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Anti-infective

Anti-infective. The anti- infectives. Anti-infective agents are drugs that are designed to act selectively on foreign organisms that have invaded and infected the body

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Anti-infective

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  1. Anti-infective

  2. The anti-infectives • Anti-infective agents are drugs that are designed to act selectively on foreign organisms that have invaded and infected the body • Anti-infectives- range from antibiotics, antifungals, antiprotozoals, antihelmintics, antivirals and antimycobacterial

  3. Antibiotics

  4. General Mechanisms of Action of Anti-Bacterial Agent • Some interfere with the biosynthesis of bacterial cell WALL • Some inhibit protein synthesis • Some change the cell membrane permeability • Some inhibit DNA synthesis

  5. Spectrum of Activity of Anti-Bacterial Agent • Narrow spectrum anti-infectivesaffect only a few bacterial types. • The early penicillin drugs are examples. • Broad-spectrum anti-infectivesaffect many bacteria. • Meropenem is an example. Because narrow spectrum antibiotics are selective, they are more active against those single organisms than the broad spectrum antibiotics.

  6. Spectrum of Activity of Anti-Bacterial • Anti-Bacterial agents that interfere with the ability of the cell to reproduce/replicate without killing them are called BACTERIOSTATIC drugs. • Antibiotics that can aggressively cause bacterial death are called BACTERICIDAL. • These properties (-cidal and –static) can also depend on the antibiotic concentration in the blood.

  7. Antibiotics • The PENICILLINS • THE CEPHALOSPORINS • The Aminoglycosides • The Macrolides • The Lincosamides • The Tetracyclines • The Fluoroquinolones • The Sulfonamides

  8. The PENICILLINS • Narrow spectrum penicillins • Penicillin G • Penicillin V • Broad Spectrum Penicillins (aminopenicillin) • Amoxicillin • Ampicillin • Bacampicillin • Penicillinase-resistant Penicillin (anti-staphyloccocalpenicillins) • Cloxacillin • Nafcillin • Methicillin • Dicloxacillin • Oxacillin • Extended-Spectrum penicillins (Anti-pseudomonalpenicillins) • Carbenicillin • Mezlocillin • Piperacillin • Ticacillin • Beta-lactamase inhibitors • Clavulanic acid • Sulbactam • Tazobactam

  9. Penicillin The structure of Penicillin • Penicillin is a beta-lactam drug, with a beta-lactam ring. The group of penicillins is called beta lactam antibiotics. The action of Penicillins: The penicillin and penicillinase-resistant penicillins produce BACTERICIDAL effects by interfering with the ability of susceptible bacteria from biosynthesizing the framework of the cell wall. The bacterium will have weakened cell wall, will swell and then burst from the osmotic pressure within the cell.

  10. Penicillin Therapeutic Indications of penicillin: • The penicillins are indicated for the treatment of streptococcal infections. Adverse Effects of Penicillins • GI system effects- the major adverse effects of penicillin therapy involve the GIT. Nausea, vomiting, diarrhea, abdominal pain, glossitis, stomatitis, gastritis, sore mouth and furry tongue. • The reason for some of these effects (superinfection) is associated with the loss of bacterial flora. • Hypersensitivity reactions- rashes, pruritus, fever. These indicate mild allergic reaction. Wheezing and diarrhea may also occur. Anaphylaxis can also happen leading to shock or death. It occurs in 5-10% of those receiving penicillins. • Pain and inflammation on injection sites

  11. THE CEPHALOSPORINS • First Generation cephalosporins- are largely effective against the same gram-positive organisms affected by penicillin. • Second generation cephalosporins- are effective against those strains as well as Haemophilus influenza, Entreobacteraerogenes and Nesseria sp. These drugs are less effective against gram positive bacteria • Third Generation cephlosporins- are relatively weak against gram-positive bacteria but more potent against gram-negative bacteria, to include Serratiamarcescens. • Fourth generation cephalosporins- are developed to fight against the resistant gram-negative bacteria. The first drug is cefepime.

  12. THE CEPHALOSPORINS • Third Generation Cephaosporins • Cefnidir • Cefixime • Cefoperazone • Cefotaxime • Cefpodoxime • Ceftazidime • Ceftibuten • Moxalactam • Fourth Generation Cephalosporin • Cefepime • First generation cephalosporins • cefadroxil • Cefazolin • Cephalexin • Cephalotin • Cephapirin • Cephadrine • Second Generation cephalosporins • Cefaclor • Cefamandole • Cefonizind • Cefotetan • Cefoxitin • Cefmetazole • Cefprozil • Cefuroxime

  13. THE CEPHALOSPORINS The mechanism of action: • The cephalosporins are primarily BACTERICIDAL. They interfere with the cell-wall building ability of bacteria when they divide. They prevent the bacteria from biosynthesizing the framework of their cell wall. The weakened cell wall will swell and burst causing cell death. • Pharmacokinetics • Only a few cephalosporins are administered orally, most are administered parenterally. • Their half-lives are short and • they are excreted mainly in the urine.

  14. THE CEPHALOSPORINS Contraindications and Precautions • The drugs are contraindicated in patients with known allergies to cephalosporins and penicillins. Adverse Effects • GI system- Nausea, vomiting, diarrhea, anorexia, abdominal pain and flatulence are common effects. • CNS – headache, dizziness, lethargy and paresthesias have been reported. • Renal system- nephrotoxicity in individuals with pre-existing renal disease Drug-Drug interactions • Aminoglycosides- if given with cephalosporins may increase the risk of kidney toxicity • Anti-coagulants- may experience increased bleeding tendencies .

  15. The Aminoglycosides The following are the aminoglycosides 1.Gentamycin 2.Tobramycin 3.Amikacin 4.Netilmicin 5.Kanamycin Mechanism of Action: • These are BACTERICIDAL. They inhibit protein synthesis in susceptible strains of gram-negative bacteria, leading to loss of functional integrity of the bacterial cell membrane, which causes cell death. Therapeutic Use of the Aminoglycosides • These drugs are used to treat serious infections caused by gram-NEGATIVE bacteria.

  16. The Aminoglycosides Contraindications and Precautions • These drugs are contraindicated in known allergies to aminoglycosides, in patients with renal failure, hepatic disease, pre-existing hearing loss, myasthenia gravis, Parkinson’s, pregnancy and lactation. Drug to drug interactions • Diuretics- increased incidence of ototoxicity, nephrotoxicity and neurotoxicity. • Anesthetics and Neuromusular blockers- increased neuromuscular blockage and paralysis may be possible • Penicillin- synergistic action

  17. The Aminoglycosides Adverse Effects of Aminoglycosides • CNS- irreversible deafness, vestibular paralysis, confusion, depression, disorietnation, numbness, tingling and weakness related to drug effects. • Kidney- renal toxicity, which may progress to renal failure caused by the direct toxicity of the aminoglycosides. • Hema- bone marrow depression resulting from direct drug effect may lead to immune suppression and superinfection. • GI system- nausea, vomiting, diarrhea, weight loss, stomatiits and hepatic toxicity. The effects are due to the direct GI irritation, loss of bacterial flora and toxicity to mucucs membrane and liver as the drugs are metabolized. • Skin effects- photosensitivity, purpura, rash, urticaria and exfoliative dermatitis • Cardiac- palpitaions, hypotension or hypertension

  18. The Macrolides The macrolides are • Azithromycin • Clarithromycin • Dirithromycin • Erythromycin Mechanism of Action : The macrolides are primarily BACTERICIDAL and sometimes bacteriostatic. They exert their effect by binding to the bacterial cell ribosomes and changing or altering protein production/function. This will lead to impaired cell metabolism and division.

  19. The Macrolides • Pharmacokinetics • Erythromycin is destroyed by the gastric juice, which is why slats are added to stabilize the drug. Food does not interfere with the absorption of the macrolides. • Therapeutic Use: • These are indicated for the treatment of the following conditions: Steptococcal infection, Mycoplasma infection, Listeria infection and group A beta hemolytic strep infection. • Contraindications and Precautions • These agents are contraindicated in the presence of known allergy to any macrolide, because cross-sensitivity occurs. • Caution should be used in patients with hepatic dysfunction that could alter the metabolism of the drug; • in lactating women because of drug excretion in breast milk • in pregnant women because potential adverse effects on the developing fetus.

  20. The Macrolides Adverse Effects: • GI system- abdominal cramping, anorexia, diarrhea, vomiting and pseudomembranous colitis. HEPATOTOXICITY can occur if the drug is taken in high doses with other hepatotoxic drugs. • CNS- confusion, abnormal thinking and uncontrollable emotions. • Hypersensitivity reactions Drug-Drug Interactions • Digoxin- increased level of dioxin can occur • Anticoagulants, theophyllines and corticosteroids- increased effects of these drugs due to impaired hepatic metabolism • Astemizole- when used with macrolides, will cause fatal cardiac arrhythmias • Clindamycin or lincomycin – should not be given with erythromycin because they compete for receptor sites. • The Nursing Process and Macrolides

  21. The Lincosamides • These agents are similar to the Macrolides but are more toxic. • They are bactericidal and bacteriostatic depending on the dose. The following are the Lincosamides: • Clindamycin • lincomycin The Mechanism of Action : These agents penetrate the cell membrane and bind to the ribosome in the bacterial cytoplasm to prevent the protein production

  22. The Lincosamides Side effects and Adverse Reactions • GIT- GI irritation, nausea, vomiting and stomatitis • Allergic reactions Drug Interactions • Lincomycin and clindamycin are incompatible with aminophyline, phenytoin, barbiturates and ampicillin.

  23. The Tetracyclines The following are the tetracyclines • Short-acting tetracyclines • tetracycline • oxytetracycline • Intermediate acting tetracyclines • demeclocycline • methacycline • Long acting tetracyclines • doxycycline • minocycline The Mechanism of Action: The tetracyclines inhibit protein synthesis in susceptible bacteria leading to the inability of the bacteria to multiply.

  24. The Tetracyclines Therapeutic indications of the Tetracycline Tetracyclines are effective against a wide range of bacteria. They are primarily BACTERIOSTATIC. Contraindications and Precautions: • These agents are contraindicated in the presence of known allergy to tetrayclines. • It is not recommended for use in pregnancy and lactation because the drug can affect the bones and teeth, causing permanent discoloration and sometimes arrest of growth. • Tetracyclines are also avoided in children less than 8 (eight) years of age because of the potential damage to the bones and permanent discoloration of the teeth.

  25. The Tetracyclines • Adverse Effects: • GI system- nausea, vomiting, diarrhea, abdominal pain, glossitis and dysphagia. • Fatal hepatotoxicityrelated to tetracycline’s irritating effect on the liver cells has been reported. • Musculoskletal- Tetracyclines have an affinity for teeth and bones; they accumulate there, leading to weakening of the bone/teeth and permanent staining and pitting. • Skin- photosensitivity and rash are expected. • Less frequent- bone marrow depression, hypersensitivity, super infections, pain and hypertension

  26. The Tetracyclines Drug-Drug Interactions • Penicillin- if taken with tetracyclines, will decrease the effectiveness of penicillin. • Oral contraceptives- if taken with tetracycline, will have decreased effectiveness (must advise alternative methods of contraception ). • Digoxin- digoxin toxicity rises when tetracyclines are used together Drug-Food Interaction • Dairy products- can complex with tetracycline and render unabsorbable. • Tetracyclines should then be given on an EMPTY stomach 1 hour before meals or 2-3 hours after any meal or other medications.

  27. The Fluoroquinolones • The fluoroquinolones are broad-spectrum antibiotics. The examples are: 1. Nalidixic acid 2. ciprofloxacin 3. oxacillin 4. norfloxacin 5.Levfofloxacin 6.Sparfloxacin

  28. The Fluoroquinolones Mechanism of action • These agents enter the bacterial cell by diffusion through cell channel. • Once inside they interfere with the action of DNA enzymes (DNA gyrase) necessary for the growth and reproduction of the bacteria. • This will lead to cell death. Therapeutic Use: These agents are indicated for the treatment of infections caused by susceptible strains of gram-negative bacteria including E. coli., Proteus, pseudomonas, Strep and Staph spp Contraindications and Precautions • Known drug allergy to these agents contraindicate their use. • Pregnancy and lactation . • These agents are found to cause significant damage to the cartilages such that they are given cautiously to growing children and adolescents less than 18 years of age.

  29. The Fluoroquinolones Adverse Effects: • CNS- dizziness, insomnia, headache, and depression related to possible effects on the CNS membrane. • GI system- nausea, vomiting, diarrhea and dry mouth related to the direct effect on the GIT • Hema- bone marrow depression related to the direct effect of the drug on the cells of the bone marrow that rapidly turn over. • Other effects- skin reactions, rash, fever and photosensitivity Drug-Drug Interaction • Iron salts, Sucralfate, mineral supplements and antacids- all of these will decrease the effectiveness of the fluoroquinolones • Quinidine, Procainamide, terfenadine, henothiazines- can prolong the QT interval when used with the fluoroquinolones

  30. The Sulfonamides • These are called sulfa drugs that inhibit folic acid synthesis. • Folic acid is necessary for the synthesis of purine and pyrimidineprecursprs of DNA and RNA. Humans cannot produce folic acid and must obtin it form the diet. While bacteria need to manufacture their own folic acid inside their cell structure. The following are the sulfonamides: 1.Sulfazalazine 2.Sulfamethoxazole 3. Sulfadiazine 4.Sulfixoxazole

  31. The Sulfonamides The Mechanism of Action: • The sulfa drugs competitively block the para-amino benzoic acid to prevent the synthesis of folic acid in susceptible bacteria that synthesize their own folates for the production of RNA and DNA. Therapeutic indications: • The spectrum of activity includes the following bacteria- Chlamydia, Nocardia, Haemophilus, E, coli and Proteus. • Sulfa drugs are used to treat trachoma and brain abscess. Contraindications and precautions • These agents are contraindicated to patients with known allergy to sulfa drugs, sulfonylureas and thiazide diuretics because they share similar structures. • It is not recommended for use in pregnancy because it can cross the placenta and cause birth defects and kernicterus. • Lactating women who take these drugs will excrete them in the breast milk potentially causing kernicterus, diarrhea and rash in the newborn.

  32. The Sulfonamides Adverse Effects of the Sulfonamides • GI system- nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis and hepatic injury, which are all related to the direct irritation of the GIT and death of normal flora. • Renal system- crystalluria, hematuria and proteinuria which can progress to a nephrotic syndrome. • CNS- headache, dizziness, vertigo, ataxia, convulsions and depression related to drug effects on the nerves • Hema- bone marrow depression related to drug effects on the cells of the bone marrow that turn over rapidly. • Dermatologic effects- photosensitivity and rash and hypersensitivity Drug-Drug Interaction • Tobultamide, tolazamide, glyburide, glipizide, acetohexamide or chlorpropamide (all are oral Anti-diabetic agents) can increase the risk of hypoglycemia if taken with the sulfa drugs

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