Pharmacokinetics in the critically ill. Intensive Care Training Program Radboud University Medical Centre Nijmegen

Size: px
Start display at page:

Download "Pharmacokinetics in the critically ill. Intensive Care Training Program Radboud University Medical Centre Nijmegen"

Transcription

1 Pharmacokinetics in the critically ill Intensive Care Training Program Radboud University Medical Centre Nijmegen

2 In general... Critically ill patients are at higher risk for ADE s and more severe ADE s These ADE s lead to increased LOS and higher costs Inclusion of a pharmacist reduces the incidence of preventable ADE s

3 113 ICU s 27 countries 1328 patients BMJ 2009;338:b814 Risk increases with: Number of organ failures, number of medications, larger ICU units, higher P/N ratio, occupancy rate

4 IATROREF Study 14 medical errors 70 ICU s 1 week 1369 patients Suction circuit failure during intubation Laryngoscope dysfunction Medication administered to wrong patient Error administering anticoagulants Error administering vasoactive drugs Error administering insulin Accidental removal CVC Accidental extubation Failure to place in semirecumbent position Overinflation of ET balloon Pneumothorax related to CVC insertion Fall Delay in surgical treatment 1192 reported ME s 26.8% of patients at least 1 ME Most frequent: insulin 9.3% of patients adverse event 2 or > AE OR for death 3.09 Garrouste-Orgeas M. Am J Respir Crit Care Med 2010;181:

5 Definition PK = movement of a drug through the body (absorption, distribution, metabolism and elimination) PD = pharmacologic response resulting from the drug once it reaches its receptor

6 What could go wrong?

7 Absorption Rate and extent a medication moves into the circulatory system Bioavailability is the fraction of the administered dose reaching the systemic circulation (often AUC) Bioavailability after enteral administration depends on amount of the drug absorbed and the first-pass effect

8 Single enteral administration Time to peak concentration Drug absorption dependent on Particle size Gastric ph Solubility Regional blood flow Lipophilicity Surface area Ionization Motility Dissociation rate constant Vasopressor use Altered gastric emptying Feeding tube AUC

9 Vasopressor use Shock and vasopressors alter splanchnic perfusion and may alter drug absorption Insufficient data available - use of i.v. route recommended

10 Paracetamol absorption test AUC Tarling MM. Intensive Care med 1997;23:

11 Vasopressor use and SC absorption Dörffler-Melly J. Lancet;359:

12 Delayed gastric emptying Incidence 40-60% based on C-13-octanoic acid breath test Slow time to peak concentration 13C octanoic acid, a medium chain fatty acid which is rapidly absorbed in the duodenum and metabolised in the liver. Following oxidation, the resulting 13CO2 is excreted into breath at a level which can easily be detected and measured by isotope ratio mass spectrometry.

13 Feeding tube and nutrient interactions Drugs may adhere to plastic - always flush with water Enteral feeding increases ph and may directly bind drugs - phenytoin and ciprofloxacin Withhold enteral feeding 1-2 hours before and after administration, increase dose or give intravenously

14 Distribution Vd describes the relation between drug dose and resultant serum concentration that volume of plasma in which the total amount of drug in the body would be required to be dissolved in order to reflect the drug concentration attained in plasma For the ICU Fluid resuscitation - plasma protein binding - tissue perfusion

15 Fluid resuscitation Increases plasma and interstitial water and increases Vd of hydrophylic drugs such as aminoglycosides and β-lactams Could result in therapeutic failures and development of antibiotic resistance Solution: therapeutic drug monitoring, higher loading doses

16 Gentamycin in septic patients 2nd day 7th day p-value Peak concentration (μg/ ml) Trough concentration (μg/ ml) 4.9 ± ± 0.0 < ± ± 0.3 ns Vd (l/kg) 0.43 ± ± 0.17 < T1/2 (h) 4.3 ± ± 0.71 < 0.05 Clearance (l/kg/h) 0.07 ± 0, ± 0.01 ns TDR (mg/kg/h) 5.14 ± ± 1.67 < Triginer C. Intensive Care Med 1990;16:

17 Plasma protein binding Principal binding proteins: albumin (acidic drugs like phenytoin) and α-1 acid glycoprotein (basic drugs like lidocaine) Albumin usually decreases and α-1 acid glycoprotein usually increases during critical illness Drug effects are mediated by free or unbound fraction With hypoalbumenemia total drug concentration but unbound

18 Anti-epileptics and hypoalbumenemia Six- to sevenfold increase in free valproate concentration Anderson GD. Br J Clin Pharmac 1994;37:

19 Midazolam Three-fold increase in Vd with delayed midazolam clearance Hypoalbumenemia increases free midazolam fraction which is lipophilic and distributes more freely in adipose tissue Solution: dose reduction or change to another drug less albumin bound

20 Morphine Critical illness increases AAG and decreases circulating free drug levels Vd decreases with> 40% and clearance decreases > 65%. This prolongs the effect of morphine

21 Tissue perfusion Decreased tissue perfusion may result in impaired delivery of hydrophylic drugs to non-central organs and peripheral tissues e.g. piperacillin in skelet muscle and subcutaneous tissue in patients with septic shock

22 Joukhadar C. Crit Care Med 2001;29:

23 Metabolism GI tract, kidney liver, lung and brain During critical illness, hepatic enzyme activity, protein concentration and liver blood flow may change Hepatic clearance = volume of blood completely cleared of drug by liver per unit time = hepatic blood flow hepatic extraction ratio

24 Hepatic clearance Extraction ratio = fraction of drug removed from blood after one pass through liver: > 0.7 high, intermediate and < 0.3 low For medications with high ER (midazolam and fentanyl) hepatic clearance depends on liver blood flow and not on liver function Vice versa for low ER (phenytoin, warfarin)

25 Hepatic metabolism Phase 1 - oxidation, reduction, hydrolysis make active or inactive metabolite: often CYP 450 (many with genetic polymorphisms Phase 2 - glucoronidation, sulfation, acetylation - rendering the compound water soluble

26 Organization of the liver - Portal acinus explains ischemic hepatitis

27 Oxygenation determines function Zone 3: glycogen synthesis, glycolysis, liponeogenesis, ketogenesis, glutamine formation and general detoxification

28 Hepatic enzyme activity Severe burns diminish CYP 450 activity Renal dysfunction decrease phase 1 & 2 activity and also the uptake of drugs and biliary excretion Cirrhosis and cholestasis decrease CYP 450 activity Inflammation decreases activity of several enzymes and increases it in others

29 Hepatic enzyme activity Therapeutic hypothermia decreases CYP 450 activity (midazolam, fentanyl, remifentanyl, phenobarbital, phenytoin, vecuronium) Lipid solubility, protein binding, hepatic blood flow and drug potency may also be altered

30 Protein binding Decreased protein binding clinically relevant for drugs with high ER such as diltiazem, fentanyl, haloperidol, lidocaine, methylprednisolone, nicardipine, propofol Less relevant for diazepam, ceftriaxone, phenytoin, warfarin and valproic acid

31 Hepatic blood flow NE, E and phenylephrine decrease hepatic blood flow

32 Elimination Renal drug clearance proportional to GFR Dose reduction often necessary but loading dose often increased due to larger Vd However - diseases with increased RBF may increase GFR and lead to lower drug levels

33 Especially for B-lactams, carbapenems and glycopeptides

DEPARTMENT OF PHARMACOLOGY AND THERAPEUTIC UNIVERSITAS SUMATERA UTARA

DEPARTMENT OF PHARMACOLOGY AND THERAPEUTIC UNIVERSITAS SUMATERA UTARA METABOLISME dr. Yunita Sari Pane DEPARTMENT OF PHARMACOLOGY AND THERAPEUTIC UNIVERSITAS SUMATERA UTARA Pharmacokinetic absorption distribution BIOTRANSFORMATION elimination Intravenous Administration Oral

More information

Determination of bioavailability

Determination of bioavailability Pharmaceutics 2 Bioavailability Bioavailability is the rate and extent to which an administered drug reaches the systemic circulation. For example, if 100 mg of a drug is administered orally and 70 mg

More information

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila

Drug Dosing in Renal Insufficiency. Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila Drug Dosing in Renal Insufficiency Coralie Therese D. Dimacali, MD College of Medicine University of the Philippines Manila Declaration of Conflict of Interest For today s lecture on Drug Dosing in Renal

More information

WHY... 8/21/2013 LEARNING OUTCOMES PHARMACOKINETICS I. A Absorption. D Distribution DEFINITION ADME AND THERAPEUIC ACTION

WHY... 8/21/2013 LEARNING OUTCOMES PHARMACOKINETICS I. A Absorption. D Distribution DEFINITION ADME AND THERAPEUIC ACTION PHARMACOKINETICS I Absorption & Distribution LEARNING OUTCOMES By the end of the lecture students will be able to.. Dr Ruwan Parakramawansha MBBS, MD, MRCP(UK),MRCPE, DMT(UK) (2013/08/21) Define pharmacokinetics,

More information

Introduction to. Pharmacokinetics. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D

Introduction to. Pharmacokinetics. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D Introduction to 1 Pharmacokinetics University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D 2 Learning objectives Understand compartment models and how they effects

More information

ICU Volume 11 - Issue 3 - Autumn Series

ICU Volume 11 - Issue 3 - Autumn Series ICU Volume 11 - Issue 3 - Autumn 2011 - Series Impact of Pharmacokinetics of Antibiotics in ICU Clinical Practice Introduction The efficacy of a drug is mainly dependent on its ability to achieve an effective

More information

Pharmacokinetics/ Pharmacodynamics

Pharmacokinetics/ Pharmacodynamics Pharmacokinetics/ Pharmacodynamics Joseph M. Swanson, Pharm.D., BCPS University of Tennessee College of Pharmacy Memphis, Tennessee Pharmacokinetics/ Pharmacodynamics Joseph M. Swanson, Pharm.D., BCPS

More information

Introduction to. Pharmacokinetics. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D

Introduction to. Pharmacokinetics. University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D Introduction to 1 Pharmacokinetics University of Hawai i Hilo Pre-Nursing Program NURS 203 General Pharmacology Danita Narciso Pharm D 2 Learning objectives Understand compartment models and how they effects

More information

Basic Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics

Basic Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics Basic Biopharmaceutics, Pharmacokinetics, and Pharmacodynamics Learning Outcomes Define biopharmaceutics Describe 4 processes of pharmacokinetics Describe factors that affect medication absorption Describe

More information

Pharmacokinetic parameters: Halflife

Pharmacokinetic parameters: Halflife Pharmacokinetic parameters: Halflife (t 1/2 ) 1. By definition t 1/2 is the time required for the concentration to fall by one half. For drugs with first order kinetics this is a constant. 2. Half-life

More information

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Second Exam Fall 2012 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL /150 pts 1 Question Set I (True or

More information

It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues.

It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues. It the process by which a drug reversibly leaves blood and enter interstitium (extracellular fluid) and/ or cells of tissues. Primarily depends on: 1.Regional blood flow. 2.Capillary permeability. 3.Protein

More information

Pharmacokinetics. Karim Rafaat

Pharmacokinetics. Karim Rafaat Pharmacokinetics Karim Rafaat Pharmacokinetics The therapeutic effect of a drug is determined by the concentration of drug at the receptor site of action. Even though the concentration of drug that reaches

More information

Pharmacokinetics of Drugs. Assistant Prof. Dr. Najlaa Saadi PhD Pharmacology Faculty of Pharmacy University of Philadelphia

Pharmacokinetics of Drugs. Assistant Prof. Dr. Najlaa Saadi PhD Pharmacology Faculty of Pharmacy University of Philadelphia Pharmacokinetics of Drugs Assistant Prof. Dr. Najlaa Saadi PhD Pharmacology Faculty of Pharmacy University of Philadelphia Absorption Is the transfer of a drug from its site of administration to the bloodstream.

More information

Drug dosing in Extremes of Weight

Drug dosing in Extremes of Weight Drug dosing in Extremes of Weight The Plump & Heavy versus The Skinny & Light Maria Minerva P. Calimag, MD, MSc, PhD, DPBA, FPSECP PROFESSOR Departments of Pharmacology, Anesthesiology and Clinical Epidemiology

More information

PHARMACOKINETICS SMALL GROUP I:

PHARMACOKINETICS SMALL GROUP I: PHARMACOKINETICS SMALL GROUP I: Question 1 Absorption of the anti-fungal agent, itraconazole, is dependent on a low gastric ph. Calculate the relative concentrations of a weak acid (with a pka of 5.4)

More information

Drug Distribution. Joseph K. Ritter, Ph.D., Assoc. Prof. Medical Sciences Building, Room

Drug Distribution. Joseph K. Ritter, Ph.D., Assoc. Prof. Medical Sciences Building, Room Drug Distribution Joseph K. Ritter, Ph.D., Assoc. Prof. Medical Sciences Building, Room 531 jkritter@vcu.edu 828-1022 Department of Pharmacology and Toxicology Medical College of Virginia Campus Virginia

More information

Pharmacokinetics of strong opioids. Susan Addie Specialist palliative care pharmacist

Pharmacokinetics of strong opioids. Susan Addie Specialist palliative care pharmacist Pharmacokinetics of strong opioids Susan Addie Specialist palliative care pharmacist What is the difference between pharmacokinetics and pharmacodynamics? Definitions Pharmacokinetics = what the body does

More information

PHA 5127 FINAL EXAM FALL On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA 5127 FINAL EXAM FALL On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 FINAL EXAM FALL 1997 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Question Points 1. /14 pts 2. /10 pts 3. /8 pts 4 /8 pts 5. /12 pts 6. /8 pts

More information

The importance of clearance

The importance of clearance The importance of clearance The calculation of clearance can be especially useful in optimizing dosing of patients The clearance includes both the volume of distribution and the elimination rate The clearance

More information

Basic pharmacokinetics. Frédérique Servin APHP hôpital Bichat Paris, FRANCE

Basic pharmacokinetics. Frédérique Servin APHP hôpital Bichat Paris, FRANCE Basic pharmacokinetics Frédérique Servin APHP hôpital Bichat Paris, FRANCE DOSE CONCENTRATION EFFECT Pharmacokinetics What the body does to the drug Pharmacodynamics What the drug does to the body Transfer

More information

DRUG ELIMINATION II BILIARY EXCRETION MAMMARY, SALIVARY AND PULMONARY EXCRETION

DRUG ELIMINATION II BILIARY EXCRETION MAMMARY, SALIVARY AND PULMONARY EXCRETION DRUG ELIMINATION II BILIARY EXCRETION MAMMARY, SALIVARY AND PULMONARY EXCRETION ROUTE OF DRUG ADMINISTRATION AND EXTRAHEPATIC DRUG METABOLISM The decline in plasma concentration after drug administration

More information

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Second Exam Fall 2011 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL /200 pts 1 Question Set I (True or

More information

Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017

Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017 Introduction to Pharmacokinetics (PK) Anson K. Abraham, Ph.D. Associate Principal Scientist, PPDM- QP2 Merck & Co. Inc., West Point, PA 5- June- 2017 1 Outline Definition & Relevance of Pharmacokinetics

More information

Excretion of Drugs. Prof. Hanan Hagar Pharmacology Unit Medical College

Excretion of Drugs. Prof. Hanan Hagar Pharmacology Unit Medical College Excretion of Drugs Prof. Hanan Hagar Pharmacology Unit Medical College Excretion of Drugs By the end of this lecture, students should be able to! Identify main and minor routes of excretion including renal

More information

Industrial Toxicology

Industrial Toxicology Industrial Toxicology Learning Objectives Know the assumptions of the doseresponse and time-course curves Be able to define and label key points of a curve Know the difference between potency and efficacy

More information

PHARMACOKINETIC & PHARMACODYNAMIC OF ANTIBIOTICS

PHARMACOKINETIC & PHARMACODYNAMIC OF ANTIBIOTICS PHARMACOKINETIC & PHARMACODYNAMIC OF ANTIBIOTICS SITI HIR HURAIZAH MD TAHIR Bpharm (UKM), MSc (Clinical Microbiology) (UoN) CLINICAL PHARMACIST HOSPITAL MELAKA WHY STUDY PHARMACOKINETICS (PK) AND PHARMACODYNAMICS

More information

Lessons from recent studies. João Gonçalves Pereira UCIP DALI

Lessons from recent studies. João Gonçalves Pereira UCIP DALI Lessons from recent studies João Gonçalves Pereira UCIP DALI 1 Patterns of Antimicrobial Activity Concentration C max Aminoglycosides Cmax/MIC>10 Metronidazol Area under the concentration curve Azithromycin

More information

Section 5.2: Pharmacokinetic properties

Section 5.2: Pharmacokinetic properties Section 5.2: Pharmacokinetic properties SmPC training presentation Note: for full information refer to the European Commission s Guideline on summary of product characteristics (SmPC) SmPC Advisory Group

More information

Understand the physiological determinants of extent and rate of absorption

Understand the physiological determinants of extent and rate of absorption Absorption and Half-Life Nick Holford Dept Pharmacology & Clinical Pharmacology University of Auckland, New Zealand Objectives Understand the physiological determinants of extent and rate of absorption

More information

Principles of Drug Action. Intro to Pharmacology: Principles of Courework Drug Action Intro to Pharmacology

Principles of Drug Action. Intro to Pharmacology: Principles of Courework Drug Action Intro to Pharmacology Principles of Drug Action Intro to Pharmacology: Principles of Courework 102.3 Drug Action Intro to Pharmacology Directions Read the PPT and complete R.E.A.D. Assignment. There are videos embedded within

More information

INTRODUCTION TO PHARMACOKINETICS

INTRODUCTION TO PHARMACOKINETICS INTRODUCTION TO PHARMACOKINETICS 1 http://www.biology.iupui.edu/biocourses/biol540/4pipeline2css.html 2 PHARMACOKINETICS 1. ABSORPTION 2. DISTRIBUTION 3. METABOLISM 4. EXCRETION ALL THESE PROCESSES ARE

More information

The general Concepts of Pharmacokinetics

The general Concepts of Pharmacokinetics The general Concepts of Pharmacokinetics What is this jargon? Is it useful? C max, clearance, Vd, half-life, AUC, bioavailability, protein binding F. Van Bambeke, E. Ampe, P.M. Tulkens (Université catholique

More information

OP01 [Mar96] With regards to pethidine s physical properties: A. It has an octanol coefficient of 10 B. It has a pka of 8.4

OP01 [Mar96] With regards to pethidine s physical properties: A. It has an octanol coefficient of 10 B. It has a pka of 8.4 Opioid MCQ OP01 [Mar96] With regards to pethidine s physical properties: A. It has an octanol coefficient of 10 B. It has a pka of 8.4 OP02 [Mar96] Which factor does NOT predispose to bradycardia with

More information

Pharmacokinetics in Drug Development. Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core

Pharmacokinetics in Drug Development. Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core Pharmacokinetics in Drug Development Edward P. Acosta, PharmD Professor & Director Division of Clinical Pharmacology Director, CCC PK/PD Core Finding new drugs: A crap shoot Clinical Development Phase

More information

Assem Al Refaei. Sameer Emeish. Dr.Alia. Hodaifa Ababneh & Abdullah Shurafa

Assem Al Refaei. Sameer Emeish. Dr.Alia. Hodaifa Ababneh & Abdullah Shurafa 8 Assem Al Refaei Sameer Emeish Hodaifa Ababneh & Abdullah Shurafa Dr.Alia Sheet Checklist Bioequivalence and Therapeutic equivalence. Factors Influencing Absorption. Revising Bioavailability. Factors

More information

Renal Excretion of Drugs

Renal Excretion of Drugs Renal Excretion of Drugs 3 1 Objectives : 1 Identify main and minor routes of Excretion including renal elimination and biliary excretion 2 Describe its consequences on duration of drugs. For better understanding:

More information

ZIN EN ONZIN VAN ANTIBIOTICASPIEGELS BIJ NEONATEN

ZIN EN ONZIN VAN ANTIBIOTICASPIEGELS BIJ NEONATEN ZIN EN ONZIN VAN ANTIBIOTICASPIEGELS BIJ NEONATEN Anne Smits Fellow neonatologie UZ Leuven Use of antibiotics in neonates 50 European hospitals 23 non-european hospitals Countries n = 14 n = 9 Pediatric

More information

Introducing Pharmacokinetics and Pharmacodynamics. Janice Davies Pharmacist Room 23 Maudland Building

Introducing Pharmacokinetics and Pharmacodynamics. Janice Davies Pharmacist Room 23 Maudland Building Introducing Pharmacokinetics and Pharmacodynamics Janice Davies Pharmacist Room 23 Maudland Building JADavies5@uclan.ac.uk 1 elearn 2 DVD Any problems / questions? 3 Learning outcomes Define and discuss

More information

PHA First Exam Fall 2003

PHA First Exam Fall 2003 PHA 5127 First Exam Fall 2003 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Question/Points 1. /14 pts 2. /6 pts 3. /15 pts 4. /12 pts 5. /20 pts 6. /10pts

More information

A. Definition. B. Epidemiology. C. Classification. i. Pharmacokinetic DIs. ii. Pharmacodynamic DIs. D. Recognition. E. Prevention

A. Definition. B. Epidemiology. C. Classification. i. Pharmacokinetic DIs. ii. Pharmacodynamic DIs. D. Recognition. E. Prevention DRUG OUTLINE A. Definition B. Epidemiology Dr Ruwan Parakramawansha MBBS, MD, MRCP(UK),MRCPE, DMT(UK) (2013/09/05) C. Classification i. Pharmacokinetic DIs ii. Pharmacodynamic DIs D. Recognition E. Prevention

More information

Pharmaceutics I صيدالنيات 1. Unit 2 Route of Drug Administration

Pharmaceutics I صيدالنيات 1. Unit 2 Route of Drug Administration Pharmaceutics I صيدالنيات 1 Unit 2 Route of Drug Administration 1 Routs of Drug administration The possible routes of drug entry into the body may be divided into two classes: Parenteral Rout Enteral Rout

More information

Basic Concepts of TDM

Basic Concepts of TDM TDM Lecture 1 5 th stage What is TDM? Basic Concepts of TDM Therapeutic drug monitoring (TDM) is a branch of clinical pharmacology that specializes in the measurement of medication concentrations in blood.

More information

Chapter Questions. Modern Pharmacology With Clinical Applications. Sixth Edition

Chapter Questions. Modern Pharmacology With Clinical Applications. Sixth Edition Chapter Questions Modern Pharmacology With Clinical Applications Sixth Edition Mechanism of Drug Action Questions 1. Receptors are macromolecules that a. Are designed to attract drugs b. Are resistant

More information

Therapeutic Hypothermia and Pharmacologic Considerations. Genelle Butz, PharmD Director of Pharmacy CarolinaEast Medical Center August 6, 2013

Therapeutic Hypothermia and Pharmacologic Considerations. Genelle Butz, PharmD Director of Pharmacy CarolinaEast Medical Center August 6, 2013 Therapeutic Hypothermia and Pharmacologic Considerations Genelle Butz, PharmD Director of Pharmacy CarolinaEast Medical Center August 6, 2013 Disclosures Disclosure tatement: I have no financial or personal

More information

Biology of Aging. Faculty Disclosure. Learning Objectives. I have no relevant financial disclosures relative to the content of this presentation.

Biology of Aging. Faculty Disclosure. Learning Objectives. I have no relevant financial disclosures relative to the content of this presentation. Biology of Aging Aging Changes That Impact Medication Management Emily P. Peron, PharmD, MS, BCPS, FASCP Assistant Professor of Geriatrics Virginia Commonwealth University School of Pharmacy Richmond,

More information

Define the terms biopharmaceutics and bioavailability.

Define the terms biopharmaceutics and bioavailability. Pharmaceutics Reading Notes Define the terms biopharmaceutics and bioavailability. Biopharmaceutics: the area of study concerning the relationship between the physical, chemical, and biological sciences

More information

Pharmacology in the Elderly

Pharmacology in the Elderly Pharmacology in the Elderly James Hardy Geriatrician, Royal North Shore Hospital A recent consultation Aspirin Clopidogrel Warfarin Coloxyl with senna Clearlax Methotrexate Paracetamol Pantoprazole Cholecalciferol

More information

Nontraditional PharmD Program PRDO 7700 Pharmacokinetics Review Self-Assessment

Nontraditional PharmD Program PRDO 7700 Pharmacokinetics Review Self-Assessment Nontraditional PharmD Program PRDO 7700 Pharmacokinetics Review Self-Assessment Please consider the following questions. If you do not feel confident about the material being covered, then it is recommended

More information

Drug CHAPTER 2. Pharmacologic Principles. NDEG 26A Eliza Rivera-Mitu, RN, MSN. Pharmacology. Drug Names. Pharmacologic Principles. Drug Names (cont'd)

Drug CHAPTER 2. Pharmacologic Principles. NDEG 26A Eliza Rivera-Mitu, RN, MSN. Pharmacology. Drug Names. Pharmacologic Principles. Drug Names (cont'd) CHAPTER 2 Pharmacologic Principles NDEG 26A Eliza Rivera-Mitu, RN, MSN Drug Any chemical that affects the physiologic processes of a living organism Pharmacology The study or science of drugs Drug Names

More information

Basic Concepts in Pharmacokinetics. Leon Aarons Manchester Pharmacy School University of Manchester

Basic Concepts in Pharmacokinetics. Leon Aarons Manchester Pharmacy School University of Manchester Basic Concepts in Pharmacokinetics Leon Aarons Manchester Pharmacy School University of Manchester Objectives 1. Define pharmacokinetics 2. Describe absorption 3. Describe distribution 4. Describe elimination

More information

4WS Neurology. Table of Contents

4WS Neurology. Table of Contents 4WS Neurology Table of Contents 1. Phenytoin Preparations... Page 2 Monitoring... Page 2 Therapeutic Range... Page 2 Loading Doses... Page 2 Maintenance Doses... Page 3 Sampling Times... Page 3 Dose Adjustment...

More information

Effects of Liver Disease on Pharmacokinetics

Effects of Liver Disease on Pharmacokinetics Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 31, 2013 National Institutes of Health Clinical Center 1 GOALS of Effects of Liver

More information

Aging Changes That Impact Medication Management

Aging Changes That Impact Medication Management Biology of Aging Aging Changes That Impact Medication Management Emily P. Peron, PharmD, MS, BCPS, FASCP Assistant Professor of Geriatrics Virginia Commonwealth University School of Pharmacy Richmond,

More information

Using Accelerator Mass Spectrometry to Explain the Pharmacokinetics of Vismodegib Cornelis E.C.A. Hop

Using Accelerator Mass Spectrometry to Explain the Pharmacokinetics of Vismodegib Cornelis E.C.A. Hop Using Accelerator Mass Spectrometry to Explain the Pharmacokinetics of Vismodegib Cornelis E.C.A. Hop Topics to be Addressed Why AMS? AMS for mass balance studies with vismodegib AMS for absolute bioavailability

More information

UNIVERSITY OF THE WEST INDIES, ST AUGUSTINE

UNIVERSITY OF THE WEST INDIES, ST AUGUSTINE UNIVERSITY OF THE WEST INDIES, ST AUGUSTINE FACULTY OF MEDICAL SCIENCES SCHOOL OF PHARMACY BACHELOR OF SCIENCE IN PHARMACY DEGREE COURSE SYLLABUS COURSE TITLE: COURSE CODE: BIOPHARMACEUTICS, NEW DRUG DELIVERY

More information

Pharmacotherapy Issues in the Pediatric Population

Pharmacotherapy Issues in the Pediatric Population Pharmacotherapy Issues in the Pediatric Population Continuing Professional Pharmacy Development Dr. Shane Pawluk, PharmD Dr. Andrea Cartwright, PharmD Dr. Maryam Khaja March 26, 2014 Outline Didactic Session

More information

Introduction to Pharmacokinetics

Introduction to Pharmacokinetics - 1 - Introduction to Pharmacokinetics Outline accompanies required webcast for Marie Biancuzzo s Lactation Exam Review and Marie Biancuzzo s Comprehensive Lactation Course Notes We will not cover this

More information

Variation in drug responses & Drug-Drug Interactions

Variation in drug responses & Drug-Drug Interactions Variation in drug responses & Drug-Drug Interactions 1 Properties of an Ideal Drug Effective Safety Selective Reversible Action Predictable Freedom from drug interactions Low cost Chemically stable Sources

More information

Package Insert. Elkar

Package Insert. Elkar Package Insert Elkar Product Summary 1. Name of the medicinal product Elkar 500 mg tablets 2. Qualitative and quantitative composition Each tablet contains levocarnitine 500 mg. 3. Pharmaceutical form

More information

Pharmacokinetics I. Dr. M.Mothilal Assistant professor

Pharmacokinetics I. Dr. M.Mothilal Assistant professor Pharmacokinetics I Dr. M.Mothilal Assistant professor DRUG TRANSPORT For a drug to produce a therapeutic effect, it must reach to its target and it must accumulate at that site to reach to the minimum

More information

Click to edit Master title style

Click to edit Master title style A Short Course in Pharmacokinetics Chris Town Research Pharmacokinetics Outline Pharmacokinetics - Definition Ideal Pharmacokinetic Parameters of a New Drug How do we optimize PK for new compounds Why

More information

PHA Final Exam Fall 2006

PHA Final Exam Fall 2006 PHA 5127 Final Exam Fall 2006 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Please transfer the answers onto the bubble sheet. The question number refers

More information

CLINICAL PHARMACOKINETICS INDEPENDENT LEARNING MODULE

CLINICAL PHARMACOKINETICS INDEPENDENT LEARNING MODULE CLINICAL PHARMACOKINETICS INDEPENDENT LEARNING MODULE Joseph K. Ritter, Ph.D. Assoc. Professor, Pharmacology and Toxicology MSB 536, 828-1022, jritter@vcu.edu This self study module will reinforce the

More information

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment.

PHA Second Exam. Fall On my honor, I have neither given nor received unauthorized aid in doing this assignment. PHA 5127 Second Exam Fall 2010 On my honor, I have neither given nor received unauthorized aid in doing this assignment. Name Put all answers on the bubble sheet TOTAL /200 pts 1 Question Set I (True or

More information

Chapter 4. Drug Biotransformation

Chapter 4. Drug Biotransformation Chapter 4 Drug Biotransformation Drug Biotransformation 1 Why is drug biotransformation necessary 2 The role of biotransformation in drug disposition 3 Where do drug biotransformation occur 4 The enzymes

More information

Metabolism. Objectives. Metabolism. 26 July Chapter 28 1

Metabolism. Objectives. Metabolism. 26 July Chapter 28 1 Metabolism bjectives Describe various processes by which drugs are metabolized Describe induction and inhibition of metabolism Use the venous equilibration model to describe hepatic clearance and the effect

More information

Technical aspects of RRT in AKI: access, anticoagulation, drug dosage and nutrition. Marlies Ostermann

Technical aspects of RRT in AKI: access, anticoagulation, drug dosage and nutrition. Marlies Ostermann Technical aspects of RRT in AKI: access, anticoagulation, drug dosage and nutrition Marlies Ostermann AKI guideline Chapter 3: Nutrition Chapter 5.3: Anticoagulation Chapter 5.4: Vascular access for RRT

More information

TDM. Measurement techniques used to determine cyclosporine level include:

TDM. Measurement techniques used to determine cyclosporine level include: TDM Lecture 15: Cyclosporine. Cyclosporine is a cyclic polypeptide medication with immunosuppressant effect. It has the ability to block the production of interleukin-2 and other cytokines by T-lymphocytes.

More information

DEFINITIONS. Pharmacokinetics. Pharmacodynamics. The process by which a drug is absorbed, distributed, metabolized and eliminated by the body

DEFINITIONS. Pharmacokinetics. Pharmacodynamics. The process by which a drug is absorbed, distributed, metabolized and eliminated by the body PHARMACOLOGY BASICS DEFINITIONS Pharmacokinetics The process by which a drug is absorbed, distributed, metabolized and eliminated by the body Pharmacodynamics The interactions of a drug and the receptors

More information

When choosing an antiepileptic ... PRESENTATION... Pharmacokinetics of the New Antiepileptic Drugs. Based on a presentation by Barry E.

When choosing an antiepileptic ... PRESENTATION... Pharmacokinetics of the New Antiepileptic Drugs. Based on a presentation by Barry E. ... PRESENTATION... Pharmacokinetics of the New Antiepileptic Drugs Based on a presentation by Barry E. Gidal, PharmD Presentation Summary A physician s choice of an antiepileptic drug (AED) usually depends

More information

Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program November 4, 2010 National

Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program November 4, 2010 National Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program November 4, 2010 National Institutes of Health Clinical Center GOALS of Liver Disease

More information

Drug Absorption and Bioavailability

Drug Absorption and Bioavailability Drug Absorption and Bioavailability Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 4, 2012 Office of Clinical Research Training and Medical Education National Institutes

More information

Pharmacodynamics & Pharmacokinetics 1

Pharmacodynamics & Pharmacokinetics 1 PCTH 325 Pharmacodynamics & Pharmacokinetics 1 Dr. Shabbits jennifer.shabbits@ubc.ca September 9, 2014 Learning objectives 1. Describe the categories of intended drug action 2. Compare and contrast agonists

More information

Metformin Associated Lactic Acidosis. Jun-Ki Park 9/6/11

Metformin Associated Lactic Acidosis. Jun-Ki Park 9/6/11 Metformin Associated Lactic Acidosis Jun-Ki Park 9/6/11 Probably the most common mechanism by which metformin elevates blood lactate is by inducing catecholamine release in those who regulate or prescribe

More information

Slide 1. Slide 2. Slide 3. Drug Action and Handling. Lesson 2.1. Lesson 2.1. Drug Action and Handling. Drug Action and Handling.

Slide 1. Slide 2. Slide 3. Drug Action and Handling. Lesson 2.1. Lesson 2.1. Drug Action and Handling. Drug Action and Handling. Slide 1 Drug Action and Handling Chapter 2 1 Slide 2 Lesson 2.1 Drug Action and Handling 1. Differentiate dose, potency, and efficacy in the context of the actions of drugs. 2. Explain the pharmacologic

More information

Adjusting phenytoin dosage in complex patients: how to win friends and influence patient outcomes

Adjusting phenytoin dosage in complex patients: how to win friends and influence patient outcomes Adjusting phenytoin dosage in complex patients: how to win friends and influence patient outcomes Brian Hardy, PharmD, FCSHP, FCCP Coordinator Education and Clinical Programs Department of Pharmacy Sunnybrook

More information

Fundamentals of Pharmacology for Veterinary Technicians Chapter 4

Fundamentals of Pharmacology for Veterinary Technicians Chapter 4 (A) (B) Figure 4-1 A, B (C) FIGURE 4-1C The active transport process moves particles against the concentration gradient from a region of low concentration to a region of high concentration. Active transport

More information

DEVELOPMENTAL PK/PD: WHAT HAVE WE LEARNT? Geoff Tucker

DEVELOPMENTAL PK/PD: WHAT HAVE WE LEARNT? Geoff Tucker DEVELOPMENTAL PK/PD: WHAT HAVE WE LEARNT? Geoff Tucker UNDERSTANDING AND PREDICTING PK/PD IN JUVENILES PHARMACOKINETICS Can we scale from juvenile animals? Can we scale from allometry? Can we scale from

More information

New drugs necessity for therapeutic drug monitoring

New drugs necessity for therapeutic drug monitoring New drugs necessity for therapeutic drug monitoring Stephan Krähenbühl Clinical Pharmacology & Toxicology University Hospital Basel kraehenbuehl@uhbs.ch Drugs suitable for TDM Narrow therapeutic range

More information

By; Ashraf El Houfi MD MS (pulmonology) MRCP (UK) FRCP (London) EDIC Consultant ICU Dubai Hospital

By; Ashraf El Houfi MD MS (pulmonology) MRCP (UK) FRCP (London) EDIC Consultant ICU Dubai Hospital By; Ashraf El Houfi MD MS (pulmonology) MRCP (UK) FRCP (London) EDIC Consultant ICU Dubai Hospital Introduction The significance of nutrition in hospital setting (especially the ICU) cannot be overstated.

More information

RESPIRATORY PHARMACOLOGY - ASTHMA. Primary Exam Teaching - Westmead ED

RESPIRATORY PHARMACOLOGY - ASTHMA. Primary Exam Teaching - Westmead ED RESPIRATORY PHARMACOLOGY - ASTHMA Primary Exam Teaching - Westmead ED Sympathomimetic agents MOA: relax airway smooth muscle and inhibit broncho constricting mediators from mast cells May also inhibit

More information

2/26/2015 PHARMACODYNAMICS OF AGING: NARROWING OF THE THERAPEUTIC INDEX IN THE FACE OF THERAPEUTIC OPPORTUNITY

2/26/2015 PHARMACODYNAMICS OF AGING: NARROWING OF THE THERAPEUTIC INDEX IN THE FACE OF THERAPEUTIC OPPORTUNITY PHARMACODYNAMICS OF AGING: NARROWING OF THE THERAPEUTIC INDEX IN THE FACE OF THERAPEUTIC OPPORTUNITY Darrell R. Abernethy, M.D., Ph.D. Associate Director for Drug Safety Office of Clinical Pharmacology

More information

Tala Saleh. Abdul Aziz ALShamali. Abdul Aziz ALShamali

Tala Saleh. Abdul Aziz ALShamali. Abdul Aziz ALShamali 9 Tala Saleh Abdul Aziz ALShamali Abdul Aziz ALShamali Alia Shatanawi Volume of Distribution (Vd) Understand the concept Imagine having a container with an unknown volume of water in it. Then 1000mg of

More information

Renal Disease and PK/PD. Anjay Rastogi MD PhD Division of Nephrology

Renal Disease and PK/PD. Anjay Rastogi MD PhD Division of Nephrology Renal Disease and PK/PD Anjay Rastogi MD PhD Division of Nephrology Drugs and Kidneys Kidney is one of the major organ of drug elimination from the human body Renal disease and dialysis alters the pharmacokinetics

More information

ADME Review. Dr. Joe Ritter Associate Professor of Pharmacology

ADME Review. Dr. Joe Ritter Associate Professor of Pharmacology ADME Review Dr. Joe Ritter Associate Professor of Pharmacology 828-1022 jkritter@vcu.edu What percent of a weak base (pka = 7.5) and weak acid (pka = 3.5) will be respectively ionized in urine of ph 5.5?

More information

Pharmacokinetics PCTH 325. Dr. Shabbits September 12, C t = C 0 e -kt. Learning Objectives

Pharmacokinetics PCTH 325. Dr. Shabbits September 12, C t = C 0 e -kt. Learning Objectives PCTH 325 Pharmacokinetics Dr. Shabbits jennifer.shabbits@ubc.ca September 12, 2013 Learning Objectives 1. Interpret Concentration vs graphs and use them to calculate half life and predict drug concentration

More information

Pharmacokinetics Dr. Iman Lec. 3

Pharmacokinetics Dr. Iman Lec. 3 Pharmacokinetics r. Iman Lec. 3 Pharmacokinetics A dequate drug doses must be delivered to the target organ to get therapeutic but not toxic levels. So, pharmacokinetic examines the movement of drug over

More information

Cytochrome P450 Drug Interaction Table Flockhart Table

Cytochrome P450 Drug Interaction Table Flockhart Table Cytochrome P450 Drug Interaction Table Flockhart Table The table contains lists of drugs in columns under the designation of specific cytochrome P450 isoforms. CYTOCHROME P450 DRUG INTERACTION TABLE A

More information

Drug Disposition in Obesity & Protein-Calorie Malnutrition

Drug Disposition in Obesity & Protein-Calorie Malnutrition Drug Disposition in Obesity & Protein-Calorie Malnutrition JBoullata, PharmD, RPh, BCNSP Associate Professor of Pharmacology & Therapeutics -and- Pharmacy Specialist in Nutrition Support University of

More information

Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 29, 2015 National

Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 29, 2015 National Effects of Liver Disease on Pharmacokinetics Juan J.L. Lertora, M.D., Ph.D. Director Clinical Pharmacology Program October 29, 2015 National Institutes of Health Clinical Center GOALS of Liver Disease

More information

One-Compartment Open Model: Intravenous Bolus Administration:

One-Compartment Open Model: Intravenous Bolus Administration: One-Compartment Open Model: Intravenous Bolus Administration: Introduction The most common and most desirable route of drug administration is orally by mouth using tablets, capsules, or oral solutions.

More information

Morbid Obesity: Multi system Considerations for Acute Care

Morbid Obesity: Multi system Considerations for Acute Care Morbid Obesity: Multi system Considerations for Acute Care BRENDA ENGLER, MSN, ACNP BC, CCRN GEISINGER MEDICAL CENTER Disclosures None 1 Obesity Statistics 30 % of the adult population of Pennsylvania

More information

Goals for sedation during mechanical ventilation

Goals for sedation during mechanical ventilation New Uses of Old Medications Gina Riggi, PharmD, BCCCP, BCPS Clinical Pharmacist Trauma ICU Jackson Memorial Hospital Disclosure I do not have anything to disclose Objectives Describe the use of ketamine

More information

Maurizio D Incalci, MD Department of Oncology Mario Negri Institute, Milan, Italy

Maurizio D Incalci, MD Department of Oncology Mario Negri Institute, Milan, Italy Maurizio D Incalci, MD Department of Oncology Mario Negri Institute, Milan, Italy Oncologic Therapy Personalization: from basic research to clinical application Limits of: BASIC RESEARCH Reggio Emilia,

More information

Pharmacokinetics Overview

Pharmacokinetics Overview Pharmacokinetics Overview Disclaimer: This handout and the associated lectures are intended as a very superficial overview of pharmacokinetics. Summary of Important Terms and Concepts - Absorption, peak

More information

Many drugs have both lipophilic and hydrophilic chemical substituents. Those drugs that are more lipid soluble tend to traverse cell membranes more

Many drugs have both lipophilic and hydrophilic chemical substituents. Those drugs that are more lipid soluble tend to traverse cell membranes more Lecture-4 Many drugs have both lipophilic and hydrophilic chemical substituents. Those drugs that are more lipid soluble tend to traverse cell membranes more easily than less lipid-soluble or more water-soluble

More information

Metabolic Changes of Drugs and Related Organic Compounds

Metabolic Changes of Drugs and Related Organic Compounds Metabolic Changes of Drugs and Related Organic Compounds 3 rd stage/ 1 st course Lecture 3 Shokhan J. Hamid 2 Metabolism plays a central role in the elimination of drugs and other foreign compounds from

More information

Chapter 3 Drug Absorption and Bioavailability

Chapter 3 Drug Absorption and Bioavailability Chapter 3 Drug Absorption and Bioavailability Debra Si Mui Sim Abstract Most drugs are prescribed as oral preparations or extravascular injections (other than intravenous injections) for the treatment

More information

PHA5128 Dose Optimization II Case Study I Spring 2013

PHA5128 Dose Optimization II Case Study I Spring 2013 Silsamicin is an investigational compound being evaluated for its antimicrobial effect. The route of administration for this drug is via intravenous bolus. Approximately 99.9% of this drug is eliminated

More information