The document provides an overview of drug metabolism. It discusses that drug metabolism is important as it converts lipophilic drugs to hydrophilic metabolites that can be readily excreted. The key sites of drug metabolism are the liver, GI tract, lungs and kidneys. Metabolism occurs via phase I and phase II reactions and can activate or deactivate drugs. Factors like enzymes, diet and disease can influence a drug's metabolism. Understanding metabolism is important for predicting drug interactions and toxicity.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
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
1. Introduction
2. Phases of metabolism
3. Phase-I Metabolism
4. Cytochrome P family
5. Phase –II Metabolism
6. First pass metabolism
7. Ante Drugs
8. Microsomal Enzymes induction
Role of metabolism in drug discovery
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with pharmacokinetics : concept of linear and non-linear compartment models.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
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
1. Introduction
2. Phases of metabolism
3. Phase-I Metabolism
4. Cytochrome P family
5. Phase –II Metabolism
6. First pass metabolism
7. Ante Drugs
8. Microsomal Enzymes induction
Role of metabolism in drug discovery
Polymorphism affecting Drug Metabolism.pptxAnagha R Anil
Genetic polymorphisms can profoundly influence drug metabolism, impacting how medications are processed in the body. Variations in genes encoding drug-metabolizing enzymes, like cytochrome P450 (CYP) enzymes, can lead to differences in drug efficacy and safety among individuals. This presentation provides a concise overview of how polymorphisms affect drug metabolism.
Introduction to drug metabolism case studies for its impacts on drug discover...SAPA-GP
2014/10/02 SAPA-GP Webinar:
Introduction to drug metabolism case studies for its impacts on drug discovery and development
Zhoupeng Zhang
Dept of Pharmacokinetics, Pharmacodynamics, and Drug Metabolism
Merck Research Laboratories
Sino-American Pharmaceutical Professionals Association (SAPA)
– A lecture for Medicinal Chemists
(October 2, 2014)
GENETIC POLYMORPHISM IN DRUG METABOLISM.pptxAmeena Kadar
Genetic Polymorphism is one of the factors that affects the Drug metabolism. Cytochrome P - 450, one of the prominent group of metabolizing enzymes. In this ppt, genetic polymorphism of cytochrome p 450 is discussed.
This is a set of powerpoint slides with self-assessment questions interspersed throuought on drug metabolism and pharmacogenetics. The aim is to understand the mechanism of clinically significant drug interactions, recognize potentially clinically significant genetic influences on drug efficacy and toxicity, and genetic predispositions to disease due to altered drug metabolism or transport. This resource is appropriate for medical students or graduate healthcare professionals such as nursing students.
2. SEMINAR
ON
DRUG METABOLISM
UNDER THE GUIDANCE OF
K.SRIKANTH GUPTA
BY ASST.PROFESSOR
SAMEERA PRIP
M-PHARMACY -1YR
(PHARMACEUTICS) UNDER THE CO-GUIDANCE OF
11CM1S0313 V.RAMA MOHAN GUPTA
PRIP. PRINCIPAL & HOD
PRIP
8. IMPORTANCE OF METABOLISM
To obtain chemical energy
To synthesize complex molecules
To convert nutrient molecule into its precursor form
for future use
9.
10. •What is drug metabolism?
•Importance of drug metabolism? Why it is
necessary?
•How it will takes place?
•Where it will takes place?(sites of drug metabolism)
•When it will takes place ?
11. WHY DRUG METABOLISM IMPORTANT?
Drugs are mostly lipid soluble, easy to cross membranes, bind to plasma
proteins & reabsorb from renal tubules
Metabolism changes them to water soluble & easily excretable products; also
become inactive or less active
12. Termination of drug action
.Activation of prodrug
.Bioactivation and toxication
.Carcinogenesis
Tetratogenesis
13. Termination of Drug Action
Conversion of drug to active metabolite to active metabolite to
inactive metabolite
• Parent compound inactive metabolite
Atropine tropic acid & tropin
propranolol hydroxyl propranolol
14. Inactive active
parent compound metabolite
Eg: Levodopa dopamine
15. Some Xenobiotics Are Metabolized to
Carcinogenic Agents
• 3,4 Benzopyrene
• Aflatoxin
• N-Acetylaminofluorene
Metabolites of these agents interact with DNA
16. Small Amounts of Acetaminophen is Converted to the
Reactive Metabolite N-Acetyl benzo quinone imine
bioactivation
Bioactivation of acetaminophen; under certain conditions, the electrophile N-acetyl
benzo quinone imine reacts with tissue macromolecules, causing liver necrosis
17. Some drugs that produce active or toxic
metabolite
Inactive drugs Active metabolite:
(Pro-drugs)
Cyclophophamide Phosphoramide musrard
Prednisone prednisolone
Active drug Active metabolite
Amitriptyline Nortriptyline
Diazepam Oxazepam
Active drug Toxic metabolite
Halothane Trifluoroacetic acid
Paracetamol N-acetyl-p-benzo-quinone-imine
18. Thalidomide is a Teratogen
(teratogenesis)
THALIDOMIDE:
Fetal malformations in humans, monkeys, and rats occur due to
metabolism of the parent compound to a teratogen. This occurs very
early in gestation
19.
20. Sites of drug metabolism
Liver is the principal organ of drug metabolism
Other sites are GI mucosa, lungs, skin and kidneys
Every tissue has some ability to metabolize drugs
Some drugs, after oral administration (clonazepam & propranolol) are
extensively metabolized in GI or liver,
before reaching systemic circulation or sit of action,
called 1st pass effect, it reduces their bioavailability
In the liver cells metabolic enzymes are located in the smooth microsomes
of endoplasmic reticulum
21. CELLULAR SITES OF DRUG
METABOLISM
Cytosol
Mitochondria
Lysosomes
Smooth endoplasmic reticulum (microsomes)
23. Phases of drug metabolism(cont…)
Drug metabolism can be categorized to:
Phase-I reactions: oxidations, reductions & hydrolysis
Phase-II reactions: conjugations
Glucuronide conjugation
Aspirin Salicylic acid
COOH COOH
COOH
OCOCH3
OH OH
O OH
HO
Phase-I
Phase-II O
COOH
31. ENZYME INDUCTION8
ENZYME INDUCTION 8
• Enzyme Induction - increased enzyme protein levels in the
cell
•Phenobarbital type induction by many drugs
•Polycyclic hydrocarbon type induction by polycyclic
hydrocarbons such as 3,4-benzopyrene and 3-
methylcholanthrene
34. Consequences of Induction
Increased rate of metabolism
Decrease in drug plasma concentration
Enhanced oral first pass metabolism
Reduced bioavailability
If metabolite is active or reactive, increased
drug effects or toxicity
35. Therapeutic Implications of Induction
Most drugs can exhibit decreased efficacy due to rapid metabolism
but drugs with active metabolites can display
increased drug effect and/or toxicity due to enzyme
induction
Dosing rates may need to be increased to maintain
effective plasma concentrations
37. Consequences of
Inhibition
Increase in the plasma concentration of parent drug
Reduction in metabolite concentration
Exaggerated and prolonged pharmacological effects
Increased liklihood of drug-induced toxicity
38. Therapeutic implications
of Inhibition
May occur rapidly with no warning
Particularly effects drug prescribing for patients on multidrug regimens
Knowledge of the CYP450 metabolic pathway provides basis for
predicting and understanding inhibition
Esp drug drug interaction
39. Enzyme inhibitors &drugs affected by them
Inhibitor Drugs affected
MAO Barbiturates,Tyramine
Coumarins Phenytoin
Allopurinol 6-mercaptopurin
PAS Phenytoin
Hexobarbitol
42. Ethnic variations in the N-Acetylation of
Isoniazid
Ethnic group % of slow % of rapid
acetylators acetylators
Whiters 45 55
(USA,Canada)
Blacks(USA) 48 52
Latin Americans 67 33
American Indians 79 21
Japanes 87 13
Eskimos 98 05
44. DIET
Charcoal broiled foods (contain polycyclic
hydrocarbons that increase certain enzyme protein in
cells)
Grapefruit juice (the active component is the
furancoumarin 6,7-dihydroxybergamottin which
inhibits a certain a group of microsomal enzymes)
46. CONCLUSION:
Final conclusion of this study is enzymes will play a major
role In drug metabolism especially cyp 450 .Lack of these
enzymes will sometimes makes the drug low efficient
47. CASE STUDY
A37-year-old woman visited her dentist for removal of her
wisdom teeth. The teeth were found to be impacted, and
removal necessitated extensive surgery. Following completion
of the procedure on one side of the mouth, the patient was given
a prescription for acetaminophen 300 mg with codeine 30 mg
(combination product) for the relief of pain. The patient took
the prescription as prescribed for approximately 2 days, but
little pain relief was achieved. She called the dentist to get a
prescription for another analgesic. What is a possible explanation
for this lack of efficacy?
48.
49. REFERENCES
SATYANARAYANA BIOCHEMISTRY
J.L.JAIN FUNDAMENTALS OF BIOCHEMISTRY
HERPER’S BIOCHEMISTRY
MARTIN’S PHYSICAL PHARMACY
INTERNET
BRAHMANKER-BIOPHARMACEUTICS
VENKATESHWARLU-BIOPHARMACEUTICS
http://www.hospitalist.net/highligh.htm
DR.A.V.S.S.RAMA RAO –A TEXT BOOK OF BIOCHEMISTRY
LIPPINCOTT-MODERN PHARMACOLOGY WITH CLINICAL
APPLICATIONS
GOODMAN GILMAN-PRINCIPLES OF PHARMACOLOGY