The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
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.
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
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.
Lecture "The food metabolome" by C. Manach (INRA Clermont-Ferrand, France) at the 1st International workshop on "The Food metabolome and biomarkers for dietary exposure. Metabolomic approaches for biomarker discovery, validation and implementation" (Glasgow, 5th July, 2013)
Drug metabolism /certified fixed orthodontic courses by Indian dental academy Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Metabolizer is a new tool from ChemAxon to predict and rank the metabolites of drugs and xenobiotics. Metabolizer contains a built-in library of human biotransformation schemes which were collected from literature although users can also add their own library to customize the calculation. The presentation will include insight to some technical details, initial results and statistics, explanation of the key metabolic indicators, and the method of major metabolite identification.
biotransformation of drug
Biotransformation/Xenobiotic metabolism/ drug metabolism/detoxification.
-Xenobiotics: a wide variety of foreign compounds to which humans get exposed in day to day life.
-It includes unknown compounds, drugs, environmental pollutants, toxins.
-Many xenobiotics can evoke biological responses.
DEFINITION
The biochemical alteration of drug or xenobiotic in the presence of various enzymes that acts as a catalyst which themselves not consumed in the reaction and there by may activate or deactivate the drug is called biotransformation.
Why Biotransformation is necessary?:
To easily eliminate the drug
To terminate drug action by inactivating it
Consequences of Biotransformation
Active to Inactive:
Phenobarbitone---- Hydroxyphenobarbitone
Inactive (prodrug) to Active :
L-Dopa ---- Dopamine
Parathion -- Paraoxon
Talampicillin -- Ampicillin
Active to equally active:
Diazepam -- Oxazepam
Amitriptyline -- Nortriptyline
Imipramine -- Des-imipramine
Codeine -- Morphine
Sites of biotransformation
In the body: Liver, small and large intestines, lungs, skin, kidney, nasal mucosa & brain.
Liver is considered “metabolite clearing house” for both endogenous substances and xenobiotics.
Intestines are considered “initial site of drug metabolism”.
FIRST PASS METABOLISM:
First pass metabolism or presystemic
metabolism or ‘first pass effect’
After oral administeration many drugs are absorbed from the small intestine - transported first via portal system to the liver, where they undergo extensive metabolism before reaching systemic circulation.
fundamental concepts in drug biotransformation
Lipid soluble drugs are poorly excreted in the urine. They tend to store in fat and/or circulate until they are converted (phase I biotransformation) to more water soluble metabolites or metabolites that conjugate (phase II biotransformation) with water soluble substances.
Water soluble drugs are more readily excreted in the urine. They may be metabolized, but generally not by the CYP enzyme systems.
Enzymes catalyzing phase I biotransformation reactions
Enzymes catalyzing phase I biotransformation reactions include:
cytochrome P-450
aldehyde and alcohol dehydrogenase
deaminases
esterases
amidases
epoxide hydratases
Addition of water
Cleavage of R-O or R-N bond accompanied by addition of H2O
CYTOCHROME P450
The cytochrome P-450 families are referred to using an arabic numeral, e.g., CYP1, CYP2, etc.
Each family has a number of subfamilies denoted by an upper case letter, e.g., CYP2A, CYP2B, etc.
The individual enzymes within each subfamily are denoted by another arabic numeral, e.g., CYP3A1, CYP3A2, etc.
www.linkedin.com/in/dr-aboobecker-siddique-p-a-200783a0
pharmacokinetics 2
fate of a drug
biotransformation :
Chemical alteration of the drug in a living organism is called bio-transformation.
Lipid soluble →Water soluble
So that not reabsorbed in Kidney
Site-Mainly liver
Others-Kidney, lungs, plasma, gut mucosa & skin
metabolism
xenonbiotics
microsomal enzyme induction
excretion
kinetics of elimination
metabolism of xenobiotis, drugs, medicine, carcinogen generation by enzymes like cyt p450 mono oxigenases, prostaglandin synthase ect. alcohol metabolism, toxin metabolism, definition of genobiotics, biotransformation, detoxification. effects on health
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
Speakers:
👨🏫 Andras Palfi, Senior Product Manager, UiPath
👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
State of ICS and IoT Cyber Threat Landscape Report 2024 previewPrayukth K V
The IoT and OT threat landscape report has been prepared by the Threat Research Team at Sectrio using data from Sectrio, cyber threat intelligence farming facilities spread across over 85 cities around the world. In addition, Sectrio also runs AI-based advanced threat and payload engagement facilities that serve as sinks to attract and engage sophisticated threat actors, and newer malware including new variants and latent threats that are at an earlier stage of development.
The latest edition of the OT/ICS and IoT security Threat Landscape Report 2024 also covers:
State of global ICS asset and network exposure
Sectoral targets and attacks as well as the cost of ransom
Global APT activity, AI usage, actor and tactic profiles, and implications
Rise in volumes of AI-powered cyberattacks
Major cyber events in 2024
Malware and malicious payload trends
Cyberattack types and targets
Vulnerability exploit attempts on CVEs
Attacks on counties – USA
Expansion of bot farms – how, where, and why
In-depth analysis of the cyber threat landscape across North America, South America, Europe, APAC, and the Middle East
Why are attacks on smart factories rising?
Cyber risk predictions
Axis of attacks – Europe
Systemic attacks in the Middle East
Download the full report from here:
https://sectrio.com/resources/ot-threat-landscape-reports/sectrio-releases-ot-ics-and-iot-security-threat-landscape-report-2024/
Kubernetes & AI - Beauty and the Beast !?! @KCD Istanbul 2024Tobias Schneck
As AI technology is pushing into IT I was wondering myself, as an “infrastructure container kubernetes guy”, how get this fancy AI technology get managed from an infrastructure operational view? Is it possible to apply our lovely cloud native principals as well? What benefit’s both technologies could bring to each other?
Let me take this questions and provide you a short journey through existing deployment models and use cases for AI software. On practical examples, we discuss what cloud/on-premise strategy we may need for applying it to our own infrastructure to get it to work from an enterprise perspective. I want to give an overview about infrastructure requirements and technologies, what could be beneficial or limiting your AI use cases in an enterprise environment. An interactive Demo will give you some insides, what approaches I got already working for real.
Connector Corner: Automate dynamic content and events by pushing a buttonDianaGray10
Here is something new! In our next Connector Corner webinar, we will demonstrate how you can use a single workflow to:
Create a campaign using Mailchimp with merge tags/fields
Send an interactive Slack channel message (using buttons)
Have the message received by managers and peers along with a test email for review
But there’s more:
In a second workflow supporting the same use case, you’ll see:
Your campaign sent to target colleagues for approval
If the “Approve” button is clicked, a Jira/Zendesk ticket is created for the marketing design team
But—if the “Reject” button is pushed, colleagues will be alerted via Slack message
Join us to learn more about this new, human-in-the-loop capability, brought to you by Integration Service connectors.
And...
Speakers:
Akshay Agnihotri, Product Manager
Charlie Greenberg, Host
Transcript: Selling digital books in 2024: Insights from industry leaders - T...BookNet Canada
The publishing industry has been selling digital audiobooks and ebooks for over a decade and has found its groove. What’s changed? What has stayed the same? Where do we go from here? Join a group of leading sales peers from across the industry for a conversation about the lessons learned since the popularization of digital books, best practices, digital book supply chain management, and more.
Link to video recording: https://bnctechforum.ca/sessions/selling-digital-books-in-2024-insights-from-industry-leaders/
Presented by BookNet Canada on May 28, 2024, with support from the Department of Canadian Heritage.
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
JMeter webinar - integration with InfluxDB and GrafanaRTTS
Watch this recorded webinar about real-time monitoring of application performance. See how to integrate Apache JMeter, the open-source leader in performance testing, with InfluxDB, the open-source time-series database, and Grafana, the open-source analytics and visualization application.
In this webinar, we will review the benefits of leveraging InfluxDB and Grafana when executing load tests and demonstrate how these tools are used to visualize performance metrics.
Length: 30 minutes
Session Overview
-------------------------------------------
During this webinar, we will cover the following topics while demonstrating the integrations of JMeter, InfluxDB and Grafana:
- What out-of-the-box solutions are available for real-time monitoring JMeter tests?
- What are the benefits of integrating InfluxDB and Grafana into the load testing stack?
- Which features are provided by Grafana?
- Demonstration of InfluxDB and Grafana using a practice web application
To view the webinar recording, go to:
https://www.rttsweb.com/jmeter-integration-webinar
Essentials of Automations: Optimizing FME Workflows with ParametersSafe Software
Are you looking to streamline your workflows and boost your projects’ efficiency? Do you find yourself searching for ways to add flexibility and control over your FME workflows? If so, you’re in the right place.
Join us for an insightful dive into the world of FME parameters, a critical element in optimizing workflow efficiency. This webinar marks the beginning of our three-part “Essentials of Automation” series. This first webinar is designed to equip you with the knowledge and skills to utilize parameters effectively: enhancing the flexibility, maintainability, and user control of your FME projects.
Here’s what you’ll gain:
- Essentials of FME Parameters: Understand the pivotal role of parameters, including Reader/Writer, Transformer, User, and FME Flow categories. Discover how they are the key to unlocking automation and optimization within your workflows.
- Practical Applications in FME Form: Delve into key user parameter types including choice, connections, and file URLs. Allow users to control how a workflow runs, making your workflows more reusable. Learn to import values and deliver the best user experience for your workflows while enhancing accuracy.
- Optimization Strategies in FME Flow: Explore the creation and strategic deployment of parameters in FME Flow, including the use of deployment and geometry parameters, to maximize workflow efficiency.
- Pro Tips for Success: Gain insights on parameterizing connections and leveraging new features like Conditional Visibility for clarity and simplicity.
We’ll wrap up with a glimpse into future webinars, followed by a Q&A session to address your specific questions surrounding this topic.
Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
2. Definition
• The metabolism of drugs and other
xenobiotics into more hydrophilic
metabolites is essential for the
elimination of these compounds from
the body and termination of their
biological activity.
3. • INACTIVATION-Generates more polar (water soluble),
inactive metabolites eg Pentobarbitone
• Readily excreted from body
• ACTIVATION-Metabolites may still have potent
biological activity (or may have toxic properties) eg
Phenylbutazone: oxyphenylbutazone
• ACTIVATION OF INACTIVATED DRUG- Prodrug concept
eg Levodopa: dopamine
• Generally applicable to metabolism of all xenobiotics
as well as endogenous compounds such as steroids,
vitamins and fatty acids
4. Site of Biotransformation
• Enzymatic in nature
• Enzyme systems involved are localized in liver
• Every tissue has some metabolic activity
• Other organs with significant metabolic
capacity are GIT, kidneys and lung
• The main biotransformation reactions are
• Nonsynthetic/ Phase I
• Synthetic/ conjugated/ Phase II
5. First-Pass Metabolism
• Following nonparenteral administration of
a drug, a significant portion of the dose
may be metabolically inactivated in either
the intestinal endothelium or the liver
before it reaches the systemic circulation
• Limits oral availability of highly metabolized
drugs
6. Phase I and Phase II Metabolism
• Phase I
–functionalization reactions
• Phase II
–conjugation reactions
7. Phase I Metabolism
Includes oxidation, reduction, hydrolysis, and
hydration and isomerization
Eg barbiturates, phenothiazines, paracetamol,
steroids, benzodiazepines
• Many drugs undergo a number of these reactions
• Main function of Phase I metabolism is to prepare the
compound for phase II metabolism
• Mixed function enzyme system found in microsomes
of many cells (liver, kidney, lung, intestine) performs
many different functionalization reactions
8. Phase I
• Converts the parent drug to a more polar
metabolite by introducing or unmasking a
functional group (-OH, -NH2, -SH).
• Usually results in loss of pharmacological activity
• Sometimes may be equally or more active than
parent (Prodrug)
9. Prodrug
• Pharmacologically inactive
• Converted rapidly to active metabolite
(usually hydrolysis of ester or amide bond)
• Maximizes the amount of active species
that reaches site of action
• Eg Enalpril to enalprilat
• Levodopa to dopamine
10. Endoplasmic Reticulum
(microsomal) and Cytosol
With respect to drug metabolizing reactions,
two sub cellular organelles are quantitatively
the most important: the endoplasmic
reticulum and the cytosol.
The Phase I oxidative enzymes are almost
exclusively localized in the endoplasmic
reticulum (Microsomal). Egs P450, Glucuronyl
transferase
Phase II enzymes are located predominantly in
the cytosol. Egs esterases, amidases,
conjugases
11.
12. Cytochrome P450 Monooxygenase
System
• Superfamily of heme containing proteins
Involved in metabolism of diverse
endogenous and exogenous compounds
– Drugs
– Environmental chemicals
– Other xenobiotics
13. Cytochrome P450 Nomenclature and
Multiple Forms
• About 1000 are currently known cytochrome
P450s, about 50 active in humans
• Basis of nomenclature system: P is
pigment, 450 absorption at 450 nm
14. • categorized into 17 families (CYPs)
– sequences > 40% identical
– identified by Arabic number, CYP1, CYP2
• further into subfamilies
– identified by a letter, CYP1A, CYP2D
15. These are the types of reactions performed by
the Cytochrome P450 system
• Aromatic hydroxylation Phenobarbital, amphetamine
• N-Dealkylation Diazepam
• Aliphatic hydroxylation Ibuprofen, cyclosporine
• Epoxidation Benzo [a] pyrene
• O- Dealkylation Codeine
• S- Dealkylation 6-Methylthiopurine
• Oxidative Deamination Diazepam, amphetamine
• N-Oxidation Chlorpheniramine
• S-Oxidation Chlorpromazine, cimetidine
• Phosphothionate oxidation Parathion
• Dehalogenation Halothane
• Alcohol oxidation Ethanol
16. Phase I Metabolism Summary
• The final product usually contains a chemical
reactive functional group OH, NH2, SH, COOH.
• This functional group can be acted upon by the
phase II or conjugative enzymes.
• Main function of Phase I metabolism is to
prepare the compound for phase II
metabolism, not excretion.
17. Phase II (conjugation reactions)
• Subsequent reaction in which a covalent linkage is
formed between a functional group on the parent
compound or Phase I metabolite and an
endogenous substrate such as glucuronic acid,
sulfate, acetate, or an amino acid
• Highly polar – rapidly excreted in urine and feces
• Usually inactive – (exception is morphine 6-
glucuronide)
• Eg sulphonamides, adrenaline, chloramphenicol
18. Phase II Metabolism
• Phase II is usually the true detoxification of
drugs
• Occurs mostly in cytosol
• Gives products that are generally water
soluble and easily excreted
• Includes sugar conjugation, sulfation,
methylation, acetylation, amino acid
conjugation, glutathione conjugation
19. Glucuronidation
• Most widespread, important of the
conjugation reactions.
• compounds with hydroxyl or carboxylic
acid group are conjugated with glucuronic
acid.
• Other sugars, glucose, xylose or ribose may
be conjugated
• Egs oral contaceptives
20. Sulfation
• Major conjugation pathway for phenols, also
alcohols and amines
• Compounds that can be glucuronidated can
also be sulfated
• Can be competition between the two
pathways
• Sulfate conjugation - low substrate
concentration
• Glucuronide conjugation - high substrate
concentration
• Compds are sulfated by sulfokinases eg
Chloramphenicol.
21. Glutathione Conjugation
• Glutathione is a protective compound
within the body for removal of potentially
toxic electrophilic compounds
• Many drugs are, or are metabolized in
phase I to, strong electrophiles eg quinone
residues
• React with glutathione to form non- toxic
conjugates
• Glutathione conjugates may be excreted
directly in urine or bile.
22.
23. Factors affecting Drug Metabolism
• Environmental Determinants
Induction
Inhibition
• Disease Factors
• Age and Sex
• Genetic Variation
24. Environmental Determinants
• Activity of most drug metabolizing enzymes can be
modulated by exposure to certain exogenous
compounds
Drugs
Dietary micronutrient (food additives,
nutritional or preservative)
Environmental factors (pesticides, industrial
chemicals)
• Can be in the form of induction or inhibition
• Contributes to interindividual variability in the
metabolism of many drugs
25. Induction of Drug Metabolism
Enzyme induction is the process:
Certain substrates (e.g., drugs, environmental
pollutants) causes increased activity/ synthesis
of certain enzymes resulting in increased
metabolism of administered drug.
26. Induction of Drug Metabolism
• Many currently used drugs are well known to
induce their own metabolism or the metabolism
of other drugs. Some examples are the
anticonvulsant medications phenobarbital and
carbamazepine.
• Cigarette smoking can cause increased
elimination of theophylline and other
compounds.
27. Consequences of Induction
1. Increased rate of metabolism
2. Decrease in drug plasma concentration
3. Enhanced oral first pass metabolism
4. Reduced bioavailability
5. If metabolite is active or reactive,
increased drug effects or toxicity
28. Therapeutic Implications of Induction
• 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
29. Inhibition of Drug Metabolism
• Drug metabolism can be subjected to
inhibition.
• Drugs and other substances can inhibit the
metabolism of other drugs.
30. Some types of inhibition
• Competition between substrates for enzyme active site
• Concentration of substrates
Affinity for binding site (drug with high affinity for an
enzyme will slow the metabolism of any low affinity
drug)
• Irreversible inactivation of enzyme: Eg Complex with
heme iron of CYP450 (cimetidine, ketoconazole),
Destruction of heme group (secobarbital)
31. 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
32. 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
33. Examples of enzyme inducers and
inhibitors in metabolism
Affected Drugs Inducers Inhibitors
Tricyclicantidepressants
Propranolol
F-Warfarin
Theophylline
Phenobarbital
Phenytoin
Rifampin
Smoking
Char-broiled meats
Cimetidine
Erythromycin
Ciprofloxacin
sulfonamides
34. Disease Factors
Liver Disease – Cirrhosis, Alcoholic liver disease,
jaundice, carcinoma
• Major location of drug metabolizing enzymes
• Dysfunction can lead to impaired drug metabolism-decreased
enzyme activity
• First pass metabolism affected
• Results in exaggerated pharmacological responses and adverse
effects
Cardiac failure causes decreased blood flow to the liver
Hormonal diseases, infections and inflammation can
change drug metabolizing capacity
35. Age
• Newborns and infants – metabolize drugs
relatively efficiently but at a rate generally
slower than adults
• Full maturity appears in second decade of
life
• Slow decline in function associated with
aging
36. • Sex: Responsiveness to certain drugs is
different for men and women
• Pregnancy – induction of certain drug
metabolizing enzymes occurs in second and third
trimester
• Hormonal changes during development have
a profound effect on drug metabolism
• Genetic predisposition: Lactose intolerance-
deficiency of lactase- results in abdominal
bloating and cramps, flatulence, diarrhea, nausea
37. Excretion
• Urine: salicylates, probenicid
• Faeces: unabsorbed fraction, from bile eg steroids and
organic bases
• Egs erythromycin, rifamipin, tetracyclin,
phenolphthalein.
• Exhaled air: gases and voletile liquids egs alcohol,
paraldehyde, general anesthetics.
• Saliva and sweat: Lithium, Pot. Iodide, thiocynates,
rifampin and heavy metals
• Milk: drug enters milk by passive diffusion. Milk pH is 7
thus basic drug get more into it. Drug should be given
cautiously to the lactating mother.
38. • Glomerular filteration: depending on their
molecular size.
• Tubular absorption: lipid solubility and
ionization at urinary pH
• Thus pH of urine affects the excretion of drug
• Poisoning: barbiturate (acidic) and salicylate,
urine is alkalinized.
• Acidified incase of morphine and
amphetamine poisoning.