Pharmacology 2: Protein Synthesis Inhibitors

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Questions and Answers

Which tetracycline is specifically used in the treatment of Lyme disease?

Demeclocycline

Doxycycline (correct)

Tetracycline

Minocycline

What is the primary reason for using tigecycline in clinical settings?

It can be administered orally.

It is preferred for treating gastrointestinal ulcers.

It is effective against respiratory infections.

It has a broad spectrum of action against resistant organisms. (correct)

Which of the following conditions are tetracyclines NOT commonly used to treat?

Malaria prevention (correct)

Respiratory infections

Amebiasis

Syphilis

What adverse effect is associated with fetal exposure to tetracyclines?

Tooth enamel dysplasia Signup and view all the answers

What is the primary method by which chloramphenicol exerts its antibacterial effect?

Inhibiting bacterial protein synthesis by targeting ribosomes Signup and view all the answers

Which of the following is a reported toxicity associated with doxycycline?

Photosensitivity Signup and view all the answers

Which of the following bacteria are known to be highly susceptible to chloramphenicol?

Haemophilus influenzae Signup and view all the answers

What unique formulation does tigecycline have compared to traditional tetracyclines?

Formulated for intravenous use only Signup and view all the answers

What is the primary reason for the limited use of chloramphenicol as a systemic drug?

Toxicity and potential for serious side effects Signup and view all the answers

Chloramphenicol resistance is often due to the production of which enzymatic factor?

Acetyltransferases Signup and view all the answers

Which antibiotic is primarily effective against Helicobacter pylori?

Tetracycline Signup and view all the answers

What condition has been attributed to the use of outdated tetracyclines?

Fanconi’s syndrome Signup and view all the answers

Which of the following clinical scenarios could warrant the use of chloramphenicol as a backup drug?

Severe infections caused by Salmonella species Signup and view all the answers

What kind of disturbances can gastrointestinal toxicity from chloramphenicol lead to?

Diarrhea and candidiasis Signup and view all the answers

In addition to being a systemic drug, what is another common use for chloramphenicol?

Topical antimicrobial agent Signup and view all the answers

Which of the following properties of chloramphenicol allows it to cross various body barriers?

Lipophilic character Signup and view all the answers

Which type of bacteria is linezolid specifically active against?

Drug-resistant gram-positive cocci Signup and view all the answers

What is a rare form of resistance associated with linezolid?

Decreased affinity for its binding site Signup and view all the answers

Which side effect is most frequently associated with linezolid in immunosuppressed patients?

Thrombocytopenia Signup and view all the answers

Which of these drugs may have increased plasma levels when taken concurrently with streptogramins?

Cyclosporine Signup and view all the answers

What is the elimination half-life range of linezolid?

4–6 hours Signup and view all the answers

What is the main cause of Gray baby syndrome?

Decreased erythrocytes Signup and view all the answers

Which of the following statements about tetracyclines is not true?

Tetracyclines are bactericidal antibiotics. Signup and view all the answers

What is the primary route of elimination for most tetracyclines?

Urine Signup and view all the answers

Which mechanism of bacterial resistance does not affect tigecycline's efficacy in most organisms?

Efflux pumps Signup and view all the answers

Which drug is formulated only for intravenous use and has a long half-life?

Tigecycline Signup and view all the answers

Which of the following tetracyclines has a longer elimination half-life than others?

Doxycycline Signup and view all the answers

What is a significant factor that can impair the absorption of tetracyclines?

Multivalent cations Signup and view all the answers

Tetracyclines are recommended for the treatment of which type of infections?

Mycoplasma pneumoniae infections Signup and view all the answers

What is unique about azithromycin compared to other macrolides regarding tissue distribution?

It achieves higher levels in tissues and phagocytes. Signup and view all the answers

Which macrolide has the longest half-life?

Azithromycin Signup and view all the answers

What is azithromycin particularly effective against due to its pharmacokinetic properties?

Chlamydia infections Signup and view all the answers

Which of the following macrolides has similar antimicrobial activity to erythromycin but is also used for prophylaxis against M avium complex?

Clarithromycin Signup and view all the answers

What is a significant adverse effect specifically associated with erythromycin?

Acute cholestatic hepatitis Signup and view all the answers

Which macrolide is known for its minimal systemic absorption when given orally?

Fidaxomicin Signup and view all the answers

What type of bacteria is fidaxomicin selectively active against?

Gram-positive aerobes and anaerobes Signup and view all the answers

Which of the following is NOT a common side effect of erythromycin?

Headaches Signup and view all the answers

What is the primary mechanism of action of telithromycin?

Inhibition of bacterial protein synthesis Signup and view all the answers

Which drug is commonly used as a backup for methicillin-resistant Staphylococcus aureus?

Clindamycin Signup and view all the answers

Which of the following adverse effects is associated with telithromycin?

Hepatic dysfunction Signup and view all the answers

What is a common mechanism of resistance seen in clindamycin?

Methylation of the binding site on the 50S ribosomal subunit Signup and view all the answers

Which bacteria is clindamycin particularly effective against?

Bacteroides spp. Signup and view all the answers

What is a significant adverse effect of clindamycin treatment?

Pseudomembranous colitis Signup and view all the answers

How is telithromycin primarily eliminated from the body?

Renal and biliary excretion Signup and view all the answers

Which phenomenon is common between clindamycin and macrolides?

Cross-resistance Signup and view all the answers

Study Notes

Pharmacology 2

Covered topics include Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, Streptogramins, and Linezolid.

Introduction

Drugs inhibit bacterial protein synthesis by binding to and interfering with ribosomes.
Most are bacteriostatic, while a few are bactericidal against specific organisms.
Tetracycline and macrolide resistance is common.

Cell Wall Synthesis

Includes Beta Lactams, Penicillins, Cephalosporins, Carbapenems, Monobactams, Vancomycin, and Bacitracin.

Nucleic Acid Synthesis

Includes Folate synthesis (Sulfonamides, Trimethoprim), DNA Gyrase (Quinolones), and RNA Polymerase (Rifampin).

Cell Membrane

Includes Polymyxins

Protein Synthesis

Includes 50S subunit and 30S subunit inhibitors (Tetracyclines, Aminoglycosides, Macrolides, Clindamycin, Linezolid, Chloramphenicol, Streptogramins).

Inhibitors of Microbial Protein Synthesis

Drugs vary in chemical structures and antimicrobial activity spectra.
Categorized as broad spectrum, moderate spectrum, and narrow spectrum based on their effects.

Mechanisms of Action

Most antibiotics in the chapter are bacteriostatic inhibitors of protein synthesis that act on the ribosomal level.
Binding sites are primarily located on the 50S ribosomal subunit.
Chloramphenicol inhibits transpeptidation by blocking the aminoacyl moiety binding to the mRNA complex.

Chloramphenicol

Simple, distinctive structure—no other similar antimicrobials have been discovered.
Effective orally and parenterally with placental and blood-brain barrier penetration.
Undergoes enterohepatic cycling; a portion is excreted unchanged in the urine.
Primarily inactivated by hepatic glucuronosyltransferase.
Bacteriostatic, with some bactericidal activity against specific organisms (Haemophilus influenzae, Neisseria meningitidis, Bacteroides).
Ineffective against Chlamydia species.
Resistance is plasmid-mediated, mediated by acetyltransferases.
Limited clinical uses due to toxicity.
Backup drug for severe Salmonella, pneumococcal, and meningococcal infections (in beta-lactam-sensitive cases).
Used sometimes in rickettsial diseases and infections caused by anaerobes (e.g., Bacteroides fragilis).
Commonly used as a topical antimicrobial agent.
Potential toxicities include gastrointestinal disturbances (especially candidiasis), bone marrow suppression (decrease in circulating erythrocytes), and gray baby syndrome (in infants, characterized by decreased red blood cells, cyanosis, and cardiovascular collapse).
Drug interactions with hepatic drug metabolizing enzymes exist, increasing elimination half-lives of other drugs (e.g., phenytoin, tolbutamide, and warfarin).

Tetracyclines

Crystalline, amphoteric substances; low solubility.
Available as hydrochlorides (more soluble).
Tetracycline solutions acidic and relatively stable.
Chelate divalent metal ions, interfering with absorption and activity.
Tigecycline is a glycylcycline and a semisynthetic derivative of minocycline.
Broad-spectrum bacteriostatic antibiotics with only minor differences in their activities against specific organisms.
Oral absorption may be impaired by foods and multivalent cations (calcium, iron, aluminum).
Penetrate the placental barrier.
Undergo enterohepatic cycling; eliminated primarily in feces and the urine; doxycycline and minocycline have longer half-lives compared to others.
Tigecycline is IV use-only; half-life of 30-36 hrs.
Resistance mechanisms include efflux pumps and ribosomal protection proteins interfering with tetracycline binding.
Resistance to tigecycline is rare; resistance is primarily associated with efflux pumps in Proteus and Pseudomonas.
Clinical uses include treatment of Mycoplasma pneumoniae infections, chlamydiae, rickettsiae, vibrios, and some spirochetes (most commonly).
Alternate treatment for community-acquired pneumonia.
Used in treatment of secondary problems such as syphilis, respiratory infections, prevention of infection in chronic bronchitis, treatment of leptospirosis, and treatment of acne.
Selective clinical uses for helicobacter pylori infections, Lyme disease, and meningococcal carrier state.
Tigecycline is a clinical use with unique features, providing a broad spectrum active against many resistant organisms. Intravenous use only.
Risk of gastrointestinal disturbances, teeth and bony structure effects, and hepatic toxicity.

Macrolides

Large cyclic lactone ring structures with attached sugars.
Drugs have good oral bioavailability, but absorption of azithromycin is often hindered by food.
Distribute to most body tissues.
Azithromycin elimination is slow, with a half-life of 2-4 days
Rapid elimination (2 or 6 hours).
Similar antibacterial activity, with extended activity against Mycobacterium avium complex and Toxoplasma species.
Used in the treatment of urogenital infections (C trachomatis), community-acquired pneumonia, as a prophylactic or treatment of AIDS-related toxoplasmosis, or as a component of ulcer treatment (H. pylori) regimens.
Fidaxomicin is a narrow-spectrum macrolide, inhibiting protein synthesis and targeting gram-positive aerobes and anaerobes.
Effective in C. difficile colitis.
Side effects include GI irritation (especially with erythromycin), skin rashes, and eosinophilia.
Potential hepatotoxicity is rare (primarily with erythromycin estolate, especially in pregnant patients).

Telithromycin

Ketolide structurally related to macrolides.
Similar mechanism of action and activity spectrum to erythromycin.
Treats community-acquired pneumonia.
Hepatic dysfunction and prolonged QT interval are possible side effects.

Clindamycin

Inhibits bacterial protein synthesis via a unique mechanism, though non-chemically related to macrolides.
Resistance mechanisms include methylation of the 50S ribosomal subunit and enzymatic inactivation.
Gram-negative aerobes are inherently resistant.
Good tissue penetration after oral absorption.
Primarily eliminated by biliary and renal excretion (both intact drug and metabolites).
Used to treat severe infections (anerobic bacteria).
Also active against gram-positive cocci (some community-acquired strains) with methicillin-resistant S aureus prophylaxis for endocarditis in patients with penicillin allergies).
Active against Pneumocystis jirovecii and used with pyrimethamine for AIDS-related toxoplasmosis.
Adverse effects: gastrointestinal irritation, skin rashes, neutropenia, hepatic dysfunction, and superinfections (such as Clostridium difficile-related colitis).

Streptogramins

Combination of quinupristin-dalfopristin, two streptogramins.
Bactericidal with longer antibacterial activity.
Treats penicillin-resistant pneumococci, methicillin-resistant MRSA and vancomycin-resistant staphylococci, and E faecium.
Administered intravenously to avoid pain and arthralgia-myalgia syndrome.
Potent inhibitors of CYP3A4; increase plasma levels of other common drugs (astemizole, cisapride, cyclosporine, diazepam, other non-nucleoside reverse transcriptase inhibitors, and warfarin).

Linezolid

First oxazolidinone antibiotic.
Active against drug-resistant gram-positive cocci (including MRSA, PRSP, and VRE).
Also active against L. monocytogenes and corynebacteria.
Binds to a unique site on the 23S ribosomal RNA of the 50S ribosomal subunit; minimal cross-resistance with other protein synthesis inhibitors.
Oral and parenteral formulations; hepatic metabolism.
Elimination half-life is 4-6 hours.
Side effects: thrombocytopenia, neutropenia (particularly in immunosuppressed patients); possible serotonin syndrome (with SSRIs).

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Description

This quiz covers key antibacterial agents including Chloramphenicol, Tetracyclines, Macrolides, and more. It explores their mechanisms of action in inhibiting bacterial protein synthesis, cell wall synthesis, and nucleic acid synthesis. Test your knowledge on these essential pharmacological concepts and drug classifications.