This document discusses the pharmacodynamics of antibiotics. It explains that the time course of drug concentration at the infection site and potential toxic effects are closely related to antibiotic effect. Pharmacodynamic factors that determine antibiotic activity include pathogen susceptibility, whether the drug is bactericidal or bacteriostatic, drug synergism/antagonism, and post-antibiotic effects. Pharmacodynamic information is important for optimizing antibiotic dosage regimens. The document also discusses concepts like minimum inhibitory concentration, minimum bactericidal concentration, and time-dependent versus concentration-dependent antibiotic killing.
Antibiotics are most common therapeutic agents used in hospitals across world, however, microbial world is becoming resistant day by day, posing special challenges to clinicians specially working in ICU set ups. There are multiple ways to curb this menace, if approached together in antibiotic stewardship way, can bring about wonders and retain therapeutic potentials of these drugs.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
Antibiotics are most common therapeutic agents used in hospitals across world, however, microbial world is becoming resistant day by day, posing special challenges to clinicians specially working in ICU set ups. There are multiple ways to curb this menace, if approached together in antibiotic stewardship way, can bring about wonders and retain therapeutic potentials of these drugs.
While MIC is a good measure of antibiotic activity, it is static and reflects in vitro activity. PK and PD of the drug needs to be considered together with MIC if we wish to obtain an in vivo prediction of drug action and success.
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
General Principles of Antimicrobial Selection - 2018Arwa M. Amin
Module: Pharmacology and Therapeutics III, (Therapeutics part)
Coordinator: Dr. Arwa M. Amin Mostafa
Academic Level: Undergraduate, B.Pharmacy
School: Dubai Pharmacy College
Year of first presented in Class: 2018
This presentation is for Educational purpose. It has no commercial value associated with it
Microbiology is the study of microorganisms.
The overall theme of the Microbiology course is to study the relationship between microbes and our lives.
Microorganisms (microbes) are organisms that are too small to be seen with the unaided eye, and usually require a microscope to be seen.
This relationship involves harmful effects such as diseases and food spoilage as well as many beneficial effects.
General Principles of Antimicrobial Selection - 2018Arwa M. Amin
Module: Pharmacology and Therapeutics III, (Therapeutics part)
Coordinator: Dr. Arwa M. Amin Mostafa
Academic Level: Undergraduate, B.Pharmacy
School: Dubai Pharmacy College
Year of first presented in Class: 2018
This presentation is for Educational purpose. It has no commercial value associated with it
Concentration vs Time Dependent Antibiotics.pptxHasan Arafat
A short presentation about the difference in pharmacodynamics of concentration-dependent vs. time dependent antibiotics and the clinical implications of this phenomenon.
GENERAL PRINCIPLES OF ANTIBIOTIC THERAPY.pptxShaanSinojia
To review about general principles of antibiotic therapy to understand more about their action and precautions while prescribing antibiotics to the patient.
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
- 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
2. • The time course of drug concentration is
closely related to the antibiotic effect at the
site of infection and to any toxic effects
• Pharmacodynamic factors include pathogen
susceptibility testing, drug bactericidal versus
bacteriostatic activity, drug synergism,
antagonism and post-antibiotic effects
• Pharmacodynamic information is important
for selection of optimal antibiotic dosage
regimens
3. Pharmacodynamics
• “What the drug does to the body”
• Includes physiological and biochemical effects
of the drug & MOA
• Integrates : organism susceptibility + patient
pharmacokinetics
4. Antibiotic activity
• Bactericidal
– Kills the organism
– Examples : B lactams , Vancomycin,
Fluroquinolones, Aminoglycosides, Daptomycin,
metronidazole
• Bacteriostatic
– Inhibits the growth
– Requires aid of host defenses
– Relapses can occur after discontinuation of drug
– Examples: Macrolides, Clindamycin,
Sulfonamides, Linezolid, chloramphenicol
5. Bacteriostatic vs Bactericidal activity
• Bacteriostatic and bactericidal agents are
equivalent for treatment of most infectious
disease in immunocompetent hosts
• Bactericidal agents should be selected over
bacteriostatic ones in circumstances of
impaired local or systemic host defenses
7. Bactericidal agents
Time-dependent killing
• Bactericidal activity continues as long as serum
concentrations are greater than the MBC
• Minimal serum conc of free drug present for
40 - 50 % of dosing interval is called
pharmacodynamic breakpoint
• If MIC is below this breakpoint, then the drug is
clinically effective (sensitive)
• If MIC is above this breakpoint, the organism is
resistant
• E.g. β lactams, Vancomycin
8. Site and Mechanism of Action of
Antibiotics
1. Inhibition of cell wall synthesis
2. Alteration of cell membrane integrity
3. Inhibition of ribosomal protein synthesis
4. Suppression of DNA synthesis
9.
10. Post-antibiotic effect
1. Bactericidal drugs
• Bacterial count reduces till conc above MBC
• When concentration falls below MBC, but
remains above MIC – bacterial count remains
stable or continues to decline
2. Bacteriostatic drugs
• Levels above MIC – bacterial counts decline
due to host factors ( immunity )
• Below MIC – persistent antibacterial effects
act
11. Post-antibiotic effect (PAE)
• A persistent antibacterial effect after a brief
antibiotic exposure that occurs even in the
absence of host defenses is termed PAE
• The organism may become more susceptible
to phagocytes – post antibiotic leucocyte
enhancement
• Concentration below MIC can alter bacterial
morphology, slows bacterial growth rate and
prolongs PAE
12. Mechanism of PAE
• Slow recovery after reversible nonlethal
damage to cell structures
• Persistence of the drug at a binding site or
within the periplasmic space
• The need to synthesize new enzymes before
growth can resume
13. PAE (cont.)
• Most antibiotic possess significant in vitro PAE
against susceptible gram-positive cocci
• Antibiotics with significant PAEs against
susceptible gram-negative bacilli are limited to
carbapenems and the agents that inhibit
protein or DNA synthesis
14. PAE (cont.)
• In vivo PAEs usually much longer than in vitro
PAEs
• Due to post-antibiotic leukocyte enhancement
(PALE) and exposure of bacteria to
subinhibitory antibiotic concentrations
• Efficacy of once-daily dosing regimens is in-
part due to PAE
15. Concepts of MIC & MBC
MIC (minimum inhibitory concentration)
• Defined as the minimal concentration of
antibiotic that prevents the clear suspension of
105 CFU/ ml from becoming turbid after
overnight incubation
• Turbidity signifies at least 10 times increase in
bacterial density
MBC (minimal bactericidal concentration)
• For Bactericidal drugs : same as MIC or upto 4
times MIC
• For Bacteriostatic drugs : many fold higher than
MIC
16. Pharmacokinetic principles
• The PK parameters define only the serum level
time course of an antibiotic
• They do not quantify the killing effect
• PK parameters :
– Cmax – the peak antibiotic concentration
– Cmin – the trough
– AUC – the area under serum concentration time
curve
17. • The PD parameters integrate organism
susceptibility (MIC) and PK parameters
• Define the killing effect
• PD parameters
– Cmax / MIC ratio
– T > MIC
– AUC 24 / MIC
– Post antibiotic effect
Pharmacodynamic principles
18. AUC
• The area under concentration – time curve at
a steady state over 24 hr period
• It is used as a reference value, if not stated,
assumed to be of 24 hours
T > MIC
• The cumulative percentage of a 24 hr. period
that the drug concentration exceeds the MIC
at a steady state
19. Patterns of antibiotic action
Pattern of
activity
PK/PD
parameter
Goal of therapy Examples
Type I Concentration
dependent
prolonged PAE
AUC/MIC
Cmax/MIC
Maximize
concentration
Aminoglycoside
Fluroquinolones
Daptomycin
Ketolides
Type II Time dependent
minimal PAE
T>MIC Maximize duration
of exposure
Penicillins
Carbapenems
Cephalosporins
Linezolids
E.mycin
Type III Time dependent
prolonged PAE
AUC/MIC Maximize amount
of drug
Azithromycin
Clindamycin
Tetracycline
Vancomycin
20. Antimicrobial drug combinations
Rationale for combination antibiotic therapy
• To provide broad-spectrum empiric therapy in
seriously ill patients
• To treat polymicrobial infections
• To decrease the emergence of resistant strains
• To decrease dose-related toxicity
• To obtain enhanced inhibition or killing
22. Mechanism of Synergistic Action
• Blockade of sequential steps in a metabolic
sequences
– E.g. Trimethoprim-sulfamethoxazole
• Inhibition of enzymatic inactivation
– E.g. β lactamase inhibitor drugs (Sulbactam)
• Enhancement of antimicrobial agent uptake
– E.g. Penicillin can increase the uptake of
aminoglycosides by a number of bacteria
23. Mechanism of Antagonistic Action
• Inhibition of cidal activity by static agents
• Bacteriostatic agents can antagonize the action of
bactericidal cell wall-active agents as cell wall-active
agents require that the bacteria be actively growing
and dividing
• Induction of enzymatic inactivation
– Some gram-negative bacilli possess inducible β
lactamase
– β lactam antibiotics are potent inducers of β
lactamase production
– If an inducing agent is combined with an intrinsically
active but hydrolysable β lactam such as piperacillin,
antagonism may result
24. Inoculum effect
• Significant increase in the MIC of an antibiotic
when the number of organisms inoculated is
increased
• Occurs with beta-lactam antibiotics in relation
to beta-lactamase-producing bacteria
• Although certain antibiotics exhibit an IE, they
are still capable of eradicating infections when
administered appropriately
• Thus, the clinical significance of this laboratory
phenomenon has yet to be elucidated
25. Pharmacodynamic differences in
Antibiotic classes
Penicillin & Beta lactams
• Primarily time dependent killing
• T > MIC is the most important determinant for
beta lactam killing effect
• Longer exposure resulted in better killing
effect as seen in E. coli
26. Aminoglycosides
• Concentration dependent killing effect
• Peak/MIC of > 8:1 is associated with treatment
success
• They demonstrate 2-10 hr, cocentration
dependent PAE for many GN organisms
Pharmacodynamics differences in
Antibiotic classes
27. Fluroquinolones
• Concentration dependent killing
• Both peak/MIC & AUC/MIC : linked to efficacy
• Estimated AUC/MIC of 350-450 – linked with
maximal killing for ciprofloxacin
• AUC/MIC of 125 -250 demonstrated optimal
killing
• levofloxacin in UTI, demonstrated optimal
efficacy with peak/MIC of 12.2
Pharmacodynamics differences in
Antibiotic classes
28. Miscellaneous nomenclature
Pharmacodynamic indices and related
AUBC
• Area under bactericidal curve
• Calculated over 24 hrs at steady state
AUIC
• Area under inhibitory curve
• Reserved for those cases where actual
inhibitory titers have been measured
29. Post Exposure Effects
In vitro PAE
• Period of suppression of bacterial growth after short
exposure of organisms to antibiotic
Sub MIC effect
• Any effect of antibiotic with concentration below MIC
Post antibiotic sub-MIC effect
• Effect of sub MIC drug concentration on bacterial
growth following serial exposure to drug concentration
exceeding MIC
Post MIC effect
• The difference in time for number of antibiotic exposed
bacteria vs controls to increase 1 log values after drug
concentration falls below the MIC
30. Terms under consideration
Mutation prevention concentration
• Concentration preventing growth at a high
inoculum (>109) using agar dilution technology
• Due to higher inoculum, higher chances of
selecting mutants
Mutant selection window
• Difference between MIC and MPC for a given
organism
Mutant prevention index
• Ration between MPC and MIC