This document discusses insulin glargine, an anti-diabetic drug. It provides information on the composition, types, mechanisms of action, and pharmacokinetics of drugs in general. Specifically for insulin glargine, it describes its structure as a modified form of human insulin, mechanism of slowly releasing insulin from microprecipitates after injection, and metabolism and excretion from the body. Physiologically based pharmacokinetic models can predict drug absorption and exposure in older patients to inform clinical trials and dosage adjustments.

1. Presented by:
Bhaskar Das
Roll No.- 17042033;3rd Semester
Centre For Studies In Biotechnology and
Bioinformatics,Dibrugarh University

2. CONTENTS
 What is a Drug?
 Composition of Drug.
 Types of Drug.
 How do drugs enter to the body?
 How do Drugs work?
• Action of anti-Diabetic Drug
 Reviewed Literature.
 References.

3. What is a drug?
 A Drug is a chemical or biological substance that interacts
with proteins in the body to affect a physiological function.
 Once these chemicals are absorbed into the systemic
circulation they bind with certain proteins and this changes the
functioning of the cell.
 Some Drugs are specific to interact with just one type of cell
or protein and this is what may cause some side effects.

4. COMPOSITION OF DRUG:-
• A Drug consists of two types of ingredients;i.e Active and
Inactive ingredient.
Active ingredient-Chemicals in the drug that affects the
physiological function. It is the ingredient that makes the drug
work.
Inactive ingredient-Also known as the excipients; have no
effect on the physiological function. They are included to fill,
bind and lubricate the Drug.

5. Types of Drug
Basically Drugs are classified into six types:
1)Stimulants
2)Depressants
3) Anti-Psychotics
4)Anti-Depressants
5)Cannabis
6)Inhalants.

6.  Ingestion-swallowed
 Inhalation-inhale and enter into lungs.
 Injection-hypodermic needle.
 Transdermal patches-placed on the skin.
 Implanted pumps-surgically implanted.
 Topical application-applied directly to area and absorbed through
skin.
How do drugs enter to the body??

7. HOW DO DRUGS WORK??
 Drugs mainly works on the basis of Receptor and the molecules
that activate them.
 Receptors are the large protein molecules embedded in the cell
wall or membrane.
 They receive chemical information from other molecules such as
hormones or neurotransmitter outside the cell.
 The outside molecules bind to the receptors on the cells and
activates it generating a biochemical signal inside the cell.

8. SOURCE:-https://www.aegislabs.com/pharmacogenetics1
General principle of Drug Action:-

9. ACTION OF ANTI-DIABETIC DRUG
Insulin Glargine
[rDNA origin] injection
Drugbank ID: DB00047
Protein chemical formula : C267H404N72O78S6
Protein average weight : 6063 Daltons
Half-life : Not reported in humans; 30 hours; in vitro in mammalian reticulocytes.
Chemical name : Chemically, insulin glargine is 21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human
insulin

10. Description :
• Insulin glargine is produced by recombinant DNA technology using a
non-pathogenic laboratory strain of Escherichia coli (K12) as the
production organism.
• It is an analogue of human insulin made by replacing the asparagine
residue at position A21 of the A-chain with glycine and adding two
arginines to the C-terminus (positions B31 and 32) of the B-chain.
• The resulting protein is soluble at pH 4 and forms microprecipitates at
physiological pH 7.4.
Insulin Glargine

11. Source-https://www.accessdata.fda.gov/drugsatfda_docs
STRUCTURE OF THE INSULINE GLARGINE

12. Pharmacodynamics
 The primary activity of insulin, including insulin glargine, is
regulation of glucose metabolism.
 Insulin glargine lowers blood glucose levels by stimulating
peripheral glucose uptake, especially by skeletal muscle and
fat, and by inhibiting hepatic glucose production.
 Insulin glargine has low solubility at neutral pH.
 After injecting into the subcutaneous tissue, the acidic solution
is neutralized, leading to formation of microprecipitates from
which small amounts of insulin glargine are slowly released.

13. Mechanism Of Action:-
 Insulin glargine binds to the insulin receptor (IR), a protein consisting of two
extracellular alpha units and two beta units.
 The binding of insulin to the alpha subunit of IR stimulates the bound
receptor to autophosphorylate and phosphorylate numerous intracellular
substrates.
 Activation of these substrates enables the downstream signaling molecules
which regulates the activity of glucose transporter.
 Upon subcuteous injection, the solution is neutralized resulting in the
formation of microprecipitates.
 Small amounts of insulin glargine are released from microprecipitates giving
the drug a relatively constant concentration over time.
 This release mechanism then allows the drug to mimic basal insulin levels
within the body.

14. Different body layers for invection
source:-www.drugfreeworld.com

15. Pharmacokinetics:-
1)Absorption and Bioavailability.
2)Metabolism.
3)Excretion
4)Toxicity
1)Absorption and Bioavailability:
 Absorption is the process of a substance entering the blood circulation..
 When this insulin garglin is injected it forms microprecipitate.
 After the slow release of subcutaneous insulin glargine, the insulin serum
concentrations indicates more prolonged absorption and it shows constant
concentration/time in comparison to human insulin.
 Serum insulin concentrations were thus consistent with the time profile of
the pharmacodynamic activity of insulin glargine.

16. 2) Metabolism:
• Insulin gargline is partly metabolized at the carboxyl terminus
of the B chain.
• In plasma,the principle circulating compound is metabolite M1.
• The exposure to M1 increase with the administered dose of
insulin glargine.
• This pharmcokinetics findings mainly indicates that the effect
of subcutaneous injection with insulin glargine is principally
based on exposure to M1.

17. Source-https://www.google.co.in/url?sa=i&source=images&cd=&cad=rja&uact=8LIQjRx
Carboxyl terminaus
31
32
A
A
G
Modification of insulin to insulin glargine

18. 3)Excretion:
 Excretion is mainly the process of eliminating the drug and
other toxic substances from the body.
 Insuline glarginegets eliminated through the urine.

19. 5)Toxicity:-
 Inappropriately high dosages relative to food intake and/or energy
expenditure may result in severe and sometimes prolonged and life-
threatening hypoglycemia.
 Neurogenic (autonomic) signs and symptoms of hypoglycemia
include trembling, palpitations, sweating, anxiety, hunger, nausea
and tingling.
 High amount of insulin will lead to symptoms of hypoglycemia
includes weakness, confusion, drowsiness, vision changes,
headache, and dizziness.

22. KEY POINTS:
 Physiologically based pharmacokinetic (PBPK) modelling
provides and understanding of the absorption and disposition
of drugs in older patients.
 PBPK models used for the prediction of absorption and
exposure of drugs after parenteral, oral and transdermal
administration are discussed.
 Comparisons are done between the predicted drug
pharmacokinetics (PK) and observed PK are presented to
illustrate the accuracy of the predictions by the PBPK models
and their potential use in informing clinical trial design and
dosage adjustments in older patients.

23. References
 Rang HP, Dale MM, Ritter JM, et al. Pharmacology(5th edition).London: Elsevier Science;2003.
 Jones AW, Holmgren A, Kugelberg FC. Concentrations of scheduled prescription drugs in blood
of impaired drivers: considerations for interpreting the results. Therapeutic Drug
Monitoring.2007:29(2):248-60.
 Xie HG, Frueh FW. Pharmacogenomics steps towards personalised medicine. Personalised
Medicine.2005:2(4)325-37.
 Bloche G. Race-based therapeutics.N Engl J Med.2004:351(20):2035-7.
 http://www.lantus.com/
 http://www.drugs.com/lantus.html
 http://www.drugs.com/drug-interactions/insulin-glargine,lantus.html
 http://www.drugs.com/drug-interactions/insulin-glargine,lantus.html