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1. Introduction to Clinical Pharmacology Chapter 8 Antibacterial Drugs That Interfere With Protein Synthesis October 2024 Nadia amro

2. To make protein, a message is made by messenger RNA (mRNA) that tells the cell how to build amino acids. The message is translated by the ribosomes to make the string of amino acids that becomes a protein. four classes of broad-spectrum antibiotics : TETRACYCLINES AMINOGLYCOSIDES MACROLIDES LINCOSAMIDES

3. Tetracyclines are bacteriostatic and exert their effect by inhibiting bacterial protein synthesis 30s , which is a process necessary for reproduction of the microorganism Effective in the treatment of infections caused by a wide range of gram-negative and gram-positive microorganisms . Tetracyclines

4. Anti- infectives composed of natural and semisynthetic compounds Brands :(demeclocycline , minocycline ) Used as broad- spectrum antibiotic when penicillin is contraindicated Excreted partially by kidney as metabolites so not effective in UTI ,50% by kidney and 50% by liver Tetracyclines

5. Uses Rickettsial diseases rickettsia-like bacteria are usually spread to people through the bites of ticks, mites, fleas, or lice that previously fed on an infected animal. Ticks, mites, fleas, and lice are called vectors because they spread (transmit) organisms that cause disease from one host to another.  Lyme disease = doxocycline Q-fever : aquired by animal products containing the bacterium Coxiella burnetii (C. burnetii ). Cholera= acute, diarrheal illness caused by infection of the intestine with the toxigenic bacterium Vibrio cholerae intestinal amebiasis ,toxoplasmosis . skin and soft tissue infections; Acne

6. Nausea and/or vomiting / Diarrhea Epigastric distress Stomatitis / Sore throat / Skin rashes Superinfection (Candida)with prolonged therapy Yellow staining of teeth so don’t give to children under 9y Liver cell injury Photosensitivity reaction Tetracyclines: Adverse Reactions Contraindicated in patients: With hypersensitivity; during pregnancy category D, lactation ; children younger than 9 years

7. Used cautiously in patients with: Impaired renal function Liver impairment Chronic care alert: May increase the risk of digitalis toxicity in patients who take digitalis drugs for heart disease Tetracyclines: Precautions

8. Tetracyclines: Interactions Interacting drug Effect of interaction Antacids containing aluminum, zinc, magnesium, or bismuth salts Decreases effectiveness of tetracyclines Oral anticoagulants Increases risk for bleeding Oral contraceptives Decreases effectiveness of contraceptive agent

9. Tetracyclines: Interactions (cont.) Interacting drug Effect of interaction Digoxin Increases the risk for digitalis toxicity Calcium- rich foods Causes potentially impaired absorption of tetracycline Do not take tetracycline with milk products, iron-containing preparations such as multivitamins, or with antacids . Take the tetracycline 1 h before or 2 h after consuming these products

10. Aminoglycosides : Actions and Uses Includes : Amikacin, gentamicin , kanamycin, neomycin, streptomycin, and tobramycin. Blocks step in protein synthesis necessary for bacterial multiplication( bactericidal effect by blocking the ribosome from reading the mRNA ,attach to 30s of protien , a step in protein synthesis necessary for bacterial multiplication.)

11. Aminoglycosides : Actions and Uses A minoglycoside are positive charge attach to negative ion of outer membrane gram negative bacteria Works against some gram positive bacteria such as staphylococci ,TB. Aminoglycosides are water soluble does not cross BBB , it can cross placenta and cause deafness for fetus

12. Aminoglycosides : Uses UTI klebsilla , E.holi Respiratory tract infections Meningitis if given intrathecal TB, Brucella and Plague Paromycine used for chronic ameba

13. Uses Cont.. Bowel preparation (used to reduce bacteria (normal flora) in the bowel when patients are having abdominal surgery) . Oral aminoglycosides are poorly absorbed, and for this reason they are useful in suppressing GI bacteria because they stay in the gut and kill the normal flora. Liver normally converted ammonia into urea and eliminates by urine

14. Cont… Hepatic coma (liver failure results in an elevation of blood ammonia levels. Most ammonia in the body formed when protein broken down by bacteria in the intestine N eomycin, and paromomycin are used orally in the management of hepatic coma . In liver failure ammonia levels increase in blood. By reducing the number of ammonia-forming bacteria in the intestines, blood ammonia levels lowered.

15. Aminoglycosides: Adverse Reactions Nausea Vomiting Anorexia Rash Urticaria Nephrotoxicity (damage to the kidneys by a toxic substance) Ototoxicity (damage to the hearing organs by a toxic substance) Neurotoxicity ( damage to the nervous system by a toxic substance)

16. Signs and symptoms of nephrotoxicity :include proteinuria (protein in the urine), hematuria (blood in the urine), an increase in the blood urea nitrogen (BUN) level, a decrease in urine output, and an increase in the serum creatinine concentration. -Nephrotoxicity is usually reversible once the drug is discontinued

17. Signs and symptoms of neurotoxicity include : numbness, skin tingling, circumoral (around the mouth) paresthesia, peripheral paresthesia, tremors, muscle twitching, convulsions, muscle weakness, and neuromuscular blockade (acute muscular paralysis and apnea)

18. ototoxicity ,8 th cranial nerve ,include tinnitus (ringing in the ears),dizziness, roaring in the ears, vertigo, and a mild to severe loss of hearing. If hearing loss occurs, it is usually permanent. Ototoxicity may occur during drug therapy or even after therapy is discontinued -The short-term administration of kanamycin and neomycin as a preparation for bowel surgery rarely causes these two adverse reactions (ototoxicity and nephrotoxicity).

19. Aminoglycosides: Contraindications and Precautions With hypersensitivity to aminoglycosides, pre- existing hearing loss, myasthenia gravis, parkinsonism; pregnancy . Long- term therapy risk: ototoxicity and nephrotoxicity. Used cautiously in: Elderly patients; patients with renal failure and neuromuscular disorders Never mix aminoglycoside in the same syringe (positive charge not mixed with negative charge antibiotic)

20. myasthenia gravis a disease that affects the myoneural junction in nerves and is manifested by extreme weakness and exhaustion of the muscles).

21. Azithromycin, Clarithromycin, Erythromycin Against gram positive bacteria Act by causing changes in protein function and synthesis It has long biological half-life , administered once Excreted in small amounts in kidney,so not used for UTI and don’t cover gram negative . excreted in liver by bile Macrolides

22. Bacteriostatic but with high concentration may be cidal Macrolids binds to 50 sub units in bacteri , it mainly goes to gram + 85% and 10% for gram negative inhibit protein synthesis While aminoglycosides bind to 30 sub units

23. in patients allergic to penicillin treatment of a wide gram- positive infections Acne vulgaris and skin infections Upper respiratory infections caused by Hemophilus influenza and other intracellular organisms -Calm my leg( c hlamydia(eye and genital infection) , m ycoplasma(atypical pneumonia , l egionella (pneumonia from air conditioners) organisms Toxoplasmosis and Heliobacter pylori in high doses clarithromycine Macrolides: Uses

24. Gastrointestinal (GI) and other reactions: Nausea Vomiting Diarrhea Abdominal pain or cramping Pseudomembranous colitis Visual disturbances Prolonged QT interval and my cause ventricular tachycardia Adverse Reactions of Macrolides

25. With a hypersensitivity to the macrolides; with pre- existing liver disease; because mainly hepatic biliary excreted No mixing of penicillin ( cidal )and macrolids (static),causes antagonism Contraindicated with statins ,it may cause myopathy Macrolides: Contraindications and Precautions

26. C lindamycin = Bacteriostatic drug Absorbed orally,can cross BBB, excreted by bile Used for treating serious infections in which penicillin or erythromycin (a macrolide) is not effective drugs with a high potential for toxicity Bone infections ( gram- ve anaerobic bacteria ) Dental infections ( anaerobic bacteria ) Toxic shock syndrome caused by staphylococci(g+) toxins (toxins are protiens ) Lincosamides

27. Cont.. Used in conjunction with other antibiotics Actions: Inhibits protein synthesis in susceptible bacteria, attach to 50s of protein subunits causing cell death Effective in the treatment of infections caused by a wide range of anerobic gram-negative and mainly aerobic gram- positive microorganisms

28. Gastrointestinal/other body reactions: Abdominal pain Esophagitis Nausea Vomiting Diarrhea Skin rash Pseudomembranous colitis Lincosamides: Adverse Reactions

29. Contraindicated in patients: With hypersensitivity to the lincosamides. Used cautiously in patients with: History of GI disorders; renal disease; liver impairm ent Lincosamides: Contraindications and Precautions

30. A client is prescribed 200 mg of minocycline oral suspension now, followed by 100 mg orally every 12 hours. The minocycline is available as an oral suspension of 50 mg/5 mL. How many milliliters does the nurse administer as the initial dose? Loading dose