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BIOPHARMACEUTICAL
THERAPEUTIC:
INSULIN
INTRODUCTION
 Insulin is a peptide hormone secreted by the Beta cells of pancreatic islets
of Langerhans and maintains normal blood glucose level by regulating
carbohydrate, lipid and protein metabolism.
 Insulin was discovered by Frederick Banting and Charles Best in 1921.
Soon afterward , manufacturing processes were developed to extract the
insulin from porcine and bovine pancreata.
 From 1921 to 1980, efforts were directed at increasing the purity of
insulin and provide different formulations for providing glucose
control.
 Purification was done by implementing chromatographic processes
,while formulations focused on improving chemical stability of insulin
molecule.
 Evolution of rDNA technology combined with improved purification
methods led to the availability of purest human insulin ever made.
 Insulin is composed of two polypeptide chains(Chain A & Chain B)
that are connected by two interchain disulfide bonds.
 The interchain disulfide linkages occur between A7-B7 and A20-B19
respectively. A third intrachain disulfide bond is located in the A
chain, between A6 –A11.
CHEMICAL DESCRIPTION
 Insulin is derived from a 74-amino-acid prohormone molecule called
proinsulin. Proinsulin is relatively inactive, and under normal
conditions only a small amount of it is secreted.
 In the endoplasmic reticulum of beta cells the proinsulin molecule is
cleaved in two places, yielding the A and B chains of insulin and an
intervening, biologically inactive C peptide.
 The A and B chains become linked together by two sulfur-sulfur
(disulfide) bonds.
•Factors stimulating insulin release:
 the concentration of glucose in the arterial (oxygenated) blood that
perfuses the islets. When blood glucose concentrations increase (i.e.,
following a meal), large amounts of glucose are taken up and
metabolized by the beta cells, and the secretion of insulin increases.
 Conversely, as blood glucose concentrations decrease, the secretion of
insulin decreases; however, even during fasting, small amounts of
insulin are secreted.
 The secretion of insulin may also be stimulated by certain amino acids,
fatty acids, keto acids (products of fatty acid oxidation), and several
hormones secreted by the gastrointestinal tract.
• Diabetes
 Inadequate production of insulin is responsible for the
condition called diabetes mellitus. Severe diabetics require
periodic injections of insulin.
 Diabetes is a group of conditions where the body cannot
produce enough or any insulin, cannot properly use the
insulin that is produced, or cannot do a combination of
either.
• Types of diabetes
The three main types of diabetes are:
 type 1 diabetes
 type 2 diabetes
 gestational Diabetes
Type 1 diabetes
 Type 1 diabetes is believed to be an autoimmune condition.
 This means your immune system mistakenly attacks and destroys
the beta cells in your pancreas that produce insulin.
 The damage is permanent.
 What prompts the attacks is not clear.
 There may be both genetic and environmental reasons. Lifestyle
factors are not believed to play a role.

Type 2 diabetes
 Type 2 diabetes starts out as insulin resistance.
 This means your body cannot use insulin efficiently, which causes your
pancreas to produce more insulin until it cannot keep up with demand.
 Insulin production then decreases, which causes high blood sugar.
 The exact cause of type 2 diabetes is unknown.
Contributing factors of type 2 diabetes may
include:
 Genetics
 A more sedentary lifestyle
 Higher weight or obesity
 There may also be other health factors and environmental reasons
Gestational diabetes
 Gestational diabetes is caused by insulin-blocking hormones that are
produced during pregnancy.
 This type of diabetes only happens during pregnancy. It is often seen in
people with pre-existing prediabetes and a family history of diabetes.
 About 50 percent of people diagnosed with gestational diabetes go on to
develop type 2 diabetes.
General symptoms of unmanaged diabetes
include:
 excessive thirst and hunger
 frequent urination
 drowsiness or fatigue
 dry, itchy skin
 blurry vision
 slow-healing wounds
 Symptoms of both types of diabetes can appear at any age, but type 1
usually appears in children and young adults.
 Type 2 typically appears in people over the age of 45. But younger
people are increasingly being diagnosed with type 2 diabetes due to
sedentary lifestyles and an increase in weight.
 There’s no cure for type 1 diabetes. It requires lifelong disease
management. But with consistent monitoring and adherence to
treatment,[must take insulin to live since damage to the pancreas is
permanent.
 type 2 diabetes can often be successfully managed or even reversed
with diet and exercise. It can also be treated with a variety of
medications to help manage blood sugar.
 The first-line medication is usually metformin (Glumetza, Glucophage,
Fortamet, Riomet). This drug works by reducing glucose production in
the liver. If metformin does not work, your doctor can prescribe another
medication.
Insulin therapy
 The goal of taking insulin is to keep your blood sugar level in a normal
range as much as possible.
 Insulin therapy replaces the insulin the body would normally make.
People with type 1 diabetes must take insulin every day.
 People with type 2 diabetes need to take insulin when other treatments
and medicines fail to control blood sugar levels.
Insulin doses are given in two main ways:
 Basal dose - provides a steady amount of insulin delivered all day and night. This
helps maintain blood glucose levels by controlling how much glucose the liver
releases (mainly at night when the time between meals is longer).
 Bolus dose - provides a dose of insulin at meals to help move absorbed sugar from
the blood into muscle and fat. Bolus doses can also help correct blood sugar when it
gets too high. Bolus doses are also called nutritional or meal-time doses.
Dosing schedule may depend on:
 Your weight
 Type of insulin you take
 How much and what you eat
 Level of physical activity
 Your blood sugar level
 Other health conditions
 There are several types of insulin available.
Insulin types are based on the following factors:
 Onset - how quickly it starts working after injection
 Peak - time when the dose is the strongest and most effective
 Duration - total time the insulin dose stays in the bloodstream and lowers
blood sugar
Types of insulin
 Rapid acting
 Regular or short acting
 Intermediate acting
 Long acting
 Premixed
Commercially available insulin products
Product Type Peculiarity Company
Humulin rh insulin Eli Lilly
Novlin Human regular Intermediate acting Novo Nordisk
Humalog Insulin lispro An insulin analogue Eli Lilly
Liprolog Bio lysprol Short acting insulin Eli Lilly
Novolog mix
70/30
Insulin aspart Short acting rh-insulin Novo Nordisk
Lantus Insulin glargine Long acting rh-insulin Aventis pharmaceuticals
Administration methods and routes
 Insulin is administered by two methods of delivery:
• Injection
• Infusion
Injection
Insulin syringe:
 This is the most common insulin delivery method. The classic injection
device is an insulin syringe.
 The plastic, disposable syringes currently are available in three sizes,
and hold up to 30, 50 or 100 units of insulin.
 The needles are fine (up to 31 gauge) with lengths ranging from 3/16th
of an inch for infants, to ½ inch or more for adults.
 The insulin is injected into the layer of fat (subcutaneous tissue) just
under the skin.
Insulin Pen:
 A popular alternative to the insulin syringe is an insulin pen.
 An insulin pen has a replaceable reservoir of insulin called a cartridge,
a replaceable needle to puncture the skin and to deliver insulin to the
subcutaneous tissue, a dial to choose the insulin dose, and a mechanical
pumping or insulin release mechanism.
 These may be disposable devices or re-useable devices with disposable
insulin cartridges.
 They are very convenient for active individuals taking multiple
injections, as well as those who are visually or dexterity-challenged.
Continuous Subcutaneous Insulin Infusion Device:
 Continuous subcutaneous insulin infusion (CSII) devices (also
known as insulin pumps) are the most sophisticated form of insulin
delivery.
 These are small, computerized devices that are programmed to deliver
insulin under the skin.
 The insulin pump is durable and lasts for years, but the insulin supply
and certain pump components (insulin reservoir, tubing and infusion
set) are changed every few days.
Infusion
 Human regular insulin may be injected directly into the vein in a
hospital setting under close medical supervision only.
 Insulin is added to intravenous fluids, and the insulin dose and blood
sugar are strictly monitored .
 The intravenous route of delivery is ONLY given under a doctor’s
orders in a hospital to facilitate the management of diabetes during
surgery or an intensive care stay.
Routes of administration
ANTIBODIES
BRINDA SREEKUMAR
ROLL NO.10
S8 BT&BCE​
CONTENTS
3 2
•ANTIBODIES
•MONOCLONAL ANTIBODIES
•APPLICATIONS
•POLYCLONAL ANTIBODIES
•USES OF POLYCLONAL ANTIBODY
•DIFFERENCE
INTRODUCTION
3 3
1.An antibody or immunoglobulin (Ig) is a glycoprotein that is made by plasma cells in
response to an antigen and can recognize and bind to the antigen that caused its
production. Antibodies bind antigen with a high degree of specificity and affinity.
Antibodies recognize a variety of three-dimensional shapes (amino acids, lipids,
carbohydrates, etc.). Antibodies have more than one antigen combining site Some
bivalent Ab molecules can combine to form multimeric Abs that have upto 10 combining
sites
2. An antibody is a protein used by the immune system to identify and neutralize foreign
objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to
its target. Monoclonal antibodies (mAb) are antibodies that are identical because they
were produced by one type of immune cell, all clones of a single parent cell. Polyclonal
antibodies are antibodies that are derived from different cell lines. They differ in
aminoacidsequence.
MONOCLONAL AND
POLYCLONAL
ANTIBODIES
MONOCLONAL ANTIBODY
• A type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the
surface of cancer cells. There are many kinds of monoclonal antibodies, and each monoclonal antibody is made so that
it binds to only one antigen. Monoclonal antibodies are being used in the diagnosis and treatment of many diseases,
including some types of cancer. They can be used alone or to carry drugs, toxins, or radioactive substances directly to
cancer cells.
• Monoclonal antibodies (mAb) are a single type of antibody that are identical and are directed against a specific
epitope (antigen, antigenic determinant). These are produced by B-cell clones of a single parent or a single hybridoma
cell line. A hybridoma cell line is formed by the fusion of a one B-cell lymphocyte with a myeloma cell. Some
myeloma cells synthesize single mAb antibodies naturally.
3 5
• Monoclonal antibodies (mAb) are a single type of antibody that are identical and are directed against a
specific epitope (antigen, antigenic determinant) and are produced by B-cell clones of a single parent or a
single hybridoma cell line.
• A hybridoma cell line is formed by the fusion of a one B- cell lymphocyte with a myeloma cell.
• Some myeloma cells synthesize single mAb antibodies naturally
3 6
PRODUCTION OF MONOCLONAL ANTIBODIES
3 7
• Immunize animal
• Isolate spleen cells (containing antibody-producing B cells)
• Fuse spleen cells with myeloma cells (e.g. using PEG - polyethylene glycol)
• Allow unfused B cells to die
• Add aminopterin to culture to kill unfused myeloma cells
• Clone remaining cells (place 1 cell/well and allow each cell to grow into a clone of cells)
• Screen supernatant of each clone for presence of the desired antibody
• Grow the chosen clone of cells in tissue culture indefinitely.
• Harvest antibody from the culture supernatant.
• (If you’re a biotech company) charge about $1,000-$2,000 per mg.
3 8
Practical steps in the production of monoclonal antibodies
EXAMPLE FOR MONOCLONAL ANTIBODY
2. Drozitumab
Drozitumab is a human monoclonal antibody in
development for the treatment of cancers. It targets Tumor
Necrosis Factor Related Apoptosis-inducing
Ligand(TRAIL), whose receptors are found on the surface
of many types of malignant cells. Drozitumab was
developed by Genentech
Although drozitumab was studied in phase II trials for
treating chondrosarcoma, colorectal cancer, non-Hodgkin
lymphoma, and non-small cell lung cancer, development
has been halted due to lack of clinical response.
1.Abagovomab
Abagovomab is a mouse anti-idiotype monoclonal
antibody whose variable epitope mirrors a tumor antigen
(CA-125) highly expressed in the epithelial ovarian cancer.
Abagovomab does not bind directly to CA-125, but it works
as a "surrogate" antigen, enabling the immune system to
identify and attack tumor cells displaying the CA-125
protein.
Through this, it is hoped that the body's immune system may
be able to combat any remaining individual tumor cells and
thus prevent recurrence of the disease.
3 9
Best Uses of Monoclonal Antibodies:
• To detect a specific antigen
• To detect a single member of a protein family
• To create consistent results between experiments/batches
• To stain cells with less background – excellent for immunohistochemistry,
immunocytochemistry, and immunofluorescence experiments
• To quantify protein expression (ex. Flow cytometry or fluorescence-activated cell sorting)
• To detect changes in molecular conformation
• To detect changes in phosphorylation states
• To detect a target for x-ray crystallography
• To create animal models lacking a specific cell type
• Immunotherapy
4 0
MONOCLONAL DIAGNOSTIC USE
• A monoclonal antibody can be used to detect pregnancy only 14 days after conception. Other
monoclonal antibodies allow rapid diagnosis of hepatitis, influenza, herpes, streptococcal, and
Chlamydia infections.
• They can be used to detect for the presence and quantity of this substance, for instance in a
Western blot test (to detect a substance in a solution) or an immunofluorescence test.
• Monoclonal antibodies can also be used to purify a substance with techniques called
immunoprecipitation and affinity chromatography.
4 1
MONOCLONAL ANTIBODIES FOR CANCER TREATMENTS
4 2
Possible treatment for cancer involves monoclonal antibodies
that bind only to cancer cells specific antigen and induce
immunological response on the target cancer cell (naked
antibodies). mAb can be modificated for delivery of [toxin],
radioisotope, cytokine.
A BREAKTHROUGH IN DIAGNOSTICS
• In Pregnancy by detecting the urinary levels of human chorionic gonadotropin.
• Cancer estimation of plasma carcinoembryonic antigen in colorectal cancer, and prostate specific
antigen for prostate cancer.
• They can be used to detect for the presence and quantity of this substance, for instance in a Western
blot test (to detect a substance in a solution) or an immunofluorescence test.
• The radioisotopes commonly used for labeling MAb are iodine—131 and technetium—99. The MAb
tagged with radioisotope are injected intravenously into the patients.
• Single photon emission computed tomography (SPECT) cameras are used to give a more sensitive 3d
appearance of the spots localized by radiolabeled— MAbs.
4 3
DIAGNOSTIC APPLICATIONS
• 1. Detects protein of interest by immune florescence or blotting.
• 2. Cardiovascular diseases.
• 3. Deep vein thrombosis.
• 4. Location of primary and secondary metastatic tumors.
• 5. Immunosuppressive therapy.
• 6. Pregnancy testing kits.
4 4
THERAPEUTIC APPLICATIONS
1. Radioisotope immune conjugates.
2. Toxin and drug immune conjugates.
3. Immunoliposome based kits.
4. In cancer.
5. Inflammatory disease.
POLYCLONAL ANTIBODY
• A polyclonal antibody refers to an antibody normally recognizing only a single antigen but within which
a number of different epitopes are recognized.
• Polyclonal antibodies (PAbs) are a mixture of antibodies that are secreted by different B cell lineages.
These antibodies are actually a collection of immunoglobulin molecules that react against a specific
antigen, each identifying a different epitope on an antigen.
• A Polyclonal Antibody represents a collection of antibodies from different B cells that recognize
multiple epitopes on the same antigen. Each of these individual antibodies recognizes a unique epitope
that is located on that antigen.
4 5
PRODUCTION OF POLYCLONAL ANTIBODY
4 6
• Antibodies used for research and diagnostic purposes are often obtained by injecting a lab animal such as
a rabbit with a specific antigen.
• Within a few weeks, the animal’s immune system will produce high levels of antibodies specific for the
antigen.
• These antibodies can be harvested in an antiserum, which is whole serum collected from an animal
following exposure to an antigen
• Because most antigens are complex structures with multiple epitopes, they result in the production of
multiple antibodies in the lab animal.
• This so-called polyclonal antibody response is also typical of the response to infection by the human
immune system.
• Antiserum drawn from an animal will thus contain antibodies from multiple clones of B cells, with each B
cell responding to a specific epitope on the antigen
• Antiserum obtained from animals will not only contain antibodies against the antigen artificially
introduced in the laboratory, but it will also contain antibodies to any other antigens to which the animal has
been exposed during its lifetime.
• For this reason, antisera must first be “purified” to remove other antibodies before using the antibodies for
research or diagnostic assays.
4 7
4 8
4 9
PRESENTATION
TITLE
ADVANTAGES OF POLYCLONAL ANTIBODIES
1. Inexpensive.
2. Easy to store.
3. Quick to produce.
4. Ready to use in under four months.
5. Highly stable and tolerant of pH or buffer changes.
6. High affinity as the antibodies bind to more than one epitope, they can help amplify the signal from target
protein even with low expression level.
5 0
• The use of polyclonal antibodies (PAbs) over monoclonal antibodies has its advantages. The technical
skills needed to produce polyclonal antibodies is not as demanding. They're inexpensive to make and
can be generated fairly quickly, taking up to several months to produce. PAbs are heterogeneous, which
allows them to bind to a wide range of antigen epitopes.
• Because PAbs are produced from a large number of B cell clones, they're more likely to successfully
bind to a specific antigen. PAbs remain stable in different environments, such as a change in pH or salt
concentration, which allows them to be more applicable in certain procedures.
• Additionally, depending on the amount needed, PAbs can be made in large quantities in relation to the
size of the animal used.
5 1
USES OF PLOYCLONAL ANTIBODIES
1. Sandwich ELISA for tumor markers or other antigens can be designed with polyclonal antibodies.
2. To detect a known or unknown is forms of antigens with high antigen homology
3. To detect low levels of a particular antigen
4. To capture as much antigen as possible
5. To detect denatured proteins
6. To detect a target in solutions with varying pH and salt concentrations
5 2
DIFFERENCE BETWEEN MONOCLONAL AND
POLYCLONAL ANTIBODY
5 3
THANK YOU
CARDIOVASCULAR
DRUGS
● Cardiovascular drug, any agent that affects the function of
the heart and blood vessels.
● Drugs that act on the cardiovascular system are among the most widely
used in medicine.
● Examples of disorders in which such drugs may be useful
include hypertension (high blood pressure), angina pectoris (chest pain
resulting from inadequate blood flow through the coronary arteries to the
heart muscle), heart failure (inadequate output of the heart muscle in
relation to the needs of the rest of the body),
and arrhythmias (disturbances of cardiac rhythm).
TYPES AND USE OF CARDIO VASCULAR DRUG
● Wide range of medications are used to treat various heart conditions. Some
examples of the drugs used in cardiovascular medicine include:
● Anticoagulants or blood thinners - These agents prevent coagulation or clotting
of the blood. Injectable forms of anticoagulants include dalteparin, enoxaparin,
tinzaparin and heparin.
● Warfarin is a commonly used blood thinner that can be taken in the form of a
tablet.
• These drugs do not dissolve existing blood clots but are preventive
agents in patients who have had a heart attack.
• Antiplatelet agents - Platelets play an important role in blood clotting
and the formation of platelet plugs that prevent bleeding.
• Examples of antiplatelet medications include aspirin, ticlopidine,
lopidogrel and dipyridamole.
• They are used as preventive agents in patients who have had a heart
attack.
● Thrombolytic agents - These agents are used to break up blood clots that
have formed and examples include streptokinase, reteplase and altepase.
● Angiotensin-converting enzyme (ACE) inhibitors - These agents
expand blood vessels by lowering levels of angiotensin II, a potent
vasoconstrictor that drives blood pressure up. ACE inhibitors are used to
treat high blood pressure, heart failure and heart attacks. Examples of
agents in this class include captopril, enalapril, fosinopril and lisinopril.
Angiotensin II receptor blockers (ARBs) - These agents prevent
angiotensin II from having any effects on the heart and blood vessels by
blocking the receptors it usually binds to. These agents are useful in the
treatment of high blood pressure, heart failure and heart attacks. Examples
of drugs in this class include candesartan, irbesartan, losartan, telmisartan
and valsartan
● Diuretics - Diuretics increase the excretion of water and sodium in the
urine, therefore decreasing the total blood volume. This reduces blood
pressure and the heart's workload. Examples of agents in this class
include chlorothiazide, amiloride, furosemide, bumetanide, indapamide
and spironolactone.
● Vasodilators - These drugs relax the blood vessels and cause blood
pressure to fall. They are useful in the treatment of high blood pressure,
heart failure, angina and heart attacks. Examples include isosorbide,
dinitrate and hydralazine.
● Digoxin - This agent is used to stimulate a heartbeat in some cases of
heart failure.
.
● Statins - These agents reduce the synthesis of blood cholesterol in the
liver. High blood cholesterol is one of the major causes of atherosclerosis.
Some of the most well known examples include atorvastatin, lovastatin
and simvastatin.
● Drugs that are used to regulate an abnormal heart rhythm include
quinidine, lidocaine, amiodarone, sotalol, verapamil, diltiazem, dofetilide
and adenosine.
● Beta blockers or beta-adrenergic blocking agents - These agents
decrease the heart rate and the final cardiac output. This lowers blood
pressure and heart rate. Beta blockers are useful therapies in high blood
pressure and some types of arrhythmia. Agents in this class include
atenolol, bisoprolol, metoprolol, propranolol and sotalol.
Calcium channel blockers - Calcium channel blockers stop the movement of
calcium into the cells of the heart and blood vessels. This relaxes the vessels and
reduces blood pressure. Calcium channel blockers are useful therapies in high
blood pressure, angina, and some forms of arrhythmia. Examples of drugs in this
class include amlodipine, felodipine, nifedipine and varapamil
ANTICOAGULANTS
● Anticoagulants are commonly known as blood thinners.
● They are chemical substances that prevent or reduce coagulation of blood,
prolonging the clotting time.
● Anticoagulants are used in therapy for thrombotic disorders.
● Oral anticoagulants (OACs) are taken by many people in pill or tablet form,
and various intravenous anticoagulant dosage forms are used in hospitals.
● Common anticoagulants include warfarin and heparin.
There are three main types of anticoagulant medications:
● Vitamin K antagonists
● Direct Oral Anticoagulants (DOACs)
● Low molecular weight heparins (LMWH)
Each type works in a different way to prevent unneeded blood clots.
VITAMIN K ANTAGONIST ANTICOAGULANTS
● Vitamin K helps in blood clot.
● We get it from green leafy vegetables like broccoli and spinach and from the action of
bacteria in your gut.
● Vitamin K “antagonists” like warfarin stop your liver from processing vitamin K into
“factors” that normally help clot your blood.
● This curbs blood clotting.
● One of the potential advantages of this type of anticoagulant is that it’s easier than others
to reverse in case you have sudden bleeding from trauma or emergency surgery.
DIRECT ORAL ANTICOAGULANTS (DOACS)
● DOACs work more quickly than vitamin K antagonists.
DOACs include:
a) Direct thrombin inhibitors:
● These drugs interfere with your body’s use of thrombin, a key enzyme
that helps clot your blood. Though it's typically injected in a vein, you
can take it in pill form as dabigatran (Pradaxa).
b) Direct factor Xa inhibitors:
● This type of anticoagulant stops the Xa factor in the clotting process from
working as it should.
● These medications, which come in pill form, include apixaban (Eliquis),
betrixaban (Bevyxxa), edoxaban (Savaysa), and rivaroxaban (Xarelto).
LOW MOLECULAR WEIGHT HEPARIN (LMWH)
ANTICOAGULANTS
● Low-molecular weight heparin is gradually replacing heparin for
treatment of most patients with venous thromboembolism and acute
coronary syndromes because it has more convenient and cost-effective
● It has similar results to heparin
● Administered by subcutaneous injection
● LOVENOX® is an example
ANTITHROMBOTIC
AGENTS
● Antithrombotic agents are medications that are used to prevent the formation
or development of blood clots within the body.
● These agents work by inhibiting platelet aggregation or by reducing blood
coagulation.
Some common antithrombotic agents include:
1. Aspirin: Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that
works by inhibiting platelet aggregation.
2. Heparin: Heparin is an anticoagulant that prevents blood from clotting by
inhibiting the action of thrombin and factor Xa.
3. Warfarin: Warfarin is an oral anticoagulant that interferes with the synthesis of
vitamin K-dependent clotting factors in the liver.
4. Direct oral anticoagulants (DOACs): DOACs, also known as novel oral
anticoagulants (NOACs), are a newer class of anticoagulants that directly inhibit
factor Xa or thrombin.
5. Clopidogrel: Clopidogrel is an antiplatelet medication that works by inhibiting
the ADP receptor on platelets.
MAIN TYPES
1. Antiplatelet agents: These agents work by inhibiting platelet activation and
aggregation. Examples include aspirin, clopidogrel, dipyridamole, and
ticagrelor
2. Anticoagulants: These agents prevent the formation of blood clots by
inhibiting the coagulation cascade. Examples include heparin, warfarin,
direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban,
apixaban, and edoxaban.
3. Thrombolytic agents: These agents are used to dissolve blood clots that
have already formed. Examples include alteplase, reteplase, and tenecteplase.
4. Anti-fibrinolytic agents: These agents work by preventing the breakdown
of blood clots. Examples include tranexamic acid and aminocaproic acid.
5. Other agents: There are also other types of antithrombotic agents, such as
prostacyclin analogues (epoprostenol, iloprost), glycoprotein IIb/IIIa
inhibitors (abciximab, eptifibatide, tirofiban), and phosphodiesterase
inhibitors (dipyridamole, cilostazol).
1. Prevention of blood clots: Antithrombotic agents are used to prevent the
formation of blood clots in people who are at high risk due to certain medical
conditions, such as atrial fibrillation, deep vein thrombosis, pulmonary
embolism, heart valve disease, or recent surgery.
2. Treatment of blood clots: Antithrombotic agents are used to treat existing
blood clots and prevent them from growing or traveling to other parts of the
body. This is particularly important in the case of deep vein thrombosis,
pulmonary embolism, or stroke.
3. Prevention of cardiovascular events: Some antithrombotic agents, such as
aspirin, are used to prevent heart attack and stroke in people with a high risk
of cardiovascular disease.
USES
HEMOSTASIS
● Hemostasis is a process to prevent and stop bleeding, meaning to keep
blood within a damaged blood vessel.
● It is the first stage of wound healing.
● This involves coagulation, which changes blood from a liquid to a gel.
● Hemostasis is maintained in the body via four mechanisms:
USES
1. Control of bleeding during surgery: Hemostasis is critical during
surgery to prevent excessive bleeding and ensure good visibility of
the surgical site.
2. Treatment of bleeding disorders: Hemostasis is important in the
management of bleeding disorders, such as hemophilia and von
Willebrand disease. Patients with these conditions may receive
transfusions of clotting factors or medications to promote blood
clotting.
3. Management of trauma: Hemostasis is critical in the immediate
management of trauma, such as in the case of severe injuries or
major surgery.
THANK YOU
CHEMOTHERAPEUTIC
DRUGS
CHEMOTHERAPY
 Chemotherapy involves the use of cytotoxic medications to cure cancer or
decrease tumour size or to prevent or treat suspected metabases.
 It interfering with the ability of the malignant cell to synthesize vital enzymes
and chemicals.
 Chemotherapy disrupts the cell cycle in various phase by interrupting cell
metabolism and replication.
 Based on the chemical makeup and biological activity, different drugs used for
cancer treatment act in specific phases and sub phases of the cell cycle.
ADJUVANT AND NEO-ADJUVANT CHEMOTHERAPY
 Adjuvant chemotherapy:- Chemotherapy given after surgery or irradiation to
destroy micrometastasis and prevent development of secondary neoplasm.
 Neo-adjuvant chemotherapy:- Chemotherapy given before surgery or
radiotherapy in order to diminish the volume of large primary neoplasm.
CLASSES OF CHEMOTHERAPY DRUGS
 Chemotherapeutic agents can be classified either by the effects of the agent on
the cell or by the pharmacological properties of the agent.
 Chemotherapeutic agents can be divided into:-
Cell cycled-specific agents
Cell cycle-nonspecific agents
CELL CYCLE-SPECIFIC AND CELL CYCLE-NONSPECIFIC
AGENTS
 Cell cycle-specific:- These are the agents effective at a specific phase (example,
S and M phases) in the cell replication by damaging cellular DNA and blocking
production of protein necessary for DNA and RNA synthesis.
 Cell cycle-nonspecific:- These are the agents effective throughout all the phases
of the cell cycle, including the resting phase.
OTHER CLASSIFICATIONS OF CHEMOTHERAPEUTIC
AGENTS
 Chemotherapeutic agents are classified based on pharmacological properties of
the agent. The classifications include:
a. Alkylating agents
b. Antimetabolites
c. Antitumour antibiotics
d. Mitotic inhibitors
e. Hormones and hormone antagonists
f. Miscellaneous agents
ALKYLATING AGENTS
 Alkylating agents are not phase specific and basically act on performed nucleic
acids by creating defects in tumour DNA. They cause crosslinking of DNA
strands and interfere with replication and transcription.
 It acts with proliferating and non proliferating cells those in G0 phase.
 The several subclasses of alkylating agents include:-
a. Nitrogen mustards:- Mechlorethamine, Melphalan, Chlorambucil,
cyclophosphamide, ifosfamide.
b. Ethyleneimine:- Thiotepa
c. Alkyl Sulfonate:- Busulfan
d. Nitrosureas:- Carmustine, lomustine, streptozocin
e. Triazines:- Dacarbazine, temozolamide
ANTIMETABOLITES
 Antimetabolites are phase specific, working best in the S phase and having little
effect in G0. It interfere with nucleic acid synthesis by displacing metabolites at
the regulatory site of a key enzyme.
 Classifications are:-
a. Folate antagonists:- Methotrexate
b. Purine antagonists:- 6 Mercaptopurine, 6 Thioguanine, Azathioprine
c. Pyrimidine antagonists:- 5 Fluorouracil, cytarabine, gemcitabine
ANTITUMOUR ANTIBIOTICS
 Antitumour antibiotics derived from natural sources that are generally too toxic
to be used as anti-bacterial agents.
 They are not phase specific and act in several ways: they disrupt DNA replication
and RNA transcription; create free radicals, which generate breaks in DNA and
other forms of damage; and interfere with DNA repair.
 These antibiotics include:-
a. Actinomycin D
b. Doxorubicin
c. Bleomycin
d. Mitomycin-C
e. Mithramycin
MITOTIC INHIBITORS
 Mitotic inhibitors are drugs that act to prevent cell division during the M phase.
Mitotic inhibitors include plant alkaloids and taxoids.
 Plant alkaloids consists of medications extracted from plant sources (periwinkle
plant): Vinca
 Alkaloids (example, vincristine and vinblastine) and etoposide.
 The toxoids acts during the G2 phase to inhibit cell divison (example, Paclitaxel
and Docetaxel).
HORMONES AND HORMONE ANTAGONISTS
 The main hormones used in cancer therapy are the corticosteroids which are
phase specific (G1).
 These act by binding to specific intracellular receptors, repressing transcription
of mRNA and therapy altering cellular function and growth.
 Hormone antagonists work with hormone binding tumours. They block the
hormones receptor site on the tumour and prevent it from receiving normal
hormonal growth stimulation.
 Example of hormone and hormone antagonists are:-
• Corticosteroids:- Prednisolone
• Oestrogens:- Ethinyl Estradiol
• Aromatase inhibitors:- Letrozole, Anastrazole, Exemestane
• Progestins:-Hydroxyprogesterone
• Anti-androgens:- Flutamide, Bicalutamide
• GnRH analogs:- Naferelin, Goserelin, Leuoprolide
• Selective oestrogen
Receptor moderator(SERM):- Tamoxifene, Toremifene
Receptor degrader(SERD):- Fulvestrant
• Enzymes:- L-asparginase
• Epipodophyllotoxins:- Etoposide, tenoposide
• Camptothecin analogs:- Topotecan, irinotecan
• Biological response modifiers:- Interferons, Interleukins
MISCELLANEOUS AGENTS
 Several miscellaneous agents act at different phases in the cell cycle.
 The miscellaneous agents are:-
Cisplatin
Carboplatin
Hydroxurea
Procarbazine
Mitotane
Imatinib
CHEMOTHERAPEUTIC
DRUGS
CHEMOTHERAPY
 Chemotherapy involves the use of cytotoxic medications to cure cancer or
decrease tumour size or to prevent or treat suspected metabases.
 It interfering with the ability of the malignant cell to synthesize vital enzymes
and chemicals.
 Chemotherapy disrupts the cell cycle in various phase by interrupting cell
metabolism and replication.
 Based on the chemical makeup and biological activity, different drugs used for
cancer treatment act in specific phases and sub phases of the cell cycle.
ADJUVANT AND NEO-ADJUVANT CHEMOTHERAPY
 Adjuvant chemotherapy:- Chemotherapy given after surgery or irradiation to
destroy micrometastasis and prevent development of secondary neoplasm.
 Neo-adjuvant chemotherapy:- Chemotherapy given before surgery or
radiotherapy in order to diminish the volume of large primary neoplasm.
CLASSES OF CHEMOTHERAPY DRUGS
 Chemotherapeutic agents can be classified either by the effects of the agent on
the cell or by the pharmacological properties of the agent.
 Chemotherapeutic agents can be divided into:-
Cell cycled-specific agents
Cell cycle-nonspecific agents
CELL CYCLE-SPECIFIC AND CELL CYCLE-NONSPECIFIC
AGENTS
 Cell cycle-specific:- These are the agents effective at a specific phase (example,
S and M phases) in the cell replication by damaging cellular DNA and blocking
production of protein necessary for DNA and RNA synthesis.
 Cell cycle-nonspecific:- These are the agents effective throughout all the phases
of the cell cycle, including the resting phase.
OTHER CLASSIFICATIONS OF CHEMOTHERAPEUTIC
AGENTS
 Chemotherapeutic agents are classified based on pharmacological properties of
the agent. The classifications include:
a. Alkylating agents
b. Antimetabolites
c. Antitumour antibiotics
d. Mitotic inhibitors
e. Hormones and hormone antagonists
f. Miscellaneous agents
ALKYLATING AGENTS
 Alkylating agents are not phase specific and basically act on performed nucleic
acids by creating defects in tumour DNA. They cause crosslinking of DNA
strands and interfere with replication and transcription.
 It acts with proliferating and non proliferating cells those in G0 phase.
 The several subclasses of alkylating agents include:-
a. Nitrogen mustards:- Mechlorethamine, Melphalan, Chlorambucil,
cyclophosphamide, ifosfamide.
b. Ethyleneimine:- Thiotepa
c. Alkyl Sulfonate:- Busulfan
d. Nitrosureas:- Carmustine, lomustine, streptozocin
e. Triazines:- Dacarbazine, temozolamide
ANTIMETABOLITES
 Antimetabolites are phase specific, working best in the S phase and having little
effect in G0. It interfere with nucleic acid synthesis by displacing metabolites at
the regulatory site of a key enzyme.
 Classifications are:-
a. Folate antagonists:- Methotrexate
b. Purine antagonists:- 6 Mercaptopurine, 6 Thioguanine, Azathioprine
c. Pyrimidine antagonists:- 5 Fluorouracil, cytarabine, gemcitabine
ANTITUMOUR ANTIBIOTICS
 Antitumour antibiotics derived from natural sources that are generally too toxic
to be used as anti-bacterial agents.
 They are not phase specific and act in several ways: they disrupt DNA replication
and RNA transcription; create free radicals, which generate breaks in DNA and
other forms of damage; and interfere with DNA repair.
 These antibiotics include:-
a. Actinomycin D
b. Doxorubicin
c. Bleomycin
d. Mitomycin-C
e. Mithramycin
MITOTIC INHIBITORS
 Mitotic inhibitors are drugs that act to prevent cell division during the M phase.
Mitotic inhibitors include plant alkaloids and taxoids.
 Plant alkaloids consists of medications extracted from plant sources (periwinkle
plant): Vinca
 Alkaloids (example, vincristine and vinblastine) and etoposide.
 The toxoids acts during the G2 phase to inhibit cell divison (example, Paclitaxel
and Docetaxel).
HORMONES AND HORMONE ANTAGONISTS
 The main hormones used in cancer therapy are the corticosteroids which are
phase specific (G1).
 These act by binding to specific intracellular receptors, repressing transcription
of mRNA and therapy altering cellular function and growth.
 Hormone antagonists work with hormone binding tumours. They block the
hormones receptor site on the tumour and prevent it from receiving normal
hormonal growth stimulation.
 Example of hormone and hormone antagonists are:-
• Corticosteroids:- Prednisolone
• Oestrogens:- Ethinyl Estradiol
• Aromatase inhibitors:- Letrozole, Anastrazole, Exemestane
• Progestins:-Hydroxyprogesterone
• Anti-androgens:- Flutamide, Bicalutamide
• GnRH analogs:- Naferelin, Goserelin, Leuoprolide
• Selective oestrogen
Receptor moderator(SERM):- Tamoxifene, Toremifene
Receptor degrader(SERD):- Fulvestrant
• Enzymes:- L-asparginase
• Epipodophyllotoxins:- Etoposide, tenoposide
• Camptothecin analogs:- Topotecan, irinotecan
• Biological response modifiers:- Interferons, Interleukins
MISCELLANEOUS AGENTS
 Several miscellaneous agents act at different phases in the cell cycle.
 The miscellaneous agents are:-
Cisplatin
Carboplatin
Hydroxurea
Procarbazine
Mitotane
Imatinib
OLIGONUCLEOTIDE
What are they?
• An oligonucleotide is a short, single-stranded DNA or RNA molecule
typically composed of 10-50 nucleotides.
• The sequence of nucleotides in an oligonucleotide can be designed to
bind specifically to a complementary sequence of nucleotides in a
target DNA or RNA molecule, allowing for applications such as gene
expression analysis, DNA sequencing, and genetic engineering.
• Oligonucleotides are widely used in research, diagnostics,
and therapeutics.
Types of Oligonucleotides
• There are several types of oligonucleotides, each with specific characteristics and
applications.
• The most common types of oligonucleotides are:
1. DNA oligonucleotides: These are short, single-stranded DNA molecules
typically composed of 10-50 nucleotides. They are widely used in molecular
biology research and in diagnostics.
2. RNA oligonucleotides: These are short, single-stranded RNA molecules
typically composed of 10-50 nucleotides. They are used in a variety of
applications, including gene expression analysis, RNA interference, and
therapeutic applications.
3. siRNA (short interfering RNA): These are double-stranded RNA molecules
typically composed of 21-23 nucleotides. They are used to silence the expression
of specific gene by targeting and degrading the mRNA molecules that encode
them.
4. miRNA (microRNA): These are short, single-stranded RNA molecules typically
composed of 20-24 nucleotides. They regulate gene expression by binding to mRNA
molecules and inhibiting their translation into proteins.
5. Antisense oligonucleotides: These are synthetic single-stranded DNA or RNA
molecules designed to hybridize with specific mRNA molecules and inhibit their
translation into proteins. They are used in therapeutic applications to target disease-
causing genes or proteins.
6. Aptamers: These are short, single-stranded DNA or RNA molecules that bind to
specific target molecules with high affinity and specificity. They are used in a
variety of applications, including diagnostics, therapeutics, and research.
Biological Importance
• Oligonucleotides are biologically important because they are essential components
of DNA and RNA, the molecules that carry genetic information in all living
organisms. They play a crucial role in many biological processes, including gene
expression, DNA replication, and protein synthesis.
• Some examples of the biological importance of oligonucleotides:
1. DNA replication: Oligonucleotides are the building blocks of DNA, which
replicates itself during cell division. The two complementary strands of DNA are
synthesized by the enzyme DNA polymerase, which uses oligonucleotides as a
template to build new strands of DNA.
2. Gene expression: Oligonucleotides are involved in the process of gene
expression, which is the process by which genetic information is used to
synthesize proteins. During gene expression, RNA molecules are synthesized
from DNA templates, and these RNA molecules contain oligonucleotide
sequences that are important for protein synthesis.
3. Protein synthesis: Oligonucleotides are involved in protein synthesis, which is the
process by which RNA molecules are translated into proteins. During this process,
ribosomes read the sequence of nucleotides in the RNA molecule and use this
information to assemble amino acids into a protein chain.
4. Genetic engineering: Oligonucleotides are essential tools for genetic engineering,
which involves manipulating DNA sequences to add, delete, or modify genes.
Oligonucleotides can be used to introduce specific mutations or to target specific
DNA sequences for editing.
Production of Oligonucleotides
• Oligonucleotides can be produced using several methods, including enzymatic
synthesis, solid-phase synthesis, and chemical synthesis.
• The general steps involved in the production of oligonucleotides using solid-phase
synthesis:
Design and selection of the target sequence: The first step is to determine the
sequence of the oligonucleotide required for the desired application. The sequence
is typically chosen based on the function of the oligonucleotide, such as primers
for PCR or probes for hybridization assays.
Synthesis of the oligonucleotide: The oligonucleotide is synthesized on a solid
support, such as polystyrene beads, using an automated oligonucleotide
synthesizer. The nucleotides are added stepwise in a specific order, with each
addition being protected by a temporary chemical group to prevent unwanted
reactions.
Deprotection and cleavage: After the synthesis is complete, the oligonucleotide is
deprotected to remove the temporary chemical groups and cleaved from the solid
support. The oligonucleotide is then purified by HPLC or another method to
remove any impurities and ensure a high degree of purity.
Analysis and quality control: The final step is to analyze the oligonucleotide to
ensure that it meets the desired specifications, including length, purity, and yield.
Quality control may involve gel electrophoresis, mass spectrometry, or other
techniques.
• The other most common methods for producing and synthesizing oligonucleotides
are :
Enzymatic synthesis: This method involves using enzymes to synthesize
oligonucleotides from nucleotide triphosphates. One of the most commonly used
enzymes for this purpose is polynucleotide phosphorylase (PNPase). This method
is often used to synthesize short RNA oligonucleotides.
Chemical synthesis: This method involves using chemical reactions to synthesize
oligonucleotides from nucleotide building blocks. One of the most commonly
used chemical methods for this purpose is phosphoramidite chemistry, which
involves the sequential addition of nucleotide building blocks to a growing chain.
This method is widely used for the synthesis of DNA oligonucleotides.
• After synthesis, oligonucleotides can be purified using a variety of methods,
including HPLC, PAGE, or ion-exchange chromatography. The purity and quality
of oligonucleotides are critical factors in their performance and applications.
Application of Oligonucleotides
• Oligonucleotides have a wide range of applications in various fields, including :
1. Research: Oligonucleotides are widely used in molecular biology research to
probe and manipulate nucleic acid sequences. They are used for gene expression
analysis, DNA sequencing, and genetic engineering.
2. Diagnostics: Oligonucleotides can be designed to specifically bind to and detect
target DNA or RNA sequences, making them useful for diagnostic applications
such as detecting infectious agents or genetic mutations.
3. Therapeutics: Oligonucleotides can be used as therapeutic agents to target
specific disease-causing genes or proteins. They can be designed to inhibit the
expression of disease-causing genes, promote the degradation of disease-
causing RNA molecules, or modulate the activity of disease-causing proteins.
4. Forensics: Oligonucleotides can be used in forensic investigations to analyze
DNA samples for identification purposes.
5. Agriculture: Oligonucleotides can be used in agriculture to genetically engineer
crops with desirable traits, such as increased yield or resistance to pests
Examples of Oligonucleotides Drugs
1. Spinraza - This antisense oligonucleotide drug is used to treat spinal muscular atrophy
(SMA), a rare genetic disorder that affects the muscles. Spinraza works by increasing
the production of the SMN protein, which is deficient in SMA patients.
2. Onpattro (patisiran) - This RNA interference (RNAi) therapeutic is used to treat
hereditary transthyretin-mediated amyloidosis (hATTR), a rare disease in which
abnormal proteins build up in the body's tissues and organs. Onpattro works by
reducing the production of the protein responsible for this buildup.
3. Tegsedi (inotersen) - Another antisense oligonucleotide drug, Tegsedi is used to treat
hATTR. It works by blocking the production of the abnormal protein that causes the
disease.
4. Givosiran (Givlaari) - This RNAi therapeutic is used to treat acute hepatic porphyria
(AHP), a rare genetic disorder that affects the liver. Givosiran works by reducing the
production of a specific enzyme that is responsible for the symptoms of the disease.
5. Lumasiran (Oxlumo) - This RNAi therapeutic is used to treat primary hyperoxaluria
type 1 (PH1), a rare genetic disorder that causes the buildup of oxalate crystals in the
kidneys and other organs. Lumasiran works by reducing the production of an enzyme
that is responsible for the overproduction of oxalate in PH1 patients.
Other examples are :
• Fomiversin for the treatment of cytomegalovirus retinitis.
• Mipomersen for high cholesterol
• Genasense against cancer
• AP 1-2009 for the treatment of high grade glimoas
ENDOCRINE DRUGS
• Consist of many glands that secrete hormones into the blood.
• When glands malfunction they secrete either by:
• Decreased amount of hormone
• Increased amount of hormone
ENDOCRINE SYSTEMS
Insulin drugs used to treat diabetes mellitus
• Insulin
• Secreted by beta cells in islets of Langerhans in the pancreas
• Plays an essential role in glucose metabolism
• Lowers blood glucose levels enabling cells to utilize glucose
• Transports glucose to the cell
• Binds with an insulin receptor on the cell membrane
• Transport glucose inside the cell
• The glucose is metabolized to provide energy
Diabetes Mellitus
• Disease of pancreas and body cells
• Type 1
• The pancreas doesn’t produce any insulin
• Type 2
• The pancreas produces too little insulin
• The number of or sensitivity of insulin receptors on body cells in decreased
Type 1 Diabetes Mellitus
• Previously known as:
• Insulin-dependent diabetes mellitus
(IDDM)
• Juvenile-onset diabetes mellitus
• Treated with subcutaneously injected insulin
Type 2 Diabetes Mellitus
• Previously known as:
• Non-insulin-dependent diabetes mellitus (NIDDM)
• Adult-onset diabetes mellitus
• Treated with antidiabetic drugs
• Insulin maybe needed
• Untreated or uncontrolled diabetes mellitus results in consistently
elevated blood glucose level.
• Eventually leads to diabetic complications of:
• Arteriosclerosis
• Ketoacidosis
• Death
• All insulin drugs are grouped according to:
• How quickly they act in the body to lower the blood glucose
• Size of insulin crystalline
• Hours their therapeutic effect continues
• Amount of protamine and zinc added to the insulin
Rapid acting insulin drugs
• Taken in the morning or before eating
• Onset of therapeutic effect is almost immediate
• Can begin to lower blood glucose levels in as little as 15 minutes
• Therapeutic effect last 2 to 12 hours .
• Also known as regular insulin
• Sometimes reflected in the drug’s trade name as the abbreviation R.
• Three types of rapid acting insulin :
• Derived from pig pancreas
• Regular I Letin II
• Created by recombinant DNA technology
• Humulin R
• Novolin R
• Insulin analog drugs created by recombinant DNA technology
Intermediate acting insulin drugs
• Slower onset but a longer effect than rapid acting insulin
• Therapeutic effect
• Onset is between 1 to 2 hours
• Last for 24 hours
• Two types:
• Those with added protamine and zinc (NPH insulin drugs ) to prolong the
therapeutic effect of insulin.
• Those with different size of insulin crystals (lente insulin drugs) to slow down
the onset of action.
Long acting insulin drugs
• Have large insulin crystals containing added zinc
• Doesn't begin to lower the blood sugar for an hour
• Therapeutic effect lasts a full 24 hours after just one dose
• Also known as ultralente insulin
Combination insulin drugs
• Contain a mixture of:
• An intermediate acting insulin
• NPH insulin
• Insulin analog
• A rapid acting insulin
• Regular insulin
• Insulin analog
Drugs used to treat diseases of thyroid gland
• Hypothyroidism
• Too little thyroid hormone secreted
• Hyperthyroidism
• Too much thyroid hormone secreted
Drugs for hypothyroidism
• Thyroid gland secretes hormones:
• Triiodothyronine (T3)
• Thyroxine (T4)
• Decreased level causes hypothyroidism
• Drugs for hypothyroidism is obtained naturally from desiccated (dried)
animal thyroid glands or manufactured synthetically.
• Drugs for hypothyroidism
• Containing only T3
• Liothyronine (Cytomel, Triostat)
• Containing only T4
• Levothyroxine (Levothroid , Synthroid)
• Containing both T3 and T4
• Desiccated thyroid (Armour thyroid )
• Liotrix (Thyrolar )
Biological functions
• T3 is considered the major regulator of mitochondrial activity
• Induces early stimulation of transcription and increases transcription factor
(TFA) expression
• Stimulate oxygen consumption by mitochondria
• Regulate the rate of overall metabolism
• T3 increases basal metabolic rate
• T3 is an important regulator of skeletal maturation at the growth
plate
• T4 is responsible for metabolism, mood and body temperature.
Drugs for hyperthyroidism
• Also known as thyrotoxicosis
• Increased levels of T3 and T4
• Drugs inhibit production of T3 and T4 in the thyroid
• Radioactive sodium iodide 131
• Used to treat hyperthyroidism and thyroid cancer
• Low level radiation emitted destroys both hyperactive benign thyroid and
cancerous thyroid tissues.
• Iodine (ThyroShield)
• Methimazole (Tapazole)
Drugs used to treat diseases of pituitary gland
• Growth hormone
• Secreted by anterior pituitary gland
• Stimulate the production of insulin like growth factor 1
• Children with failure to grow can have an abnormality in any of these areas:
• Decreased amount of growth hormone
• Antibodies against growth hormone
• Abnormalities of growth hormone receptors on cells
• Deceased amount of insulin like growth factor 1
Drugs for acromegaly
• Acromegaly
• Over production of growth hormone (anterior pituitary)
• Causes widening and enlargement of facial features, hands and feet
• Drugs for acromegaly
• Decrease production of growth hormone
• Block growth hormone by anterior pituitary or block growth hormone from
activating receptors on cell membrane
Growth hormone replacement drugs
• Drugs are used as replacement therapy
• Sermorelin (Geref )
• Somatropin ( Humatrope, Nutropin )
• Somatrem (Protropin)
Drugs used to treat adrenal gland dysfunction
• Drugs for crushing syndrome
• Too much adrenal gland hormone is secreted
• Tumour on adrenal gland cortex
• Causes increase in amount of cortisol produced
• Removal by surgery preferred option
• Drugs suppresses cortisol secretion in patients who cannot have surgery
Drugs for addison disease
• Autoimmune disease in which body’s own antibodies destroys adrenal cortex
• Too little adrenal gland hormone is secreted
• Causes fatigue, weight loss
• Decreased ability to tolerate :
• Stress
• Disease
• Surgery
• Patients have unusual bronzed colour to the skin
• Drugs for addison disease
• Cortisone
• Hydrocortisone (Cortef)
Cortisone functions:
• Provide relief for inflamed areas of the body
• They lessen swelling, redness, itching and allergic reactions
• Most commonly injected into joints such as ankle, elbow, hip, knee,
shoulders, spine or wrist
Corticosteroid drugs
• Adrenal cortex secrete glucocorticoid hormones
• Cortisol
• Powerful anti-inflammatory effect
• Act as a natural hormone secreted by the adrenal cortex
• Used as a replacement therapy to treat addison disease
• Given by mouth or injection to treat inflammatory reactions in various parts of the
body
• Used to treat systemic inflammation caused by autoimmune diseases (Rheumatoid
arthritis, Multiple sclerosis etc)
Cortisol function
• Plays an important role in the stress response
• Regulates a wide range of vital processes throughout the
body , including metabolism and immune response
Drugs used to treat diseases of the testes
• Testosterone
• Androgen
• Most abundant and biologically active male sex hormone
• Androgen drugs
• Treat diseases of hypo secretion due to:
• Cryptorchidism
• Orchitis
• Delayed puberty
• Chemotherapy
• Alcoholism
• Surgical removal of testes
• Fluoxymesterone
• Methyltestosterone
• Testosterone
TNF - 𝞪
TNF- 𝞪
Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory
cytokine produced by macrophages/monocytes during acute
inflammation and is responsible for a diverse range of signalling
events within cells, leading to necrosis or apoptosis.
Tumor necrosis factor (TNF) is a multifunctional cytokine that plays
important roles in diverse cellular events such as cell survival,
proliferation, differentiation, and death. As a pro-inflammatory
cytokine, TNF is secreted by inflammatory cells, which may be
involved in inflammation-associated carcinogenesis or in other words
TNF signals cells to die.
TNFs are primarily produced by macrophages and are responsible for regulation of inflammatory
and immune responses in cell death.
They occur in 2 distinct forms
1. Membrane integrated
2. Soluble form - exists in form of homotrimers
These TNFs bind to the receptors TNFR1 & TNFR2
TNFR1 is found in most of the tissues and responds to the soluble form of TNF- 𝞪. It
increases inflammation and induces powerful immune responses.
TNFR2 is found in immune cells and responds to membrane bound form of TNF-𝞪. It exhibits
anti inflammatory property and promotes cell proliferation
Structure
Role of TNFs
● The TNF signaling pathway plays an important role in various
physiological and pathological processes, including cell proliferation,
differentiation, apoptosis, and modulation of immune responses and
induction of inflammation.
● TNF (Tumor Necrosis Factor) is a multifunctional proinflammatory
cytokine, with effects on lipid metabolism, coagulation, insulin
resistance, and endothelial function.
● Ever since its discovery two decades ago, TNF has been considered
as an anti-cancer agent.
● Members of the TNFR (TNF Receptor) super family can send both
survival and death signals to cells.
TNF signaling has been implicated in many other
diseases
● Tumor necrosis factor alpha (TNF-α) was initially recognized as a
factor that causes the necrosis of tumors, but it has been recently
identified to have additional important functions as a pathological
component of autoimmune diseases.
● TNF-α binds to two different receptors, which initiate signal
transduction pathways. These pathways lead to various cellular
responses, including cell survival, differentiation, and proliferation.
● However, the inappropriate or excessive activation of TNF-α
signaling is associated with chronic inflammation and can eventually
lead to the development of pathological complications such as
autoimmune diseases.
● Understanding of the TNF-α signaling mechanism has been expanded
and applied for the treatment of immune diseases, which has
resulted in the development of effective therapeutic tools, including
TNF-α inhibitors.
● Currently, clinically approved TNF-α inhibitors have shown noticeable
potency in a variety of autoimmune diseases, and novel TNF-α
signaling inhibitors are being clinically evaluated.
● Rheumatoid Arthritis
● Psoriatic Arthritis
● Inflammatory Bowel Disease
● Psoriasis
● Noninfectious Uveitis
bpt module 5.pptx
bpt module 5.pptx

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bpt module 5.pptx

  • 2. INTRODUCTION  Insulin is a peptide hormone secreted by the Beta cells of pancreatic islets of Langerhans and maintains normal blood glucose level by regulating carbohydrate, lipid and protein metabolism.  Insulin was discovered by Frederick Banting and Charles Best in 1921. Soon afterward , manufacturing processes were developed to extract the insulin from porcine and bovine pancreata.
  • 3.  From 1921 to 1980, efforts were directed at increasing the purity of insulin and provide different formulations for providing glucose control.  Purification was done by implementing chromatographic processes ,while formulations focused on improving chemical stability of insulin molecule.  Evolution of rDNA technology combined with improved purification methods led to the availability of purest human insulin ever made.
  • 4.  Insulin is composed of two polypeptide chains(Chain A & Chain B) that are connected by two interchain disulfide bonds.  The interchain disulfide linkages occur between A7-B7 and A20-B19 respectively. A third intrachain disulfide bond is located in the A chain, between A6 –A11.
  • 6.  Insulin is derived from a 74-amino-acid prohormone molecule called proinsulin. Proinsulin is relatively inactive, and under normal conditions only a small amount of it is secreted.  In the endoplasmic reticulum of beta cells the proinsulin molecule is cleaved in two places, yielding the A and B chains of insulin and an intervening, biologically inactive C peptide.  The A and B chains become linked together by two sulfur-sulfur (disulfide) bonds.
  • 7. •Factors stimulating insulin release:  the concentration of glucose in the arterial (oxygenated) blood that perfuses the islets. When blood glucose concentrations increase (i.e., following a meal), large amounts of glucose are taken up and metabolized by the beta cells, and the secretion of insulin increases.  Conversely, as blood glucose concentrations decrease, the secretion of insulin decreases; however, even during fasting, small amounts of insulin are secreted.  The secretion of insulin may also be stimulated by certain amino acids, fatty acids, keto acids (products of fatty acid oxidation), and several hormones secreted by the gastrointestinal tract.
  • 8. • Diabetes  Inadequate production of insulin is responsible for the condition called diabetes mellitus. Severe diabetics require periodic injections of insulin.  Diabetes is a group of conditions where the body cannot produce enough or any insulin, cannot properly use the insulin that is produced, or cannot do a combination of either.
  • 9. • Types of diabetes The three main types of diabetes are:  type 1 diabetes  type 2 diabetes  gestational Diabetes
  • 10. Type 1 diabetes  Type 1 diabetes is believed to be an autoimmune condition.  This means your immune system mistakenly attacks and destroys the beta cells in your pancreas that produce insulin.  The damage is permanent.  What prompts the attacks is not clear.  There may be both genetic and environmental reasons. Lifestyle factors are not believed to play a role. 
  • 11. Type 2 diabetes  Type 2 diabetes starts out as insulin resistance.  This means your body cannot use insulin efficiently, which causes your pancreas to produce more insulin until it cannot keep up with demand.  Insulin production then decreases, which causes high blood sugar.  The exact cause of type 2 diabetes is unknown.
  • 12. Contributing factors of type 2 diabetes may include:  Genetics  A more sedentary lifestyle  Higher weight or obesity  There may also be other health factors and environmental reasons
  • 13. Gestational diabetes  Gestational diabetes is caused by insulin-blocking hormones that are produced during pregnancy.  This type of diabetes only happens during pregnancy. It is often seen in people with pre-existing prediabetes and a family history of diabetes.  About 50 percent of people diagnosed with gestational diabetes go on to develop type 2 diabetes.
  • 14. General symptoms of unmanaged diabetes include:  excessive thirst and hunger  frequent urination  drowsiness or fatigue  dry, itchy skin  blurry vision  slow-healing wounds
  • 15.  Symptoms of both types of diabetes can appear at any age, but type 1 usually appears in children and young adults.  Type 2 typically appears in people over the age of 45. But younger people are increasingly being diagnosed with type 2 diabetes due to sedentary lifestyles and an increase in weight.  There’s no cure for type 1 diabetes. It requires lifelong disease management. But with consistent monitoring and adherence to treatment,[must take insulin to live since damage to the pancreas is permanent.
  • 16.  type 2 diabetes can often be successfully managed or even reversed with diet and exercise. It can also be treated with a variety of medications to help manage blood sugar.  The first-line medication is usually metformin (Glumetza, Glucophage, Fortamet, Riomet). This drug works by reducing glucose production in the liver. If metformin does not work, your doctor can prescribe another medication.
  • 17. Insulin therapy  The goal of taking insulin is to keep your blood sugar level in a normal range as much as possible.  Insulin therapy replaces the insulin the body would normally make. People with type 1 diabetes must take insulin every day.  People with type 2 diabetes need to take insulin when other treatments and medicines fail to control blood sugar levels.
  • 18. Insulin doses are given in two main ways:  Basal dose - provides a steady amount of insulin delivered all day and night. This helps maintain blood glucose levels by controlling how much glucose the liver releases (mainly at night when the time between meals is longer).  Bolus dose - provides a dose of insulin at meals to help move absorbed sugar from the blood into muscle and fat. Bolus doses can also help correct blood sugar when it gets too high. Bolus doses are also called nutritional or meal-time doses.
  • 19. Dosing schedule may depend on:  Your weight  Type of insulin you take  How much and what you eat  Level of physical activity  Your blood sugar level  Other health conditions
  • 20.  There are several types of insulin available. Insulin types are based on the following factors:  Onset - how quickly it starts working after injection  Peak - time when the dose is the strongest and most effective  Duration - total time the insulin dose stays in the bloodstream and lowers blood sugar
  • 21. Types of insulin  Rapid acting  Regular or short acting  Intermediate acting  Long acting  Premixed
  • 22.
  • 23. Commercially available insulin products Product Type Peculiarity Company Humulin rh insulin Eli Lilly Novlin Human regular Intermediate acting Novo Nordisk Humalog Insulin lispro An insulin analogue Eli Lilly Liprolog Bio lysprol Short acting insulin Eli Lilly Novolog mix 70/30 Insulin aspart Short acting rh-insulin Novo Nordisk Lantus Insulin glargine Long acting rh-insulin Aventis pharmaceuticals
  • 24. Administration methods and routes  Insulin is administered by two methods of delivery: • Injection • Infusion
  • 25.
  • 26. Injection Insulin syringe:  This is the most common insulin delivery method. The classic injection device is an insulin syringe.  The plastic, disposable syringes currently are available in three sizes, and hold up to 30, 50 or 100 units of insulin.  The needles are fine (up to 31 gauge) with lengths ranging from 3/16th of an inch for infants, to ½ inch or more for adults.  The insulin is injected into the layer of fat (subcutaneous tissue) just under the skin.
  • 27. Insulin Pen:  A popular alternative to the insulin syringe is an insulin pen.  An insulin pen has a replaceable reservoir of insulin called a cartridge, a replaceable needle to puncture the skin and to deliver insulin to the subcutaneous tissue, a dial to choose the insulin dose, and a mechanical pumping or insulin release mechanism.  These may be disposable devices or re-useable devices with disposable insulin cartridges.  They are very convenient for active individuals taking multiple injections, as well as those who are visually or dexterity-challenged.
  • 28. Continuous Subcutaneous Insulin Infusion Device:  Continuous subcutaneous insulin infusion (CSII) devices (also known as insulin pumps) are the most sophisticated form of insulin delivery.  These are small, computerized devices that are programmed to deliver insulin under the skin.  The insulin pump is durable and lasts for years, but the insulin supply and certain pump components (insulin reservoir, tubing and infusion set) are changed every few days.
  • 29. Infusion  Human regular insulin may be injected directly into the vein in a hospital setting under close medical supervision only.  Insulin is added to intravenous fluids, and the insulin dose and blood sugar are strictly monitored .  The intravenous route of delivery is ONLY given under a doctor’s orders in a hospital to facilitate the management of diabetes during surgery or an intensive care stay.
  • 32. CONTENTS 3 2 •ANTIBODIES •MONOCLONAL ANTIBODIES •APPLICATIONS •POLYCLONAL ANTIBODIES •USES OF POLYCLONAL ANTIBODY •DIFFERENCE
  • 33. INTRODUCTION 3 3 1.An antibody or immunoglobulin (Ig) is a glycoprotein that is made by plasma cells in response to an antigen and can recognize and bind to the antigen that caused its production. Antibodies bind antigen with a high degree of specificity and affinity. Antibodies recognize a variety of three-dimensional shapes (amino acids, lipids, carbohydrates, etc.). Antibodies have more than one antigen combining site Some bivalent Ab molecules can combine to form multimeric Abs that have upto 10 combining sites 2. An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one type of immune cell, all clones of a single parent cell. Polyclonal antibodies are antibodies that are derived from different cell lines. They differ in aminoacidsequence.
  • 35. MONOCLONAL ANTIBODY • A type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the surface of cancer cells. There are many kinds of monoclonal antibodies, and each monoclonal antibody is made so that it binds to only one antigen. Monoclonal antibodies are being used in the diagnosis and treatment of many diseases, including some types of cancer. They can be used alone or to carry drugs, toxins, or radioactive substances directly to cancer cells. • Monoclonal antibodies (mAb) are a single type of antibody that are identical and are directed against a specific epitope (antigen, antigenic determinant). These are produced by B-cell clones of a single parent or a single hybridoma cell line. A hybridoma cell line is formed by the fusion of a one B-cell lymphocyte with a myeloma cell. Some myeloma cells synthesize single mAb antibodies naturally. 3 5
  • 36. • Monoclonal antibodies (mAb) are a single type of antibody that are identical and are directed against a specific epitope (antigen, antigenic determinant) and are produced by B-cell clones of a single parent or a single hybridoma cell line. • A hybridoma cell line is formed by the fusion of a one B- cell lymphocyte with a myeloma cell. • Some myeloma cells synthesize single mAb antibodies naturally 3 6
  • 37. PRODUCTION OF MONOCLONAL ANTIBODIES 3 7
  • 38. • Immunize animal • Isolate spleen cells (containing antibody-producing B cells) • Fuse spleen cells with myeloma cells (e.g. using PEG - polyethylene glycol) • Allow unfused B cells to die • Add aminopterin to culture to kill unfused myeloma cells • Clone remaining cells (place 1 cell/well and allow each cell to grow into a clone of cells) • Screen supernatant of each clone for presence of the desired antibody • Grow the chosen clone of cells in tissue culture indefinitely. • Harvest antibody from the culture supernatant. • (If you’re a biotech company) charge about $1,000-$2,000 per mg. 3 8 Practical steps in the production of monoclonal antibodies
  • 39. EXAMPLE FOR MONOCLONAL ANTIBODY 2. Drozitumab Drozitumab is a human monoclonal antibody in development for the treatment of cancers. It targets Tumor Necrosis Factor Related Apoptosis-inducing Ligand(TRAIL), whose receptors are found on the surface of many types of malignant cells. Drozitumab was developed by Genentech Although drozitumab was studied in phase II trials for treating chondrosarcoma, colorectal cancer, non-Hodgkin lymphoma, and non-small cell lung cancer, development has been halted due to lack of clinical response. 1.Abagovomab Abagovomab is a mouse anti-idiotype monoclonal antibody whose variable epitope mirrors a tumor antigen (CA-125) highly expressed in the epithelial ovarian cancer. Abagovomab does not bind directly to CA-125, but it works as a "surrogate" antigen, enabling the immune system to identify and attack tumor cells displaying the CA-125 protein. Through this, it is hoped that the body's immune system may be able to combat any remaining individual tumor cells and thus prevent recurrence of the disease. 3 9
  • 40. Best Uses of Monoclonal Antibodies: • To detect a specific antigen • To detect a single member of a protein family • To create consistent results between experiments/batches • To stain cells with less background – excellent for immunohistochemistry, immunocytochemistry, and immunofluorescence experiments • To quantify protein expression (ex. Flow cytometry or fluorescence-activated cell sorting) • To detect changes in molecular conformation • To detect changes in phosphorylation states • To detect a target for x-ray crystallography • To create animal models lacking a specific cell type • Immunotherapy 4 0
  • 41. MONOCLONAL DIAGNOSTIC USE • A monoclonal antibody can be used to detect pregnancy only 14 days after conception. Other monoclonal antibodies allow rapid diagnosis of hepatitis, influenza, herpes, streptococcal, and Chlamydia infections. • They can be used to detect for the presence and quantity of this substance, for instance in a Western blot test (to detect a substance in a solution) or an immunofluorescence test. • Monoclonal antibodies can also be used to purify a substance with techniques called immunoprecipitation and affinity chromatography. 4 1
  • 42. MONOCLONAL ANTIBODIES FOR CANCER TREATMENTS 4 2 Possible treatment for cancer involves monoclonal antibodies that bind only to cancer cells specific antigen and induce immunological response on the target cancer cell (naked antibodies). mAb can be modificated for delivery of [toxin], radioisotope, cytokine.
  • 43. A BREAKTHROUGH IN DIAGNOSTICS • In Pregnancy by detecting the urinary levels of human chorionic gonadotropin. • Cancer estimation of plasma carcinoembryonic antigen in colorectal cancer, and prostate specific antigen for prostate cancer. • They can be used to detect for the presence and quantity of this substance, for instance in a Western blot test (to detect a substance in a solution) or an immunofluorescence test. • The radioisotopes commonly used for labeling MAb are iodine—131 and technetium—99. The MAb tagged with radioisotope are injected intravenously into the patients. • Single photon emission computed tomography (SPECT) cameras are used to give a more sensitive 3d appearance of the spots localized by radiolabeled— MAbs. 4 3
  • 44. DIAGNOSTIC APPLICATIONS • 1. Detects protein of interest by immune florescence or blotting. • 2. Cardiovascular diseases. • 3. Deep vein thrombosis. • 4. Location of primary and secondary metastatic tumors. • 5. Immunosuppressive therapy. • 6. Pregnancy testing kits. 4 4 THERAPEUTIC APPLICATIONS 1. Radioisotope immune conjugates. 2. Toxin and drug immune conjugates. 3. Immunoliposome based kits. 4. In cancer. 5. Inflammatory disease.
  • 45. POLYCLONAL ANTIBODY • A polyclonal antibody refers to an antibody normally recognizing only a single antigen but within which a number of different epitopes are recognized. • Polyclonal antibodies (PAbs) are a mixture of antibodies that are secreted by different B cell lineages. These antibodies are actually a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope on an antigen. • A Polyclonal Antibody represents a collection of antibodies from different B cells that recognize multiple epitopes on the same antigen. Each of these individual antibodies recognizes a unique epitope that is located on that antigen. 4 5
  • 46. PRODUCTION OF POLYCLONAL ANTIBODY 4 6 • Antibodies used for research and diagnostic purposes are often obtained by injecting a lab animal such as a rabbit with a specific antigen. • Within a few weeks, the animal’s immune system will produce high levels of antibodies specific for the antigen. • These antibodies can be harvested in an antiserum, which is whole serum collected from an animal following exposure to an antigen • Because most antigens are complex structures with multiple epitopes, they result in the production of multiple antibodies in the lab animal. • This so-called polyclonal antibody response is also typical of the response to infection by the human immune system.
  • 47. • Antiserum drawn from an animal will thus contain antibodies from multiple clones of B cells, with each B cell responding to a specific epitope on the antigen • Antiserum obtained from animals will not only contain antibodies against the antigen artificially introduced in the laboratory, but it will also contain antibodies to any other antigens to which the animal has been exposed during its lifetime. • For this reason, antisera must first be “purified” to remove other antibodies before using the antibodies for research or diagnostic assays. 4 7
  • 48. 4 8
  • 50. ADVANTAGES OF POLYCLONAL ANTIBODIES 1. Inexpensive. 2. Easy to store. 3. Quick to produce. 4. Ready to use in under four months. 5. Highly stable and tolerant of pH or buffer changes. 6. High affinity as the antibodies bind to more than one epitope, they can help amplify the signal from target protein even with low expression level. 5 0
  • 51. • The use of polyclonal antibodies (PAbs) over monoclonal antibodies has its advantages. The technical skills needed to produce polyclonal antibodies is not as demanding. They're inexpensive to make and can be generated fairly quickly, taking up to several months to produce. PAbs are heterogeneous, which allows them to bind to a wide range of antigen epitopes. • Because PAbs are produced from a large number of B cell clones, they're more likely to successfully bind to a specific antigen. PAbs remain stable in different environments, such as a change in pH or salt concentration, which allows them to be more applicable in certain procedures. • Additionally, depending on the amount needed, PAbs can be made in large quantities in relation to the size of the animal used. 5 1
  • 52. USES OF PLOYCLONAL ANTIBODIES 1. Sandwich ELISA for tumor markers or other antigens can be designed with polyclonal antibodies. 2. To detect a known or unknown is forms of antigens with high antigen homology 3. To detect low levels of a particular antigen 4. To capture as much antigen as possible 5. To detect denatured proteins 6. To detect a target in solutions with varying pH and salt concentrations 5 2
  • 53. DIFFERENCE BETWEEN MONOCLONAL AND POLYCLONAL ANTIBODY 5 3
  • 56. ● Cardiovascular drug, any agent that affects the function of the heart and blood vessels. ● Drugs that act on the cardiovascular system are among the most widely used in medicine. ● Examples of disorders in which such drugs may be useful include hypertension (high blood pressure), angina pectoris (chest pain resulting from inadequate blood flow through the coronary arteries to the heart muscle), heart failure (inadequate output of the heart muscle in relation to the needs of the rest of the body), and arrhythmias (disturbances of cardiac rhythm).
  • 57. TYPES AND USE OF CARDIO VASCULAR DRUG ● Wide range of medications are used to treat various heart conditions. Some examples of the drugs used in cardiovascular medicine include: ● Anticoagulants or blood thinners - These agents prevent coagulation or clotting of the blood. Injectable forms of anticoagulants include dalteparin, enoxaparin, tinzaparin and heparin. ● Warfarin is a commonly used blood thinner that can be taken in the form of a tablet.
  • 58. • These drugs do not dissolve existing blood clots but are preventive agents in patients who have had a heart attack. • Antiplatelet agents - Platelets play an important role in blood clotting and the formation of platelet plugs that prevent bleeding. • Examples of antiplatelet medications include aspirin, ticlopidine, lopidogrel and dipyridamole. • They are used as preventive agents in patients who have had a heart attack.
  • 59. ● Thrombolytic agents - These agents are used to break up blood clots that have formed and examples include streptokinase, reteplase and altepase. ● Angiotensin-converting enzyme (ACE) inhibitors - These agents expand blood vessels by lowering levels of angiotensin II, a potent vasoconstrictor that drives blood pressure up. ACE inhibitors are used to treat high blood pressure, heart failure and heart attacks. Examples of agents in this class include captopril, enalapril, fosinopril and lisinopril.
  • 60. Angiotensin II receptor blockers (ARBs) - These agents prevent angiotensin II from having any effects on the heart and blood vessels by blocking the receptors it usually binds to. These agents are useful in the treatment of high blood pressure, heart failure and heart attacks. Examples of drugs in this class include candesartan, irbesartan, losartan, telmisartan and valsartan
  • 61. ● Diuretics - Diuretics increase the excretion of water and sodium in the urine, therefore decreasing the total blood volume. This reduces blood pressure and the heart's workload. Examples of agents in this class include chlorothiazide, amiloride, furosemide, bumetanide, indapamide and spironolactone. ● Vasodilators - These drugs relax the blood vessels and cause blood pressure to fall. They are useful in the treatment of high blood pressure, heart failure, angina and heart attacks. Examples include isosorbide, dinitrate and hydralazine. ● Digoxin - This agent is used to stimulate a heartbeat in some cases of heart failure.
  • 62. . ● Statins - These agents reduce the synthesis of blood cholesterol in the liver. High blood cholesterol is one of the major causes of atherosclerosis. Some of the most well known examples include atorvastatin, lovastatin and simvastatin. ● Drugs that are used to regulate an abnormal heart rhythm include quinidine, lidocaine, amiodarone, sotalol, verapamil, diltiazem, dofetilide and adenosine. ● Beta blockers or beta-adrenergic blocking agents - These agents decrease the heart rate and the final cardiac output. This lowers blood pressure and heart rate. Beta blockers are useful therapies in high blood pressure and some types of arrhythmia. Agents in this class include atenolol, bisoprolol, metoprolol, propranolol and sotalol.
  • 63. Calcium channel blockers - Calcium channel blockers stop the movement of calcium into the cells of the heart and blood vessels. This relaxes the vessels and reduces blood pressure. Calcium channel blockers are useful therapies in high blood pressure, angina, and some forms of arrhythmia. Examples of drugs in this class include amlodipine, felodipine, nifedipine and varapamil
  • 65. ● Anticoagulants are commonly known as blood thinners. ● They are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. ● Anticoagulants are used in therapy for thrombotic disorders. ● Oral anticoagulants (OACs) are taken by many people in pill or tablet form, and various intravenous anticoagulant dosage forms are used in hospitals. ● Common anticoagulants include warfarin and heparin.
  • 66. There are three main types of anticoagulant medications: ● Vitamin K antagonists ● Direct Oral Anticoagulants (DOACs) ● Low molecular weight heparins (LMWH) Each type works in a different way to prevent unneeded blood clots.
  • 67. VITAMIN K ANTAGONIST ANTICOAGULANTS ● Vitamin K helps in blood clot. ● We get it from green leafy vegetables like broccoli and spinach and from the action of bacteria in your gut. ● Vitamin K “antagonists” like warfarin stop your liver from processing vitamin K into “factors” that normally help clot your blood. ● This curbs blood clotting. ● One of the potential advantages of this type of anticoagulant is that it’s easier than others to reverse in case you have sudden bleeding from trauma or emergency surgery.
  • 68. DIRECT ORAL ANTICOAGULANTS (DOACS) ● DOACs work more quickly than vitamin K antagonists. DOACs include: a) Direct thrombin inhibitors: ● These drugs interfere with your body’s use of thrombin, a key enzyme that helps clot your blood. Though it's typically injected in a vein, you can take it in pill form as dabigatran (Pradaxa).
  • 69. b) Direct factor Xa inhibitors: ● This type of anticoagulant stops the Xa factor in the clotting process from working as it should. ● These medications, which come in pill form, include apixaban (Eliquis), betrixaban (Bevyxxa), edoxaban (Savaysa), and rivaroxaban (Xarelto).
  • 70. LOW MOLECULAR WEIGHT HEPARIN (LMWH) ANTICOAGULANTS ● Low-molecular weight heparin is gradually replacing heparin for treatment of most patients with venous thromboembolism and acute coronary syndromes because it has more convenient and cost-effective ● It has similar results to heparin ● Administered by subcutaneous injection ● LOVENOX® is an example
  • 72. ● Antithrombotic agents are medications that are used to prevent the formation or development of blood clots within the body. ● These agents work by inhibiting platelet aggregation or by reducing blood coagulation. Some common antithrombotic agents include: 1. Aspirin: Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that works by inhibiting platelet aggregation. 2. Heparin: Heparin is an anticoagulant that prevents blood from clotting by inhibiting the action of thrombin and factor Xa.
  • 73. 3. Warfarin: Warfarin is an oral anticoagulant that interferes with the synthesis of vitamin K-dependent clotting factors in the liver. 4. Direct oral anticoagulants (DOACs): DOACs, also known as novel oral anticoagulants (NOACs), are a newer class of anticoagulants that directly inhibit factor Xa or thrombin. 5. Clopidogrel: Clopidogrel is an antiplatelet medication that works by inhibiting the ADP receptor on platelets.
  • 74. MAIN TYPES 1. Antiplatelet agents: These agents work by inhibiting platelet activation and aggregation. Examples include aspirin, clopidogrel, dipyridamole, and ticagrelor 2. Anticoagulants: These agents prevent the formation of blood clots by inhibiting the coagulation cascade. Examples include heparin, warfarin, direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban.
  • 75. 3. Thrombolytic agents: These agents are used to dissolve blood clots that have already formed. Examples include alteplase, reteplase, and tenecteplase. 4. Anti-fibrinolytic agents: These agents work by preventing the breakdown of blood clots. Examples include tranexamic acid and aminocaproic acid. 5. Other agents: There are also other types of antithrombotic agents, such as prostacyclin analogues (epoprostenol, iloprost), glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), and phosphodiesterase inhibitors (dipyridamole, cilostazol).
  • 76. 1. Prevention of blood clots: Antithrombotic agents are used to prevent the formation of blood clots in people who are at high risk due to certain medical conditions, such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, heart valve disease, or recent surgery. 2. Treatment of blood clots: Antithrombotic agents are used to treat existing blood clots and prevent them from growing or traveling to other parts of the body. This is particularly important in the case of deep vein thrombosis, pulmonary embolism, or stroke. 3. Prevention of cardiovascular events: Some antithrombotic agents, such as aspirin, are used to prevent heart attack and stroke in people with a high risk of cardiovascular disease. USES
  • 78. ● Hemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel. ● It is the first stage of wound healing. ● This involves coagulation, which changes blood from a liquid to a gel. ● Hemostasis is maintained in the body via four mechanisms:
  • 79.
  • 80.
  • 81. USES 1. Control of bleeding during surgery: Hemostasis is critical during surgery to prevent excessive bleeding and ensure good visibility of the surgical site. 2. Treatment of bleeding disorders: Hemostasis is important in the management of bleeding disorders, such as hemophilia and von Willebrand disease. Patients with these conditions may receive transfusions of clotting factors or medications to promote blood clotting. 3. Management of trauma: Hemostasis is critical in the immediate management of trauma, such as in the case of severe injuries or major surgery.
  • 84. CHEMOTHERAPY  Chemotherapy involves the use of cytotoxic medications to cure cancer or decrease tumour size or to prevent or treat suspected metabases.  It interfering with the ability of the malignant cell to synthesize vital enzymes and chemicals.  Chemotherapy disrupts the cell cycle in various phase by interrupting cell metabolism and replication.  Based on the chemical makeup and biological activity, different drugs used for cancer treatment act in specific phases and sub phases of the cell cycle.
  • 85. ADJUVANT AND NEO-ADJUVANT CHEMOTHERAPY  Adjuvant chemotherapy:- Chemotherapy given after surgery or irradiation to destroy micrometastasis and prevent development of secondary neoplasm.  Neo-adjuvant chemotherapy:- Chemotherapy given before surgery or radiotherapy in order to diminish the volume of large primary neoplasm.
  • 86. CLASSES OF CHEMOTHERAPY DRUGS  Chemotherapeutic agents can be classified either by the effects of the agent on the cell or by the pharmacological properties of the agent.  Chemotherapeutic agents can be divided into:- Cell cycled-specific agents Cell cycle-nonspecific agents
  • 87. CELL CYCLE-SPECIFIC AND CELL CYCLE-NONSPECIFIC AGENTS  Cell cycle-specific:- These are the agents effective at a specific phase (example, S and M phases) in the cell replication by damaging cellular DNA and blocking production of protein necessary for DNA and RNA synthesis.  Cell cycle-nonspecific:- These are the agents effective throughout all the phases of the cell cycle, including the resting phase.
  • 88. OTHER CLASSIFICATIONS OF CHEMOTHERAPEUTIC AGENTS  Chemotherapeutic agents are classified based on pharmacological properties of the agent. The classifications include: a. Alkylating agents b. Antimetabolites c. Antitumour antibiotics d. Mitotic inhibitors e. Hormones and hormone antagonists f. Miscellaneous agents
  • 89. ALKYLATING AGENTS  Alkylating agents are not phase specific and basically act on performed nucleic acids by creating defects in tumour DNA. They cause crosslinking of DNA strands and interfere with replication and transcription.  It acts with proliferating and non proliferating cells those in G0 phase.  The several subclasses of alkylating agents include:- a. Nitrogen mustards:- Mechlorethamine, Melphalan, Chlorambucil, cyclophosphamide, ifosfamide. b. Ethyleneimine:- Thiotepa c. Alkyl Sulfonate:- Busulfan d. Nitrosureas:- Carmustine, lomustine, streptozocin e. Triazines:- Dacarbazine, temozolamide
  • 90. ANTIMETABOLITES  Antimetabolites are phase specific, working best in the S phase and having little effect in G0. It interfere with nucleic acid synthesis by displacing metabolites at the regulatory site of a key enzyme.  Classifications are:- a. Folate antagonists:- Methotrexate b. Purine antagonists:- 6 Mercaptopurine, 6 Thioguanine, Azathioprine c. Pyrimidine antagonists:- 5 Fluorouracil, cytarabine, gemcitabine
  • 91. ANTITUMOUR ANTIBIOTICS  Antitumour antibiotics derived from natural sources that are generally too toxic to be used as anti-bacterial agents.  They are not phase specific and act in several ways: they disrupt DNA replication and RNA transcription; create free radicals, which generate breaks in DNA and other forms of damage; and interfere with DNA repair.  These antibiotics include:- a. Actinomycin D b. Doxorubicin c. Bleomycin d. Mitomycin-C e. Mithramycin
  • 92. MITOTIC INHIBITORS  Mitotic inhibitors are drugs that act to prevent cell division during the M phase. Mitotic inhibitors include plant alkaloids and taxoids.  Plant alkaloids consists of medications extracted from plant sources (periwinkle plant): Vinca  Alkaloids (example, vincristine and vinblastine) and etoposide.  The toxoids acts during the G2 phase to inhibit cell divison (example, Paclitaxel and Docetaxel).
  • 93. HORMONES AND HORMONE ANTAGONISTS  The main hormones used in cancer therapy are the corticosteroids which are phase specific (G1).  These act by binding to specific intracellular receptors, repressing transcription of mRNA and therapy altering cellular function and growth.  Hormone antagonists work with hormone binding tumours. They block the hormones receptor site on the tumour and prevent it from receiving normal hormonal growth stimulation.  Example of hormone and hormone antagonists are:- • Corticosteroids:- Prednisolone • Oestrogens:- Ethinyl Estradiol • Aromatase inhibitors:- Letrozole, Anastrazole, Exemestane • Progestins:-Hydroxyprogesterone
  • 94. • Anti-androgens:- Flutamide, Bicalutamide • GnRH analogs:- Naferelin, Goserelin, Leuoprolide • Selective oestrogen Receptor moderator(SERM):- Tamoxifene, Toremifene Receptor degrader(SERD):- Fulvestrant • Enzymes:- L-asparginase • Epipodophyllotoxins:- Etoposide, tenoposide • Camptothecin analogs:- Topotecan, irinotecan • Biological response modifiers:- Interferons, Interleukins
  • 95. MISCELLANEOUS AGENTS  Several miscellaneous agents act at different phases in the cell cycle.  The miscellaneous agents are:- Cisplatin Carboplatin Hydroxurea Procarbazine Mitotane Imatinib
  • 97. CHEMOTHERAPY  Chemotherapy involves the use of cytotoxic medications to cure cancer or decrease tumour size or to prevent or treat suspected metabases.  It interfering with the ability of the malignant cell to synthesize vital enzymes and chemicals.  Chemotherapy disrupts the cell cycle in various phase by interrupting cell metabolism and replication.  Based on the chemical makeup and biological activity, different drugs used for cancer treatment act in specific phases and sub phases of the cell cycle.
  • 98. ADJUVANT AND NEO-ADJUVANT CHEMOTHERAPY  Adjuvant chemotherapy:- Chemotherapy given after surgery or irradiation to destroy micrometastasis and prevent development of secondary neoplasm.  Neo-adjuvant chemotherapy:- Chemotherapy given before surgery or radiotherapy in order to diminish the volume of large primary neoplasm.
  • 99. CLASSES OF CHEMOTHERAPY DRUGS  Chemotherapeutic agents can be classified either by the effects of the agent on the cell or by the pharmacological properties of the agent.  Chemotherapeutic agents can be divided into:- Cell cycled-specific agents Cell cycle-nonspecific agents
  • 100. CELL CYCLE-SPECIFIC AND CELL CYCLE-NONSPECIFIC AGENTS  Cell cycle-specific:- These are the agents effective at a specific phase (example, S and M phases) in the cell replication by damaging cellular DNA and blocking production of protein necessary for DNA and RNA synthesis.  Cell cycle-nonspecific:- These are the agents effective throughout all the phases of the cell cycle, including the resting phase.
  • 101. OTHER CLASSIFICATIONS OF CHEMOTHERAPEUTIC AGENTS  Chemotherapeutic agents are classified based on pharmacological properties of the agent. The classifications include: a. Alkylating agents b. Antimetabolites c. Antitumour antibiotics d. Mitotic inhibitors e. Hormones and hormone antagonists f. Miscellaneous agents
  • 102. ALKYLATING AGENTS  Alkylating agents are not phase specific and basically act on performed nucleic acids by creating defects in tumour DNA. They cause crosslinking of DNA strands and interfere with replication and transcription.  It acts with proliferating and non proliferating cells those in G0 phase.  The several subclasses of alkylating agents include:- a. Nitrogen mustards:- Mechlorethamine, Melphalan, Chlorambucil, cyclophosphamide, ifosfamide. b. Ethyleneimine:- Thiotepa c. Alkyl Sulfonate:- Busulfan d. Nitrosureas:- Carmustine, lomustine, streptozocin e. Triazines:- Dacarbazine, temozolamide
  • 103. ANTIMETABOLITES  Antimetabolites are phase specific, working best in the S phase and having little effect in G0. It interfere with nucleic acid synthesis by displacing metabolites at the regulatory site of a key enzyme.  Classifications are:- a. Folate antagonists:- Methotrexate b. Purine antagonists:- 6 Mercaptopurine, 6 Thioguanine, Azathioprine c. Pyrimidine antagonists:- 5 Fluorouracil, cytarabine, gemcitabine
  • 104. ANTITUMOUR ANTIBIOTICS  Antitumour antibiotics derived from natural sources that are generally too toxic to be used as anti-bacterial agents.  They are not phase specific and act in several ways: they disrupt DNA replication and RNA transcription; create free radicals, which generate breaks in DNA and other forms of damage; and interfere with DNA repair.  These antibiotics include:- a. Actinomycin D b. Doxorubicin c. Bleomycin d. Mitomycin-C e. Mithramycin
  • 105. MITOTIC INHIBITORS  Mitotic inhibitors are drugs that act to prevent cell division during the M phase. Mitotic inhibitors include plant alkaloids and taxoids.  Plant alkaloids consists of medications extracted from plant sources (periwinkle plant): Vinca  Alkaloids (example, vincristine and vinblastine) and etoposide.  The toxoids acts during the G2 phase to inhibit cell divison (example, Paclitaxel and Docetaxel).
  • 106. HORMONES AND HORMONE ANTAGONISTS  The main hormones used in cancer therapy are the corticosteroids which are phase specific (G1).  These act by binding to specific intracellular receptors, repressing transcription of mRNA and therapy altering cellular function and growth.  Hormone antagonists work with hormone binding tumours. They block the hormones receptor site on the tumour and prevent it from receiving normal hormonal growth stimulation.  Example of hormone and hormone antagonists are:- • Corticosteroids:- Prednisolone • Oestrogens:- Ethinyl Estradiol • Aromatase inhibitors:- Letrozole, Anastrazole, Exemestane • Progestins:-Hydroxyprogesterone
  • 107. • Anti-androgens:- Flutamide, Bicalutamide • GnRH analogs:- Naferelin, Goserelin, Leuoprolide • Selective oestrogen Receptor moderator(SERM):- Tamoxifene, Toremifene Receptor degrader(SERD):- Fulvestrant • Enzymes:- L-asparginase • Epipodophyllotoxins:- Etoposide, tenoposide • Camptothecin analogs:- Topotecan, irinotecan • Biological response modifiers:- Interferons, Interleukins
  • 108. MISCELLANEOUS AGENTS  Several miscellaneous agents act at different phases in the cell cycle.  The miscellaneous agents are:- Cisplatin Carboplatin Hydroxurea Procarbazine Mitotane Imatinib
  • 110. What are they? • An oligonucleotide is a short, single-stranded DNA or RNA molecule typically composed of 10-50 nucleotides. • The sequence of nucleotides in an oligonucleotide can be designed to bind specifically to a complementary sequence of nucleotides in a target DNA or RNA molecule, allowing for applications such as gene expression analysis, DNA sequencing, and genetic engineering. • Oligonucleotides are widely used in research, diagnostics, and therapeutics.
  • 111. Types of Oligonucleotides • There are several types of oligonucleotides, each with specific characteristics and applications. • The most common types of oligonucleotides are: 1. DNA oligonucleotides: These are short, single-stranded DNA molecules typically composed of 10-50 nucleotides. They are widely used in molecular biology research and in diagnostics. 2. RNA oligonucleotides: These are short, single-stranded RNA molecules typically composed of 10-50 nucleotides. They are used in a variety of applications, including gene expression analysis, RNA interference, and therapeutic applications. 3. siRNA (short interfering RNA): These are double-stranded RNA molecules typically composed of 21-23 nucleotides. They are used to silence the expression of specific gene by targeting and degrading the mRNA molecules that encode them.
  • 112. 4. miRNA (microRNA): These are short, single-stranded RNA molecules typically composed of 20-24 nucleotides. They regulate gene expression by binding to mRNA molecules and inhibiting their translation into proteins. 5. Antisense oligonucleotides: These are synthetic single-stranded DNA or RNA molecules designed to hybridize with specific mRNA molecules and inhibit their translation into proteins. They are used in therapeutic applications to target disease- causing genes or proteins. 6. Aptamers: These are short, single-stranded DNA or RNA molecules that bind to specific target molecules with high affinity and specificity. They are used in a variety of applications, including diagnostics, therapeutics, and research.
  • 113. Biological Importance • Oligonucleotides are biologically important because they are essential components of DNA and RNA, the molecules that carry genetic information in all living organisms. They play a crucial role in many biological processes, including gene expression, DNA replication, and protein synthesis. • Some examples of the biological importance of oligonucleotides: 1. DNA replication: Oligonucleotides are the building blocks of DNA, which replicates itself during cell division. The two complementary strands of DNA are synthesized by the enzyme DNA polymerase, which uses oligonucleotides as a template to build new strands of DNA. 2. Gene expression: Oligonucleotides are involved in the process of gene expression, which is the process by which genetic information is used to synthesize proteins. During gene expression, RNA molecules are synthesized from DNA templates, and these RNA molecules contain oligonucleotide sequences that are important for protein synthesis.
  • 114. 3. Protein synthesis: Oligonucleotides are involved in protein synthesis, which is the process by which RNA molecules are translated into proteins. During this process, ribosomes read the sequence of nucleotides in the RNA molecule and use this information to assemble amino acids into a protein chain. 4. Genetic engineering: Oligonucleotides are essential tools for genetic engineering, which involves manipulating DNA sequences to add, delete, or modify genes. Oligonucleotides can be used to introduce specific mutations or to target specific DNA sequences for editing.
  • 115. Production of Oligonucleotides • Oligonucleotides can be produced using several methods, including enzymatic synthesis, solid-phase synthesis, and chemical synthesis. • The general steps involved in the production of oligonucleotides using solid-phase synthesis: Design and selection of the target sequence: The first step is to determine the sequence of the oligonucleotide required for the desired application. The sequence is typically chosen based on the function of the oligonucleotide, such as primers for PCR or probes for hybridization assays. Synthesis of the oligonucleotide: The oligonucleotide is synthesized on a solid support, such as polystyrene beads, using an automated oligonucleotide synthesizer. The nucleotides are added stepwise in a specific order, with each addition being protected by a temporary chemical group to prevent unwanted reactions.
  • 116. Deprotection and cleavage: After the synthesis is complete, the oligonucleotide is deprotected to remove the temporary chemical groups and cleaved from the solid support. The oligonucleotide is then purified by HPLC or another method to remove any impurities and ensure a high degree of purity. Analysis and quality control: The final step is to analyze the oligonucleotide to ensure that it meets the desired specifications, including length, purity, and yield. Quality control may involve gel electrophoresis, mass spectrometry, or other techniques.
  • 117. • The other most common methods for producing and synthesizing oligonucleotides are : Enzymatic synthesis: This method involves using enzymes to synthesize oligonucleotides from nucleotide triphosphates. One of the most commonly used enzymes for this purpose is polynucleotide phosphorylase (PNPase). This method is often used to synthesize short RNA oligonucleotides. Chemical synthesis: This method involves using chemical reactions to synthesize oligonucleotides from nucleotide building blocks. One of the most commonly used chemical methods for this purpose is phosphoramidite chemistry, which involves the sequential addition of nucleotide building blocks to a growing chain. This method is widely used for the synthesis of DNA oligonucleotides. • After synthesis, oligonucleotides can be purified using a variety of methods, including HPLC, PAGE, or ion-exchange chromatography. The purity and quality of oligonucleotides are critical factors in their performance and applications.
  • 118. Application of Oligonucleotides • Oligonucleotides have a wide range of applications in various fields, including : 1. Research: Oligonucleotides are widely used in molecular biology research to probe and manipulate nucleic acid sequences. They are used for gene expression analysis, DNA sequencing, and genetic engineering. 2. Diagnostics: Oligonucleotides can be designed to specifically bind to and detect target DNA or RNA sequences, making them useful for diagnostic applications such as detecting infectious agents or genetic mutations. 3. Therapeutics: Oligonucleotides can be used as therapeutic agents to target specific disease-causing genes or proteins. They can be designed to inhibit the expression of disease-causing genes, promote the degradation of disease- causing RNA molecules, or modulate the activity of disease-causing proteins. 4. Forensics: Oligonucleotides can be used in forensic investigations to analyze DNA samples for identification purposes. 5. Agriculture: Oligonucleotides can be used in agriculture to genetically engineer crops with desirable traits, such as increased yield or resistance to pests
  • 119. Examples of Oligonucleotides Drugs 1. Spinraza - This antisense oligonucleotide drug is used to treat spinal muscular atrophy (SMA), a rare genetic disorder that affects the muscles. Spinraza works by increasing the production of the SMN protein, which is deficient in SMA patients. 2. Onpattro (patisiran) - This RNA interference (RNAi) therapeutic is used to treat hereditary transthyretin-mediated amyloidosis (hATTR), a rare disease in which abnormal proteins build up in the body's tissues and organs. Onpattro works by reducing the production of the protein responsible for this buildup. 3. Tegsedi (inotersen) - Another antisense oligonucleotide drug, Tegsedi is used to treat hATTR. It works by blocking the production of the abnormal protein that causes the disease. 4. Givosiran (Givlaari) - This RNAi therapeutic is used to treat acute hepatic porphyria (AHP), a rare genetic disorder that affects the liver. Givosiran works by reducing the production of a specific enzyme that is responsible for the symptoms of the disease. 5. Lumasiran (Oxlumo) - This RNAi therapeutic is used to treat primary hyperoxaluria type 1 (PH1), a rare genetic disorder that causes the buildup of oxalate crystals in the kidneys and other organs. Lumasiran works by reducing the production of an enzyme that is responsible for the overproduction of oxalate in PH1 patients.
  • 120. Other examples are : • Fomiversin for the treatment of cytomegalovirus retinitis. • Mipomersen for high cholesterol • Genasense against cancer • AP 1-2009 for the treatment of high grade glimoas
  • 122. • Consist of many glands that secrete hormones into the blood. • When glands malfunction they secrete either by: • Decreased amount of hormone • Increased amount of hormone ENDOCRINE SYSTEMS
  • 123.
  • 124. Insulin drugs used to treat diabetes mellitus • Insulin • Secreted by beta cells in islets of Langerhans in the pancreas • Plays an essential role in glucose metabolism • Lowers blood glucose levels enabling cells to utilize glucose • Transports glucose to the cell • Binds with an insulin receptor on the cell membrane • Transport glucose inside the cell • The glucose is metabolized to provide energy
  • 125. Diabetes Mellitus • Disease of pancreas and body cells • Type 1 • The pancreas doesn’t produce any insulin • Type 2 • The pancreas produces too little insulin • The number of or sensitivity of insulin receptors on body cells in decreased
  • 126. Type 1 Diabetes Mellitus • Previously known as: • Insulin-dependent diabetes mellitus (IDDM) • Juvenile-onset diabetes mellitus • Treated with subcutaneously injected insulin
  • 127. Type 2 Diabetes Mellitus • Previously known as: • Non-insulin-dependent diabetes mellitus (NIDDM) • Adult-onset diabetes mellitus • Treated with antidiabetic drugs • Insulin maybe needed • Untreated or uncontrolled diabetes mellitus results in consistently elevated blood glucose level. • Eventually leads to diabetic complications of: • Arteriosclerosis • Ketoacidosis • Death
  • 128. • All insulin drugs are grouped according to: • How quickly they act in the body to lower the blood glucose • Size of insulin crystalline • Hours their therapeutic effect continues • Amount of protamine and zinc added to the insulin
  • 129. Rapid acting insulin drugs • Taken in the morning or before eating • Onset of therapeutic effect is almost immediate • Can begin to lower blood glucose levels in as little as 15 minutes • Therapeutic effect last 2 to 12 hours . • Also known as regular insulin • Sometimes reflected in the drug’s trade name as the abbreviation R.
  • 130. • Three types of rapid acting insulin : • Derived from pig pancreas • Regular I Letin II • Created by recombinant DNA technology • Humulin R • Novolin R • Insulin analog drugs created by recombinant DNA technology
  • 131. Intermediate acting insulin drugs • Slower onset but a longer effect than rapid acting insulin • Therapeutic effect • Onset is between 1 to 2 hours • Last for 24 hours • Two types: • Those with added protamine and zinc (NPH insulin drugs ) to prolong the therapeutic effect of insulin. • Those with different size of insulin crystals (lente insulin drugs) to slow down the onset of action.
  • 132. Long acting insulin drugs • Have large insulin crystals containing added zinc • Doesn't begin to lower the blood sugar for an hour • Therapeutic effect lasts a full 24 hours after just one dose • Also known as ultralente insulin
  • 133. Combination insulin drugs • Contain a mixture of: • An intermediate acting insulin • NPH insulin • Insulin analog • A rapid acting insulin • Regular insulin • Insulin analog
  • 134. Drugs used to treat diseases of thyroid gland • Hypothyroidism • Too little thyroid hormone secreted • Hyperthyroidism • Too much thyroid hormone secreted
  • 135. Drugs for hypothyroidism • Thyroid gland secretes hormones: • Triiodothyronine (T3) • Thyroxine (T4) • Decreased level causes hypothyroidism • Drugs for hypothyroidism is obtained naturally from desiccated (dried) animal thyroid glands or manufactured synthetically. • Drugs for hypothyroidism • Containing only T3 • Liothyronine (Cytomel, Triostat) • Containing only T4 • Levothyroxine (Levothroid , Synthroid) • Containing both T3 and T4 • Desiccated thyroid (Armour thyroid ) • Liotrix (Thyrolar )
  • 136. Biological functions • T3 is considered the major regulator of mitochondrial activity • Induces early stimulation of transcription and increases transcription factor (TFA) expression • Stimulate oxygen consumption by mitochondria • Regulate the rate of overall metabolism • T3 increases basal metabolic rate • T3 is an important regulator of skeletal maturation at the growth plate • T4 is responsible for metabolism, mood and body temperature.
  • 137. Drugs for hyperthyroidism • Also known as thyrotoxicosis • Increased levels of T3 and T4 • Drugs inhibit production of T3 and T4 in the thyroid • Radioactive sodium iodide 131 • Used to treat hyperthyroidism and thyroid cancer • Low level radiation emitted destroys both hyperactive benign thyroid and cancerous thyroid tissues. • Iodine (ThyroShield) • Methimazole (Tapazole)
  • 138. Drugs used to treat diseases of pituitary gland • Growth hormone • Secreted by anterior pituitary gland • Stimulate the production of insulin like growth factor 1 • Children with failure to grow can have an abnormality in any of these areas: • Decreased amount of growth hormone • Antibodies against growth hormone • Abnormalities of growth hormone receptors on cells • Deceased amount of insulin like growth factor 1
  • 139. Drugs for acromegaly • Acromegaly • Over production of growth hormone (anterior pituitary) • Causes widening and enlargement of facial features, hands and feet • Drugs for acromegaly • Decrease production of growth hormone • Block growth hormone by anterior pituitary or block growth hormone from activating receptors on cell membrane
  • 140. Growth hormone replacement drugs • Drugs are used as replacement therapy • Sermorelin (Geref ) • Somatropin ( Humatrope, Nutropin ) • Somatrem (Protropin)
  • 141. Drugs used to treat adrenal gland dysfunction • Drugs for crushing syndrome • Too much adrenal gland hormone is secreted • Tumour on adrenal gland cortex • Causes increase in amount of cortisol produced • Removal by surgery preferred option • Drugs suppresses cortisol secretion in patients who cannot have surgery
  • 142. Drugs for addison disease • Autoimmune disease in which body’s own antibodies destroys adrenal cortex • Too little adrenal gland hormone is secreted • Causes fatigue, weight loss • Decreased ability to tolerate : • Stress • Disease • Surgery • Patients have unusual bronzed colour to the skin
  • 143. • Drugs for addison disease • Cortisone • Hydrocortisone (Cortef) Cortisone functions: • Provide relief for inflamed areas of the body • They lessen swelling, redness, itching and allergic reactions • Most commonly injected into joints such as ankle, elbow, hip, knee, shoulders, spine or wrist
  • 144. Corticosteroid drugs • Adrenal cortex secrete glucocorticoid hormones • Cortisol • Powerful anti-inflammatory effect • Act as a natural hormone secreted by the adrenal cortex • Used as a replacement therapy to treat addison disease • Given by mouth or injection to treat inflammatory reactions in various parts of the body • Used to treat systemic inflammation caused by autoimmune diseases (Rheumatoid arthritis, Multiple sclerosis etc)
  • 145. Cortisol function • Plays an important role in the stress response • Regulates a wide range of vital processes throughout the body , including metabolism and immune response
  • 146. Drugs used to treat diseases of the testes • Testosterone • Androgen • Most abundant and biologically active male sex hormone • Androgen drugs • Treat diseases of hypo secretion due to: • Cryptorchidism • Orchitis • Delayed puberty • Chemotherapy • Alcoholism • Surgical removal of testes
  • 149. TNF- 𝞪 Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis. Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular events such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis or in other words TNF signals cells to die.
  • 150. TNFs are primarily produced by macrophages and are responsible for regulation of inflammatory and immune responses in cell death. They occur in 2 distinct forms 1. Membrane integrated 2. Soluble form - exists in form of homotrimers These TNFs bind to the receptors TNFR1 & TNFR2 TNFR1 is found in most of the tissues and responds to the soluble form of TNF- 𝞪. It increases inflammation and induces powerful immune responses. TNFR2 is found in immune cells and responds to membrane bound form of TNF-𝞪. It exhibits anti inflammatory property and promotes cell proliferation
  • 152. Role of TNFs ● The TNF signaling pathway plays an important role in various physiological and pathological processes, including cell proliferation, differentiation, apoptosis, and modulation of immune responses and induction of inflammation. ● TNF (Tumor Necrosis Factor) is a multifunctional proinflammatory cytokine, with effects on lipid metabolism, coagulation, insulin resistance, and endothelial function. ● Ever since its discovery two decades ago, TNF has been considered as an anti-cancer agent. ● Members of the TNFR (TNF Receptor) super family can send both survival and death signals to cells.
  • 153. TNF signaling has been implicated in many other diseases ● Tumor necrosis factor alpha (TNF-α) was initially recognized as a factor that causes the necrosis of tumors, but it has been recently identified to have additional important functions as a pathological component of autoimmune diseases. ● TNF-α binds to two different receptors, which initiate signal transduction pathways. These pathways lead to various cellular responses, including cell survival, differentiation, and proliferation. ● However, the inappropriate or excessive activation of TNF-α signaling is associated with chronic inflammation and can eventually lead to the development of pathological complications such as autoimmune diseases. ● Understanding of the TNF-α signaling mechanism has been expanded and applied for the treatment of immune diseases, which has resulted in the development of effective therapeutic tools, including TNF-α inhibitors. ● Currently, clinically approved TNF-α inhibitors have shown noticeable potency in a variety of autoimmune diseases, and novel TNF-α signaling inhibitors are being clinically evaluated.
  • 154. ● Rheumatoid Arthritis ● Psoriatic Arthritis ● Inflammatory Bowel Disease ● Psoriasis ● Noninfectious Uveitis