Anti-infective agents work by selectively targeting foreign microorganisms that have infected the body. The document discusses the pharmacology of antibiotics including their mechanisms of action, sources, modes of action against bacteria, and factors that determine likelihood of infection. It also covers development of antibiotic resistance in bacteria, adverse drug reactions, pharmacokinetics and interactions of major classes of antibiotics like penicillins and cephalosporins.
Pharmacology of Penicllins (Beta lactam antibiotics), description of their mechanism of action, mechanism of resistance, classification, indications and adverse effects
The current slide include the pharmacology og cephalosporins.
Contents
Introduction to Cephalosporins
Classification of Cephalosporins
Cefazolin
Cephalexin
Cefuroxime
Cefuroxime axetil
Cefotaxime
Cefixime
Cefpodoxime proxetil
Cefepime
Adverse effects of Cephalosporins
Uses of Cephalosporins
Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation
An antifungal medication is a pharmaceutical fungicide used to treat and prevent mycoses such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available OTC (over-the-counter).
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism with fewer adverse effects to the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the biological level. This makes it more difficult to discover drugs that target fungi without affecting human cells. As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be life-threatening if the drugs are not used properly.
This presentation is about MRSA which is also known a 'superbug.' It consist of information on MRSA,MRSA infection,its genetics,types,symptoms,prevention,research,etc
Pharmacology of Penicllins (Beta lactam antibiotics), description of their mechanism of action, mechanism of resistance, classification, indications and adverse effects
The current slide include the pharmacology og cephalosporins.
Contents
Introduction to Cephalosporins
Classification of Cephalosporins
Cefazolin
Cephalexin
Cefuroxime
Cefuroxime axetil
Cefotaxime
Cefixime
Cefpodoxime proxetil
Cefepime
Adverse effects of Cephalosporins
Uses of Cephalosporins
Definition
History
Chemistry
Properties
Classification & its Generation
Pharmacokinetics
Mechanism of action
Indication
Contraindication
Therapeutic use
Adverse effect
Resistance
Comparison with penicillin
Market preparation
An antifungal medication is a pharmaceutical fungicide used to treat and prevent mycoses such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available OTC (over-the-counter).
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism with fewer adverse effects to the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the biological level. This makes it more difficult to discover drugs that target fungi without affecting human cells. As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be life-threatening if the drugs are not used properly.
This presentation is about MRSA which is also known a 'superbug.' It consist of information on MRSA,MRSA infection,its genetics,types,symptoms,prevention,research,etc
Nimalox is a non steroidal anti inflammatory drug with
analgesic and antipyretic properties and cox-2
selective inhibition
it's a study to re-branding Nimalox
MBA Cairo University
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Antibiotics In Acute Respiratory Failureshabeel pn
abscess advanced trauma life support anterio advanced trauma life support antibiotics apically repositioned flap dental diseases dr dr shabeel drshabeel’s face eye trauma lidocaine anodontia management medical medicine misuse and abuse orthodontics teeth braces pharmacy pn preparation dental students for community based ed presentations s abscess abscess tooth active orthodonti shabeel shabeel"s shabeel’s shabeelpn trends of antimicrobial usage in dental practice View all
’s abscess abscess advanced trauma life support anterio abscess tooth active orthodontics adolescent advanced trauma life support aesthetic dentistry airway management alignment of teeth amalgam anesthesia in dentistry anesthetics in dentistry anterior open bite antibiotic resistanace antibiotics antibiotics and leukopenia aphthous ulcers apically repositioned flap apicoectomy appliances arch dental arch form orthodontics braces arch length orthodontics braces arch wire orthodontist braces ayurvedha baby teeth bloger boil books braces braces teeth cancer canker sore pain cavity preparation children community based learning congenitally missing teeth cosmetic dentistry csf leaks dental dental anesthetics dental restorations dental teeth dento alveolar fractures disease
Description of the major classes of antimicrobial drug, resistant mechanisms developed by bacteria to combat the action of antimicrobials, and the control measures needed to limit this horizontal gene transfer.
The newer antibiotics added to Our Arsenal against resistant bacteria. Know about the upcoming antibiotics and newer antibiotics in use.
Free text at
http://medchrome.com/basic-science/pharmacology/newer-antibiotics-review/
DISPERCAM, Marketing Plan for 2011
Markeiting & IMC plan for pharmaceutical product. using modern and emotional communication concept can be used for direct marketing by medical reps.
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http://www.slideshare.net/AbdulrhmanTantawy/atantawy-visual-resume
Bacteria have their own enzymes for
1. Cell wall formation
2. Protein synthesis
3. DNA replication
4. RNA synthesis
5. Synthesis of essential metabolites
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
2. The anti-infective drugsThe anti-infective drugs
Anti-infective agents are drugs that
are designed to act selectively on
foreign organisms that have invaded
and infected the body
2
5. General Mechanisms of Action of anti-
infective agents
The mechanisms are:
1.Inhibition the biosynthesis of bacterial
cell WALL
2.Inhibition of protein synthesis
3.Some change the cell membrane
permeability
4.Some inhibit DNA synthesis
5
10. Features of Antimicrobial Drugs
• Selective toxicity: Drug kills pathogens without damaging
the host.
• Therapeutic index: ratio between toxic dose and
therapeutic dose – or ratio of LD50 to ED50
High therapeutic index ⇒ less toxic
• Antimicrobial action – Bacteriostatic vs. bactericidal
• Activity Spectrum – Broad-spectrum vs. narrow- spectrum
• Tissue distribution, metabolism, and excretion – BBB;
Unstable in acid; half-life duration
10
12. Spectrum of Activity of Anti-infectives
Antibiotics agents can also be:
• Bacteriostatic
Erythromycin, tetracyclines,clindamycin,
chloramphenicol, spectinomycin, sulfonamides
• Bactericidal
Penicillins, Cephalosphorins, Metronidazole,
Aminoglycosides, Vancomycin, Polymyxin
12
13. Spectrum of Activity of Anti-infectives
• Anti-infectives that interfere with the
ability of the cell to reproduce/replicate
without killing them are called
BACTERIOSTATIC drugs.
• Tetracycline is an example.
13
14. Spectrum of Activity of Anti-infectives
• 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.
• (e.g. Erythromycin and Clindamycin may be
bactericidal at higher blood levels)
14
15. Factors That Determine the Likehood Of a
microorganism Causing an Infection:
Factors That Determine the Likehood Of a
microorganism Causing an Infection:
1. Virulence of the microorganism
2. Number of the microorganism
present
3. Resistance of the host
15
17. Pharmacodynamic properties of
antibiotics
Type of bactericidal
profile
Important
parameter
Dosage optimization
Dose-dependent
Aminoglycosides,
quinolones
Cmax / MIC
Prolonged PAE
Single daily dose
Time-dependent
Penicillin, cephalosporins
T > MIC No PAE
Multiple DD or
continuous infusion
Cumulative-dose
dependent
Clarithromycin,
clindamycin
AUC / MIC
Prolonged PAE
Total dose and
duration
PAE: Post-Antibiotic Activity17
18. S. aureus
Penicillin
[1950s
]
Penicillin-resistant
S. aureus
Evolution of Drug Resistance inEvolution of Drug Resistance in S.S.
aureusaureus
Methicillin
[1970s]
Methicillin-
resistant
S. aureus (MRSA)
Vancomycin-resistant
enterococci (VRE)
Vancomycin
[1990s]
[1997]
Vancomycin
intermediate-
resistant
S. aureus
(VISA)
[ 2002 ]
Vancomycin-
resistant
S. aureus
18
19. Antibiotic Resistance
• A variety of mutations can lead to antibiotic resistance
• Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug
• Resistance genes are often on plasmids or transposons
that can be transferred between bacteria.
19
22. Only three of the
approved antibiotics in
the last 10 years (25%
of total) have of new
mode of action
Superbugs, is the situation really that bad?
22
23. Lots of drugs Not so many
Superbugs, is the situation really that bad?
23
25. Common Adverse Reactions to
Anti-infective Therapy
The most common adverse effects are due to
the direct action of the drugs in the following
organ system- Neuro, nephro and GI system
25
26. Common Adverse Reactions to Anti-
infective Therapy
1. Nephrotoxicity
• Antibiotics that are metabolized and
excreted in the kidney most frequently
cause kidney damage..
26
27. Common Adverse Reactions to Anti-
infective Therapy
2. Gastro-intestinal toxicity
• Direct toxic effect to the cells of the GI tract
can cause nausea, vomiting, stomach pain
and diarrhea.
• Some drugs are toxic to liver cells and can
cause hepatitis or liver failure.
27
28. Common Adverse Reactions to Anti-
infective Therapy
3. CNS toxicity
• When drugs can pass through the brain
barrier and accumulate in the nervous
tissues, they can interfere with neuronal
function.
28
29. Common Adverse Reactions to Anti-
infective Therapy
4. Hypersensitivity
• Most protein antibiotics can induce the
body’s immune system to produce allergic
responses.
• Drugs are considered foreign substances and
when taken by the individual, it encounters
the body’s immune cells.
29
30. Common Adverse Reactions to Anti-
infective Therapy
5. Super-infections
• Opportunistic infections that develop during
the course of antibiotic therapy are called
SUPERINFECTIONS.
30
34. Penicillin
Penicillin is a beta-lactam drug, with a
beta-lactam ring.
The group of penicillins is called beta
lactam antibiotics.
34
35. Penicillin
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. 35
38. Penicillin cont.
Penicillinase (β-lactamase): bacterial enzyme that
destroys natural penicillins
Penicillinase resistant penicillins: methicilin replaced by
oxacilin and nafcilin due to MRSA
Extended-spectrum penicilins: Ampicilin, amoxicilin; new:
carboxypenicilins and ureidopenicillins (also good against
P. aeruginosa)
Fig 20.8
38
41. Penicillin
Therapeutic Indications of penicillin:-
No other class of antibacterial drugs
provides as wide a spectrum of antimicrobial
activity as the penicillins.
As a class, they cover gram-positive, gram-
negative, and anaerobic organisms, although
specific penicillins are more effective against
specific organisms.
41
42. 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.
42
43. Summary of the
adverse effects of
penicillin
Summary of the
adverse effects of
penicillin
43
44. Adverse Effects of Penicillins
• Hypersensitivity reactions- rashes, pruritus,
fever and urticaria
• Anaphylaxis can also happen leading to shock
or death. It occurs in 5-10% of those receiving
penicillins.
• Pain and inflammation on injection sites
44
47. Cephalosporins
Fungi of genus
Cephalosporium ⇒ 4
Generations of
cephalosporins
1. First-generation: Narrow spectrum, gram-positive
2. Second-generation: Extended spectrum includes gram-
negative
3. Third-generation: Includes pseudomonads; mostly
injected, some oral.
4. Fourth-generation: Most extended spectrum
47
48. Cephalosporins cont.
Structure and mode of action resembles penicilins
1. More stable to
bacterial β-
lactamases than
penicilins
2. Broader spectrum
⇒ used against
penicillin-resistant
strains
48
50. 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, Entreobacter
aerogenes and Nesseria sp. These drugs are
less effective against gram positive bacteria
50
51. THE CEPHALOSPORINS
• Third Generation cephlosporins- are relatively
weak against gram-positive bacteria but more
potent against gram-negative bacteria, to
include Serratia marcescens.
• Fourth generation cephalosporins- are
developed to fight against the resistant gram-
negative bacteria. The first drug is cefepime.
51
52. Cephalosporin
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. 52
53. Administration and fate of the
cephalosporins
Administration and fate of the
cephalosporins
53
54. Cephalosporin
• 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.
• Contraindications and Precautions
–The drugs are contraindicated in patients
with known allergies to cephalosporins and
penicillins.
54
56. Cephalosporin
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
• Hypersensitivity
56
57. Cephalosporin
Drug-Drug interactions
• ALCOHOL- many patients experience a
disulfiram-like reactions when taken with
some specific cephlosporins ( cefamandole,
cefoperazone or moxalactam).
• The patient may experience flushing,
headache, nausea, vomiting and muscular
cramps. This may occur even up to 72
hours of cephalosporin discontinuance.
57
58. Carbapenems are a class of beta-
lactam antibacterials that includes:
1.ertapenem
2.imipenem-cilastatin sodium (a
combination drug)
3.meropenem.
Carbapenems
58
59. The antibacterial spectrum of activity for imipenem-cilastatin is
broader than that of any other antibacterial studied to date.
Because of this broad spectrum of activity, it’s used for serious or
life-threatening infection, especially gram-positive and gram-
negative health-care acquired infections
Pharmacodynamics
• Imipenem-cilastatin, ertapenem, and meropenem are
bactericidal.
• They exert antibacterial activity by inhibiting bacterial cell-wall
synthesis.
Pharmacotherapeutics
Imipenem has the broadest spectrum of activity of currently
available beta-lactam antibiotics:-
1. It’s effective against aerobic gram-positive species, such as
Streptococcus, S. aureus, and S. epidermidis.
2. It inhibits most Enterobacter species.
3. It also inhibits P. aeruginosa (including strains resistant to
59
60. Common adverse reactions to ertapenem, imipenem-
cilastatin, and meropenem include:
nausea and vomiting
diarrhea.
Hypersensitivity reactions, such as rashes, may occur,
particularly in the patient with a known hypersensitivity
to penicillins.
Kidney conditions (In the patient with decreased or
impaired renal function, the dosage may need to be
adjusted).
Adverse reactions to carbapenems
60
61. Aztreonam is the first member in the class of
monobactam antibiotics and the only one currently
available.
It’s a synthetic monobactam with a narrow spectrum
of activity that includes many gram-negative aerobic
bacteria.
Pharmacokinetics
• After parenteral administration, aztreonam is rapidly
and completely absorbed and widely distributed
throughout the body.
• It’s metabolized partially and excreted primarily in
urine as unchanged drug.
Monobactams
61
63. Pharmacotherapeutics
Aztreonam is indicated in a range of therapeutic situations:-
1)It’s effective against a wide variety of gram-negative aerobic
organisms, including P. aeruginosa.
2)It’s effective against most strains of the following organisms: E.
coli, Enterobacter, Klebsiella pneumoniae, K. oxytoca, Proteus
mirabilis, Serratia marcescens, H. influenzae, and Citrobacter.
3)It’s also used to treat complicated and uncomplicated UTIs,
septicemia, and lower respiratory tract, skin and skin-structure,
intra-abdominal, and gynecologic infections caused by susceptible
gram-negative aerobic bacteria.
4)It’s usually active against gram-negative aerobic organisms that
are resistant to antibiotics hydrolyzed by beta-lactamases.
63
64. Aztreonam can cause some adverse reactions
including:-
diarrhea
hypersensitivity and skin reactions
hypotension
nausea and vomiting
transient electrocardiogram changes (including
ventricular arrhythmias)
transient increases in serum liver enzyme levels.
Adverse reactions to aztreonam
64
65. Vancomycin
– Glycopeptide from Streptomyces
– Inhibition of cell wall synthesis
– Used to kill MRSA
– Emerging Vancomycin
resistance: VRE and VRSA
65
66. Pharmacodynamics
Vancomycin inhibits bacterial cell-wall synthesis, damaging the
bacterial plasma membrane.
When the bacterial cell wall is damaged, the body’s natural
defenses can attack the organism.
Pharmacotherapeutics
Vancomycin is active against gram-positive organisms, such as S.
aureus, S. epidermidis, S. pyogenes, Enterococcus, and S.
pneumoniae.
In the I.V. league
I.V. vancomycin is the therapy of choice for the patient with a
serious resistant staphylococcal infection who’s hypersensitive to
penicillins.
66
67. Pharmacokinetics
Because vancomycin is not absorbed from the GI tract, it must be
given I.V. to treat systemic infections.
an oral form of vancomycin is used to treat pseudomembranous
colitis.
Vancomycin diffuses well into pleural, pericardial, synovial joint
ascitic fluids.
Normal T ½ of vancomycin is 6 to 10 hr , compared to over 200 hr
in end-stage renal disease.
No switching!
Remember that I.V. vancomycin can’t be used in place of oral
vancomycin and vice versa. The two forms aren’t interchangeable.
Metabolism and excretion
The metabolism of vancomycin is minimal .
About 90% of the dose is excreted unchanged in urine within 24
hours.
67
68. Antimicrobial spectrum of vancomycinAntimicrobial spectrum of vancomycin
Some adverse effects of vancomycinSome adverse effects of vancomycin
68
69. Oral history
Oral vancomycin is used for the patient with antibiotic-associated
Clostridium difficile colitis who can’t take or has responded poorly to
metronidazole.
The 1 in the 1-2 punch
Vancomycin, when used with an aminoglycoside, is also the
treatment of choice for E. faecalis endocarditis in the patient who’s
allergic to penicillin.
Drug interactions
Vancomycin may increase the risk of toxicity when administered with
other drugs toxic to the kidneys and organs of hearing, such as
aminoglycosides, amphotericin B, bacitracin, cisplatin, colistin, and
polymyxin B.
69
70. Adverse reactions to vancomycin, although rare, include:
1)hypersensitivity and anaphylactic reactions
2)drug fever
3)eosinophilia (an increased number of eosinophils)
4)neutropenia
5)hearing loss (transient or permanent), dose dependent ototoxicty
s (as when it’s given with other ototoxic drugs).
Rash behavior(red man’s syndrome):-
Severe hypotension may occur with rapid I.V. administration of
vancomycin and may be accompanied by a red rash with flat and
raised lesions on the face, neck, chest, and arms
Infusion of 1 g or less should be given over 1 hour.
Adverse reactions to vancomycinAdverse reactions to vancomycin
70
71. 71
Daptomycin is a cyclic lipopeptide antibiotic that is an alternative
to other agents, such as linezolid and quinupristin/dalfopristin, for
treating infections caused by resistant gram-positive organisms,
including MRSA and vancomycin-resistant enterococci (VRE).
Mode of action
Upon binding to the bacterial cytoplasmic membrane,
daptomycin induces rapid depolarization of the membrane, thus
disrupting multiple aspects of membrane function and inhibiting
intracellular synthesis of DNA, RNA, and protein.
Daptomycin is bactericidal, and bacterial killing is concentration
dependent.
DaptomycinDaptomycin
72. 72
Antibacterial spectrum
Daptomycin has a spectrum of activity limited
to gram-positive organisms, which includes:-
methicillin-susceptible
methicillin-resistant S. aureus
penicillin resistant Strept.pneumoniae
Streptococcus pyogenes
Corynebacterium jeikeium
E. faecalis
E. faecium (including VRE)
73. 73
Adverse effects
•The most common adverse effects reported in clinical trials
included:-
constipation,
nausea,
headache
insomnia.
Increased hepatic transaminases
elevations in creatin phosphokinases
•Although no clinically significant interactions have been
identified, it is recommended to temporarily discontinue 3-
hydroxy-3-methylglutary coenzyme A reductase inhibitors
(statins) while receiving daptomycin due to the potential for
additive muscle toxicity.
74. 74
Quinupristin/dalfopristin is a mixture of two
streptogramins in a ratio of 30 to70, respectively.
They are derived from a streptomycete and then
chemically modified.
The drug is normally reserved for the treatment of
vancomycin-resistant Enterococcus faecium (VRE).
Mechanism of action
Each component of this combination drug binds to a
separate site on the 50S bacterial ribosome, forming a
stable ternary complex.
Thus, they synergistically interrupt protein synthesis.
The combination drug is bactericidal and has a long
postantibiotic effect.
Quinupristin/DalfopristinQuinupristin/Dalfopristin
76. 76
Antibacterial spectrum
The combination drug is active primarily against gram-positive cocci,
including those resistant to other antibiotics (for example, methicillin-
resistant staphylococci).
Its primary use is in the treatment of E. faecium infections, including
VRE strains.
The drug is not effective against Enterococcus faecalis.
Pharmacokinetics
Quinupristin/dalfopristin is injected intravenously in a 5 percent
dextrose solution (the drug is incompatible with saline medium).
The combination drug penetrates macrophages and
polymorphonucleocytes, a property that is important, because VRE
are intracellular.
77. 77
Adverse effects
1.Venous irritation: This commonly occurs when
quinupristin/dalfopristin is administered through a
peripheral rather than a central line.
2.Arthralgia and myalgia: These have been reported when
higher levels 2. of the drugs are employed.
3.Hyperbilirubinemia: Total bilirubin is elevated in about
25 percent of patients, resulting from a competition with
the antibiotic for excretion.
Interactions:
1.Because of the ability of quinupristin/dalfopristin to inhibit the
cytochrome P450 (CYP3A4)isozyme,
2.drug interaction with digoxin appears to occur by the same
mechanism as that caused by erythromycin (lead to toxicities ).
79. 79
Linezolid is a totally synthetic oxazolidinone
It was introduced recently to combat resistant gram-
positive organisms, such as :-
methicillin and vancomycin-resistant Staphylococcus
aureus,
vancomycin-resistant E. faecium and E. faecalis,
Penicillin-resistant streptococci.
Mechanism of action
•The drug inhibits bacterial protein synthesis by inhibiting
the formation of the 70S initiation complex.
•Linezolid binds to a site on the 50S subunit near the
interface with the 30S subunit.
LinezolidLinezolid
81. 81
Adverse effects
Linezolid is well-tolerated, with some reports of
gastrointestinal upset
Nausea
Diarrhea
headaches
rash
Thrombocytopenia was found to occur in
longer than 2 weeks use .
83. The Aminoglycosides
The following are the aminoglycosides:-
1) Amikacin sulfate
2) Gentamicin sulfate
3) Kanamycin sulfate
4) Neomycin sulfate
5) Paromomycin sulfate
6) Streptomycin sulfate
7) Tobramycin sulfate
83
84. The Aminoglycosides
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.
84
86. The Aminoglycosides
Therapeutic Use of the Aminoglycosides:-
infections caused by gram-negative bacilli
serious nosocomial (hospital-acquired) infections,
such as gram-negative bacteremia, peritonitis, and
pneumonia, in critically ill patients
urinary tract infections (UTIs) caused by enteric
bacilli that are resistant to less toxic antibiotics,
such as penicillins and cephalosporins
infections of the central nervous system (CNS) and
the eye (treated with local instillation).
86
88. The Aminoglycosides
Serious adverse reactions limit the
use of aminoglycosides include:
1.neuromuscular reactions, ranging from
peripheral nerve toxicity to
neuromuscular blockade
2.ototoxicity
3.renal toxicity.
Oral history
Adverse reactions to oral
aminoglycosides include:
1.nausea and vomiting
2.diarrhea.
88
89. The Aminoglycosides
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
• 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.
89
91. The Macrolides
Mechanism of Action of the Macrolides
–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.
91
92. 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.
92
93. Administration and fate of the
macrolide antibiotics
Administration and fate of the
macrolide antibiotics properties of the macrolide antibioticsproperties of the macrolide antibiotics
93
95. The Macrolides
Therapeutic Use of Macrolides:-
• It provides a broad spectrum of antimicrobial activity
against gram-positive and gram-negative bacteria,
including Mycobacterium, Treponema, Mycoplasma, and
Chlamydia.
• It’s also effective against pneumococci and group A
streptococci. Staphylococcus aureus is sensitive to
erythromycin; however, resistant strains may appear
during therapy.
• Erythromycin is the drug of choice for treating
Mycoplasma pneumoniae infections as well as
pneumonia caused by Legionella pneumophila.
95
96. The Macrolides
Adverse Effects of Macrolides
• 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
96
97. Some adverse effects of macrolide antibioticsSome adverse effects of macrolide antibiotics
Inhibition of the cytochrome P450 system
by erythromycin, clarithromycin, and
telithromycin.
Inhibition of the cytochrome P450 system
by erythromycin, clarithromycin, and
telithromycin. 97
98. The Macrolides
Contraindications and Precautions in the Use of
Macrolides:-
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 and in pregnant women because
potential adverse effects on the developing
fetus. 98
99. The Lincosamides
These agents are similar to the Macrolides but are
more toxic.
1. Clindamycin
2. Lincomycin
Lincomycin is less effective than clindamycin and is
rarely used.
Lincomycin shouldn’t be used in the treatment of
minor infections but would be used to treat serious
respiratory or skin infections in the patient who’s
allergic to other antibiotics indicated for the infection.
99
100. The Lincosamides
Pharmacokinetics
Clindamycin is absorbed well orally and distributed widely
throughout the body.
It’s metabolized by the liver and excreted by the kidneys and
biliary pathways.
The bioavilability of lincomycin is about 20% to 30% .food
delays its absorption.
Lincomycin is partially metabolized in the liver and is excreted
in the urine, stool, and bile.
Pharmacodynamics
Clindamycin and lincomycin inhibit bacterial protein synthesis
by inhibiting the binding of bacterial ribosomes.
At therapeutic concentrations, clindamycin is primarily
bacteriostatic against most organisms.
100
102. Pharmacotherapeutics
Because of their potential for causing serious toxicity and
pseudomembranous colitis, these drugs are limited to a few
clinical situations in which safer alternative antibacterials
aren’t available.
1.Clindamycin is potent against most aerobic gram-positive organisms,
including staphylococci, streptococci (except Enterococcus faecalis), and
pneumococci.
2.Clindamycin is effective against most clinically important anaerobes
and is used primarily to treat anaerobic intraabdominal, pleural, or
pulmonary infections caused by Bacteroides fragilis.
3.It’s also used as an alternative to penicillin in treating Clostridium
perfringens infections.
4.Clindamycin and lincomycin may be used as alternatives to penicillin
in treating staphylococcal infections in a patient who’s allergic to
penicillin.
102
103. The Lincosamides
Side effects and Adverse Reactions:-
1. GIT- GI irritation, diarrhea
2. Nausea, vomiting and stomatitis
3. Allergic reactions
4. Pseudomembranous colitis (most serious reaction to
clindamycin)
Drug Interactions
• Lincomycin and clindamycin are incompatible with
aminophyline, phenytoin, barbiturates and ampicillin.
Pseudomembranous colitis syndrome can be fatal ,characterized by
severe diarrhea, abdominal pain, fever, and mucus and blood in
stool and requires prompt discontinuation of the drug as well as
aggressive fluid and electrolyte management
Pseudomembranous colitis syndrome can be fatal ,characterized by
severe diarrhea, abdominal pain, fever, and mucus and blood in
stool and requires prompt discontinuation of the drug as well as
aggressive fluid and electrolyte management
103
104. The Tetracyclines
These agents were first isolated from Streptomyces
The following are the tetracyclines:-
–Short-acting tetracyclines
tetracycline
oxytetracycline
–Intermediate acting tetracyclines
demeclocycline
methacycline
–Long acting tetracyclines
doxycycline
minocycline
104
107. The Tetracyclines
Contraindications and Precautions in the use
of Tetracyclines
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.
107
108. The Tetracyclines
Adverse Effects of the Tetracycline
• GI system- nausea, vomiting, diarrhea, abdominal pain, glossitis
and dysphagia.
• Fatal hepatotoxicity related 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
108
110. 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.
• Digoxin- digoxin toxicity rises when tetracyclines are
used together
110
111. The Tetracyclines
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.
111
112. 112
Tigecycline is the first available member of a new class
of antimicrobial agents called glycylcyclines.
Tigecycline, a derivative of minocycline, is structurally
similar to the tetracyclines and has a broadspectrum
activity against multidrug-resistant gram-positive
pathogens, some gram-negative organisms, and
anaerobic organisms.
Tigecycline is indicated for treatment of complicated
skin and soft tissue infections as well as complicated
intra-abdominal infections
Glycylcyclines
113. 113
Mechanism of action
Tigecycline exhibits bacteriostatic action by reversibly binding to the
30S ribosomal subunit and inhibiting protein translation.
Antibacterial spectrum
Tigecycline exhibits expanded broad-spectrum activity that includes
methicillin-resistant staphylococci
Multidrug-resistant Streptococcus pneumoniae
vancomycin-resistant enterococci
extended-spectrum B-lactamase producing gram-negative
bacteria
Acinetobacter baumannii
many anaerobic organisms.
N.B. tigecycline is not active against Proteus, Providencia,and
Pseudomonas species.
114. 114
Adverse effects
Tigecycline is well tolerated, with the main adverse
effects being similar to those of the tetracycline
class include:-
nausea and vomiting(most common)
photosensitivity
pseudotumor cerebri
discoloration of permanent teeth when used
during tooth development
fetal harm(teratogenic)
115. 115
• Chloramphenicol is active against a wide range of gram-
positive and gram-negative organisms.
• because of its toxicity, its use is restricted to life-threatening
infections for which no alternatives exist.
Mechanism of action
The drug binds to the bacterial 50S ribosomal subunit and
inhibits protein synthesis at the peptidyl transferase reaction
Because of the similarity of mammalian mitochondrial
ribosomes to those of bacteria, protein synthesis in these
organelles may be inhibited at high circulating chloramphenicol
levels, producing bone marrow toxicity.
Chloramphenicol
118. 118
Antimicrobial spectrum
Chloramphenicol, a broad-spectrum antibiotic, is active against
other microorganisms, such as rickettsiae.
Pseudomonas aeruginosa is not affected, nor are the chlamydiae.
Chloramphenicol has excellent activity against anaerobes.
The drug is either bactericidal or (more commonly) bacteriostatic,
depending on the organism.
Interactions:
•Chloramphenicol is able to inhibit some of the hepatic mixed-
function oxidases
•It blocks the metabolism of such drugs as warfarin, phenytoin,
tolbutamide, and chlorpropamide( elevating their concentrations
and potentiating their effects).
119. 119
1- Gastrointestinal upsets, overgrowth of Candida albicans
on mucous membranes.
2- Anemias:
Hemolytic anemia occurs in patients with low levels of glucose 6-phosphate
dehydrogenase.
Aplastic anemia is independent of dose and may occur after therapy has ceased.
3- Gray baby syndrome:
Neonates have a low capacity to glucuronylate the antibiotic, and they have
underdeveloped renal function .
neonates have a decreased ability to excrete the drug, which accumulates to levels
that interfere with the function of mitochondrial ribosomes.
This leads to poor feeding, depressed breathing, cardiovascular collapse, cyanosis
120. The Fluoroquinolones
The fluoroquinolones are broad-spectrum antibiotics.
They are usually manufactured synthetically and are
associated with mild adverse reactions.
The examples are:
1)Nalidixic acid
2)ciprofloxacin
3)ofloxacin
4)norfloxacin
5)Levfofloxacin
6)Sparfloxacin
120
121. The Fluoroquinolones
Pharmacodynamics: Mechanism of action
of the Fluoroquinolones
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.
121
122. Administration and fate of the fluoroquinolonesAdministration and fate of the fluoroquinolones
122
125. Fluoroquinolones
Adverse Effects of the
Fluoroquinolones
• 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 125
126. The Fluoroquinolones
• Contraindications and Precautions:-
a) Pregnancy and lactation are also
contraindications.
b) 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
126
128. Inhibition of tetrahydrofolate synthesis by sulfonamides
and trimethoprim
Inhibition of tetrahydrofolate synthesis by sulfonamides
and trimethoprim
128
129. Sulfonamides
Pharmacodynamics
–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.
129
130. Some adverse reactions to sulfonamidesSome adverse reactions to sulfonamides
Administration and fate of the sulfonamidesAdministration and fate of the sulfonamides
130
131. Sulfonamides
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.
131
132. 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
132
133. Trimethoprim a potent inhibitor of
bacterial dihydrofolate reductase,
exhibits an antibacterial spectrum
similar to that of the sulfonamides.
Trimethoprim is most often
compounded with
sulfamethoxazole, producing the
combination called cotrimoxazole
Trimethoprim
Synergism between trimethoprim
and sulfamethoxazole133
137. Mechanisms of action
Isoniazid Interferes with DNA
synthesis of bacterium
Rifampicin Interferes with RNA
synthesis
Pyrazinamide Interferes with bacterial
wall synthesis
Ethambutol Prevent multiplication
137
138. Common Side effects
Isoniazid Interferes with B6
Peripheral neuritis
Rifampicin Red-orange discoloration of the
secretions
Hepatitis
Pyrazinamide Hyperuricemia
Ethambutol Optic neuritis
138
140. General Responsibilities
• Advise patient to take the DRUGS as
prescribed
• Multiple drugs are taken to prevent
RESISTANCE
• Periodically check the liver function tests
• Supplemental Intake of Vitamin B6
140
141. An elderly diabetic patient is admitted to the hospital with
pneumonia. The sputum culture stains for a gram-negative
rod. The patient is started on IV ampicillin. Two days later,
the patient is not improving, and the microbiology laboratory
reports the organism to be a B-lactamase producing H.
influenzae. What course of treatment is indicated?
A. Continue with the IV ampicillin.
B. Switch to IV cefotaxime.
C. Switch to oral vancomycin.
D. Add gentamicin to the ampicillin therapy.
Study Questions
141
142. A 70-year-old alcoholic male with poor dental hygiene is to
have his remaining teeth extracted for subsequent
dentures. He has mitral valve stenosis with mild cardiac
insufficiency and is being treated with captopril, digoxin,
and furosemide. The dentist decides that his medical
history warrants prophylactic antibiotic therapy prior to
the procedure and prescribes which of the following
drugs?
A. Vancomycin.
B. Amoxicillin.
C. Tetracycline.
D. Cotrimoxazole.
E. Imipenem. 142
143. A patient with degenerative joint disease is to
undergo insertion of a hip prosthesis. To avoid
complications due to postoperative infection, the
surgeon will pretreat this patient with an antibiotic.
This hospital has a significant problem with MRSA.
Which of the following antibiotics should the
surgeon select?
A. Ampicillin.
B. Imipenem/cilastatin.
C. Gentamicin/piperacillin.
D. Vancomycin.
E. Cefazolin 143
144. A 25-year-old male returns home from a holiday in
the Far East and complains of 3 days of dysuria
and a purulent urethral discharge. You diagnose
this to be a case of gonorrhea. Which of the
following is appropriate treatment?
A. Ceftriaxone IM.
B. Penicillin G IM.
C. Gentamicin IM.
D. Piperacillin/tazobactam IV.
E. Vancomycin IV.
144
145. A patient with a gunshot wound to the abdomen, which has
resulted in spillage of intestinal contents, is brought to the
emergency room. Which antibiotic would you select to effectively
treat an infection due to Bacteroides fragilis?
A. Aztreonam.
B. Clindamycin.
C. Gentamicin.
D. Azithromycin.
E. Doxycycline.
Children younger than 8 years of age should not receive
tetracyclines because these agents:
A. Cause rupture of tendons.
B. Do not cross into the CSF.
C. Are not bactericidal.
D. Deposit in tissues undergoing calcification.
E. Can cause aplastic anemia. 145
146. A pregnant woman was hospitalized and catheterized
with a Foley catheter. She developed a urinary tract
infection caused by Pseudomonas aeruginosa and was
treated with gentamicin. Which of the following adverse
effects was a risk to the fetus when the woman was on
gentamicin?
A. Skeletal deformity.
B. Hearing loss.
C. Teratogenesis.
D. Blindness.
E. Mental retardation.
146
147. A 46-year-old woman is in the intensive care unit for
treatment of a vancomycin-resistant strain of
Enterococcus faecium caused bacteremia. You want to
limit the risk of drug interactions in this woman, who
is receiving five other medications. Which one of the
following antibiotics would you choose?
A. Azithromycin.
B. Clindamycin.
C. Doxycycline.
D. Linezolid.
E. Quinupristin/dalfopristin.
147
148. A 30-year-old male is diagnosed to be human immunodeficiency
virus (HIV) positive. His CD4+ count is 200 cells/mm3 and his viral
load is 10,000 copies/mL. In addition to receiving antiviral therapy,
which of the following is indicated to protect him against
pneumonia due to Pneumocystis jiroveci?
A. Trimethoprim.
B. Ciprofloxacin.
C. Cotrimoxazole.
D. Clindamycin.
A 26-year-old young man presents with the symptoms of
gonorrhea. Because this condition is often associated with an
infection due to Chlamydia trachomatis, which of the following
quinolones would be the best choice for treating him?
A. Ciprofloxacin.
B. Nalidixic acid.
C. Norfloxacin.
D. Levofloxacin. 148
149. In which one of the following infections is ciprofloxacin ineffective?
A. Urinary tract infections due to a B-lactamase producing strain of
Klebsiella.
B. Pneumonia due to Streptococcus pneumoniae.
C. Exacerbation of chronic bronchitis due to Moraxella catarrhalis.
D. UTI due to Escherichia coli.
E. UTIs due to Pseudomonas aeruginosa.
Sulfonamides increase the risk of neonatal kernicterus, because
they:
A. Diminish the production of plasma albumin.
B. Increase the turnover of red blood cells.
C. Inhibit the metabolism of bilirubin.
D. Compete for bilirubin-binding sites on plasma albumin.
E. Depress the bone marrow.
149
Editor's Notes
The ratio of the dose required to produce toxic or lethal effects to dose required to produce nonadverse or therapeutic response.www.ficus.usf.edu/docs/glossary/t.htm
As everyone here knows, antimicrobial resistance is nothing new, in fact,
by the 1950s, penicillin-resistant S. aureus were a major threat in hospitals and nurseries.
By the 1970s, methicillin-resistant S. aureus had emerged and spread, a phenomenon that encouraged widespread use of vancomycin.
In the 1990s, vancomycin-resistant enterococci emerged.
By 1997 the first strains of vancomycin-intermediate resistant S. aureus.
And in June 2002 the first case of vancomycin-resistant S. aureus with an MIC >32 was detected in woman in Michigan.
Their broad spectrum of activity and safety profile make the cephalosporins one of the most widely prescribed class of antimicrobials. The earlier generation cephalosporins are commonly used for community-acquired infections, while the later generation agents, with their better spectrum of activity against gram-negative bacteria make them useful for hospital-acquired infections or complicated community-acquired infections.
The Professor of Hygiene of the University of Cagliari, Giuseppe Brotzu (1895-1976), wondered why typhoid fever was less virulent in his city than elsewhere. He had formulated various hypotheses, all in vain. One day, while he was passing through the neighbourhood of the bay of "Su Siccu" he saw some young people bathing in the sea , just in the waters where Cagliari sewer system debouches without contracting the disease. So he took a sample of the water to test its effect on a culture of salmonella typhi. Since it was wartime and there was no meat to make the broth for the culture medium, Brotzu used the placentas obtained from parturient women in the maternity ward, that he then boiled in order to obtain the medium. With the help of his assistant Antonio Spanedda (1907-1998), he isolated a fungus from this water that produced an effective substance against Gram-negative bacteria- (the typhoid is in fact caused by Salmonella Typhi, which like all the enterobacteriaceae is Gram- negative) however, the fungal extract he had prepared was a raw compound which could not be produced on a larges scale. When Brotzu asked for funding from the Italian Committee for research it was not given to him for political reasons since he had previously adhered to Fascism, as did almost all Italian university professors. Moreover, Brotzu dedicated himself less to research because he got more involved in politics, first becoming Mayor of Cagliari and then President of the Region of Sardinia.
During fascist times, Brotzu had already been involved in the fight against malaria. After the war he was a consultant to the Rockefeller Foundation which, thanks to land reclamation and the massive use of DDT, succeeded in eradicating malaria (1950) by eliminating its carrier. Notwithstanding his great merits (for having discovered the cephalosporium he was proposed for the Nobel Prize) he is not usually mentioned in Italian texts, whereas, in contrast, he is named in pharmacological textbooks throughout the world. Brotzu received neither honour, nor money. In fact, he consigned several strains of cefalosporium fungus to an English sanitary official who had come to Sardinia in the anti-malaria campaign. In turn, this official gave the material to Edward Abraham (1913-1999), a student of Fleming, who isolated the cephalosporin. The drug was then sold throughout the world by the pharmaceutical companies Glaxo and Lilly making a good profit for them.
Their broad spectrum of activity and safety profile make the cephalosporins one of the most widely prescribed class of antimicrobials. The earlier generation cephalosporins are commonly used for community-acquired infections, while the later generation agents, with their better spectrum of activity against gram-negative bacteria make them useful for hospital-acquired infections or complicated community-acquired infections.
The Professor of Hygiene of the University of Cagliari, Giuseppe Brotzu (1895-1976), wondered why typhoid fever was less virulent in his city than elsewhere. He had formulated various hypotheses, all in vain. One day, while he was passing through the neighbourhood of the bay of "Su Siccu" he saw some young people bathing in the sea , just in the waters where Cagliari sewer system debouches without contracting the disease. So he took a sample of the water to test its effect on a culture of salmonella typhi. Since it was wartime and there was no meat to make the broth for the culture medium, Brotzu used the placentas obtained from parturient women in the maternity ward, that he then boiled in order to obtain the medium. With the help of his assistant Antonio Spanedda (1907-1998), he isolated a fungus from this water that produced an effective substance against Gram-negative bacteria- (the typhoid is in fact caused by Salmonella Typhi, which like all the enterobacteriaceae is Gram- negative) however, the fungal extract he had prepared was a raw compound which could not be produced on a larges scale. When Brotzu asked for funding from the Italian Committee for research it was not given to him for political reasons since he had previously adhered to Fascism, as did almost all Italian university professors. Moreover, Brotzu dedicated himself less to research because he got more involved in politics, first becoming Mayor of Cagliari and then President of the Region of Sardinia.
During fascist times, Brotzu had already been involved in the fight against malaria. After the war he was a consultant to the Rockefeller Foundation which, thanks to land reclamation and the massive use of DDT, succeeded in eradicating malaria (1950) by eliminating its carrier. Notwithstanding his great merits (for having discovered the cephalosporium he was proposed for the Nobel Prize) he is not usually mentioned in Italian texts, whereas, in contrast, he is named in pharmacological textbooks throughout the world. Brotzu received neither honour, nor money. In fact, he consigned several strains of cefalosporium fungus to an English sanitary official who had come to Sardinia in the anti-malaria campaign. In turn, this official gave the material to Edward Abraham (1913-1999), a student of Fleming, who isolated the cephalosporin. The drug was then sold throughout the world by the pharmaceutical companies Glaxo and Lilly making a good profit for them.