus,Actinomyces.Treponema Pallidum, T.Pertene (2)Ampicillin Listeria, Enterococcus faecalis. (3)Vancomycin MRSA, Coagulase-negative Staphylococcus, Enterococcus faecium. (4)Erythromycin Corynebacterium (5)Doxycycline Bacillus anthracis, Borrelia burgdorferi, B.Recurrentis. Chalmydia & Rickettsiae. (6) Cotrimoxazole Nocardia (7) Azithromycin Hemophilus ducreyi & Mycoplasma . (8) Ceftriaxone Proteus,E.coli,Salmonella (9)Carbapenems Serratia,Enterobacter,Acinetobacter (10)(Metronidazole Bacteriocides (11)Ceftazidime Burkholderia pseudomallei Drugs Of Choice List in pregnancy (12)Choloroquine Drug of choice for malaria in pregnancy (13) Alpha-Methyldopa DoC for hypertension in pregnancy (14)Heparin DOC for anticoagulation in pregnancy. (15)Labetalol DOC for hypertensive crisis in pregnant women. (16)Acetaminophen Analgesic DOC (17)Phenobarbitone DoC for epilepsy in pregnant women. (18)Doxylamine & Pyridoxine DoC for nausea in pregnancy. Drugs Of Choice List for various types of seizures (19)Valproate Tonic seizures Absence seizures Grand mal (GTCS) Clonic seizures Atonic seizures Myoclonic seizures (20)Carbamazepine Partial seizures (21)Vigabatrin Infantile spasm with tuberous sclerosis (22)ACTH Infantile spasm (23)Lorazepam (IV) Status epilepticus (24)Diazepam Febrile seizures (25)Magnesium Sulphate Seizure in eclampsia Drugs Of Choice List in poisoning (26)Physostigmine Atropine, Belladonna  & Dhatura poisoning (27)Atropine Carbamate, Early mushroom poisoning, Organophosphate poisoning. (28)Flumazenil Benzodiazepine poisoning (29)Acetylcysteine Acetaminophen poisoning (30)Naloxone Opioid poisoning (31)Deferiprone Chronic iron poisoning (32)Desferrioxamine Acute iron poisoning (33)Glucagon Beta-blockers poisoning (34)Amyl nitrate Cyanide poisoning Drugs Of Choice List in bronchial asthma  (35)Salbutamol An acute attack of bronchial asthma in normal patient and pregnant women. Exercise & Aspirin-induced acute attack of bronchial asthma. (36)Ipratropium An acute attack of bronchial asthma during labor. An acute attack of bronchial asthma on beta-blocker therapy. (37)Corticosteroids Prophylaxis of bronchial asthma,exercise-induced, and aspirin-induced asthma. Drugs Of Choice List In Antimicrobials Prophylaxis (38)Ampicillin Group B streptococcus infection (39)Amoxicillin Endocarditis and Otitis media (40)Azithromycin Mycobacterium avium complex (MAC) Pertussis (41)Benzathine penicillin Rheumatic fever (42)Procaine Penicillin Gonorrhea and syphilis (43)Tetracycline Rickettsial infection and plague. (44)Cefazoline Surgical Prophylaxis (45)Doxycycline Anthrax (46)Trimethoprim and sulphamethoxazole Toxoplasmosis, Pneumocystis service UTI (47)Rifampicin Hemophilus influenza type B. (48)Oseltamivir Influenza Type A & B. Anesthetic Drugs Of Choice List (49)Propofol Daycare (50)Sevoflurane Congenital heart disease,ASD,VSD,PDA (51)Etomidate Ischemic heart disease (52)Ketamine Asthma and COPD Shock CHF, and congenital heart disease (Right to left shunt) (53)Thiopentone Epilepsy Thyrotoxicosis (54)Methohexitone Electroconvulsive therapy (55)Isoflurane Cardiac surgery Neurosurgery For producing deliberate hypotension Drugs Of Choice List in Endocrinological Disorders (56)Insulin Type 1 DM Diabetes Mellitus in pregnancy. Diabetic Ketoacidosis. Uncontrolled DM. (57)Metformin Type 2 DM Diabetes mellitus in obesity (58)Sildenafil Erectile Dysfunction (59)Hydrocortisone Acute and chronic adrenal insufficiency. (60)Nateglinide Postprandial hyperglycemia. (61)Methotrexate Ectopic pregnancy (62)Oxytocin Postpartum hemorrhage Induction of labor (63)Cabergoline Acromegaly Hyperprolactinemia. (64)Finasteride Anogenital alopecia. (65)Alendronate Osteoporosis Drugs of choice in fungal infections (66)Amphotericin B Meningeal histoplasmosis Endocarditis by candida Sever or CNS blastomycosis Induction  cryptococcal meningitis(For 2 weeks) Exserohium (67)Fluconazole Candida albicans Maintainance in cryptococcal meningitis (68)itraconazole Nonmeningeal histoplasmosis Sporotrichosis Para Coccidioidomycosis Mild or non-CNS blastomycosis Chromoblastomycosis Penicillium mameffei (69)Prednisolone+itraconazole/Voriconazole Allergic bronchopulmonary aspergillosis. (70)Caspofungin Candida glabrate,and Candida krusei. Drugs of choice in gastrointestinal disorders (71)PPIs (Proton Pump Inhibitors) Gastric ulcer, Duodenal ulcer, stress ulcer, NSAIDs-induced ulcer. GERD,& Zollinger Ellison syndrome. (72)Metoclopramide A migraine associated or drug or disease associated vomiting (73)Domperidone Levodopa-induced vomiting (74)Ondansetron Postoperative or radiation-induced vomiting (75)5HT3 antagonist Cisplatin-induced early vomiting By Nurses hub Like share and comment. Subscribe this channel
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Micro
 
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Critical Care Paramedic 6:  Introduction to Pharmacology - Part 2
 
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This Wisconsin Critical Care Paramedic module covers pharmacology as associated with critical care interfacility transports.
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