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The nervous system is the most complex and delicate of all the body systems. At the
center of the nervous system is brain. The brain sends and receives messages through
a network of nerves. This network can be explained as similar to road network
The spinal cord is thick bundle of nerves, which runs down the center of the spine.
Along the spinal cord smaller bunches of nerves branch out. From these bundles,
smaller bundles of nerves branch out again. Finally, individual nerves branch out to
every part of the body.
This network of brain allows the brain to communicate with every part of the body.
Nerves transmit information as electrical impulses from area of the body to another.
Some nerves carry information to the brain. This allows us to see, hear, smell, taste and
touch. Other nerves carry information from the brain to the muscles to control our body’s
movement.
NERVOUS SYSTEM
CENTRAL PERIPHERAL
SYMPATHETIC PARASYMPATHETIC
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The Nervous System is divided into –
• Peripheral nervous system (PNS)
• Central nervous system (CNS)
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• Cranial neuron – connects the brain with periphery
Spinal neuron – connects the spinal cord with the periphery.
• Somatic neuron – connects the skin or muscle with the CNS
Visceral neuron – connects the internal organs with the CNS.
NEURON
Structure of neuron:
Myelin sheath: it is an electrical insulator that serves to speed the conduction of nerve
impulses. Myelin sheath is formed from plasma membranes of specialized glial cells
known as Schwann cells in the PNS and of Oligodendrocytes in CNS.
Node of Ranvier: The myelin insulation does not cover the entire axon. There are
breaks in the wrapping. These breaks are called nodes of ranvier. The distance
between these nodes is between 0.2 & 2mm.
Signals jumping from node to node travel hundreds of times faster than signals
travelling along the surface of the axon. This allows your brain to communicate with
your toes in a few thousands of a second.
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Types of Neuron:
There are 3 types of neurons required to transmit impulses.
• Sensory neuron: Typically have a long dendrite and short axon, and carry
messages from sensory receptors to the CNS.
• Motor neurons: Have a long axon and short dendrites and transmit messages
from the CNS to the muscles or to glands.
• Interneurons: Are found only in the CNS that internally communicate &
intervene between the sensory inputs and motor inputs.
Synapse:
The junction between a nerve cell and another cell is called a synapse. Messages travel
within the neuron as an electrical action potential.
Synaptic cleft: the space between the two cells is known as the synaptic cleft.
Neurotransmitters:
• Are chemical messengers that traverse the synaptic cleft between the neurons.
• Neurotransmitters are stored in small synaptic vesicles clustered at the tip of the
axon.
• When released by sending neuron, neurotransmitters travel across the synapse
and bind to receptor site on the receiving neuron, thereby influencing whether it
will generate a neural impulse.
• Neurotransmitters can be excitatory or inhibitory.
The major neurotransmitters are –
• Dopamine
• Serotonin
• Nor epinephrine (and epinephrine)
• Gamma-amino butyric acid (GABA)
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• Acetylcholine
IMMUNITY SYSTEM
The immune system is a complex of organs, all of which work together to clear
infection from the body.
Located at Blood, Lymph Nodes, Spleen, Liver, Thymus, Bone Marrow, Tonsils,
Lungs and Intestines.
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IMMUNITY
ACTIVE PASSIVE
Blood
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WBC
GRANULOCYTES AGRANULOCYTES
LYMPHOCYTE MONOCYTE
EOSINOPHIL NEUTROPHIL
BASOPHIL
B LYMPHOCYTE T LYMPHOCYTE
3rd TIER
Consists Lymphocytes.
Divided into 2 types, the T and B-Lymphocytes.
T Lymphocytes are the one that mature at the THYMUS.
B Lymphocytes mature at BONE MARROW
T LYMPHOCYTES
B – LYMPHOCYTES 2 Types
Plasma B and Memory B
Plasma B cells produce Antibodies or Immunoglobulins to kill the bacteria/virus,
Promote phagocytosis and form Antigen/Antibody complex.
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Memory B cells for response to another encounter with the same antigen.
HOW IMMUNE SYSTEM WORKS?
ANTIBODY DIAG
ANTIBODY
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Autoimmune Disorders
Autoimmune disorders affect the nervous system. Autoimmune disorders occurs when
body's natural defense mistakenly attacks body's own tissue.
It can affect any part of the nervous system.
Since neurons are affected, conduction capacity of nervous system goes down.
Products like GENEXGLOB, Succimed and Myestin are used in the treatment of
Autoimmune disorders
Neurological Disorders:
CNS - Multiple Sclerosis, Spasticity of skeletal muscles related to spinal cord. PNS -
Guillain Barre Syndrome, CIDP, Multifocal Motor Neuropathy.
THERAPY CHOICES
Immuno Suppression--Through Glucocorticosteroids
Immunosupplementation/Modulation--Through IVIG preparations.
Plasmapheresis--Cleaning or washing of the whole body fluid to remove the faulty
antibody containing plasma and replace with fresh plasma through centrifugation.
Physiotherapy
IMMUNOGLOBULINS
Immunoglobulins (Antibodies) are Proteins produced by Plasma cells which control
immune response by binding with Antigen
On the basis of structure and biological activity, Immunoglobulins are divided into
IgG, IgM, IgA, IgD and IgE.
Ig -- Immunoglobulins/Gammaglobulins.
Used to treat Autoimmune disorders and Primary Immunodeficiencies..
IgG
Most active Immunoglobulin.
Monomeric in nature.
Formed on exposure to antigen.
Only Ig type to cross placenta.
Made of two light and two heavy chains of polypeptides.
Major constituent of IVIG preparations.
IgM
Cyclic pentamer
Referred to as polymer also.
First kind of Immunoglobulin to be produced in an immune response before IgG.
IgM enriched preparations are also of therapeutic value for some other indications.
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IgA
IgD
Present very less in human body.
Major Immunoglobulin on the surface of B-Lymphocytes.
Plays an important role in Antigen recognition.
Structure resembles, IgG
IgE
Present in traces in serum.
Involved in Anaphylactic and hypersensitivity reaction.
Links Antigen to mast cells, which release histamine.
MECHANISM OF ACTION
2 TYPES.
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IgG levels / pharmacokinetics
Autoimmune Disorders
Autoimmune disorders arise when the body’s natural defenses (the immune system)
mistakenly attacks the body’s own tissue. It can affect any part of the nervous system.
Neurons are affected and therefore the conduction capacity of nervous system goes
down
Neurological disorders:
CNS: multiple sclerosis, spasticity of skeletal muscles related to spinal cord.
PNS: Guillain Barre Syndrome, CIDP, and, Multifocal Motor Neuropathy.
Neuromuscular junctional diorders: Myasthenia Gravis.
• The nerves of the GBS patient are attacked by the body's own defense system.
• As a result of this Autoimmune attack, the nerve insulation (myelin) and sometimes
even the covered conducting part of the nerve (axon) are damaged.
• It can strike at any age and both sexes are equally prone to the disorder.
• The syndrome is rare, however, affecting only about one person in 100,000.
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• It is a neurological disorder characterized by slowly progressive weakness and
sensory dysfunction of the legs and arms.
• Although it can occur at any age and in both genders, CIDP is more common in
young adults, and in men more so than women.
• Cause: Idiopathic. 60 % of patients suffer from a throat infection or intestinal
infection, Influenza/ stress symptoms in previous 2 weeks.
Multiple sclerosis:
• A disorder of the Central Nervous System (brain and spinal cord), which is
characterized by decreased nerve function due to myelin loss and secondary axonal
damage.
• It is a disease of the “White matter” tissue.
• The white matter is made up of nerve fibers, which are responsible for transmitting
communication signals both internally within the CNS and between the CNS and the
nerves supplying rest of the body.
• In people affected by MS, patches of damage called plaques or lesion appear in
seemingly random areas of the CNS white matter.
• At the site of a lesion, a nerve insulating material, called myelin, is lost.
• Affects mostly women between age 20 and 40.
Kawasaki Disease:
• Cause: Idiopathic. (Assumed to start from an infection or from exposure to some
toxins). Some doctors think it may be caused by a virus or bacteria.
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• Occurrence: Children under age 5. 1-2 yr. of age mostly. Asian children are more
prone.
• Most children recover completely.
• Arthritis, meningitis and rarely death is also seen.
• PID’s are caused by intrinsic defects in the cells of the immune system and are often
caused by inherited genetic defects.
• The primary immunodeficiencies appear to affect males and females about equally.
• These are sometimes life threatening and complex and vary considerably in nature,
incidence and severity.
• Affected people are sometimes completely unable to fight off infection and have to
have replacement Immunoglobulin therapy and use antibiotics all their lives.
Inflammatory Myopathies:
Types Of Myopathies:
1) Dermatomyositis
2) Polymyositis
3) Inclusion Body Myositis.
Dermatomyositis:
• The most easily recognized of the inflammatory myopathies due to its distinctive
rash. T- cell attacks the muscle fiber.
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• Rash occurs as a patchy, dusky, reddish rash on the eyelids, cheeks, and bridge of
the nose, and on the back or upper chest, elbows, knees and knuckles followed by
muscle weakness.
Myasthenia Gravis:
• In MG, faulty antibodies block, alter, or destroy the acetylcholine receptors at the
neuromuscular junction which prevents the muscle contraction from occurring
• These antibodies are produced by the body's own immune system. Thus, MG is an
autoimmune disease.
In early stages MG primarily affects muscles that control eye movement (extraocular
muscles) and those that control facial expression, chewing and swallowing. If untreated,
the disorder may affect muscles that control breathing (respiration), causing acute
respiratory failure (myasthenia crisis).
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Normal neuromuscular junction versus neuromuscular junction in MG
Types of MG:
Treatment of MG:
MG is the most treatable neuromuscular disorder. The choice of treatment depends on
several factors, including, age, overall health, severity of disease, and rate of disease
progression.
Medications:
Anticholinesterase medications such as neostigmine and pyridostigmine usually
prescribed. These drugs prevent ACh destruction and increase the accumulation of ACh
at neuromuscular junctions, improving the ability of the muscles to contract.
Side effects include excessive salivation, involuntary muscle twitching (fasciculation),
abdominal pain, nausea, and diarrhea. A drug called kaolin may be used with
anticholinesterase medications to reduce gastrointestinal side effects.
Corticosteroids (e.g., prednisone) suppress the antibodies that block AChR at the
neuromuscular junction and may be used in conjunction with anticholinesterase.
Corticosteroids improve symptoms within a few weeks and once improvement
stabilizes, the dose is slowly decreased.
A low dosage may be used indefinitely to treat MG; however,
Side effects such as gastric ulcers, osteoporosis (bone thinning), weight gain, high
blood sugar (hyperglycemia), and increased risk for infection may develop over the long
term.
Immunosuppressants such as azathioprine and cyclophosphamide are used to treat
generalized MG when other medications fail to reduce symptoms.
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Side effects may be severe and include low white blood cell count (leukopenia), liver
dysfunction, nausea, vomiting, and hair loss.
Immunosuppressants are not used to treat congenital MG because this condition is not
the result of an immune system malfunction.
Other Treatments
Plasmapheresis, or plasma exchange, is used to modify the immune system
malfunction. It can be used to treat severe worsening of symptoms (exacerbations) or in
preparation for surgery (thymectomy).
In this procedure, blood is removed from the body and blood cells are separated from
the liquid portion of the blood (plasma). Then, AChR antibodies are removed and blood
cells are diluted with artificial plasma (usually a solution of saline and sterilized human
albumin protein) and infused back into the body.
Typically, 2 to 3 liters of plasma is removed and replaced during a single treatment,
which takes several hours. Most patients undergo several sessions over the course of 2
weeks or more. Plasmapheresis improves MG symptoms within days and improvement
lasts 6–8 weeks.
Risks include low blood pressure, dizziness, blurred vision, and formation of blood clots
(thrombosis).
Thymectomy is surgical removal of the thymus gland. It is usually performed on
patients with a tumor of the thymus (thymoma) and patients younger than age 55 with
generalized MG. Benefits of Thymectomy develop gradually and most improvement
occurs years after the procedure is performed.
Prognosis
Symptoms of myasthenia gravis usually progress to maximum severity within 3 years.
After 3 years, patients usually stabilize or improve. Infants with transient neonatal MG
may develop acute respiratory failure within a few weeks after birth.
Advances in medical care have reduced the mortality rate from respiratory failure in MG
patients to approximately 3%. Patients over the age of 40, those with a short history of
severe disease and those with thymoma have a worse prognosis.
Prevention
Myasthenia gravis cannot be prevented, but avoiding the following triggers may help
patients prevent exacerbations:
• Emotional stress
• Exposure to extreme temperatures
• Fever
• Illness (e.g., respiratory infection, pneumonia, tooth abscess)
• Low levels of potassium in the blood (hypokalemia; caused by diuretics, frequent
vomiting)
• Medications (e.g., muscle relaxants, anticonvulsants, certain antibiotics)
• Overexertion
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GENEXGLOB
• Maltose base.
CONVENTIONAL MANUFACTURING
PURIFICATION PROCESSES
12 purification processes
2 Viral inactivation steps
7 viral elimination processes.
Eliminates even trace virus and viral sub proteins unlike conventional processes.
The double viral inactivation techniques are Pasteurisation and Low pH method.
VIRAL INACTIVATION
SURPASSING STANDARDS
According to BP any IVIG should have >95% IgG, But GENEXGLOB has 100%
IgG.
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>90% should be the Monomer/Dimer content according to BP, but GENEXGLOB
has 100% Monomer/Dimer content.
Total protein content according to BP should be > 30G/L, But GENEXGLOB has
53.6 G/L protein content.
PRESERVATIVES
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LABELLED INDICATIONS IN INDIA
Primary Immunodeficiencies.
Kawasaki Syndrome.
Idiopathic Thrombocytopenic Purpura.
Bone Marrow Transplantation.
Chronic B cells Lymphocytic Leukemia.
Pediatric HIV 1 infection.
DOSAGE
ADMINISTRATION
IV/IM route
GENEXGLOB is administered by only IV route.
Infusion rate: 0.01 to 0.02 ml/kgBwt/Min for 30 min. If well tolerated increase upto 0.08
ml/kg/min.
Infused through separate line.
Not compatible with saline.
5% Dextrose can be used.
TARGET CUSTOMERS
Neurologists
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Pediatric Neurologists
Infectious specialists
Burns units
Intensivists
Physicians
Dermatologists
Rheumatologists
RIVALS
NORGLOBIN / CLARIS:
GAMMA IV / BSV
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VERGLOB / SUN
90 % IgG
Manufactured by Ethanol Fractionation.
Lyophilised/Chances of trace virus survival.
Dextrose 50% base.
Single viral inactivation by PEG treatment.
% IgA /IgM data not available.
KOREAN SOURCE.
OTHERS
PRESERVATIVE FREE?
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GENEXGLOB follows such a stringent manufacturing process that makes it possible
to be presented without a preservative. Also safer for patients at higher doses.
12/7/2 viral purification processes ensures utmost purity and stability.
Also preservatives are sometimes found to protect potentially dangerous viral
contaminants.
COMPARISON
Corticosteroids suppress the immune system by masking the production of faulty
antibodies and so the damage is reduced.
Other infections may not show up and may be dangerous since the antigen*antibody
reaction is suppressed by these agents.
PLASMAPHERESIS: Fluid part of the blood, plasma is removed through cell separator,
cells injected back with fresh normal plasma into the body and the plasma containing
faulty antibodies is discarded.
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