SlideShare ist ein Scribd-Unternehmen logo
1 von 34
Downloaden Sie, um offline zu lesen
Stereochemistry&drug action- mounika.perli
STEREOCHEMISTRY AND DRUG ACTION
PRESENTED BY:
MOUNIKA.PERLI
I/II M.PHARMACY
REG NO:Y18MPH0225
UNDER THE GUIDENCE OF
RAMALINGESWARARAO.KASULA
(M.PHARM)
HINDU COLLEGE OF PHARMACY
CONTENTS
• STEREOCHEMISTRY
• TYPES OF ISOMERS
• CHIRALITY OF DRUGS
• EXAMPLES OF CHIRAL DRUGS
• PHARMACOKINETICS STEREOSELECTIVITY
stereochemistry
A branch of chemistry
that deals with the
spatial arrangement of
atoms and groups in
molecules
"stereo”- means “three
dimensionality’’
IMPORTANT DEFINITIONS
• CHIRALITY:
A chiral molecule/ion is non-
superposable on its mirror
image. The presence of an
asymmetric carbon center
is one of several structural
features that induce chirality in
organic and inorganic molecules.
• STEREOISOMERS: Isomers that have same molecular
formula and connectivity but differ in a way that
atoms are oriented in space – i.e; Difference between
isomers lies only in 3D arrangements of atoms.
• ENANTIOMER: Greek word: enantio : opposite
merons : parts
Stereoisomers with non superimposable mirror
images.
• DIASTEREOMER : Diastereomers are
stereoisomers that are not mirror images of
one another and are non-superimposable on
one another. Stereoisomers with two or more
stereocenters can be diastereomers.
TYPES OF ISOMERISMS
Stereoisomers
1. Configurational isomer :
# Geometric isomers :
(a) cis & trans system / E & Z system
# Relative configuration / Fischer projection ( L & D
configuration)
# Absolute configuration (R & S configuration)
L & D CONFIGURATION
R & S CONFIGURATION
•Priority of an atom is determined
by its atomic number
• Order of substituents going
from highest to lowest priority.
• Clockwise – R (rectus).
• Anticlockwise – S (sinister).
• Unless established
experimentally no idea whether
(+) or (-) rotation is associated
with R or S configuration
CHIRALITY OF DRUGS
• Chiral center arises when a carbon atom has
four structurally different groups attach to it.
• When a compound contain one or more
chiral center it is able to rotate plane polarized
light to the right (+) or the left (-)
• E.g; Adrenaline can exist as two Enantiomers
that are mirror images of each others and thus
known as non-superimposable
ADRENALINE
• Adrenaline Enantiomers have identical ,physical and
chemical properties , the only in their properties is that the
Enantiomers rotate plane polarize light in opposite
direction , both Enantiomers have different biological
properties
• The negative Enantiomers exert stronger effect i.e; Heart
rate increases
• Device which is used to determine the direction in which a
molecule rotate plane polarize light is polarimeter.
• X-ray crystallography of adrenaline Enantiomers shown
that negative form has R configuration and the positive
form has S configuration
Importance of the chirality in drugs
• This stereoisomerism results in different physical and
chemical properties of the compound. If this compound
happens to be drug then it results in different
pharmacokinetic and pharmacodynamic properties
• The importance of chiral drugs in the drug development
space cannot be understated. In pharmaceutical industries,
56% of the drugs currently in use are chiral molecules and
88% of the last ones are marketed as racemates (or racemic
mixtures), consisting of an equimolar mixture of two
enantiomers.
Thalidomide-disastrous biological
activity of the wrong enantiomer
• In 1960 in Europe, racemic thalidomide
was given to pregnant females to cure
morning sickness.
• This led to deformations in babies and
neurotoxic effects.
• These were due to S-thalidomide.
• R-thalidomide contained the desired
therapeutic activity
EXAMPLES OF CHIRAL DRUGS
• INTRAVENOUS ANAESTHETICS
• LOCAL ANAESTHETICS
• INHALATIONAL AGENTS
• NUEROMUSCULAR BLOCKING AGENTS
• SOME OTHER DRUGS
Intravenous anaesthetics
1.Etomidate
• Administered as a single isomer: R-isomer.
• Site of action: GABAA receptor.
• R-isomer is 15 times more potent than the S-isomer.
• S-isomer lacks hypnotic activity.
2. Ketamine
• S- Ketamine is 2-4 times more potent than R Ketamine as an
anaesthetic and analgesic agent.Rketamine: Emergence
reactions like hallucinations, vivid dreams and agitation
•Metabolism of S- Ketamine by liver microsomes is 20%
greater than R- Ketamine and 10% greater than the racemate
– faster clearance of the drug.
LOCAL ANAESTEHTICS
1.BUPIVACAINE
Long acting local anaesthetic marketed as 50:50 racemic
mixture.
Reports of death due to
• Bupivacaine induced CNS toxicity and
cardiotoxicity on accidental intravenous injection
and difficult resuscitation following cardiotoxicity.
Safer alternatives
• Levobupivacaine
• Ropivacaine
These are S- enantiomers of bupivacaine.
• Ropivacaine is the first ‘pure’ enantiomer containing
>99% of the S-form.
INHALATIONAL AGENTS
Isoflurane
•Some studies have found S(+)-isoflurane to be 50%
more potent than R(-)- isoflurane while other studies
have found no significant difference.
•Both enantiomers are equally soluble in the lipid bilayers.
•S- isoflurane induced about 50% longer sleep
times than R- isoflurane
•Majority of the inhalational agents
•currently used are chiral except, Sevoflurane
NEUROMUSCULAR BLOCKING AGENTS
1. Atracurium
• Intermediate duration non-depolarizing
neuromuscular blocker.
• Causes histamine release, transient hypotension,
tachycardia, facial or truncal flushing.
• Continuous infusion in critical patients can lead to
laudanosine accumulation, which is
epileptogenic.
• Its structure contains 4 chiral centres and is a
mixture of 10 optical and geometric isomers.
Potential advantages of single
enantiomer products
• Less complex, more selective
pharmacodynamic profile
• Potential for an improved therapeutic index
• Less complex pharmacokinetic profile
Reduced potential for complex drug interactions
• Less complex relationship between
plasma concentration and effect
Biological Discrimination
Pharmacokineticsstereoselectivity
1.Absorption
* Passive intestinal absorption
* Carrier transporter stereoselectivity
2.Distribution
* Protein binding
* Tissue distribution
3.Metabolism
* first pass metabolism
* Phase I and phase II metabolism
4.Elimination
Absorption and stereoselectivity
Passive intestinal absorption
For the majority of racemic drugs, absorption appears
to be by passive diffusion , provided no
stereoselectivity.
Carrier mediated
transporter
Stereo selective
intestinal transporter is
the main cause for
marked differences in
the oral absorption of
enantiomers.
L-Methotrexate have
40 fold higher Cmax
and AUC than
D-Methotrexate.
Distribution
Protein binding
Stereo selective plasma protein binding could influence
distribution and elimination because the major
determinant of drug distribution and elimination is
protein binding.
The enantiomers may display different magnitudes of
stereoselectivity between the various proteins found in
plasma
Ex// the R- propranolol binding to albumin is greater than
S- propranolol and the opposite is observed for 1 -acid
glycoprotein.
* Highly albumin bound
* Less potent
*highly bound to AAG
available as unbound
* 40-100 time more
potent
Metabolism
first pass metabolism
Stereo selective drug
metabolism is commonly
observed in vitro for
racemic drugs and can
results in substantial
differences in the vivo
plasma concentration -
time profiles between
enantiomers due to
stereo selective
bioavailability or drug
disposition.
Phase I and phase II metabolism
The magnitude of stereoselectivity depends on the
metabolic pathways involved drug metabolism.
some time the two isomers compete with each
other to bind the enzyme binding site, this result in
inhibition the metabolism of the one enantiomer.
Ex// propaphenon
Stereochemistry&drug action- mounika.perli
REFERENCES
• https://www.slideshare.net/AZMINMOGAL/stereoch
emistry-83184901?qid=6fc35486-740a-
45b083bdf812d3804882&v=&b=&from_search=3
• https://www.slideshare.net/arzoodharasandiya/case
-study-of-stereochemistry-and-drug-design-
85443779?qid=6fc35486-740a-45b0-83bd-
f812d3804882&v=&b=&from_search=2
• https://www.slideshare.net/rudramadhab1/chiral-
drug?qid=37d78d5f-a23d-4f72-8268-
08b3b65105f7&v=&b=&from_search=7
Stereochemistry&drug action- mounika.perli

Weitere ähnliche Inhalte

Was ist angesagt?

study of natural products as leads for new pharmaceuticals for the various cl...
study of natural products as leads for new pharmaceuticals for the various cl...study of natural products as leads for new pharmaceuticals for the various cl...
study of natural products as leads for new pharmaceuticals for the various cl...Subham Kumar Vishwakarma
 
ANALOG DESIGN.pdf
ANALOG DESIGN.pdfANALOG DESIGN.pdf
ANALOG DESIGN.pdfShivalingMP
 
QSAR applications: Hansch analysis and Free Wilson analysis, CADD
QSAR applications: Hansch analysis and Free Wilson analysis, CADDQSAR applications: Hansch analysis and Free Wilson analysis, CADD
QSAR applications: Hansch analysis and Free Wilson analysis, CADDGagangowda58
 
Characterization of penicillin.pptx
Characterization of penicillin.pptxCharacterization of penicillin.pptx
Characterization of penicillin.pptxPranav Ambast
 
Combating Drug resistance
Combating Drug resistanceCombating Drug resistance
Combating Drug resistanceHarendra Bisht
 
Biological Drug Targets.pptx
Biological Drug Targets.pptxBiological Drug Targets.pptx
Biological Drug Targets.pptxVarshaJindaniya
 
PRODRUG DESIGN [M.PHARM]
PRODRUG DESIGN [M.PHARM]PRODRUG DESIGN [M.PHARM]
PRODRUG DESIGN [M.PHARM]Shikha Popali
 
Case study of stereo-chemistry and drug design
Case study of stereo-chemistry and drug designCase study of stereo-chemistry and drug design
Case study of stereo-chemistry and drug designarzoo dharasandiya
 
Active constituent of drugs used in diabetic therapy
Active constituent of drugs used in diabetic therapyActive constituent of drugs used in diabetic therapy
Active constituent of drugs used in diabetic therapyAkshay Kank
 
Synthesis Of Hetero-cyclic Drugs
Synthesis Of Hetero-cyclic DrugsSynthesis Of Hetero-cyclic Drugs
Synthesis Of Hetero-cyclic DrugsNirali Mistry
 
Elucidation of flavonoids
Elucidation of flavonoidsElucidation of flavonoids
Elucidation of flavonoidsPraveen Parkali
 
Reactions of heterocyclic chemistry
 Reactions of heterocyclic chemistry Reactions of heterocyclic chemistry
Reactions of heterocyclic chemistrysuraj wanjari
 
Role of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agentRole of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agentKaranvir Rajput
 
Rational design of non- covalently and covalently binding.pptx
Rational design of non- covalently and covalently binding.pptxRational design of non- covalently and covalently binding.pptx
Rational design of non- covalently and covalently binding.pptxRashuRaju
 
QSAR by hansch analysis
QSAR by hansch analysisQSAR by hansch analysis
QSAR by hansch analysiskholood adil
 
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]Shikha Popali
 
Bernthsen acridine synthesis (CHEMISTRIAN)
Bernthsen acridine synthesis (CHEMISTRIAN)Bernthsen acridine synthesis (CHEMISTRIAN)
Bernthsen acridine synthesis (CHEMISTRIAN)Shikha Popali
 

Was ist angesagt? (20)

study of natural products as leads for new pharmaceuticals for the various cl...
study of natural products as leads for new pharmaceuticals for the various cl...study of natural products as leads for new pharmaceuticals for the various cl...
study of natural products as leads for new pharmaceuticals for the various cl...
 
ANALOG DESIGN.pdf
ANALOG DESIGN.pdfANALOG DESIGN.pdf
ANALOG DESIGN.pdf
 
QSAR applications: Hansch analysis and Free Wilson analysis, CADD
QSAR applications: Hansch analysis and Free Wilson analysis, CADDQSAR applications: Hansch analysis and Free Wilson analysis, CADD
QSAR applications: Hansch analysis and Free Wilson analysis, CADD
 
Characterization of penicillin.pptx
Characterization of penicillin.pptxCharacterization of penicillin.pptx
Characterization of penicillin.pptx
 
Combating Drug resistance
Combating Drug resistanceCombating Drug resistance
Combating Drug resistance
 
Biological Drug Targets.pptx
Biological Drug Targets.pptxBiological Drug Targets.pptx
Biological Drug Targets.pptx
 
PRODRUG DESIGN [M.PHARM]
PRODRUG DESIGN [M.PHARM]PRODRUG DESIGN [M.PHARM]
PRODRUG DESIGN [M.PHARM]
 
Case study of stereo-chemistry and drug design
Case study of stereo-chemistry and drug designCase study of stereo-chemistry and drug design
Case study of stereo-chemistry and drug design
 
Active constituent of drugs used in diabetic therapy
Active constituent of drugs used in diabetic therapyActive constituent of drugs used in diabetic therapy
Active constituent of drugs used in diabetic therapy
 
Peptidomimetics
PeptidomimeticsPeptidomimetics
Peptidomimetics
 
Synthesis Of Hetero-cyclic Drugs
Synthesis Of Hetero-cyclic DrugsSynthesis Of Hetero-cyclic Drugs
Synthesis Of Hetero-cyclic Drugs
 
Elucidation of flavonoids
Elucidation of flavonoidsElucidation of flavonoids
Elucidation of flavonoids
 
Reactions of heterocyclic chemistry
 Reactions of heterocyclic chemistry Reactions of heterocyclic chemistry
Reactions of heterocyclic chemistry
 
Role of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agentRole of chirality in stereoselective and specific theraputic agent
Role of chirality in stereoselective and specific theraputic agent
 
Rational design of non- covalently and covalently binding.pptx
Rational design of non- covalently and covalently binding.pptxRational design of non- covalently and covalently binding.pptx
Rational design of non- covalently and covalently binding.pptx
 
QSAR by hansch analysis
QSAR by hansch analysisQSAR by hansch analysis
QSAR by hansch analysis
 
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
PEPTIDOMIMETICS [M.PHARM, BSC, MSC, B.PHARM]
 
Bernthsen acridine synthesis (CHEMISTRIAN)
Bernthsen acridine synthesis (CHEMISTRIAN)Bernthsen acridine synthesis (CHEMISTRIAN)
Bernthsen acridine synthesis (CHEMISTRIAN)
 
Traube purine synthesis
Traube purine synthesisTraube purine synthesis
Traube purine synthesis
 
Prodrug Design
Prodrug DesignProdrug Design
Prodrug Design
 

Ähnlich wie Stereochemistry&drug action- mounika.perli

Realization that stereo selectivity is a pre-requisite for evolution.pptx
Realization that stereo selectivity is a pre-requisite for evolution.pptxRealization that stereo selectivity is a pre-requisite for evolution.pptx
Realization that stereo selectivity is a pre-requisite for evolution.pptxParthaGhosh498013
 
Clinical pharmacokinetics and pharmacodynamics of stereo isomeric drugs
Clinical pharmacokinetics and pharmacodynamics of stereo isomeric drugsClinical pharmacokinetics and pharmacodynamics of stereo isomeric drugs
Clinical pharmacokinetics and pharmacodynamics of stereo isomeric drugsSazan Jamil Ali
 
stereoisomersautosaved-190208040126.pptx
stereoisomersautosaved-190208040126.pptxstereoisomersautosaved-190208040126.pptx
stereoisomersautosaved-190208040126.pptxNoorelhuda2
 
Role of Enantiomers in Pharmacology
Role of Enantiomers in PharmacologyRole of Enantiomers in Pharmacology
Role of Enantiomers in PharmacologyDr. Prashant Shukla
 
Stereoisomers in pharmacology
Stereoisomers in pharmacologyStereoisomers in pharmacology
Stereoisomers in pharmacologychandiniyrao
 
chiral pharmacokinetic
chiral pharmacokineticchiral pharmacokinetic
chiral pharmacokineticmaryam kazemi
 
Overview and determination of enantiomeric impurities
Overview and determination of enantiomeric impuritiesOverview and determination of enantiomeric impurities
Overview and determination of enantiomeric impuritiesVeeprho Laboratories
 
Drug excipient interaction assignment
Drug excipient interaction assignmentDrug excipient interaction assignment
Drug excipient interaction assignmentAtul Chaudhary
 
Drug excipient compatibility studies
Drug excipient compatibility studiesDrug excipient compatibility studies
Drug excipient compatibility studiesVaishnavi pandya
 

Ähnlich wie Stereochemistry&drug action- mounika.perli (20)

STEREOCHEMISTRY.pptx
STEREOCHEMISTRY.pptxSTEREOCHEMISTRY.pptx
STEREOCHEMISTRY.pptx
 
Chiral drugs
Chiral drugsChiral drugs
Chiral drugs
 
Realization that stereo selectivity is a pre-requisite for evolution.pptx
Realization that stereo selectivity is a pre-requisite for evolution.pptxRealization that stereo selectivity is a pre-requisite for evolution.pptx
Realization that stereo selectivity is a pre-requisite for evolution.pptx
 
Clinical pharmacokinetics and pharmacodynamics of stereo isomeric drugs
Clinical pharmacokinetics and pharmacodynamics of stereo isomeric drugsClinical pharmacokinetics and pharmacodynamics of stereo isomeric drugs
Clinical pharmacokinetics and pharmacodynamics of stereo isomeric drugs
 
medicinal chemistry .pptx
medicinal chemistry .pptxmedicinal chemistry .pptx
medicinal chemistry .pptx
 
Chiral drug
Chiral drugChiral drug
Chiral drug
 
stereoisomersautosaved-190208040126.pptx
stereoisomersautosaved-190208040126.pptxstereoisomersautosaved-190208040126.pptx
stereoisomersautosaved-190208040126.pptx
 
Regulatory requirements-Chiral drugs.pptx
Regulatory requirements-Chiral drugs.pptxRegulatory requirements-Chiral drugs.pptx
Regulatory requirements-Chiral drugs.pptx
 
Role of Enantiomers in Pharmacology
Role of Enantiomers in PharmacologyRole of Enantiomers in Pharmacology
Role of Enantiomers in Pharmacology
 
Stereoisomers in pharmacology
Stereoisomers in pharmacologyStereoisomers in pharmacology
Stereoisomers in pharmacology
 
chiral pharmacokinetic
chiral pharmacokineticchiral pharmacokinetic
chiral pharmacokinetic
 
Overview and determination of enantiomeric impurities
Overview and determination of enantiomeric impuritiesOverview and determination of enantiomeric impurities
Overview and determination of enantiomeric impurities
 
Peiper 1
Peiper 1Peiper 1
Peiper 1
 
Strereochemistry of drugs
Strereochemistry of drugsStrereochemistry of drugs
Strereochemistry of drugs
 
Drug excipient interaction assignment
Drug excipient interaction assignmentDrug excipient interaction assignment
Drug excipient interaction assignment
 
Drug excipient compatibility studies
Drug excipient compatibility studiesDrug excipient compatibility studies
Drug excipient compatibility studies
 
Drug discovery and design
Drug discovery and designDrug discovery and design
Drug discovery and design
 
Chiral catalysts
Chiral catalystsChiral catalysts
Chiral catalysts
 
Stereochemistry
StereochemistryStereochemistry
Stereochemistry
 
SAR of Morphine
SAR of MorphineSAR of Morphine
SAR of Morphine
 

Kürzlich hochgeladen

How to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesHow to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesCeline George
 
HED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdfHED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdfMohonDas
 
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptxClinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptxraviapr7
 
General views of Histopathology and step
General views of Histopathology and stepGeneral views of Histopathology and step
General views of Histopathology and stepobaje godwin sunday
 
M-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptxM-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptxDr. Santhosh Kumar. N
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17Celine George
 
3.21.24 The Origins of Black Power.pptx
3.21.24  The Origins of Black Power.pptx3.21.24  The Origins of Black Power.pptx
3.21.24 The Origins of Black Power.pptxmary850239
 
CAULIFLOWER BREEDING 1 Parmar pptx
CAULIFLOWER BREEDING 1 Parmar pptxCAULIFLOWER BREEDING 1 Parmar pptx
CAULIFLOWER BREEDING 1 Parmar pptxSaurabhParmar42
 
Quality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICEQuality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICESayali Powar
 
What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?TechSoup
 
Practical Research 1: Lesson 8 Writing the Thesis Statement.pptx
Practical Research 1: Lesson 8 Writing the Thesis Statement.pptxPractical Research 1: Lesson 8 Writing the Thesis Statement.pptx
Practical Research 1: Lesson 8 Writing the Thesis Statement.pptxKatherine Villaluna
 
Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.raviapr7
 
How to Use api.constrains ( ) in Odoo 17
How to Use api.constrains ( ) in Odoo 17How to Use api.constrains ( ) in Odoo 17
How to Use api.constrains ( ) in Odoo 17Celine George
 
Maximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdf
Maximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdfMaximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdf
Maximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdfTechSoup
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17Celine George
 
Human-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming ClassesHuman-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming ClassesMohammad Hassany
 
How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17Celine George
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxDr. Asif Anas
 
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptxPISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptxEduSkills OECD
 

Kürzlich hochgeladen (20)

How to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 SalesHow to Manage Cross-Selling in Odoo 17 Sales
How to Manage Cross-Selling in Odoo 17 Sales
 
HED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdfHED Office Sohayok Exam Question Solution 2023.pdf
HED Office Sohayok Exam Question Solution 2023.pdf
 
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptxClinical Pharmacy  Introduction to Clinical Pharmacy, Concept of clinical pptx
Clinical Pharmacy Introduction to Clinical Pharmacy, Concept of clinical pptx
 
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdfPersonal Resilience in Project Management 2 - TV Edit 1a.pdf
Personal Resilience in Project Management 2 - TV Edit 1a.pdf
 
General views of Histopathology and step
General views of Histopathology and stepGeneral views of Histopathology and step
General views of Histopathology and step
 
M-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptxM-2- General Reactions of amino acids.pptx
M-2- General Reactions of amino acids.pptx
 
How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17How to Add a New Field in Existing Kanban View in Odoo 17
How to Add a New Field in Existing Kanban View in Odoo 17
 
3.21.24 The Origins of Black Power.pptx
3.21.24  The Origins of Black Power.pptx3.21.24  The Origins of Black Power.pptx
3.21.24 The Origins of Black Power.pptx
 
CAULIFLOWER BREEDING 1 Parmar pptx
CAULIFLOWER BREEDING 1 Parmar pptxCAULIFLOWER BREEDING 1 Parmar pptx
CAULIFLOWER BREEDING 1 Parmar pptx
 
Quality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICEQuality Assurance_GOOD LABORATORY PRACTICE
Quality Assurance_GOOD LABORATORY PRACTICE
 
What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?What is the Future of QuickBooks DeskTop?
What is the Future of QuickBooks DeskTop?
 
Practical Research 1: Lesson 8 Writing the Thesis Statement.pptx
Practical Research 1: Lesson 8 Writing the Thesis Statement.pptxPractical Research 1: Lesson 8 Writing the Thesis Statement.pptx
Practical Research 1: Lesson 8 Writing the Thesis Statement.pptx
 
Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.Drug Information Services- DIC and Sources.
Drug Information Services- DIC and Sources.
 
How to Use api.constrains ( ) in Odoo 17
How to Use api.constrains ( ) in Odoo 17How to Use api.constrains ( ) in Odoo 17
How to Use api.constrains ( ) in Odoo 17
 
Maximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdf
Maximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdfMaximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdf
Maximizing Impact_ Nonprofit Website Planning, Budgeting, and Design.pdf
 
How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17How to Make a Field read-only in Odoo 17
How to Make a Field read-only in Odoo 17
 
Human-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming ClassesHuman-AI Co-Creation of Worked Examples for Programming Classes
Human-AI Co-Creation of Worked Examples for Programming Classes
 
How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17How to Show Error_Warning Messages in Odoo 17
How to Show Error_Warning Messages in Odoo 17
 
Ultra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptxUltra structure and life cycle of Plasmodium.pptx
Ultra structure and life cycle of Plasmodium.pptx
 
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptxPISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
PISA-VET launch_El Iza Mohamedou_19 March 2024.pptx
 

Stereochemistry&drug action- mounika.perli

  • 2. STEREOCHEMISTRY AND DRUG ACTION PRESENTED BY: MOUNIKA.PERLI I/II M.PHARMACY REG NO:Y18MPH0225 UNDER THE GUIDENCE OF RAMALINGESWARARAO.KASULA (M.PHARM) HINDU COLLEGE OF PHARMACY
  • 3. CONTENTS • STEREOCHEMISTRY • TYPES OF ISOMERS • CHIRALITY OF DRUGS • EXAMPLES OF CHIRAL DRUGS • PHARMACOKINETICS STEREOSELECTIVITY
  • 4. stereochemistry A branch of chemistry that deals with the spatial arrangement of atoms and groups in molecules "stereo”- means “three dimensionality’’
  • 5. IMPORTANT DEFINITIONS • CHIRALITY: A chiral molecule/ion is non- superposable on its mirror image. The presence of an asymmetric carbon center is one of several structural features that induce chirality in organic and inorganic molecules.
  • 6. • STEREOISOMERS: Isomers that have same molecular formula and connectivity but differ in a way that atoms are oriented in space – i.e; Difference between isomers lies only in 3D arrangements of atoms.
  • 7. • ENANTIOMER: Greek word: enantio : opposite merons : parts Stereoisomers with non superimposable mirror images. • DIASTEREOMER : Diastereomers are stereoisomers that are not mirror images of one another and are non-superimposable on one another. Stereoisomers with two or more stereocenters can be diastereomers.
  • 9. Stereoisomers 1. Configurational isomer : # Geometric isomers : (a) cis & trans system / E & Z system # Relative configuration / Fischer projection ( L & D configuration) # Absolute configuration (R & S configuration)
  • 10. L & D CONFIGURATION
  • 11. R & S CONFIGURATION •Priority of an atom is determined by its atomic number • Order of substituents going from highest to lowest priority. • Clockwise – R (rectus). • Anticlockwise – S (sinister). • Unless established experimentally no idea whether (+) or (-) rotation is associated with R or S configuration
  • 12. CHIRALITY OF DRUGS • Chiral center arises when a carbon atom has four structurally different groups attach to it. • When a compound contain one or more chiral center it is able to rotate plane polarized light to the right (+) or the left (-) • E.g; Adrenaline can exist as two Enantiomers that are mirror images of each others and thus known as non-superimposable
  • 13. ADRENALINE • Adrenaline Enantiomers have identical ,physical and chemical properties , the only in their properties is that the Enantiomers rotate plane polarize light in opposite direction , both Enantiomers have different biological properties • The negative Enantiomers exert stronger effect i.e; Heart rate increases • Device which is used to determine the direction in which a molecule rotate plane polarize light is polarimeter. • X-ray crystallography of adrenaline Enantiomers shown that negative form has R configuration and the positive form has S configuration
  • 14. Importance of the chirality in drugs • This stereoisomerism results in different physical and chemical properties of the compound. If this compound happens to be drug then it results in different pharmacokinetic and pharmacodynamic properties • The importance of chiral drugs in the drug development space cannot be understated. In pharmaceutical industries, 56% of the drugs currently in use are chiral molecules and 88% of the last ones are marketed as racemates (or racemic mixtures), consisting of an equimolar mixture of two enantiomers.
  • 15. Thalidomide-disastrous biological activity of the wrong enantiomer • In 1960 in Europe, racemic thalidomide was given to pregnant females to cure morning sickness. • This led to deformations in babies and neurotoxic effects. • These were due to S-thalidomide. • R-thalidomide contained the desired therapeutic activity
  • 16. EXAMPLES OF CHIRAL DRUGS • INTRAVENOUS ANAESTHETICS • LOCAL ANAESTHETICS • INHALATIONAL AGENTS • NUEROMUSCULAR BLOCKING AGENTS • SOME OTHER DRUGS
  • 17. Intravenous anaesthetics 1.Etomidate • Administered as a single isomer: R-isomer. • Site of action: GABAA receptor. • R-isomer is 15 times more potent than the S-isomer. • S-isomer lacks hypnotic activity.
  • 18. 2. Ketamine • S- Ketamine is 2-4 times more potent than R Ketamine as an anaesthetic and analgesic agent.Rketamine: Emergence reactions like hallucinations, vivid dreams and agitation •Metabolism of S- Ketamine by liver microsomes is 20% greater than R- Ketamine and 10% greater than the racemate – faster clearance of the drug.
  • 19. LOCAL ANAESTEHTICS 1.BUPIVACAINE Long acting local anaesthetic marketed as 50:50 racemic mixture. Reports of death due to • Bupivacaine induced CNS toxicity and cardiotoxicity on accidental intravenous injection and difficult resuscitation following cardiotoxicity. Safer alternatives • Levobupivacaine • Ropivacaine These are S- enantiomers of bupivacaine. • Ropivacaine is the first ‘pure’ enantiomer containing >99% of the S-form.
  • 20. INHALATIONAL AGENTS Isoflurane •Some studies have found S(+)-isoflurane to be 50% more potent than R(-)- isoflurane while other studies have found no significant difference. •Both enantiomers are equally soluble in the lipid bilayers. •S- isoflurane induced about 50% longer sleep times than R- isoflurane •Majority of the inhalational agents •currently used are chiral except, Sevoflurane
  • 21. NEUROMUSCULAR BLOCKING AGENTS 1. Atracurium • Intermediate duration non-depolarizing neuromuscular blocker. • Causes histamine release, transient hypotension, tachycardia, facial or truncal flushing. • Continuous infusion in critical patients can lead to laudanosine accumulation, which is epileptogenic. • Its structure contains 4 chiral centres and is a mixture of 10 optical and geometric isomers.
  • 22. Potential advantages of single enantiomer products • Less complex, more selective pharmacodynamic profile • Potential for an improved therapeutic index • Less complex pharmacokinetic profile Reduced potential for complex drug interactions • Less complex relationship between plasma concentration and effect
  • 24. Pharmacokineticsstereoselectivity 1.Absorption * Passive intestinal absorption * Carrier transporter stereoselectivity 2.Distribution * Protein binding * Tissue distribution 3.Metabolism * first pass metabolism * Phase I and phase II metabolism 4.Elimination
  • 25. Absorption and stereoselectivity Passive intestinal absorption For the majority of racemic drugs, absorption appears to be by passive diffusion , provided no stereoselectivity.
  • 26. Carrier mediated transporter Stereo selective intestinal transporter is the main cause for marked differences in the oral absorption of enantiomers. L-Methotrexate have 40 fold higher Cmax and AUC than D-Methotrexate.
  • 27. Distribution Protein binding Stereo selective plasma protein binding could influence distribution and elimination because the major determinant of drug distribution and elimination is protein binding. The enantiomers may display different magnitudes of stereoselectivity between the various proteins found in plasma
  • 28. Ex// the R- propranolol binding to albumin is greater than S- propranolol and the opposite is observed for 1 -acid glycoprotein. * Highly albumin bound * Less potent *highly bound to AAG available as unbound * 40-100 time more potent
  • 29. Metabolism first pass metabolism Stereo selective drug metabolism is commonly observed in vitro for racemic drugs and can results in substantial differences in the vivo plasma concentration - time profiles between enantiomers due to stereo selective bioavailability or drug disposition.
  • 30. Phase I and phase II metabolism The magnitude of stereoselectivity depends on the metabolic pathways involved drug metabolism.
  • 31. some time the two isomers compete with each other to bind the enzyme binding site, this result in inhibition the metabolism of the one enantiomer. Ex// propaphenon