Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)
1)CALCINEURIN INHIBITORS
i. CYCLOSPORIN/ CYCLOSPORINE
ii. SIROLIMUS
iii. TACROLIMUS
iv. EVAROLIMUS
2) ANTIPROLIFERATIVE/ANTIMETABOLIC AGENTS,
i. MYCOPHENOLATE
ii. AZATHIOPRINE
3) BIOLOGICS (ANTIBODIES)
i. MUROMONAB-CD3 (OKT3)
ii. BASILIXIMAB
iii. DACLIZUMAB
iv. ALEMTUZUMAB
v. ANTITHYMOCYTE GLOBULIN
4)GLUCOCORTICOIDS,
clinical pharmacokinetics and therapeutic drug monitoring ----- fifth pharm D notes
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)
1)CALCINEURIN INHIBITORS
i. CYCLOSPORIN/ CYCLOSPORINE
ii. SIROLIMUS
iii. TACROLIMUS
iv. EVAROLIMUS
2) ANTIPROLIFERATIVE/ANTIMETABOLIC AGENTS,
i. MYCOPHENOLATE
ii. AZATHIOPRINE
3) BIOLOGICS (ANTIBODIES)
i. MUROMONAB-CD3 (OKT3)
ii. BASILIXIMAB
iii. DACLIZUMAB
iv. ALEMTUZUMAB
v. ANTITHYMOCYTE GLOBULIN
4)GLUCOCORTICOIDS,
clinical pharmacokinetics and therapeutic drug monitoring ----- fifth pharm D notes
The Provision Of Written And/Or Verbal Information About Drugs And Drug Therapy In Response To A Request From Other Healthcare Providing Organizations, Committees, Patients, And Public Community
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Role of the pharmacist in medication safety.Subash321
Role of the pharmacist in medication safety. In this you know about the medication safety, medication error & how to prevent medication error. And the role of the pharmacists in medication safety.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Therapeutic Drug Monitoring (TDM) | Criteria and Indications of TDM | Why TDM...Shaikh Abusufyan
For all III YouTube Live Video lecture series of this topic click:
https://youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
- For More Such Learning You Can Subscribe to My YouTube Channel.
https://www.youtube.com/channel/UC5o-WkzmDJaF7udyAP2jtgw/featured?sub_confirmation=1
Facebook Page: https://www.facebook.com/asacademylearningforever
Website Blog: https://itasacademy.blogspot.com/
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
The Provision Of Written And/Or Verbal Information About Drugs And Drug Therapy In Response To A Request From Other Healthcare Providing Organizations, Committees, Patients, And Public Community
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Role of the pharmacist in medication safety.Subash321
Role of the pharmacist in medication safety. In this you know about the medication safety, medication error & how to prevent medication error. And the role of the pharmacists in medication safety.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
Therapeutic Drug Monitoring (TDM) | Criteria and Indications of TDM | Why TDM...Shaikh Abusufyan
For all III YouTube Live Video lecture series of this topic click:
https://youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
- For More Such Learning You Can Subscribe to My YouTube Channel.
https://www.youtube.com/channel/UC5o-WkzmDJaF7udyAP2jtgw/featured?sub_confirmation=1
Facebook Page: https://www.facebook.com/asacademylearningforever
Website Blog: https://itasacademy.blogspot.com/
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
This presentation is aimed at providing information on automation in the GLP practices in the pharmaceutical industry.
-Standard Operating Procedures.
-Documentation in GALP.
-Logs and Related Forms.
Good Manufacturing Practice (GMP) 2day course Jo Havemann
The following topics were presented to the participants through lectures, group discussions and exercises during 16 hours:
- Core values and guidelines of Good Laboratory Practice (GLP)
- Factors that might lead to questionable research & manufacturing practices and their impact
- GMP compliance, national & international regulations, guidelines and authorities
- Quality Management and Assessment
- Digital GMP Solutions
Receptor types, mechanism, receptor pharmacology, drug receptor interactions, theories of receptor pharmacology, spare receptors and new concepts like biased agonism
Therapeutic Drug Monitoring (TDM)
Discuss the logic for therapeutic drug monitoring, which refer to as (TDM)
List various classes of drugs that require TDM
General description of this therapeutic drag TD
Discuss the proper sample timing and method for TDM
And Discuss analytical methods available for TDM
List various drugs that not require TDM
Steady state
Therapeutic Drug Groups
Digoxin, quinidine, procainamide, disopyramide.
- Aminoglycosides (amikacin, gentamicin, kanamycin, tobramycin) - vancomycin
leucovorin rescue ?
First-pass metabolism
HPLC methods
Laboratory offering TDM for Immunosuppressive Drugs needs to understands their pharmacodynamics & clinical applications so that the results value add in the patient care
This extensive presentation contains information about process of drug discovery, clinical trails, pharmacovigilance, approval of the drug, drug discovery timeline, costs involved in developing a new drug, pharmacokinetics, receptors & ligands, pharmacokinetic parameters like plasma concentration, half life, volume of distribution, clearance, steady state plasma concentration, etc.
Clinical Pharmacokinetics of Voriconazole Omar Negm
The presentation discusses the clinical pharmacokinetics of Voriconazole as anti fungal drug, in addition, it illustrates the drug pharmacology, side effects, indications, dose adjustment in special populations, and therapeutic drug monitoring.
clinical pharmacokinetics half-life first-order elimination zero order elimination steady-state conc applied aspect of steady-state applied aspect of half-life advantage and disadvantage
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
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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.
Follow us on: Pinterest
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
4. Oral vs IV
Oral Administration
• Follows ADME
• Hepatic first pass metabolism
• Place of absorption depends
on pK of the drug
• (Effect of enteric coat – acid
liable drugs destroyed in
stomach, to prevent it a coat is
applied)
IV administration
• All available for biological
Activity
• No hepatic first pass effect
• All drug [] available for
action
• Free form active
• Bound form- inactive
5. Composition of body water and its
effects of drug distribution
Hydrophobic drugs – moves to ECF as
well ICF (Vd high)
Better for intracellular organisms
Hydrophillic drugs- Ionized and remain
only within ISF and Plasma (Vd less)
Better for infections within Interstitial
fluid – Majority of infection
6. When the pK of drug similar to pH of the environment it remain unionized
Absorption or Transfer across cells is greater
Unionized form↓↓
gradually
Unionized form ↑↑↑
Unionized form↓↓
gradually
7. oral and IV
administration of
a single dose Clearence
Determination of the bioavailability of a drug. (AUC = area
under curve.)
8. Drug concentrations in serum after a
single injection of drug at time = 0.
Assume that the drug distributes but is
not eliminated.
Ex- Renally eliminated drug in renal
failure
Drug concentrations in serum after a
single injection of drug at time = 0.
Assume that the drug distributes and is
subsequently eliminated.
10. Rate of attainment of steady-state concentration of a drug in the plasma during
an continuous infusion – Elimination of drug after stoppage of infusion
After 3 to 5 t ½,
not detectable in
plasma
11. At steady state, input (rate of infusion) equals
output (rate of elimination).
If Vd – is large a
loading dose is
necessary
If Vd – small, a no
loading dose necessary
12. Effect of infusion rate on the steady-state concentration of drug in the plasma. (Ro
= rate of infusion of a drug.)
14. Antimicrobial activity
•
They are not contact poisons
•
For action
–
–
–
–
–
–
•
•
should reach the target site
Should achieve optimal concentration
come into contact with micro organisms
Bind to target and remain there for sufficient time to exert the effect
Should resist inactivity or Clearance
Should not be inactivated at target site
Above are Pharmacodyamic properties of antibiotics
Bacterial destruction is described in following manner
– time-dependence,
– concentration-dependence, and
– persistent effects.
•
If the rate of killing ᾀ exposure time (time-dependent),
•
Rate of killing ᾀ (concentration-dependent).
•
•
Persistent effects - Post-Antibiotic Effect (PAE) and PALE
.
15. Pharmacodynamic Predictors of
antibiotic efficacy
• The target we plan to achieve at the site of infection
• Under activity →Treatment Failure, Resistance
Development
• Over activity at the site- Toxicity and ↑ cost
• Three predictors
– % T /MIC value
– AUC0 to 24hr / MIC
– Cmax/MIC
16.
17.
18. What factor is common to all
predictors?
• When MIC is high, Efficacy ↓
• When MIC is low, Efficacy ↑
19. Target parameter for each drug,
organisms are different…..
Drug type
Penicillins
PD
parameter
% T / MIC
Cephalosporins
Fluoroquinolones AUC0 to 24hr /
Glycopeptides
MIC
Glycylcyclins
Aminoglycosides Cmax/MIC
Target
[ ] least 40% time of day
should be above the MIC
[ ] at least 50% time of day
should be above the MIC
ratio should be > 200
Ration should be > 20
22. target attainment profiles of 3.375 g
of piperacillin-tazobactam every 6 or
4 h as a 0.5-h infusion
for hospitalized patients
target attainment profiles of 3.375 g of
piperacillin-tazobactam every 6 or 4 h as a
0.5-h infusion
for healthy subjects.
23. Probability of target attainment
PD parameter for
pip-tazo
Target
40% time of day
At least 90% of the target
should be above the need to be attained with
MIC
the dose
Probability of target attainment
1. When MIC is < 4, the target is attained
with 6hrly as well as 4 hrly dose
2. When MIC < 8, Target is achieved 100%
with 4 hrly , regimen while only 90%
achieved with 6hrly regime
3. When MIC is 16, 90% of target achieved
with 4hrly regime, 70% is achieved with
6hrly regime
4. When MIC is 32, target is achieved only
20% time with 6hrly regime, while only
60% of the target is achieved with 4hrly
regime
24. What did you learn?
• Activity of antibiotics in human host depend on many
factors
• PK parameters decide antibiotic [] reaching the site of
infection
• PD parameters decide microbial killing at target site
• At least 90% of the target should be attained at the
site of infection
• Human body physiology influence the outcome
• MIC of the organism, is the only a in-vitro, parameter
which decide on outcome
25. Introduction
• Antibiotic-induced adverse events leads to
– host injury
– diagnostic confusion
– excessive medical costs.
• a "spin-off" of antibiotic-induced adverse
events is the emergence and dissemination of
drug-resistant organisms.
26. Antibiotic adverse effects occur by
three mechanisms
• Exaggerated response (to known pharmacological
effects)
• Immunologic reactions to drug or its metabolites,
• Toxic effects of the compound or its metabolites.
• Most adverse events due to
– drug's normal pharmacology
• avoided by→ dosage adjustment.
27. Effects of Antibiotics
Desired Effects
Cure
Undesired Effects
Toxicity and side effects
Clinical Cure- Symptomatic
Microbiological Cure
Dose related -Predictable
Dose unrelated -unpredictable
28. Classification of Adverse drug
reactions
• According to
– Cause
– Seriousness and severity
– Overall Drug Risk
– Location
29. Classification of Adverse drug reactions
Cause
Seriousness and
severity (FDA)
Overall Drug Risk
Location of the
adverse effect
Type A:
↑ pharmacologic effects –
dose dependent and predictable
Intolerance
Side Effects
Death
Red (high risk)
Local
Type B: Bizarre effects ---or
idiosyncratic - dose independent
and unpredictable
Life-threatening
Orange (elevated
risk)
Systemic
Type C: Chronic effects
Hospitalization
Yellow (guarded
risk)
Type D: Delayed effects
Disability
Blue (general risk)
Type D: Delayed effects
Congenital anomaly
Green (low risk)
Type E: End-of-treatment effects
30. Rare events
• Some adverse reactions occur rarely
• Unique to certain drugs only.
– Chloramphenicol-induced aplastic anemia
– Sulfonamide-induced TEN or Stevens-Johnson
syndrome
31. Factors affecting side effects or ADR
• Genetic factors
• Integrity of drug elimination mechanisms(renal
and hepatic dysfunction)
• Concomitant medical disorders– in HIV positives infected patients
• oxacillin-induced hepatitis a
• cutaneous reactions with trimethoprim-sulfamethoxazole or
aminopenicillins
32. Monitoring for toxicity of antibiotics in
patients
• Direct method – Check for drug levels
• Indirect Method
– Clinical features suggestive of side effects
– Laboratory indicators of end organ damage(in
likely organ damage)
33. Toxicity and adverse events are common to any drugEven with the drugs which tagged safe,
• Penicillin group → good safety profiles, well tolerated.
• Can cause
– wide range of hypersensitivity reactions, including fever, rash (maculopapular and
urticarial),
– anaphylaxis,
– exfoliative dermatitis, erythema multiforme, serum sickness, and hemolytic anemia.[
• IV high doses in renal impairment central nervous system toxicity,
– myoclonic jerks,
– seizures or
– coma.
• Some members cause particular side effects
– ampicillin, amoxicillin, and amoxicillin/clavulanate with diarrhea and C. difficile
colitis,
– In CLL pts → nafcillin-induced neutropenia;
• Carbenicillin and ticarcillin (with/without clavulanic acid) hypokalemia,
– platelet dysfunction, and
– fluid overload;
• Methicillin and ampicillin
– interstitial nephritis.[6
35. Most drugs are well
tolerated
Some are not tolerated well Some types of drugs, Ae3s
may be common, but under
special circumstances
Wide therapeutic Index
Narrow therapeutic Index
β-lactams,
macrolides and
quinolones
Monitoring often not
required
Aminoglycosides
vancomycin,
Monitoring of levels
indicated in order to
prevent toxicities
Intermediate
Teicoplanin,
Flucloxacillin and
the antifungal agents
itraconazole,
flucytosine and
fluconazole
Monitoring may required in
special circumstances exrenal, hepatic failures
36. Why monitor only aminoglycosides
(and Vancomycin?)
• Low therapeutic index.
• Bactericidal efficacy ᾀ peak concentrations
• Toxicity is related to total drug exposure
• Nephrotoxicity (usually reversible) and ototoxicity
(often irreversible)
• The desired plasma concentration-time profile for
aminoglycosides differs to most other drugs.
37. Patho-physiology of Aminoglycoside
Nephrotoxicity
• AGs → obligate nephrotoxins
• Long term treatment→ invariable renal damage
• AGs- enter into PCT cells and Inhibit protein (Next Slide)
• It accumulates within lysosomes phospholipd complexLead to rupture and cell death
• Is a tubulopathy
– tubular cell damage and
– tubular dysfunction
38. Aminoglycoside Toxicity
• AGs accumulate in the kidney,
– Around 40%of the total
– About 85% in renal cortex
• Drug entry from the lumen through binding to brush
border receptor – megalin
• Animals made Megalin –Deficient – No renal toxicity
• Toxicity varies depending on type of AGs – Gent and
Netil > Tobra and AK
• This accumulation follows satuarable kinetics – when
exceed the capacity no further entry (15 μg/ml) –Basis
of once daily ↓ toxicity
39. Pathophysiology cont…..
• Results
– ↑ in Tubular Glomerular feedback (TGF),
– ↓in GFR,
– Activation of RAAM and
– contraction of renal vessels and mesangeal cells
• Lead to Acute Renal damage (Nephrotoxicity)
41. Influx of AG into proximal tubule
• Mediated by a carrier- which follow Zero order kinetics
(Saturable)
• Intake – dose independent(↑*AG+ in lumen does not
increase uptake in to PCT cells
• Basis of once daily dose
• Demonstrated in animal studies- that renal toxicity
occur >>> with divided doses than daily single large
doses
42. Nephrotoxicity ↑ when concurrent
administration of
• Drugs such as
– loop diuretics,
– cyclosporin,
– cisplatin, and
– vancomycin, (not teicoplanin)
• And when ↓ Renal blood flow
– Dehydration
– Diarrhea etc
– Renal failure (need to monitor)
43. Otto toxicity mechanism and
manifestations
• Ototoxicity
– auditory (cochlear) and
– vestibular toxicity,
• Damage to sensory hair cells (cochlea) and cells in labyrinth
• Mechanism of cell damage, similar (start with cloudy swelling and necrosis)
• Bot may not occur concurrently
• Manifests as
–
–
–
–
Balance difficulty
Bouncing, unsteady vision
tinnitus
Difficulty multi-tasking, particularly when standing
• Irreversible
44. Ototoxicity
• Aminoglycosides penetrate into the endolymph, vestibular and
cochlear tissue
• Damages sensory hairy cells in cochlear tissue by entering to
endolymph
– AG enters to the endolymph slowly,
– Leaves even slower
• Risk factors for oto-toxicity
– Prolonged therapy for 10 days or more (safe if discontinue in 5 to 6 days)
– Preexisting renal impairment(Dose adjustment)
– Prior treatment with AGs.
• Damage - manifest as auditory (cochlear) and vestibular toxicity,
• Can appear separately (Never together)Oto-toxicity is rare if
treatment restricted to 5 to 6 days
• Rare herditory condition –Ototoxicity within few doses (avoid if
family history of similar event)
46. Effect of P-kinetics in AG toxicity
• V and CL change plasma concentration of
drugs.
• ↑V is reported with (high doses required to
achieve desired effects)
– Burns
– Edema
• ↓ Clearance with dehydration – ↑ toxicity
Change with fluid replacement and resolution
of the infection.
47. Measurement of aminoglycosides (for
BD or TDS doses
• Desired concentration-time profile is
– a high peak concentration (for efficacy)
– low trough concentration (to prevent accumulation).
• Traditionally tested for
– Peak [] – for Efficacy
– Trough []- for accumulation
• With once-daily dosing- Peak trough testing need to
reconsider
48. Gentamicin levels
Therapeutic BD or TDS
Synergistic for IE
Single dose
Recommended
dose
Therapeutic with 1.7
mg/kg per dose divided
1mg/kg BD or TDS
BSAC- BD dose
SANFORD- TDS dose
5 to 7 mg/kg IV
Target Peak
Measuring at
15 to 30 minutes after
dose , usually measured 3
to 5 doses after initiation
Same
No peak
Target Trough
dose
Immediately before a dose Same
No trough – Measure
12 to 18 hrs after
(usually after first
dose)
Target Peak
6–10 mg l−
3 to 5 mg l−1
According to the value
decide next dose by
normogram
Target Trough
≤ 2 mg l−
1 to 3 mg l−1
Toxicity suspect
if,
≥2
≥2
If target higher,
Omit or delay next dose
[ ]24hrs of
0.5–2
mg l−1 reflects
accumulation, usual [
]24hrs undetectable
49. Q’s
• A pt with normal renal functions was put on c.pen and
gentamicin.
• How long would you plan for treatment,
• If patient had three blood cultures of a S.viridans sensitive
and lower level of MIC
• What is the dose you select
• C.pen
• Gent
• When are planning to asses Gent level, Describe the basis?
• If levels are as follows, what would be your intervention
Peak
Trough
4
<.5
8
3
5
3
50. Once-daily dosing
• At 24hrs, levels are un-recordable with normal
renal functions
• []24hrs of 0.5–2 mg l−1 → accumulation or over
dose
• Concept of a trough concentration is not relevant
to once-daily dosing.
• 12 to 18 hrs dosage
51. Collection of specimens for AG assay
• Do not draw from iv line used to give AG
• Take one blood sample (ideally 5 to 10mL)
between 6 and 14 hours after the start of first
infusion in a plain tube (clotted blood)
• Document
– Patient details and
– EXACT time and date infusion was set up and
EXACT time and date sample was taken in
52. Selecting dose interval
Falls in area designated 24
hours, 36 hours or 48 hours,
dosing interval is 24, 36 or 48
hourly respectively
If level falls on a line
between dosing
intervals, choose
longer interval.
If level is above 48
hour line then STOP
the treatment. If
gentamicin is to be
continued, take daily
levels, but do not give
any more gentamicin
until level falls below
2mg/L
54. Repeat monitoring
• Check U & Es and creatinine daily to
monitor renal function.
• If serum creatinine is rising significantly
(≥20%) and time is within 6-14 hours of
infusion, measure level ASAP, otherwise
contact Microbiologist for advice.
55. Extended interval (once daily)
gentamicin / tobramycin
• Take a pre-dose level 18-24 hours after 1st
dose.
• Levels should be <1mg/l
• Normal renal function - (creatinine clearance
>60ml/min) give next dose when due.
• Check pre-dose levels every 3-5 days.
• Impaired renal function – monitor levels daily
61. Summary
Initial Dose
Hartford Extended Interval
dosing
7mg/kg, with dose frequency altering
according to nomogram based
upon gentamicin serum
concentration
Infusion in 50-100ml Sodium
Administration
Chloride 0.9% over 30
minutes
Blood levels
One sample taken 6-14 hours
taken
after the infusion
commences
Pharmacokinetic Dosing
Adults: 2mg/kg loading dose, then refer to pharmacy
or microbiology for maintenance dose
Synergistic dosing for endocarditis
1mg/kg TDS (or less frequently)
Paediatrics: 2.5mg/kg TDS
Adjust dose and frequency based upon gentamicin
serum concentration
Bolus over at least 3 minutes
Just before the dose (pre-dose sample) and 1
hour (post-dose sample)
Standard:
Pre-dose <2mg/L,
Post-dose 6-10mg/L
Target
No target - use the nomogram to
concentrations
identify the patient's required Synergistic dosing for endocarditis:
dosing interval.
Pre-dose <1mg/L,
Post-dose 3-5mg/L
62. Rules for Aminoglycoside Treatment
• Usually Aminoglycoside should not prescribe for
longer than 7 days (Practice at TH Kandy <3d)
– Exception – Infective endocarditis, or by inhalation for
cystic fibrosis.
• Monitoring need to be individualized
– If patient is unstable - more often
– if stable- Less often
• With once-daily dosing it is logical to follow the
same rules until new information allows these
rules to be re-formulated.
63. Why monitor vancomycin?
• It too has low Therapeutic Index,
• Can cause
– nephrotoxicity
– ototoxicity.
• Toxicity of Vancomycin differ to that of Aminoglycoside –
– Peak levels – Not necessary –
– acceptable PD is %T>MIC
• toxicity – related to total exposures than peak
– >4g/day toxicity likely
• New formulae – No impurities – Less toxicity
64. PK of Vancomycin
• The PK vancomycin relatively simple,
– with low protein binding,
– 100% renally elimination,
– No metabolism
– no pharmacogenetic problems.
• V is around 0.4 l kg−1 and the CL approximates that
of glomerular filtration rate.
• t1/2 is approximately 6 h in patients with normal
renal function ..
65. Monitoring Guide of Vanco
• No peak is necessary
• Trough need to be above the MIC of the
targeting organism
• VancomycinMIC is approximately 1.5 mg l−1 for
many susceptible organisms.
66. Question on Vancomycin dosing>
• Assume 50% protein binding with MIC of the concerned pathogen
around, 1.5mg/L,
– Calculate the minimum required trough for vacomycin in a person with
eGFR of >90.
• If you get a report of [Vanc]trough of 20mg/L,
– What should you do? Explain what should your advice to the attending
physician?
• What is your advice to a person who has a eGFR of 50, receiving
vancomycin?
– If, serum creatinine was 2.9mmol/l, what is your advice? Calculate the
dose?
– If, serum creatinine is 450mg/l, what is your advice?
• What is the level you should achieve for Rx of MRSA Bacteremia?
67. Question
• In severe life threatening situation would you
recommend same trough? Or would you
sought to a higher trough?
68. Answer
• Total trough concentration necessary should be
at least 3 mg l−1
• Average of 5 to 10 mg l−1 would be enough (for
mild to moderate infections)
• In severe infection – Can have at a trough of 15 to
20 mg/l
• MRSA Bacteremia – a trough level of 15 to 20
mg/dl need to be acheived
69. Individualization of Vancomycin Dose - Normogram
Degree
of renal
failure
Initial dose and
maintainance
Mild to
Moderat
e
Initial dose <15mg/kg
Severe
Give 250 to 1000mg
several days apart
than giving frequent
small doses
Anuria
15mg/lkg until
therapeutic []
achieved
Maintenance dose is
1.9mg/kg/day, Better
to give higher dose
over several days
apart
70. Vancomycin Rules,
• Take pre-dose levels prior to 3rd dose.
– Give the 3rd dose as prescribed and amend 4th dose according to
levels
• Pre-dose level 5-15mg/l (in severe infection levels up to
20mg/l may be required)
• Normal renal function - (creatinine clearance >60ml/min)
check levels every 3-5 days.
• Impaired renal function – monitor levels daily
• For severe infections higher levels may be advised by
microbiology.
71. Monitoring of Teicoplanin
• Monitoring is required for impaired renal function / to
ensure therapeutic plasma levels.
• Ensure that usual BD loading dose is given
– Take pre-dose level on day 4 to 7.
– Severe infection –
• pre-dose level 20-60mg/l
– Mild – moderate infection –
• pre-dose level 10-60mg/l
• Regular monitoring may be required in renal
impairment
72. Monitoring of Amikacin – (multiple
daily dosing)
• Pre-dose level 5-10mg/l
• 1 hour peak 20-25mg/l
• When using the normogram, value to
calculate next dose should be taken as
follows:[Amikacin] 6 to 14hrs level/2;
76. Questions - one
• 32 year mother of one child, presented to
obstetric casualty in the night with high fever,
headache, vomiting with two episodes of LOC.
• On presentation→
• Febrile with 102.5F
• HR -110/min, BP-90/60
• No rash
• PMH- on a VP shunt- inserted 3 years back
77. • On-call obstetrician rings you in the night.
What steps would you take?
• What is the tentative diagnosis?
• How do you manage the acute episode?
78. • The following day on-call neurosurgeon sees the
patient.
• Take the abdominal end out and allows it to drain
freely, Headache settles.
• Fever remains. Pt becomes conscious and claims
that she feels fine compared to time of
admission.
– What tests would you request?
– What microbiological tests would you recommend?
79. • CSF culture and gram stain? Obtained through
the distal end of the VP shunt.
– Gram Positive cells seen with diplo arrangement. No
pus cells.
– Culture – Streptococcus pneumoniae isolated
–
–
–
–
WBC-17,000 with 87% Neutrophils.
Platelet count -170,000/ml
CRP ->96
Blood culture – Negative with single
80. • What information would you like to have?
• Describe how you handle the case from time
of first contact?
81. At the time of admission
Vancomycin and
Meropenem
24hrs
Culture positive with
pneumococci,
Continued
24hrs
Zone of oxacillin
>20 mm
MIC pen
0.01 mg/l
Pen along
Issue – Penicillin sensitive pneumococcus isolate→ is it a contaminant or not,
How to solve the problem?
82. Case 02
• 73yr old doctors mother admitted to
neurologist with sudden onset of LOC. CT scan
reveal a SAH.
• Managed at Neurology unit.
– Pt has no fever, Pulse-90.min
– WBC 9500/ 78% N
– ESR -60
– CRP 144
83. • Blood culture obtained at day 6 gave a
positivity with gram positive cocci in two
occassions, Identified as enterococci
– CT Scan - SAH
– Pt gives a allergic history for amoxycillin
85. Treatment
– Started IV Vancomycin,
• Comment on the dose?
• If the patient is severely ill, would you recommend a
loading dose? Explain?
• After 13th day of treatment,
• Vancomycin levels as follows
– Pre-dose – 22mg/l, 30 min after 1 hr infusion[]- 55mg/l,
• If, laboratory policy is performing only single level on a
patient, what level (pre or post)would you request?
86. Question 3
• A 24 year old patient admitted to cardiology
unit with a history of fever for 10 days. He had
a history of taking treatment for infective
endocarditis from a DGH in North Central
Province.
• No blood culture results were available
• Results of FBC and other tests is shown below
Day 1
Day 1 Eve
Day 3
Day 4
Total
11,000
14,000
12,000
13,500
N%
76%
80%
75%
75%
L%
19%
16%
20%
20%
E%
5%
3%
3%
5%
Platelet
460,000
530,000
297,000
210,000
87. Qs
• His CRP was 196, ESR was 100mm/hr
•
•
•
•
•
Urine culture – NAD
CXR- NAD
SAT- O -1/160, A H and Typi H- 1/40
Echo – Oscillating Mass on Mitral Valve
Serum Ferritin – 9,000
88. Qs
• Patient was started on IV C.penicillin and IV
Gentamicin- contimued it for 4 days,
• No responseter 4 days. and patient left against
medical advice to TH Kandy,
• HE presented to private hospital and admitted
to TH Kandy with a letter to microbiologist.
89. Qs
• The night on-call doctor, contacts the
microbiologist,
• If you are the microbiologist, what questions
would you ask from the doctor calling you?
• What are you going to start? Give reasons?
90. Qs
• Patient was started IV cetriaxone, IV gentamicin on
that night.
• The following day the patient was sitting
comfortably on bed and reading the “Lankadeepa”
news paper.
– The following day patient felt ok, appetite ok
• Explain how do you ask from the patient about his
symptomatic improvement?
91. Qs
• Do you agree with the diagnosis of IE in this
patient?
• If not, why?
• If yes, why?
• What investigations would you like?
92. • Pt was OK for 3 days, and develop very high
fever, patients condition was worsening,
• Counts as follows –
Day 8
Day 9
WBC
5,000
3100
N
60%
62%
L
38%
30%
Platelets
97,000
45,000
S.creatinen
1.4
1.4
CRP
-
197
93. • Now, what should you do?
• Identify the problems/issues?
• How would you mange the patient?
• Started IV Vancomycin and Gentamicin
94. • Explain what has gone wrong?
• Now patient is really sick. Serum Creatinine is
going up. Platelet count is going down. WBC is
coming further down.
• What should you do?
95. • Medical Referral done, Heamatologist and
nephrologists referral done.
• A diagnosis of Heamophagocytic syndrom
arrived? Pt was admitted to the MICU.
• Early mane, cardiologist called and suggest
whether changing to linazolid would be of any
use. Microbiologist OKS.
96. In spite of all efforts,
• Patient dies.
• What possibly has gone wrong in this case
scenario?
• If is you, how would you manage the patient.
97. • Select your treatment option?
• Why do you use
– 1. AK
– 2. CAZ
• IF you are using Amikacin, what should you do
prior to start it?
98. • 76 yr old female 5 days after CABG in ICU
develop Gram Negative Septicemia,
• AST as follows
• CAZ – S
CN -R
• CTX- R
Netil -R
• CPM- R
AK -S
• Cipro –R
AZT -R
• Levo – S
Pip-TZ- R
• Mero –R
• Imp -R
99. • What dosage /frequency do you use?
– 7mg/12hrly
– 15 mg daily
• If, 6 hrs after first dose, AK levels were found
to be 6 mg/l, when do you give the next dose?
• If, you fail to collect the first dose, at
6hrs, when can you collect blood for AK
levels?
100. • Then what would be the AK level?
• In once daily therapy, do you arrange for a pre
dose []? Explain why?
• If after 8 hours, [AK] = 6ng/l, when do you
administer the next dose?
101.
102. If levels are not available
For Empirical therapy → Gentamicin maximum of 48 hr for all
The initial dose → based on age and weight,
Interval for subsequent doses -depends on renal functions
For a patient with normal renal function MAXIMUM OF three
doses
0, 24 and 48 hours.
monitoring of plasma concentrations is not required as it not
exceeding 3 doses
Subsequent doses for treatment should guided by AST
• Susceptibility results should be used to guide ongoing therapy.
• If susceptibility results are not available by 72 hours and
empirical intravenous therapy is still required, the gentamicin
containing regimen should be ceased and an alternativeregimen
used.
103. Remember
• Drug level monitoring is a compulsory
requirement when potentially toxic drugs.
• It is done to monitor for side effects as well as
find out whether adequate concentration has
achieved at the site for optimum activity.
• It is a way of “optimizing antibiotic therapy”