Antimicrobial Drugs PDF

Antimicrobial Drugs MERVAT BARAKAT Pharmacology Department Faculty of Medicine Alex. University  What are antimicrobial drugs? ⚫ Antimicrobial drug – a chemical that destroys pathogens, includes antibiotics and chemically synthesized drugs ⚫ Antibiotic...

Antimicrobial Drugs MERVAT BARAKAT Pharmacology Department Faculty of Medicine Alex. University  What are antimicrobial drugs? ⚫ Antimicrobial drug – a chemical that destroys pathogens, includes antibiotics and chemically synthesized drugs ⚫ Antibiotic – an antimicrobial agent produced naturally by a bacterium or fungus ⚫ Have target specificity. Injure target organism without affecting the host. What are the principles of antimicrobial therapy ? ⚫ Appropriate indication ⚫ Appropriate dosage ⚫ Suitable length of treatment period (usually given for 7-10 days) ⚫ When to start treatment ⚫ Target of therapy (prophylaxis or treatment). ⚫ Host defense mechanism should be intact ⚫ Good knowledge of the drug's pharmacokinetics and potential risk. ⚫ Combination only under certain conditions and right 3 choice of combination. Identification culture and sensitivityof the organism : Acute ill patient as: Selection of antibiotic as directed Meningitis or neutropenic patient by site of infection, patient history, community acquired or hospital acquired and age Coverage by antibiotic combination against G+ve, G-ve and anaerobes Combination of G-ve and G+ve or broad spectrum antibiotic. Status of the Patient: (Patients factors) 1.Immune system 2. Renal dysfunction 3.Hepatic dysfunction 4.Pregnancy 5.Lactation 6.Age Bacteriostatic versus Bacteriocidal drugs Bacteriostatic: Arrest the growth and replication of bacteria, thus limiting the spread of infection while the body’s immune system attack, immobilize and eliminates the pathogens. Bacteriocidal: Kill bacteria and the total number of viable organisms decrease. Spectrum of Activity – Broad spectrum ⚫ affecta wide range ⚫ can disrupt the normal flora of the body ⚫ cases of rapid onset life-threatening infections, no time to culture the causative agent – Extended spectrum – Narrow spectrum ⚫ limitedrange ⚫ requires the identification of the pathogen  Prophylaxis GOALS OF ANTIBIOTICS USE Prevent an initial infection or its recurrence after infection  Meningitis; ciprofloxacin in > 12 yrs or rifampicin in < 12 yrs or ceftriaxone in pregnant contacts Empiric Therapy Infecting organism(s) not yet identified. More “broad spectrum”(usually up to 72 hours) Definitive Therapy Organism(s) identified and specific therapy chosen. More “narrow” spectrum  Principles of antibiotics use 1. Antibiotics can't distinguish between the "good" and the "bad" bacteria. There is a delicate balance of billions of bacteria inside the body. Bifido bacteria in large intestine and acidophilus in small intestine and vagina protect against infection by yeast and other bad bacteria. Also "friendly" bacteria found on the skin protect against bad bacteria, yeast and fungal infections. ◦ Continued use of antibiotics, especially broad-spectrum antibiotics, can seriously disrupt the normal ecology of the body and render anyone more susceptible to pathogenic (disease causing) bacteria, yeast, viral and parasitic infection. 2. The worst thing one can do is to take antibiotics shorter than prescribed ◦Shortened course of antibiotics often kills only the most vulnerable bacteria, while allowing relatively resistant bacteria to survive. Not only do they survive, but since they have "seen" the antibiotic, they can change their structure so that antibiotic will not kill them in the future(antibiotic resistance) 3. The dosage is a very important factor in antibiotic effectiveness  If the dosage of the antibiotic is not adequate, it will not be effective for treatment of the infection and bacteria are more likely to develop resistance. 4. Broad spectrum Antibiotics may interfere with immune system development.  It is necessary to have a broad spectrum of flora to stimulate a healthy immune system.”  Children who are given broad-spectrum antibiotics before two years of age are three times more likely to develop asthma than are children who are not given such antibiotics. Antibiotics destroy bacteria that are helpful to the developing immune system.  What are the purposes for use of antibiotics ? (Target of therapy ) ⚫ Prophylaxis A – Medical: 1. Exposure to virulent pathogen (HIV, N. meningitis. Pretreatment may prevent tuberculosis or meningitis among individuals who are in close contact with infected patients. 2. Pretreatment may prevent streptococcal infections in patients with a history of rheumatic heart disease. Patients may require years of treatment. B –surgical Pretreating of patients undergoing dental extractions who have implanted prosthetic devices, such as articial heart valves, prevents Endocarditis 12 ⚫ Treatment  Combinations Of Antimicrobial Drugs Indication: 1. Treatment of severe infection of unknown etiology 2. In mixed infections 3. To delay emergence of resistant strains (TB) 4. To achieve an effect not obtained by either alone 5. To reduce the incidence and intensity of adverse reactions 13  Drug resistance ⚫ Bacteria are said to be resistant to an antibiotic if their growth is not halted by the maximal level of that antibiotic that can be tolerated by the host  What are the causes of Misuse of antibiotics? ⚫ Treatment of untreatable infection ⚫ Treatment of fever of undetermined origin ⚫ Improper dose ⚫ Reliance on chemotherapy with omission of surgical drainage of purulent exudates or necrotic or vascular infected tissue ⚫ Lack of adequate bacteriological information 15 Complication of antibiotic therapy 1. Hypersensitivity reactions, ex: penicillin can produce from urticaria to anaphylactic shock 2. Direct toxicity: High serum level → toxicity Ex: aminoglycosides → ototoxicity by direct toxic effect the membrane in hair cell 3. Super infection: by using broad spectrum antibiotic→ alterations of normal flora in upper respiratory, intestinal and geniotourinary tract → overgrowth of opportunistic organisms specially fungi and resistant bacteria which is difficult to treat Failure of treatment Incorrect indication. Ineffective antibiotic. Inappropriate dosage. Inadequate duration. Development of resistance. Change of causative pathogens. Classify Antibiotics ⚫ Classification of Antibiotics according: ⚫ Chemical Structure ⚫ Spectrum of Activity& effects ⚫ Mechanism of Action 18 Classify Antibiotics ⚫ Spectrum of Antibiotic activity – Narrow spectrum Antibiotic – Broad spectrum Antibiotic ⚫ Effects of Antibiotics – Bacteriostatic – Bacteriocidal Mechanism of action (site of action) What are main targets of Antibiotics?  The Beta-lactams ⚫ Beta-lactams are a broad class of antibiotics that have in common a four membered beta-lactam ring structure. They include: 1. Penicillins, 2. Cephalosporins, 3. Carbapenems, 4. Monobactam 22  -lactam Antibiotics All of the drugs in this group contain a β-lactam ring in their structure S S Share similar N N O O features of Penicillins chemistry, Cephalosporins mechanism of action, pharmacologic and clinical effects. N N O O Carbapenems Monobactams 23 PENICILLINS ⚫ Bacteriocidal ⚫ Mainly against G+ve Penicillin are among the most widely effective and the least toxic drugs known. nafcilin & oxacilin What is the mechanism of action of penicillin ? ⚫ Penicillins enter the bacteria via the cell wall ⚫ Inside the cell, they bind to penicillin-binding protein ⚫ Once bound, normal cell wall synthesis is disrupted ⚫ Result: bacteria cells die from cell lyses ⚫ Penicillins do not kill other cells in the body 26