SlideShare a Scribd company logo
1 of 35
INDIVIDUALIZATION OF DRUG
DOSAGE REGIMENS
Dr. S P Srinivas Nayak,
PharmD, RPh, MSc., (PGDND) (PhD)
Assistant Professor, Dept. of Pharmacy Practice, PU.
Dr S P NAYAK MED EASY
INTRODUCTION
• THERAPEUTIC DRUG MONITORING(TDM):
TDM is a process of measuring drug concentration in
plasma to optimise the therapy for the drugs having
relationship between the plasma drug concentration
and the desired clinical effect or between the plasma
drug concentration and an adverse effect i.e drugs
with a narrow therapeutic window (also known as
critical-dose drugs and narrow therapeutic index (NTI)
drugs), such as
digoxin, aminoglycosides, antiarrhythmics,
anticoagulants, anticonvulsants, and some
antiasthmatics, such as theophylline.
• Critical-dose drugs are defined as those drugs
where comparatively small differences in dose or
concentration lead to dose- and concentration-
dependent, serious therapeutic failures and/or
serious adverse drug reactions
• For those drugs in which plasma drug concentration
and clinical effect are not directly related, other
pharmacodynamic parameters may be monitored.
• For example, clotting time may be measured directly
in patients on warfarin anticoagulant therapy.
• Glucose concentrations are often monitored in
diabetic patients using insulin products.
• Asthmatic patients may use the bronchodilator,
albuterol taken by inhalation via a metered-dose
inhaler. For these patients, FEV1 (forced expiratory
volume) may be used as a measure of drug efficacy.
• In cancer chemotherapy, dose adjustment for
individual patients may depend more on the severity
of side effects and the patient’s ability to tolerate the
drug.
Example, therapeutic range for
theophylline is 10–20 μg/mL.
patients may exhibits various
effects at various drug plasma
levels:
• Mild symptoms of
toxicity included nausea,
vomiting, headache, and
insomnia.
• A potentially serious
effect was sinus
tachycardia.
• severe toxicity shows
life-threatening cardiac
arrhythmias and
seizures.
• Many drugs like NSAIDs - ibuprofen,
• CCBs - nifedipine, have a wide therapeutic
range and do not need therapeutic drug
monitoring
• OTC drugs such as various cough and cold
remedies, analgesics, and other products are
also generally safe when used as directed.
INDIVIDUALIZATION OF
DRUG DOSAGE REGIMENS
Individuals respond differently to the given
drugs, some drugs may have no effect on one
individual while it may work effectively in
others.
For patients who needs less dose, instead of
using wide therapeutic range, the dosage can
be selected based on each patients individual
need with a low incidence of ADRs
VARIABILITY
• Because of interpatient variability in drug
absorption, distribution, and elimination as
well as changing pathophysiologic conditions
in the patient, therapeutic drug monitoring
(TDM) or clinical pharmacokinetic (laboratory)
services (CPKS) have been established in many
hospitals to evaluate the response of the
patient to the recommended dosage regimen.
AGE (CHILDREN)
New born have low GFR & tubular transport is not
matured. Similarly, hepatic drug metabolizing
system is inadequate in new born.
BBB is more permeable, hence drugs attain higher
concentration in CNS.
Drug absorption may also be altered in infants
because of lower gastric acidity & slower intestinal
transit.
As skin is thin, transdermal absorption of drugs is
faster & is more permeable.
At one year, drug metabolism is faster than in adults
Ex. Theophylline, Phenytoin, CBZ hence higher dose
may be required.
The dose of a drug for children is often
calculated from adult dose
Young’s formula child dose = age/age+12 X AD
Dilling’s formula child dose=age/20 X AD
Clerk’s rule: wt in pounds/150 X AD
Fried’s rule: age in months/150 X AD
AGE
As the age progresses, the renal functions are progressively
declines
Decline in liver blood flow & reduction in hepatic microsomal
enzymes results in drug accumulation
Slow absorption due to reduced intestinal motility &
decreased blood flow, decreased plasma protein binding
due to low plasma albumin
Increased chances of drug interactions as a result of
polypharmacy
DISEASE
GI disease:
Alter absorption of orally administered drugs
Decreased absorption of amoxycillin in coeliac disease
Decreased absorption in achlorhydria.
Liver disease:
Bioavailability of drugs which have high first pass metabolism is
increased
Decreased serum albumin decreased protein binding of acidic
drugs increased free form of drugs
Decreased metabolism & elimination hence reduce the dose
Prefer alternate drugs that do not depend on hepatic
metabolism for elimination or those have short half-life
Ex. Consider oxazepam or lorazepam instead of diazepam
Avoid prodrugs as they need hepatic metabolism for activation
Kidney disease: Clearence of drugs such as
aminoglycosides, digoxin, phenobarbitone
decreases
Altered structure of plasma protein (albumin) in
renal failure results in decreased binding of acidic
drugs
Throid disease:
Hypothyroid patients are more sensitive to digoxin,
morphine & CNS depressants
Hyperthyroid patients are relatively resistant to
inotropic action but more prone to arrhythmic
action of digoxin
Body weight:
Influences the concentration of drug at the site
of action
An adult dose refers to an individual of medium
built Hence for obese or lean individuals & for
children the dose must be calculated based on
body weight
Individual dose = BW x Avg.adult dose/70
BSA provides accurate basis for dose calculations
because total body water, ECF volume &
metabolic activity are better paralleled by BSA
Individual dose = BSA X Avg. Adult dose / 1.7
Drug interactions:
Pharmacokinetic
Absorbtion
Distribution
Metabolism
Excretion
pharmacodynamic
ABSORBTION DRUG INTERACTIONS
INHIBITION OF DRUG ABSORPTION
• Various drugs and dietary supplements can decrease the
absorption of drugs from the GIT. Antacids containing magnesium
and aluminum hydroxide often interfere with absorption of many
drugs. Coadministration of magnesium and aluminum hydroxide
caused a decrease of plasma levels of PERFLOXACIN,
TETRACYCLINS, DIGOXIN, THYROXIN etc.
• These drugs should be given at least 2 hours before the antacid to
ensure sufficient therapeutic efficacy
• Sucralfate used for ulcer, is an aluminum glycopyranoside complex
that is not absorbed but retards the oral absorption of
ciprofloxacin.. Cholestyramine is an anion-exchange resin that
binds bile acid and many drugs in the gastrointestinal tract.
Cholestyramine can bind digitoxin in the GI tract and shorten the
elimination half-life of digitoxin by approximately 30%–40%.
Absorption of thyroxine may be reduced by 50% when it is
administered closely with cholestyramine.
• Nonhepatic enzymes can be involved in drug interactions.
For example, drug interactions have been reported for
patients taking linezolid (Zyvox) who are concurrently
taking certain psychiatric medications.
• Linezolid is a reversible monoamine oxidase inhibitor
(MAOI). Serotonergic psychiatric antidepressant drugs such
as citalopram, paroxetine, fluoxetine, sertraline, and other
drugs that affect the serotonergic pathway in the brain.
MAOIs, such as phenelzine and isocarboxazid, are also
contraindicated., linezolid inhibits the action of monoamine
oxidase A responsible for breaking down serotonin in the
brain. It is believed that when linezolid is given to patients
taking serotonergic psychiatric medications, high levels of
serotonin can build up in the brain, causing toxicity. This is
referred to as serotonin syndrome. Its signs and symptoms
include mental changes (confusion, hyperactivity, memory
problems), muscle twitching,
Grapefruit–Drug Interactions
• grapefruit juice, can significantly inhibit the
metabolism by gut-wall cytochrome P-450 3A4
(CYP3A4)
• For example, grapefruit juice increases average
felodipine levels about threefold, increases
cyclosporine levels, and increases the levels of
terfenadine, a common antihistamine. In the case of
terfenadine, Spence (1997) reported the death of a 29-
year-old man who had been taking terfenadine and
drinking grapefruit juice 2–3 times per week. Death
was attributed to terfenadine toxicity.
• Grapefruit juice can also affect P-gp-mediated efflux of
some drugs.
ALTERED RENAL REABSORPTION DUE
TO CHANGING URINARY pH
• The normal adult urinary pH ranges from 4.8 to
7.5 but can increase due to chronic antacid use.
This change in urinary pH affects the ionization
and reabsorption of weak electrolyte drugs.
• An increased ionization of salicylate due to an
increase in urine pH reduces salicylate
reabsorption in the renal tubule, resulting in
increased renal excretion.
• Basic drugs tend to have longer half-lives when
urinary pH is increased.
Genetics:
Genetic differences determine the disposition of
a given drug in an individual
Drug disposition is determined by rate kinetics
of ADME, hence genetic differences
determining various physiological processes
affect the plasma levels of drugs eventually
determining the differences in drug response
by an individual
CytP 450 major enz system involved with
metabolism of all xenobiotics.
The metabolic capacity of this enz system is not
equal in all members of a population
Hence we observe a wide inter individual
variations in the rates of metabolism of some
drugs
Pantoprazole/omeprazole metabolises in liver
via cyt CYP2C19 & CYP3A48
Antidepressants paroxetine & fluoxatine
extensively metabolised via cyt CYP2D6
Glimipride via cyt CYP2C9
Cyt p typically show large inter individual
differences in activity that lead to differences
in drug response
Hence metabolism & excretion of drugs vary
between individuals
3% of caucasians & 15% asians are poor
metabolizers
12% of north indians are poor metabolizers
(pantoprazole)
Collectively several hundred genes & their alleles &
protein products determine the overall drug
disposition in an individual
In pharmacogenomics, attempts are made to
determine & quantify these genetic variations &
use them in predicting drug disposition by an
individual
Genotyping techniques for cyt p 450 enz can be
used to predict one’s disposition to a given class
of drugs without doing any evaluation of PK
parameters
Which can be used for deciding choice of drug & its
dose
Based on genotyping methods individuals may be
classified as poor , intermediate, extensive & ultra
rapid metabolizers for a group of given drugs
Poor metabolizers will develop higher SDC in comparison
with extensive metabolizers, hence they are at
increased risk of developing concentration dependent
ADRs
Ultra rapid metabolizers will not reach therapeutic SDC
upon treatment with standard doses, hence fail to
respond to treatment
If the parent compound is a prodrug, which
requires bio activation by the enz to a active
form, the effect of polymorphism can be quite
complex in poor metabolizers and ultra rapid
metabolizers
Hence these individuals differences in drug
disposition could be compensated by dosage
adjustment according to metabolic capacity,
determination of drug metabolism genotypes
• Poor metabolizers and ultra rapid
metabolizers can be identified & dosage could
be tailored to the individual patient in order to
reach therapeutic levels of drug in plasma,
which may help to avoid ADRs or therapeutic
failures
Atypical pseudocholinesterase – prolonged
succinylcholine apneoa
G6PD deficiency- hemolysis with primaquine,
sulfonamides, dapsone, quinine, chloroquine etc
Acetylator polymorphism-INH neuropathy, procainamide
& hydralazine induced lupus in slow acetylators
Acute intermittent porphyria- precipitated by
barbiturates due to genetic defects in repression of
porphyrin synthesis
THANK YOU

More Related Content

What's hot

Analysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysisAnalysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysis
Gayathri Ravi
 
Clinical pharmacokinetics and its application
Clinical pharmacokinetics and its applicationClinical pharmacokinetics and its application
Clinical pharmacokinetics and its application
pavithra vinayak
 

What's hot (20)

Effects of Liver disease on Pharmacokinetics
Effects of Liver disease on Pharmacokinetics Effects of Liver disease on Pharmacokinetics
Effects of Liver disease on Pharmacokinetics
 
Genetic polymorphism in drug transport and drug targets.
Genetic polymorphism in drug transport and drug targets.Genetic polymorphism in drug transport and drug targets.
Genetic polymorphism in drug transport and drug targets.
 
Pharmacokinetic and pharmacodynamic correlation
Pharmacokinetic and pharmacodynamic correlationPharmacokinetic and pharmacodynamic correlation
Pharmacokinetic and pharmacodynamic correlation
 
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimen
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenconversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimen
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimen
 
NOMOGRAMS AND TABULATIONS IN DESIGNING DOSAGE REGIMEN.pptx
NOMOGRAMS AND TABULATIONS IN   DESIGNING DOSAGE REGIMEN.pptxNOMOGRAMS AND TABULATIONS IN   DESIGNING DOSAGE REGIMEN.pptx
NOMOGRAMS AND TABULATIONS IN DESIGNING DOSAGE REGIMEN.pptx
 
Drug dosing in elderly, infant and obese patient slide share
Drug dosing in elderly, infant and obese patient slide shareDrug dosing in elderly, infant and obese patient slide share
Drug dosing in elderly, infant and obese patient slide share
 
DIGOXIN: Therapeutic Drug Monitoring
DIGOXIN: Therapeutic Drug MonitoringDIGOXIN: Therapeutic Drug Monitoring
DIGOXIN: Therapeutic Drug Monitoring
 
Determination of dose and dosing interval
Determination of dose and dosing intervalDetermination of dose and dosing interval
Determination of dose and dosing interval
 
introduction to Pharmacoepidemiology
introduction to Pharmacoepidemiology introduction to Pharmacoepidemiology
introduction to Pharmacoepidemiology
 
Protocol for tdm
Protocol for tdmProtocol for tdm
Protocol for tdm
 
Analysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysisAnalysis of pk data- Pop PK analysis
Analysis of pk data- Pop PK analysis
 
Dose adjustment in renal disease
Dose adjustment in renal diseaseDose adjustment in renal disease
Dose adjustment in renal disease
 
Dose in uremia
Dose in uremiaDose in uremia
Dose in uremia
 
Clinical pharmacokinetics and its application
Clinical pharmacokinetics and its applicationClinical pharmacokinetics and its application
Clinical pharmacokinetics and its application
 
Bayesian theory
Bayesian theoryBayesian theory
Bayesian theory
 
TDM of drugs used in seizure disorders
TDM of drugs used in seizure disordersTDM of drugs used in seizure disorders
TDM of drugs used in seizure disorders
 
Dosing in obese patient
Dosing in obese patientDosing in obese patient
Dosing in obese patient
 
Dosing in elderly
Dosing in elderly Dosing in elderly
Dosing in elderly
 
Drug utilization evaluation
Drug utilization evaluationDrug utilization evaluation
Drug utilization evaluation
 
Measurement of outcome v5
Measurement  of outcome v5Measurement  of outcome v5
Measurement of outcome v5
 

Similar to Individualization of dosage regimen

Similar to Individualization of dosage regimen (20)

Prescribing in physiological and pathological conditions
Prescribing in physiological and pathological conditionsPrescribing in physiological and pathological conditions
Prescribing in physiological and pathological conditions
 
Drug interactions
Drug interactionsDrug interactions
Drug interactions
 
Drug interactions
Drug interactionsDrug interactions
Drug interactions
 
Pharmacovigila final 2
Pharmacovigila final 2Pharmacovigila final 2
Pharmacovigila final 2
 
Pharmacology part 4
Pharmacology part 4Pharmacology part 4
Pharmacology part 4
 
Factors affecting drug action
Factors affecting drug actionFactors affecting drug action
Factors affecting drug action
 
Geriatric pharmacology - Introduction
Geriatric pharmacology - Introduction Geriatric pharmacology - Introduction
Geriatric pharmacology - Introduction
 
Factors modifying dose and action of drugs
Factors modifying dose and action of drugsFactors modifying dose and action of drugs
Factors modifying dose and action of drugs
 
Therapeutic Drug Monitoring
Therapeutic Drug MonitoringTherapeutic Drug Monitoring
Therapeutic Drug Monitoring
 
Therapeutic Drug Monitoring.pptx
Therapeutic Drug Monitoring.pptxTherapeutic Drug Monitoring.pptx
Therapeutic Drug Monitoring.pptx
 
Drug interactions in dentistry
Drug interactions in dentistryDrug interactions in dentistry
Drug interactions in dentistry
 
drugs.pptx
drugs.pptxdrugs.pptx
drugs.pptx
 
Pharmacotherapy considerations in elderly adults
Pharmacotherapy considerations in elderly adultsPharmacotherapy considerations in elderly adults
Pharmacotherapy considerations in elderly adults
 
Pharmakokinetics & pharmakodynamics of chemotherapy drugs
Pharmakokinetics & pharmakodynamics of chemotherapy drugsPharmakokinetics & pharmakodynamics of chemotherapy drugs
Pharmakokinetics & pharmakodynamics of chemotherapy drugs
 
Posology.pptx
Posology.pptxPosology.pptx
Posology.pptx
 
Therapuetic drug monitoring
Therapuetic drug monitoringTherapuetic drug monitoring
Therapuetic drug monitoring
 
FOOD DRUG INTERACTIONS.pptx
FOOD DRUG INTERACTIONS.pptxFOOD DRUG INTERACTIONS.pptx
FOOD DRUG INTERACTIONS.pptx
 
QUM in Geriatric Patients.pptx
QUM in Geriatric Patients.pptxQUM in Geriatric Patients.pptx
QUM in Geriatric Patients.pptx
 
Drug interaction in dentistry
Drug interaction in dentistry Drug interaction in dentistry
Drug interaction in dentistry
 
Factors affecting drug action in Pharmacology
Factors affecting drug action in PharmacologyFactors affecting drug action in Pharmacology
Factors affecting drug action in Pharmacology
 

More from PARUL UNIVERSITY

A study on the pharmacological management of mineral bone disease in chronick...
A study on the pharmacological management of mineral bone disease in chronick...A study on the pharmacological management of mineral bone disease in chronick...
A study on the pharmacological management of mineral bone disease in chronick...
PARUL UNIVERSITY
 
A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...
A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...
A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...
PARUL UNIVERSITY
 

More from PARUL UNIVERSITY (20)

prostate disease CASE DISCUSSION
prostate disease CASE DISCUSSIONprostate disease CASE DISCUSSION
prostate disease CASE DISCUSSION
 
8. respiratory system
8. respiratory system8. respiratory system
8. respiratory system
 
7. pharmacogenetics
7. pharmacogenetics7. pharmacogenetics
7. pharmacogenetics
 
6. population pharmacokinetics
6. population pharmacokinetics6. population pharmacokinetics
6. population pharmacokinetics
 
CP and TDM unit.1 5TH YEAR NOTES
CP and TDM unit.1 5TH YEAR NOTESCP and TDM unit.1 5TH YEAR NOTES
CP and TDM unit.1 5TH YEAR NOTES
 
Cadiac cycle and heart sound
Cadiac cycle and heart soundCadiac cycle and heart sound
Cadiac cycle and heart sound
 
Heamopoetic system
Heamopoetic systemHeamopoetic system
Heamopoetic system
 
Advances in migraine therapy pedagogy session 27/11/21
Advances in migraine therapy pedagogy session 27/11/21Advances in migraine therapy pedagogy session 27/11/21
Advances in migraine therapy pedagogy session 27/11/21
 
CARDIO VASCULAR SYSTEM THE HEART
CARDIO VASCULAR SYSTEM THE HEARTCARDIO VASCULAR SYSTEM THE HEART
CARDIO VASCULAR SYSTEM THE HEART
 
Vasopressin PHARMACOLOGY
Vasopressin PHARMACOLOGYVasopressin PHARMACOLOGY
Vasopressin PHARMACOLOGY
 
Management of Peripheral Neuropathy and Cardiovascular Effects in Vitamin B1...
Management of Peripheral Neuropathy and Cardiovascular Effects in  Vitamin B1...Management of Peripheral Neuropathy and Cardiovascular Effects in  Vitamin B1...
Management of Peripheral Neuropathy and Cardiovascular Effects in Vitamin B1...
 
31 moya moya disease ijprs
31 moya moya disease ijprs31 moya moya disease ijprs
31 moya moya disease ijprs
 
A case report on Rheumatoid Arthritis with sickle cell trait
A case report on Rheumatoid Arthritis with sickle cell traitA case report on Rheumatoid Arthritis with sickle cell trait
A case report on Rheumatoid Arthritis with sickle cell trait
 
Appendicular skeleton
Appendicular skeletonAppendicular skeleton
Appendicular skeleton
 
Axial skeleton ANATOMY AND PHYSIOLOGY
Axial skeleton ANATOMY AND PHYSIOLOGYAxial skeleton ANATOMY AND PHYSIOLOGY
Axial skeleton ANATOMY AND PHYSIOLOGY
 
Histamines and antihistamine pharmacology
Histamines and antihistamine pharmacologyHistamines and antihistamine pharmacology
Histamines and antihistamine pharmacology
 
Steroids complete lecture ppt
Steroids complete lecture pptSteroids complete lecture ppt
Steroids complete lecture ppt
 
Case discussion 3 HHS, DKA
Case discussion 3 HHS, DKACase discussion 3 HHS, DKA
Case discussion 3 HHS, DKA
 
A study on the pharmacological management of mineral bone disease in chronick...
A study on the pharmacological management of mineral bone disease in chronick...A study on the pharmacological management of mineral bone disease in chronick...
A study on the pharmacological management of mineral bone disease in chronick...
 
A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...
A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...
A Retrospective Study of Clinical and Biochemical Profile in Geriatric Patien...
 

Recently uploaded

Circulation through Special Regions -characteristics and regulation
Circulation through Special Regions -characteristics and regulationCirculation through Special Regions -characteristics and regulation
Circulation through Special Regions -characteristics and regulation
MedicoseAcademics
 
Cardiac Impulse: Rhythmical Excitation and Conduction in the Heart
Cardiac Impulse: Rhythmical Excitation and Conduction in the HeartCardiac Impulse: Rhythmical Excitation and Conduction in the Heart
Cardiac Impulse: Rhythmical Excitation and Conduction in the Heart
MedicoseAcademics
 
THORACOTOMY . SURGICAL PERSPECTIVES VOL 1
THORACOTOMY . SURGICAL PERSPECTIVES VOL 1THORACOTOMY . SURGICAL PERSPECTIVES VOL 1
THORACOTOMY . SURGICAL PERSPECTIVES VOL 1
DR SETH JOTHAM
 

Recently uploaded (20)

Compare home pulse pressure components collected directly from home
Compare home pulse pressure components collected directly from homeCompare home pulse pressure components collected directly from home
Compare home pulse pressure components collected directly from home
 
5CL-ADB powder supplier 5cl adb 5cladba 5cl raw materials vendor on sale now
5CL-ADB powder supplier 5cl adb 5cladba 5cl raw materials vendor on sale now5CL-ADB powder supplier 5cl adb 5cladba 5cl raw materials vendor on sale now
5CL-ADB powder supplier 5cl adb 5cladba 5cl raw materials vendor on sale now
 
TUBERCULINUM-2.BHMS.MATERIA MEDICA.HOMOEOPATHY
TUBERCULINUM-2.BHMS.MATERIA MEDICA.HOMOEOPATHYTUBERCULINUM-2.BHMS.MATERIA MEDICA.HOMOEOPATHY
TUBERCULINUM-2.BHMS.MATERIA MEDICA.HOMOEOPATHY
 
Creating Accessible Public Health Communications
Creating Accessible Public Health CommunicationsCreating Accessible Public Health Communications
Creating Accessible Public Health Communications
 
CNN-based plastic waste detection system
CNN-based plastic waste detection systemCNN-based plastic waste detection system
CNN-based plastic waste detection system
 
Muscle Energy Technique (MET) with variant and techniques.
Muscle Energy Technique (MET) with variant and techniques.Muscle Energy Technique (MET) with variant and techniques.
Muscle Energy Technique (MET) with variant and techniques.
 
Video capsule endoscopy (VCE ) in children
Video capsule endoscopy (VCE ) in childrenVideo capsule endoscopy (VCE ) in children
Video capsule endoscopy (VCE ) in children
 
Cervical screening – taking care of your health flipchart (Vietnamese)
Cervical screening – taking care of your health flipchart (Vietnamese)Cervical screening – taking care of your health flipchart (Vietnamese)
Cervical screening – taking care of your health flipchart (Vietnamese)
 
Effects of vaping e-cigarettes on arterial health
Effects of vaping e-cigarettes on arterial healthEffects of vaping e-cigarettes on arterial health
Effects of vaping e-cigarettes on arterial health
 
DIGITAL RADIOGRAPHY-SABBU KHATOON .pptx
DIGITAL RADIOGRAPHY-SABBU KHATOON  .pptxDIGITAL RADIOGRAPHY-SABBU KHATOON  .pptx
DIGITAL RADIOGRAPHY-SABBU KHATOON .pptx
 
DECIPHERING COMMON ECG FINDINGS IN ED.pptx
DECIPHERING COMMON ECG FINDINGS IN ED.pptxDECIPHERING COMMON ECG FINDINGS IN ED.pptx
DECIPHERING COMMON ECG FINDINGS IN ED.pptx
 
Impact of cancers therapies on the loss in cardiac function, myocardial fffic...
Impact of cancers therapies on the loss in cardiac function, myocardial fffic...Impact of cancers therapies on the loss in cardiac function, myocardial fffic...
Impact of cancers therapies on the loss in cardiac function, myocardial fffic...
 
Circulation through Special Regions -characteristics and regulation
Circulation through Special Regions -characteristics and regulationCirculation through Special Regions -characteristics and regulation
Circulation through Special Regions -characteristics and regulation
 
Cardiac Impulse: Rhythmical Excitation and Conduction in the Heart
Cardiac Impulse: Rhythmical Excitation and Conduction in the HeartCardiac Impulse: Rhythmical Excitation and Conduction in the Heart
Cardiac Impulse: Rhythmical Excitation and Conduction in the Heart
 
Antiplatelets in IHD, Dose Duration, DAPT vs SAPT
Antiplatelets in IHD, Dose Duration, DAPT vs SAPTAntiplatelets in IHD, Dose Duration, DAPT vs SAPT
Antiplatelets in IHD, Dose Duration, DAPT vs SAPT
 
Relationship between vascular system disfunction, neurofluid flow and Alzheim...
Relationship between vascular system disfunction, neurofluid flow and Alzheim...Relationship between vascular system disfunction, neurofluid flow and Alzheim...
Relationship between vascular system disfunction, neurofluid flow and Alzheim...
 
linearity concept of significance, standard deviation, chi square test, stude...
linearity concept of significance, standard deviation, chi square test, stude...linearity concept of significance, standard deviation, chi square test, stude...
linearity concept of significance, standard deviation, chi square test, stude...
 
THORACOTOMY . SURGICAL PERSPECTIVES VOL 1
THORACOTOMY . SURGICAL PERSPECTIVES VOL 1THORACOTOMY . SURGICAL PERSPECTIVES VOL 1
THORACOTOMY . SURGICAL PERSPECTIVES VOL 1
 
Scientificity and feasibility study of non-invasive central arterial pressure...
Scientificity and feasibility study of non-invasive central arterial pressure...Scientificity and feasibility study of non-invasive central arterial pressure...
Scientificity and feasibility study of non-invasive central arterial pressure...
 
SURGICAL ANATOMY OF ORAL IMPLANTOLOGY.pptx
SURGICAL ANATOMY OF ORAL IMPLANTOLOGY.pptxSURGICAL ANATOMY OF ORAL IMPLANTOLOGY.pptx
SURGICAL ANATOMY OF ORAL IMPLANTOLOGY.pptx
 

Individualization of dosage regimen

  • 1. INDIVIDUALIZATION OF DRUG DOSAGE REGIMENS Dr. S P Srinivas Nayak, PharmD, RPh, MSc., (PGDND) (PhD) Assistant Professor, Dept. of Pharmacy Practice, PU. Dr S P NAYAK MED EASY
  • 2. INTRODUCTION • THERAPEUTIC DRUG MONITORING(TDM): TDM is a process of measuring drug concentration in plasma to optimise the therapy for the drugs having relationship between the plasma drug concentration and the desired clinical effect or between the plasma drug concentration and an adverse effect i.e drugs with a narrow therapeutic window (also known as critical-dose drugs and narrow therapeutic index (NTI) drugs), such as digoxin, aminoglycosides, antiarrhythmics, anticoagulants, anticonvulsants, and some antiasthmatics, such as theophylline.
  • 3. • Critical-dose drugs are defined as those drugs where comparatively small differences in dose or concentration lead to dose- and concentration- dependent, serious therapeutic failures and/or serious adverse drug reactions
  • 4. • For those drugs in which plasma drug concentration and clinical effect are not directly related, other pharmacodynamic parameters may be monitored. • For example, clotting time may be measured directly in patients on warfarin anticoagulant therapy. • Glucose concentrations are often monitored in diabetic patients using insulin products. • Asthmatic patients may use the bronchodilator, albuterol taken by inhalation via a metered-dose inhaler. For these patients, FEV1 (forced expiratory volume) may be used as a measure of drug efficacy. • In cancer chemotherapy, dose adjustment for individual patients may depend more on the severity of side effects and the patient’s ability to tolerate the drug.
  • 5.
  • 6. Example, therapeutic range for theophylline is 10–20 μg/mL. patients may exhibits various effects at various drug plasma levels: • Mild symptoms of toxicity included nausea, vomiting, headache, and insomnia. • A potentially serious effect was sinus tachycardia. • severe toxicity shows life-threatening cardiac arrhythmias and seizures.
  • 7. • Many drugs like NSAIDs - ibuprofen, • CCBs - nifedipine, have a wide therapeutic range and do not need therapeutic drug monitoring • OTC drugs such as various cough and cold remedies, analgesics, and other products are also generally safe when used as directed.
  • 8. INDIVIDUALIZATION OF DRUG DOSAGE REGIMENS Individuals respond differently to the given drugs, some drugs may have no effect on one individual while it may work effectively in others. For patients who needs less dose, instead of using wide therapeutic range, the dosage can be selected based on each patients individual need with a low incidence of ADRs
  • 9. VARIABILITY • Because of interpatient variability in drug absorption, distribution, and elimination as well as changing pathophysiologic conditions in the patient, therapeutic drug monitoring (TDM) or clinical pharmacokinetic (laboratory) services (CPKS) have been established in many hospitals to evaluate the response of the patient to the recommended dosage regimen.
  • 10.
  • 11. AGE (CHILDREN) New born have low GFR & tubular transport is not matured. Similarly, hepatic drug metabolizing system is inadequate in new born. BBB is more permeable, hence drugs attain higher concentration in CNS. Drug absorption may also be altered in infants because of lower gastric acidity & slower intestinal transit. As skin is thin, transdermal absorption of drugs is faster & is more permeable. At one year, drug metabolism is faster than in adults Ex. Theophylline, Phenytoin, CBZ hence higher dose may be required.
  • 12. The dose of a drug for children is often calculated from adult dose Young’s formula child dose = age/age+12 X AD Dilling’s formula child dose=age/20 X AD Clerk’s rule: wt in pounds/150 X AD Fried’s rule: age in months/150 X AD
  • 13. AGE As the age progresses, the renal functions are progressively declines Decline in liver blood flow & reduction in hepatic microsomal enzymes results in drug accumulation Slow absorption due to reduced intestinal motility & decreased blood flow, decreased plasma protein binding due to low plasma albumin Increased chances of drug interactions as a result of polypharmacy
  • 14. DISEASE GI disease: Alter absorption of orally administered drugs Decreased absorption of amoxycillin in coeliac disease Decreased absorption in achlorhydria. Liver disease: Bioavailability of drugs which have high first pass metabolism is increased Decreased serum albumin decreased protein binding of acidic drugs increased free form of drugs Decreased metabolism & elimination hence reduce the dose Prefer alternate drugs that do not depend on hepatic metabolism for elimination or those have short half-life Ex. Consider oxazepam or lorazepam instead of diazepam Avoid prodrugs as they need hepatic metabolism for activation
  • 15. Kidney disease: Clearence of drugs such as aminoglycosides, digoxin, phenobarbitone decreases Altered structure of plasma protein (albumin) in renal failure results in decreased binding of acidic drugs Throid disease: Hypothyroid patients are more sensitive to digoxin, morphine & CNS depressants Hyperthyroid patients are relatively resistant to inotropic action but more prone to arrhythmic action of digoxin
  • 16. Body weight: Influences the concentration of drug at the site of action An adult dose refers to an individual of medium built Hence for obese or lean individuals & for children the dose must be calculated based on body weight Individual dose = BW x Avg.adult dose/70 BSA provides accurate basis for dose calculations because total body water, ECF volume & metabolic activity are better paralleled by BSA Individual dose = BSA X Avg. Adult dose / 1.7
  • 18. ABSORBTION DRUG INTERACTIONS INHIBITION OF DRUG ABSORPTION • Various drugs and dietary supplements can decrease the absorption of drugs from the GIT. Antacids containing magnesium and aluminum hydroxide often interfere with absorption of many drugs. Coadministration of magnesium and aluminum hydroxide caused a decrease of plasma levels of PERFLOXACIN, TETRACYCLINS, DIGOXIN, THYROXIN etc. • These drugs should be given at least 2 hours before the antacid to ensure sufficient therapeutic efficacy • Sucralfate used for ulcer, is an aluminum glycopyranoside complex that is not absorbed but retards the oral absorption of ciprofloxacin.. Cholestyramine is an anion-exchange resin that binds bile acid and many drugs in the gastrointestinal tract. Cholestyramine can bind digitoxin in the GI tract and shorten the elimination half-life of digitoxin by approximately 30%–40%. Absorption of thyroxine may be reduced by 50% when it is administered closely with cholestyramine.
  • 19.
  • 20.
  • 21.
  • 22. • Nonhepatic enzymes can be involved in drug interactions. For example, drug interactions have been reported for patients taking linezolid (Zyvox) who are concurrently taking certain psychiatric medications. • Linezolid is a reversible monoamine oxidase inhibitor (MAOI). Serotonergic psychiatric antidepressant drugs such as citalopram, paroxetine, fluoxetine, sertraline, and other drugs that affect the serotonergic pathway in the brain. MAOIs, such as phenelzine and isocarboxazid, are also contraindicated., linezolid inhibits the action of monoamine oxidase A responsible for breaking down serotonin in the brain. It is believed that when linezolid is given to patients taking serotonergic psychiatric medications, high levels of serotonin can build up in the brain, causing toxicity. This is referred to as serotonin syndrome. Its signs and symptoms include mental changes (confusion, hyperactivity, memory problems), muscle twitching,
  • 23. Grapefruit–Drug Interactions • grapefruit juice, can significantly inhibit the metabolism by gut-wall cytochrome P-450 3A4 (CYP3A4) • For example, grapefruit juice increases average felodipine levels about threefold, increases cyclosporine levels, and increases the levels of terfenadine, a common antihistamine. In the case of terfenadine, Spence (1997) reported the death of a 29- year-old man who had been taking terfenadine and drinking grapefruit juice 2–3 times per week. Death was attributed to terfenadine toxicity. • Grapefruit juice can also affect P-gp-mediated efflux of some drugs.
  • 24. ALTERED RENAL REABSORPTION DUE TO CHANGING URINARY pH • The normal adult urinary pH ranges from 4.8 to 7.5 but can increase due to chronic antacid use. This change in urinary pH affects the ionization and reabsorption of weak electrolyte drugs. • An increased ionization of salicylate due to an increase in urine pH reduces salicylate reabsorption in the renal tubule, resulting in increased renal excretion. • Basic drugs tend to have longer half-lives when urinary pH is increased.
  • 25.
  • 26. Genetics: Genetic differences determine the disposition of a given drug in an individual Drug disposition is determined by rate kinetics of ADME, hence genetic differences determining various physiological processes affect the plasma levels of drugs eventually determining the differences in drug response by an individual
  • 27. CytP 450 major enz system involved with metabolism of all xenobiotics. The metabolic capacity of this enz system is not equal in all members of a population Hence we observe a wide inter individual variations in the rates of metabolism of some drugs
  • 28. Pantoprazole/omeprazole metabolises in liver via cyt CYP2C19 & CYP3A48 Antidepressants paroxetine & fluoxatine extensively metabolised via cyt CYP2D6 Glimipride via cyt CYP2C9 Cyt p typically show large inter individual differences in activity that lead to differences in drug response
  • 29. Hence metabolism & excretion of drugs vary between individuals 3% of caucasians & 15% asians are poor metabolizers 12% of north indians are poor metabolizers (pantoprazole) Collectively several hundred genes & their alleles & protein products determine the overall drug disposition in an individual
  • 30. In pharmacogenomics, attempts are made to determine & quantify these genetic variations & use them in predicting drug disposition by an individual Genotyping techniques for cyt p 450 enz can be used to predict one’s disposition to a given class of drugs without doing any evaluation of PK parameters Which can be used for deciding choice of drug & its dose
  • 31. Based on genotyping methods individuals may be classified as poor , intermediate, extensive & ultra rapid metabolizers for a group of given drugs Poor metabolizers will develop higher SDC in comparison with extensive metabolizers, hence they are at increased risk of developing concentration dependent ADRs Ultra rapid metabolizers will not reach therapeutic SDC upon treatment with standard doses, hence fail to respond to treatment
  • 32. If the parent compound is a prodrug, which requires bio activation by the enz to a active form, the effect of polymorphism can be quite complex in poor metabolizers and ultra rapid metabolizers Hence these individuals differences in drug disposition could be compensated by dosage adjustment according to metabolic capacity, determination of drug metabolism genotypes
  • 33. • Poor metabolizers and ultra rapid metabolizers can be identified & dosage could be tailored to the individual patient in order to reach therapeutic levels of drug in plasma, which may help to avoid ADRs or therapeutic failures
  • 34. Atypical pseudocholinesterase – prolonged succinylcholine apneoa G6PD deficiency- hemolysis with primaquine, sulfonamides, dapsone, quinine, chloroquine etc Acetylator polymorphism-INH neuropathy, procainamide & hydralazine induced lupus in slow acetylators Acute intermittent porphyria- precipitated by barbiturates due to genetic defects in repression of porphyrin synthesis