This document discusses various classes of antibiotics that target bacterial protein synthesis, including tetracyclines, glycylcyclines (tigecycline), and aminoglycosides. It describes their mechanisms of action, which involve binding to the bacterial ribosome to inhibit protein synthesis. Specifics are provided on their antimicrobial spectra, pharmacokinetics, mechanisms of resistance, and adverse effects. The document contains detailed information on the structure, uses, and properties of several important antibiotics in these classes.
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. All of the antibiotics that target bacterial protein synthesis do so by interacting with the bacterial ribosome and inhibiting its function. The ribosome might not seem like a very good target for selective toxicity, because all cells, including our own, use ribosomes for protein synthesis.The good thing is that bacteria and eukaryotes have ribosomes that are structurally different. Bacteria have so-called 70S ribosomes and eukaryotes have 80S ribosomes. No, not '70s and '80s ribosomes, although that would be pretty entertaining. The S stands for 'Svedberg unit,' and it refers to the rate at which particles sediment down into the tube during high-speed ultracentrifugation. Basically, it tells us about the ribosome's molecular weight and shape.
70S and 80S ribosomes are different enough that antibiotics can specifically target one and not the other. Let's take a closer look at the bacterial 70S ribosome and see where some different kinds of antibiotics act on it. Remember that ribosomes are made of RNA and protein and that they have two subunits, one large and one small.
The bacterial 70S ribosome's subunits are the 50S subunit and the 30S subunit. Yes, I know, 50 + 30 = 80, not 70, but this is not a math mistake. Using the Svedberg unit to measure ribosomes means that things don't always add up perfectly, because rates of sedimentation are not additive like molecular weights are.
Before we get into the specifics of how antibiotics inhibit bacterial ribosomes, let's briefly review how ribosomes work. First, a tRNA loaded with a particular amino acid enters the ribosome at the A site. The tRNA's anticodon has to match the codon, or group of three nucleotides on the mRNA. Then, at the P site of the ribosome, a peptide bond forms between the previous amino acid and the new amino acid. Finally, the empty tRNA exits at the E site. This process repeats for the whole length of the mRNA, and the polypeptide chain continues to grow.
The presentation include semisynthetic penicillin introduction and classification.
Contents
Semisynthetic penicillins- Introduction
Classification
Acid-resistant alternative to Penicillin G
Penicillinase- resistant penicillins
Extended spectrum penicillins
Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation
antibiotics that inhibit synthesis of the bacterial cell wall. includes tetracyclines, aminoglycosides, macrolides and ketolides , chloramphenicol among others. this presentation highlights the clinical uses, adverse effects, common contraindications modes of action and susceptibility scores
Sulphonamides Pharmacology For Pharmacy studentsMalay Pandya
This is the PowerPoint presentation of the Antimicrobial drug - SULPHOANMIDE.
Sulphonamide is the first antimicrobial agent
It Can be employed for suppressive therapy of chronic urinary tract infection, streptococcal pharyngitis and gum infection.
Combined with trimethoprim (cotrimoxazole) sulfamethoxazole is used for many bacterial infections.
This will be useful to all Pharmacy Student ...
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. All of the antibiotics that target bacterial protein synthesis do so by interacting with the bacterial ribosome and inhibiting its function. The ribosome might not seem like a very good target for selective toxicity, because all cells, including our own, use ribosomes for protein synthesis.The good thing is that bacteria and eukaryotes have ribosomes that are structurally different. Bacteria have so-called 70S ribosomes and eukaryotes have 80S ribosomes. No, not '70s and '80s ribosomes, although that would be pretty entertaining. The S stands for 'Svedberg unit,' and it refers to the rate at which particles sediment down into the tube during high-speed ultracentrifugation. Basically, it tells us about the ribosome's molecular weight and shape.
70S and 80S ribosomes are different enough that antibiotics can specifically target one and not the other. Let's take a closer look at the bacterial 70S ribosome and see where some different kinds of antibiotics act on it. Remember that ribosomes are made of RNA and protein and that they have two subunits, one large and one small.
The bacterial 70S ribosome's subunits are the 50S subunit and the 30S subunit. Yes, I know, 50 + 30 = 80, not 70, but this is not a math mistake. Using the Svedberg unit to measure ribosomes means that things don't always add up perfectly, because rates of sedimentation are not additive like molecular weights are.
Before we get into the specifics of how antibiotics inhibit bacterial ribosomes, let's briefly review how ribosomes work. First, a tRNA loaded with a particular amino acid enters the ribosome at the A site. The tRNA's anticodon has to match the codon, or group of three nucleotides on the mRNA. Then, at the P site of the ribosome, a peptide bond forms between the previous amino acid and the new amino acid. Finally, the empty tRNA exits at the E site. This process repeats for the whole length of the mRNA, and the polypeptide chain continues to grow.
The presentation include semisynthetic penicillin introduction and classification.
Contents
Semisynthetic penicillins- Introduction
Classification
Acid-resistant alternative to Penicillin G
Penicillinase- resistant penicillins
Extended spectrum penicillins
Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation
antibiotics that inhibit synthesis of the bacterial cell wall. includes tetracyclines, aminoglycosides, macrolides and ketolides , chloramphenicol among others. this presentation highlights the clinical uses, adverse effects, common contraindications modes of action and susceptibility scores
Sulphonamides Pharmacology For Pharmacy studentsMalay Pandya
This is the PowerPoint presentation of the Antimicrobial drug - SULPHOANMIDE.
Sulphonamide is the first antimicrobial agent
It Can be employed for suppressive therapy of chronic urinary tract infection, streptococcal pharyngitis and gum infection.
Combined with trimethoprim (cotrimoxazole) sulfamethoxazole is used for many bacterial infections.
This will be useful to all Pharmacy Student ...
Pahrmaceutical care practise- Multiple Sclerosis Case (MS)Areej Abu Hanieh
Diagnosis : Transverse Myelitis (TM) with possible Remote Multiple Sclerosis (MS) versus Recurring Transverse Myelitis (RTM) .
By : Areej Abu Hanieh
Birzeit University - Palestine
Quinolones , The Quinolone are class of antimicrobial agents that was not isolated from living organisms but, rather, was synthesized by chemists.
They are a group of synthetic broad spectrum antibacterial drugs that target DNA Synthesis. The prolific development of the Quinolones began in 1962, when Lesher et al. made the accidental discovery of nalidixic acid as a by-product of the synthesis of the antimalarial compound chloroquine.
Antibiotics and Their Types, Uses Indication Contraindication Dose Side Effects &Adverse effect.Cephalosporins are grouped into "generations" by their antimicrobial properties. Cephalosporins are categorized
chronically, and are therefore divided into first, second, and third generations.The later-generation
cephalosporins have greater effect against resistant bacteria.Fluoroquinolones are known as broad-spectrum antibiotics, meaning they are effective against many bacteria.
Fluoroquinolones are used to treat most common urinary tract infections, skin infections, and respiratory
infections (such as sinusitis, pneumonia, bronchitis).Tetracyclines are a family of antibiotics used to treat a broad spectrum of bacterial infections.
The lectures in points :-
1- quinolones general information.
2-Fluoroquinolones action , side actions & interactions .
3-Fluroquinolones group members in detail .
4-Fluroquinolones in the clinical use .
5-Practical tips .
6-Rapid review .
7- Test yourself .
Antibiotics used in dentistry
Terminologies
History
Classification of antibiotics
Principles of antibiotics use
Commonly used antibiotics
Drug interaction
Drug combination
Antibiotic resistance
Summary
Hello friends. In this PPT I am talking about anti-cancer drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Announcement about my previous presentations - Thank youAreej Abu Hanieh
ANNOUNCEMENT Thank you for all of you, my followers who sent me messages with a lot of love and appreciations, I finally graduated after 6 years of studying in Birzeit University , In doctor of Pharmacy department I hope all of you benefited from all the presentations posted before Thank you a new PharmD GraduatedAreej ^^
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
2. • A number of antibiotics exert their antimicrobial effects by targeting
bacterial ribosomes and inhibiting bacterial protein synthesis.
• Bacterial ribosomes differ structurally from mammalian cytoplasmic
ribosomes and are composed of 30S and 50S subunits
• (mammalian ribosomes have 40S and 60S subunits).
3. • In general, selectivity for bacterial ribosomes minimizes potential
adverse consequences encountered with the disruption of protein
synthesis in mammalian host cells.
• However, high concentrations of drugs such as chloramphenicol or
the tetracyclines may cause toxic effects as a result of interaction with
mitochondrial mammalian ribosomes, since the structure of
mitochondrial ribosomes more closely resembles bacterial ribosomes.
4. II. TETRACYCLINES
• Tetracyclines consist of four fused rings with a system of conjugated
double bonds.
• Substitutions on these rings alter the individual pharmacokinetics and
spectrum of antimicrobial activity.
5. A. Mechanism of action
• Tetracyclines enter susceptible organisms via
• passive diffusion and also by
• an energy-dependent transport protein mechanism unique to the bacterial inner
cytoplasmic membrane.
• Tetracyclines concentrate intracellularly in susceptible organisms.
• The drugs bind reversibly to the 30S subunit of the bacterial ribosome.
• This action prevents binding of tRNA to the mRNA–ribosome complex,
thereby inhibiting bacterial protein synthesis
6. B. Antibacterial spectrum
• The tetracyclines are bacteriostatic antibiotics effective against a wide
variety of organisms, including
• gram-positive and
• gram-negative bacteria,
• protozoa,
• spirochetes,
• mycobacteria, and
• atypical species
• They are commonly used in the treatment of acne and Chlamydia
infections (doxycycline).
7.
8. C. Resistance
• The most commonly encountered naturally occurring resistance to
tetracyclines is an efflux pump that expels drug out of the cell, thus
preventing intracellular accumulation.
• Other mechanisms of bacterial resistance to tetracyclines include
enzymatic inactivation of the drug and
• production of bacterial proteins that prevent tetracyclines from binding to
the ribosome.
• Resistance to one tetracycline does not confer universal resistance to all
tetracyclines.
9. D. Pharmacokinetics
• 1. Absorption:
• Tetracyclines are adequately absorbed after oral ingestion.
• Administration with dairy products or other substances that contain
divalent and trivalent cations (for example, magnesium and aluminum
antacids or iron supplements) decreases absorption, particularly for
tetracycline, due to the formation of nonabsorbable chelates
• Both doxycycline [dox-i-SYE-kleen] and minocycline [min-oh-SYE-
kleen] are available as oral and intravenous (IV) preparations.
10.
11. • 2. Distribution:
• The tetracyclines concentrate well in the bile, liver, kidney, gingival fluid, and skin.
• Moreover, they bind to tissues undergoing calcification (for example, teeth and bones) or
to tumors that have a high calcium content.
• Penetration into most body fluids is adequate.
• Only minocycline and doxycycline achieve therapeutic levels in the cerebrospinal fluid
(CSF).
• Minocycline also achieves high levels in saliva and tears, rendering it useful in eradicating
the meningococcal carrier state.
12. • All tetracyclines cross the placental barrier and concentrate in fetal
bones and dentition.
13.
14. • 3. Elimination:
• Tetracycline is primarily eliminated unchanged in the urine, whereas
• minocycline undergoes hepatic metabolism and is eliminated to a
lesser extent via the kidney.
• In renally compromised patients, doxycycline is preferred, as it is
primarily eliminated via the bile into the feces.
15. E. Adverse effects
• 1. Gastric discomfort:
• Epigastric distress commonly results from irritation of the gastric
mucosa and is often responsible for noncompliance with
tetracyclines.
• Esophagitis may be minimized through coadministration with food
(other than dairy products) or fluids and the use of capsules rather
than tablets.
• [Note: Tetracycline should be taken on an empty stomach.]
16. • 2. Effects on calcified tissues:
• Deposition in the bone and primary dentition occurs during the
calcification process in growing children.
• This may cause discoloration and hypoplasia of teeth and a temporary
stunting of growth.
• The use of tetracyclines is limited in pediatrics.
17. • 3. Hepatotoxicity:
• Rarely hepatotoxicity may occur with high doses,
• particularly in pregnant women and those with preexisting hepatic
dysfunction or renal impairment.
18. • 4. Phototoxicity:
• Severe sunburn may occur in patients receiving a tetracycline who are
exposed to sun or ultraviolet rays.
• This toxicity is encountered with any tetracycline, but more frequently
with tetracycline and demeclocycline [dem-e-kloe-SYE-kleen].
• Patients should be advised to wear adequate sun protection.
19. • 5. Vestibular dysfunction:
• Dizziness, vertigo, and tinnitus may occur particularly with
minocycline, which concentrates in the endolymph of the ear and
affects function.
• Doxycycline may also cause vestibular dysfunction.
20. • 6. Pseudotumor cerebri:
• Benign, intracranial hypertension characterized by headache and
blurred vision may occur rarely in adults.
• Although discontinuation of the drug reverses this condition, it is not
clear whether permanent sequelae may occur.
21. • 7. Contraindications:
• Pregnant or
• breast-feeding women or in
• children less than 8 years of age.
22.
23. III. GLYCYLCYCLINES
• Tigecycline [tye-ge-SYE-kleen], a derivative of minocycline, is the first
available member of the glycylcycline antimicrobial class.
• It is indicated for the treatment of complicated skin and soft tissue
infections, as well as complicated intra-abdominal infections.
24. • A. Mechanism of action
• Tigecycline exhibits bacteriostatic action by reversibly binding to the
30S ribosomal subunit and inhibiting protein synthesis.
25. • B. Antibacterial spectrum
• Tigecycline exhibits broad-spectrum activity that includes
• methicillinresistant staphylococci (MRSA),
• multidrug-resistant streptococci,
• vancomycin-resistant enterococci (VRE),
• extended-spectrum β-lactamase–producing gram-negative bacteria,
• Acinetobacter baumannii, and many anaerobic organisms.
• However, tigecycline is not active against Morganella, Proteus,
Providencia, or Pseudomonas species.
26. • D. Pharmacokinetics
• Following IV infusion, tigecycline exhibits a large volume of distribution.
• It penetrates tissues well but has low plasma concentrations.
• Consequently, tigecycline is a poor option for bloodstream infections.
• The primary route of elimination is biliary/fecal.
• No dosage adjustments are necessary for patients with renal impairment.
• However, a dose reduction is recommended in severe hepatic dysfunction.
27. • E. Adverse effects
• Tigecycline is associated with significant nausea and vomiting.
• Acute pancreatitis, including fatality, has been reported with therapy.
• Elevations in liver enzymes and serum creatinine may also occur.
• Other adverse effects are similar to those of the tetracyclines and include
• photosensitivity,
• pseudotumor cerebri,
• discoloration of permanent teeth when used during tooth development, and
• fetal harm when administered in pregnancy.
• Tigecycline may decrease the clearance of warfarin and increase prothrombin
time. Therefore, the international normalized ratio should be monitored closely
when tigecycline is coadministered with warfarin.
28. IV. AMINOGLYCOSIDES
• amikacin [am-i-KAY-sin],
• gentamicin [jen-ta-MYE-sin],
• tobramycin [toe-bra-MYE-sin], and
• streptomycin [strep-toe-MYE-sin
• neomycin [nee-oh-MYEsin
29. IV. AMINOGLYCOSIDES
• Aminoglycosides are used for the treatment of serious infections due to
aerobic gram-negative bacilli.
• However, their clinical utility is limited by serious toxicities.
• The term “aminoglycoside” stems from their structure—two amino sugars
joined by a glycosidic linkage to a central hexose nucleus.
• Aminoglycosides are derived from either Streptomyces sp. (have –mycin
suffixes) or Micromonospora sp. (end in -micin).
30. A. Mechanism of action
• Aminoglycosides diffuse through porin channels in the outer
membrane of susceptible organisms.
• These organisms also have an oxygen-dependent system that
transports the drug across the cytoplasmic membrane.
• Inside the cell, they bind the 30S ribosomal subunit, where they
interfere with assembly of the functional ribosomal apparatus and/or
cause the 30S subunit of the completed ribosome to misread the
genetic code
31. • Antibiotics that disrupt protein synthesis are generally bacteriostatic; however, aminoglycosides
are unique in that they are bactericidal.
• The bactericidal effect of aminoglycosides is concentration dependent; that is, efficacy is
dependent on the maximum concentration (Cmax) of drug above the minimum inhibitory
concentration (MIC) of the organism.
• For aminoglycosides, the target Cmax is eight to ten times the MIC.
• They also exhibit a postantibiotic effect (PAE), which is continued bacterial suppression after drug
levels fall below the MIC.
• The larger the dose, the longer the PAE. Because of these properties, extended interval dosing (a
single large dose given once daily) is now more commonly utilized than divided daily doses. This
reduces the risk of nephrotoxicity and increases convenience.
32. B. Antibacterial spectrum
• The aminoglycosides are effective for the majority of aerobic gram negative
bacilli, including those that may be multidrug resistant, such as
Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter sp.
• Additionally, aminoglycosides are often combined with a β-lactam
antibiotic to employ a synergistic effect, particularly in the treatment of
Enterococcus faecalis and Enterococcus faecium infective endocarditis.
• Some therapeutic applications of four commonly used aminoglycosides—
• ]—are shown in Figure 39.7.
33.
34. C. Resistance
• Resistance to aminoglycosides occurs via:
• 1) efflux pumps,
• 2) decreased uptake, and/or
• 3) modification and inactivation by plasmid-associated synthesis of enzymes.
Each of these enzymes has its own aminoglycoside specificity; therefore,
cross-resistance cannot be presumed.
• [Note: Amikacin is less vulnerable to these enzymes than other
antibiotics in this group.]
35. D. Pharmacokinetics
• 1. Absorption:
• The highly polar, polycationic structure of the aminoglycosides prevents
adequate absorption after oral administration.
• Therefore, all aminoglycosides (except neomycin [nee-oh-MYEsin]) must be
given parenterally to achieve adequate serum levels
• (Figure 39.8).
• [Note: Neomycin is not given parenterally due to severe nephrotoxicity. It is
administered topically for skin infections or orally for bowel preparation
prior to colorectal surgery.]
36. 2. Distribution:
• Due to their hydrophilicity, tissue concentrations may be subtherapeutic, and
penetration into most body fluids is variable.
• [Note: Due to low distribution into fatty tissue, the aminoglycosides
• are dosed based on lean body mass, not actual body weight.]
• Concentrations in CSF are inadequate, even in the presence of inflamed meninges.
• For central nervous system infections, the intrathecal (IT) route may be utilized.
• All aminoglycosides cross the placental barrier and may accumulate in fetal plasma and
amniotic fluid
37. • 3. Elimination:
• More than 90% of the parenteral aminoglycosides are excreted
unchanged in the urine
• Accumulation occurs in patients with renal dysfunction, and dose
adjustments are required.
38. E. Adverse effects
• Therapeutic drug monitoring of gentamicin, tobramycin, and amikacin
plasma levels is imperative to ensure adequacy of dosing and to
minimize dose-related toxicities .
• The elderly are particularly susceptible to nephrotoxicity and
ototoxicity.
39. • 1. Ototoxicity: Ototoxicity (vestibular and auditory) is directly related to high
peak plasma levels and the duration of treatment.
• The antibiotic accumulates in the endolymph and perilymph of the inner ear.
• Deafness may be irreversible and has been known to affect developing fetuses.
• Patients simultaneously receiving concomitant ototoxic drugs, such as cisplatin or
loop diuretics, are particularly at risk.
• Vertigo (especially in patients receiving streptomycin) may also occur.
40. • 2. Nephrotoxicity:
• Retention of the aminoglycosides by the proximal tubular cells
disrupts calcium-mediated transport processes.
• This results in kidney damage ranging from
• mild, reversible renal impairment to
• severe, potentially irreversible, acute tubular necrosis.
41. • 3. Neuromuscular paralysis:
• This adverse effect is associated with a rapid increase in
concentrations (for example, high doses infused over a short period.)
or concurrent administration with neuromuscular blockers.
• Patients with myasthenia gravis are particularly at risk.
• Prompt administration of calcium gluconate or neostigmine can
reverse the block that causes neuromuscular paralysis.
42. • 4. Allergic reactions:
• Contact dermatitis is a common reaction to
• topically applied neomycin.
43. V. MACROLIDES AND KETOLIDES
• Erythromycin [er-ith-roe-MYE-sin] was the first of these drugs to find
clinical application, both as a drug of first choice and as an alternative to
penicillin in individuals with an allergy to β-lactam antibiotics.
• Clarithromycin [klarith- roe-MYE-sin] (a methylated form of erythromycin)
and azithromycin [a-zith-roe-MYE-sin] (having a larger lactone ring) have
some features in common with, and others that improve upon
erythromycin.
• Telithromycin [tel-ith-roe-MYE-sin], a semisynthetic derivative of
erythromycin, is the first “ketolide” antimicrobial agent.
• Ketolides and macrolides have similar antimicrobial coverage. However, the
ketolides are active against many macrolide-resistant gram-positive strains.
44. A. Mechanism of action
• The macrolides bind irreversibly to a site on the 50S subunit of the
bacterial ribosome, thus inhibiting translocation steps of protein
synthesis .
• They may also interfere with other steps, such as transpeptidation.
• Generally considered to be bacteriostatic, they may be bactericidal at
higher doses.
• Their binding site is either identical to or in close proximity to that for
clindamycin and chloramphenicol.
45. B. Antibacterial spectrum
• 1. Erythromycin: This drug is effective against many of the same organisms
as penicillin G. Therefore, it may be used
• in patients with penicillin allergy.
• 2. Clarithromycin: Clarithromycin has activity similar to erythromycin, but it
is also effective against
• Haemophilus influenzae. Its activity against intracellular pathogens, such as
• Chlamydia,
• Legionella,
• Moraxella,
• Ureaplasma species and
• Helicobacter pylori, is higher than that of erythromycin.
46. • 3. Azithromycin:
• Although less active against streptococci and staphylococci than erythromycin,
azithromycin is far more active against respiratory infections due to H. influenzae
and Moraxella catarrhalis.
• Extensive use of azithromycin has resulted in growing Streptococcus pneumoniae
resistance.
• Azithromycin is the preferred therapy for urethritis caused by Chlamydia
trachomatis.
• Mycobacterium avium is preferentially treated with a macrolide-containing
regimen, including clarithromycin or azithromycin.
47. • 4. Telithromycin:
• This drug has an antimicrobial spectrum similar to that of
azithromycin.
• Moreover, the structural modification within ketolides neutralizes the
most common resistance mechanisms (methylase-mediated and
efflux-mediated) that make macrolides ineffective.
48.
49. C. Resistance
• Resistance to macrolides is associated with:
• 1) the inability of the organism to take up the antibiotic,
• 2) the presence of efflux pumps,
• 3) a decreased affinity of the 50S ribosomal subunit for the antibiotic, resulting from the
methylation of an adenine in the 23S bacterial ribosomal RNA in gram-positive organisms, and
• 4) the presence of plasmid associated erythromycin esterases in gram-negative organisms such as
Enterobacteriaceae.
• Resistance to erythromycin has been increasing, thereby limiting its clinical use
(particularly for S. pneumoniae).
• Both clarithromycin and azithromycin share some cross-resistance with erythromycin,
but telithromycin may be effective against macrolide resistant organisms.
50. D. Pharmacokinetics
• 1. Administration:
• The erythromycin base is destroyed by gastric acid.
• Thus, either enteric-coated tablets or esterified forms of the antibiotic are administered.
• All are adequately absorbed upon oral administration .
• Clarithromycin, azithromycin, and telithromycin are stable in stomach acid and are readily
absorbed.
• Food interferes with the absorption of erythromycin and azithromycin but can increase that of
clarithromycin.
• Erythromycin and azithromycin are available in IV formulations.
51. • 2. Distribution:
• Erythromycin distributes well to all body fluids except the CSF.
• It is one of the few antibiotics that diffuses into prostatic fluid, and it also accumulates in macrophages.
• All four drugs concentrate in the liver.
• Clarithromycin, azithromycin, and telithromycin are widely distributed in the tissues.
• Azithromycin concentrates in neutrophils, macrophages, and fibroblasts, and serum levels are low.
• It has the longest half-life and the largest volume of distribution of the four drugs
52. • 3. Elimination:
• Erythromycin and telithromycin are extensively metabolized
hepatically.
• They inhibit the oxidation of a number of drugs through their
interaction with the cytochrome P450 system.
• Interference with the metabolism of drugs, such as theophylline,
statins, and numerous antiepileptics, has been reported for
clarithromycin.
53. • 4. Excretion:
• Erythromycin and azithromycin are primarily concentrated and excreted in
the bile as active drugs.
• Partial reabsorption occurs through the enterohepatic circulation.
• In contrast, clarithromycin and its metabolites are eliminated by the kidney
as well as the liver.
• The dosage of this drug should be adjusted in patients with renal
impairment.
54.
55.
56. E. Adverse effects
• 1. Gastric distress and motility:
• Gastric upset is the most common adverse effect of the macrolides and
may lead to poor patient compliance (especially with erythromycin).
• Clarithromycin and azithromycin seem to be better tolerated.
• Higher doses of erythromycin lead to smooth muscle contractions that
result in the movement of gastric contents to the duodenum, an adverse
effect sometimes used therapeutically for the treatment of gastroparesis or
postoperative ileus.
57. • 2. Cholestatic jaundice:
• This side effect occurs especially with the estolate form (not used in
the United States) of erythromycin; however, it has been reported
with other formulations.
58. • 3. Ototoxicity:
• Transient deafness has been associated with erythromycin, especially
at high dosages.
• Azithromycin has also been associated with irreversible sensorineural
hearing loss.
59. • 4. Contraindications:
• Patients with hepatic dysfunction should be treated cautiously with
erythromycin, telithromycin, or azithromycin, because these drugs
accumulate in the liver.
• Severe hepatotoxicity with telithromycin has limited its use, given the
availability of alternative therapies.
• Additionally, macrolides and ketolides may prolong the QTc interval and
should be used with caution in those patients with proarrhythmic
conditions or concomitant use of proarrhythmic agents.
60. 5. Drug interactions:
• Erythromycin, telithromycin, and clarithromycin inhibit the hepatic
metabolism of a number of drugs, which can lead to toxic
accumulation of these compounds.
• An interaction with digoxin may occur. In this case, the antibiotic
eliminates a species of intestinal flora that ordinarily inactivates
digoxin, thus leading to greater reabsorption of the drug from the
enterohepatic circulation.