enzymes in therapy gpg

DR GOGGY KVG MEDICAL COLLEGE SULLIA

ENZYMES IN THERAPY

BIOLOGICALLY ACTIVE PROTEINS

CATALYST THAT SPEEDS UP BIOCHEMICAL REACTIONS

THE MORE ENZYMES EXPENDED ON DIGESTION , THE LESS ENZYMES AVAILABLE FOR METABOLIC FUNCTION

THERE IS A DIRECT CORRELATION BETWEEN HEALTH AND ENZYME LOSS HIGH ENZYME LEVELS EQUALS GRETAER DISEASE –FIGHTING CAPABILITY

HYALURONIDASE PREPARED FROM MAMMALIAN TESTES

CERTAIN SNAKE AND BEE VENOM ALSO CONTAINS THE ENZYME

HYALURONIC ACID -ESSENTIAL COMPONENT OF INTERCELLULAR GROUND SUBSTANCE

DETERMINES THE PERMEABILITY OF TISSUE

MECHANISM OF ACTION

In most mammalian fertilization,

hyaluronidase is released by the acrosome of the sperm cell after it has reached the oocyte, by digesting hyaluronan in the corona radiata, thus enabling conception

ACTS BY DEPOLYMERIZING HYALURONIC ACID

ADMINISTERED SUBCUTANEOUSLY INCREASES THE PERMEABILITY OF TISSUE

ODOURLESS,FLUFFY POWDER CONTAINING LESS THAN 300 UNITS OF ACTIVITY PER MG

USES

THERAPEUTICALLY ,IT IS EMPLOYED TO PROMOTE THE RAPID ABSORPTION OF DRUGS/FLUIDS GIVEN SC/IM

FOR HYPODERMOCLYSIS 1500 UNITS ARE ADDED TO EACH LITRE OF FLUID TO BE ADMINISTERED

IN RADIOGRAPHY-SUBSTANCE ARE RAPIDLY ABSORBED ON IM INJECTION ,WITH THE ALTERNATIVE OF IV ADMINISTRATION

FOR ABSORPTION OF BLOOD AND FLUID IN TRAUMATIC OR POST OPERATIVE OEDEMA

HIGHLY PURIFIED FORM IS USED IN OPTHALMIC SURGICAL PROCEDURE

PRECAUTIONS IT SHOULD NOT BE APPLIED

DIRECTLY TO CORNEA

SHOULD NOT BE USED TO REDUCE THE SWELLING OF BITES AND STINGS

IT IS ANTIGENIC OCCASIONALLY PRODUCE ALLERGIC REACTIONS

CONTRAINDICATIONS MALIGNANCY INFECTED AREA

ADENOSINE DEAMINASE In 1990, Adagen1, a form of bovine

adenosine deaminase (ADA) treated with polyethylene glycol (PEG) was approved to treat patients afflicted with a type of Severe combined immunodeficiency disease (SCID), which is caused by the chronic deficiency of ADA.

Adagen1 was the first therapeutic enzyme approved by the FDA under the Orphan Drug Act. The Orphan Drug Act was passed in

1983 in the United States to encourage pharmaceutical companies to develop treatments for diseases affecting only small numbers of people (less than 200 ,00)

RHODNASE Rhodanese is a mitochondrial 

enzyme that detoxifies cyanide (CN-) by converting it to thiocyanate (SCN-).

Rhodanese and a sulfur compound given therapeutically to mice when symptoms of cyanide poisoning had occurred, also had a very good antidote effect

STREPTOKINASE PRODUCED BY BETA HEMOLYTIC

STREPTOCOCCI GROUP C

DISSOLUTION OF CLOT BY CONVERTING INTRINSIC PLASMINOGEN PRESENT IN THE CLOT TO ACTIVE PLASMIN

MAXIMUM ACTIVITY AT Ph 7.3-7.6 of( 11-13 minutes)

T1/2 is around 30-80 minutes

PRECAUTIONS IT IS ANTIGENIC CAN CAUSE

HYPERSENSITIVITY REACTIONS WHEN USED FOR THE SECOND TIME

SIDE EFFECTS FEVERHYPOTENSIONARRHYTHMIAS

IT IS AVAILABLE AS (FREEZE DRIED POWDER IN VIALS )

STREPTASE-2.5,7.5,15LAC IU/VIALUSES

FOR MI:7.5-15LAC IU INFUSED IV OVER 1 HOUR

FOR DVT AND PULMONARY EMBOLISM:2.5LAC LOADING DOSE OVER 1 HR FOLLOWED BY

1 LAC IU/HR FOR 24 HOURS

USED;IN INTRACAVITARY INSTILLATION AS IN EMPYEMA OF PLEURAL CAVITY

STREPTODORNASE GROUP OF RAPIDLY ACTING ENZYMES

DEPOLYMERIZATION OF COMPLEX NUCLEOPROTEINS-FROM DEGENERATED LEUCOCYTES AND INJURED TISSUE CELLS

DOESN’T ATTACK NUCLEOPROTEIN OF LIVING CELLS

OPTIMUM ACTIVITY IS BETWEEN THE pH 7-8.5

USESCOMBINATION OF STREPTOKINASE

AND STREPTODORNASE IS USED FOR DEBRIDEMENT OF CHRONIC ULCERS

L ASPARAGINASE(L-ASP) KIDD (1953) WERE THE FIRST TO REPORT

THAT GUINEA PIG SERUM HAS ANTILEUKEMIC PROPERTY AND IDENTIFIED L-ASPARAGINASE(L-ASP)

STANDARD AGENT FOR TREATING ALL

MECHANISM OF ACTIONNORMAL TISSUE SYNTHESIZE L-ASPARAGINE

BUT LYMPHOCYTIC LEUKAEMIA LACKS ASPARAGINE SYNTHETASE SO THEY HAVE TO TAKE FROM PLASMA

L-ASP ,BY CATALYZING THE HYDROLYSIS OF CIRCULATING ASPARAGINE TO ASPARTIC ACID AND AMMONIA DEPRIVING THE CANCER CELLS FROM GETTING L-ASPARAGINE

L –ASP TWO FORMS ARE USED CLINICALLY

E-COLI DERIVED PEGASPARGASE(POLYETHYLENE

GLYCOL)

Enzyme levels must be maintained at >0.2 IU/mL in plasma to deplete asparagine in the bloodstream

E-COLI DERIVED t1/2 - 24 hours .

It is given in doses of 6000-10,000 IU every third day for 3-4 weeks,

Doses up to 25,000 IU once per week may be more effective in childhood ALL

PEGASPARGASE(POLYETHYLENE GLYCOL) Pegaspargase (PEG-l-asparaginase; ONCASPAR) a

preparation in which the enzyme is conjugated to 5000-Da units of monomethoxy polyethylene glycol

t1/2 of 6-7 days,

Doses of 2500 IU/m2 intramuscularly no more frequently than every 14 days, producing rapid and complete depletion of plasma and tumor cell asparagine for 21 days in most patients . Pegaspargase has much reduced immunogenicity (<20% of patients develop antibodies)

Approved for first-line ALL therapy.

TRYPSIN OBTAINED FROM OX PANCREAS

AVAILABLE AS WHITE POWDER IN WATER

HYDROLYZES NATURAL PROTEINS INCLUDING RESPIRATORY MUCINS

USES SMALL GELATIN CAPSULES

CONTAINING THE ENZYMES MAY BE INSERTED INTO INIRRIGABLE SINUSES AND FISTULAES

IT is also given in combination with bromelain and rutin for treatment of osteoarthritis

CHYMOTRYPSIN PROTEOLYTIC ENZYME FROM BOVINE

PANCREAS 50,OOO UNITS OF ENZYMES PER TABLET TO REDUCE INFLAMMATION AND

OEDEMA OF SOFT TISSUEUSES To reduce tissue damage in burn

patients: a 6:1 ratio (trypsin:chymotrypsin), in a combined amount of 200,000 units USP four times daily for ten days orally

ALPHA CHYMOTRYPSIN PROTEOLYTIC ENZYME USESFOR DISSOLVING THE SUSPENSORY

LIGAMENT OF LENS DURING INTRACAPSULAR EXTRACTION OF CATARACT

ADVERSE EFFECTSTRANSIENT GLAUCOMA WOUND DISRUPTION RETINAL DAMAGE

Enzymes for the treatment of infectious diseases

Lysozyme has been used as a naturally occurring antibacterial agent in many foods and consumer products, because of its ability to break carbohydrate chains in the cell wall of bacteria.

RNase A and urinary RNase U, which

selectively degrade viral RNA opening some exciting possibilities for the treatment

of HIV infection.

Naturally occurring antimicrobial agents are the chitinases. As an element of the cell

wall of various pathogenic organisms, including fungi,protozoa and helminths, chitin is a good target for antimicrobials

The cell walls of Streptococcus pneumonia, Bacillus anthracis and Clostridium

perfringens have been targeted with the use of bacteriophage-derived lytic enzymes . The use of lytic bacteriophages themselves as a treatment for infections is also being developed and could prove useful against new drug resistant bacterial strains.

COLLAGENASE DERIVED FROM FERMENTATION OF

CL.HISTOLYTICUM ACTS ON DENATURED AND

UNDENATURED COLLAGEN

USES DEBRIDEMENT OF DERMAL ULCERS

AND SEVERE BURNS

Alzheimer disease. There is increasing evidence that deficient

clearance β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD).

Several Aβ-degrading enzymes, including Neprilysin (NEP), Insulin-degrading enzyme, and Endothelin-converting enzyme reduce Aβ levels and protect against cognitive impairment in mouse models of AD. The activity of several Aβ-degrading enzymes rises with age and increases still further in AD, perhaps as a physiological response to minimize the buildup of Aβ..

The age- and disease-related changes in expression of more recently recognized Aβ-degrading enzymes (e.g. NEP-2 and cathepsin B) remain to be investigated, and there is strong evidence that reduced NEP activity contributes to the development of cerebral amyloid angiopathy

Regardless of the role of Aβ-degrading enzymes in the development of AD, experimental data indicate that increasing the activity of these enzymes (NEP in particular) has therapeutic potential in AD, although targeting their delivery to the brain remains a major challenge

. The most promising current approaches include the peripheral administration of agents that enhance the activity of Aβ-degrading enzymes and the direct intracerebral delivery of NEP by convection-enhanced delivery. In the longer term, genetic approaches to increasing the intracerebral expression of NEP or other Aβ-degrading enzymes may offer advantages.

DEOXYRIBONUCLEASE

DNA RELEASED FROM NEUTRPHIL CONTRIBUTE TO THE VISCOSITY OF SPUTUM IN CYSTIC FIBROSIS

INHALED DEOXYRIBONUCLEASE CLEAVES DNA HAS BEEN TRIED IN PATIENT WITH CYSTIC FIBROSIS

SERRATIOPEPTIDASE PROTEOLYTIC ENZYME DIGESTS NECROTIC TISSUE ,CELL

DEBRIS ,CELLULAR EXUDATE AND COAGULATED BLOOD

USED FOR THE TREATMENT OF INFLAMMATORY OEDEMA AND HAEMATOMA

Urate oxidase, or uricase Urate oxidase, or uricase , is a

peroxisomal liver enzyme that catalyses the enzymatic oxidation of uric acid into the more water-soluble allantoin

It is used in humans for the control of increased serum uric acid in patients with acute tumour lysis syndrome after receiving chemotherapy.

 Rasburicase , a recombinant urate oxidase expressed in Saccharomyces cerevisiae, has been demonstrated to be superior to allopurinol in the control of uric acid in a randomized trial of paediatric and adult patients at risk of acute tumour lysis syndrome

Enzyme replacement therapy  The concept of enzyme replacement

therapy for LYSOSOMAL STOREGE DISEASES was enunciated by DE Duve in 1964.

Enzyme replacement therapy (ERT) is a medical treatment replacing an enzyme in patients in whom that particular enzyme is deficient or absent. Usually this is done by giving the patient an intravenous (IV) infusion containing the enzyme

. Enzyme replacement therapy is currently available for some lysosomal diseases: 

Gaucher disease-THE ENZYME DEFICIENT IS   glucocerebrosidase

Fabry disease-THE ENZYME DEFICIENT IS  Alpha galactosidase A

MPS I -THE ENZYME DEFICIENT IS α-L-iduronidase

MPS II (Hunter syndrome)-THE ENZYME DEFICIENT IS Iduronate sulfatase

 MPS VI and

 Glycogen storage disease type II.-THE ENZYME DEFICIENT IS Acid maltase

FEW ENZYMES UNDER INVESTIGATIONS

Superoxide dismutase (human)-Protection of donor organ tissue from damage or injury mediated by oxygen-derived free radicals that are generated during the necessary periods of ischemia (hypoxia, anoxia), and especially reperfusion

Butyrylcholinesterase-Reduction and clearance of toxic blood levels of cocaine encountered during a drug overdose

Treatment of post-surgical apnea

PEGylated arginine deiminase-Treatment of invasive malignant melanoma

Treatment of hepatocellular carcinoma

Clostridial collagenase-Treatment of advanced (involutional or residual stage) Dupuytren’s disease

Lipase, amylase and protease-Treatment of pancreatic insufficiency

Recombinant human porphobilinogen deaminase-Treatment of acute intermittent porphyria attacks

Phenylalanine ammonia-lyase-Treatment of hyperphenylalaninemia