enzymes in therapy-pharmacology

1. DR GOGGY
KVG MEDICAL COLLEGE
SULLIA
ENZYMES INTHERAPY

2.  BIOLOGICALLY ACTIVE PROTEINS
CATALYST THAT SPEEDS UP BIOCHEMICAL
REACTIONS

3.  THE MORE ENZYMES EXPENDED ON
DIGESTION ,THE LESS ENZYMES
AVAILABLE FOR METABOLIC FUNCTION
 THERE IS A DIRECT CORRELATION
BETWEEN HEALTHAND ENZYME LOSS
HIGH ENZYME LEVELS EQUALS GRETAER
DISEASE –FIGHTING CAPABILITY

4. HYALURONIDASE
 PREPARED FROM MAMMALIANTESTES
 CERTAIN SNAKEAND BEEVENOMALSO
CONTAINS THE ENZYME
 HYALURONIC ACID -ESSENTIAL COMPONENT
OF INTERCELLULAR GROUND SUBSTANCE
 DETERMINESTHE PERMEABILITY OFTISSUE

5. 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

6.  ADMINISTERED SUBCUTANEOUSLY
INCREASES THE PERMEABILITY OFTISSUE
 ODOURLESS,FLUFFY POWDER CONTAINING
LESSTHAN 300 UNITS OF ACTIVITY PER MG
USES
 THERAPEUTICALLY ,IT IS EMPLOYEDTO
PROMOTETHE RAPID ABSORPTIONOF
DRUGS/FLUIDS GIVEN SC/IM

8.  FOR HYPODERMOCLYSIS 1500 UNITS ARE
ADDEDTO EACH LITRE OF FLUIDTO BE
ADMINISTERED
 IN RADIOGRAPHY-SUBSTANCEARE RAPIDLY
ABSORBED ON IM INJECTION ,WITHTHE
ALTERNATIVE OF IV ADMINISTRATION
 FOR ABSORPTIONOF BLOODAND FLUID IN
TRAUMATIC OR POST OPERATIVEOEDEMA

9.  HIGHLY PURIFIED FORM IS USED IN
OPTHALMIC SURGICAL PROCEDURE
PRECAUTIONS
 IT SHOULD NOT BE APPLIED DIRECTLYTO
CORNEA
 SHOULD NOT BE USEDTO REDUCETHE
SWELLING OF BITES AND STINGS
 IT IS ANTIGENIC OCCASIONALLY PRODUCE
ALLERGIC REACTIONS

10. CONTRAINDICATIONS
 MALIGNANCY
 INFECTED AREA

11. 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)

12. 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

13. STREPTOKINASE
 PRODUCED BY BETA HEMOLYTIC
STREPTOCOCCIGROUP C
 DISSOLUTION OF CLOT BY CONVERTING
INTRINSIC PLASMINOGEN PRESENT INTHE
CLOT TO ACTIVE PLASMIN
 MAXIMUM ACTIVITY AT Ph 7.3-7.6 of( 11-13
minutes)
 T1/2 is around 30-80 minutes

14. PRECAUTIONS
IT IS ANTIGENIC CAN CAUSE
HYPERSENSITIVITY REACTIONS WHEN
USED FORTHE SECONDTIME
SIDE EFFECTS
FEVER
HYPOTENSION
ARRHYTHMIAS

15. IT IS AVAILABLE AS (FREEZE DRIED POWDER IN
VIALS )
STREPTASE-2.5,7.5,15LAC IU/VIAL
USES
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

16. STREPTODORNASE
 GROUP OF RAPIDLY ACTING ENZYMES
 DEPOLYMERIZATION OF COMPLEX
NUCLEOPROTEINS-FROM DEGENERATED
LEUCOCYTESAND INJUREDTISSUE CELLS
 DOESN’TATTACK NUCLEOPROTEINOF
LIVING CELLS
 OPTIMUM ACTIVITY IS BETWEENTHE pH 7-
8.5

17. USES
COMBINATION OF STREPTOKINASEAND
STREPTODORNASE IS USED FOR
DEBRIDEMENT OF CHRONIC ULCERS

18. L ASPARAGINASE(L-ASP)
 KIDD (1953) WERETHE FIRSTTO REPORTTHAT
GUINEA PIG SERUM HAS ANTILEUKEMIC
PROPERTY AND IDENTIFIED L-
ASPARAGINASE(L-ASP)
 STANDARD AGENT FORTREATING ALL
 MECHANISM OF ACTION
NORMALTISSUE SYNTHESIZE L-ASPARAGINE
BUT LYMPHOCYTIC LEUKAEMIA LACKS
ASPARAGINE SYNTHETASE SOTHEY HAVETO
TAKE FROM PLASMA

19.  L-ASP ,BY CATALYZINGTHE HYDROLYSISOF
CIRCULATING ASPARAGINETO ASPARTIC
ACID AND AMMONIA DEPRIVINGTHE
CANCER CELLS FROM GETTING L-
ASPARAGINE
 L –ASP TWO FORMS ARE USED CLINICALLY
 E-COLI DERIVED
 PEGASPARGASE(POLYETHYLENEGLYCOL)

20.  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

21. 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-lineALL therapy.

22. TRYPSIN
 OBTAINED FROM OX PANCREAS
 AVAILABLE ASWHITE POWDER INWATER
 HYDROLYZES NATURAL PROTEINS
INCLUDING RESPIRATORY MUCINS
USES
 SMALL GELATINCAPSULES CONTAINING
THE ENZYMES MAY BE INSERTED INTO
INIRRIGABLE SINUSESAND FISTULAES

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

24. CHYMOTRYPSIN
 PROTEOLYTIC ENZYME FROM BOVINE
PANCREAS
 50,OOO UNITS OF ENZYMES PERTABLET
 TO REDUCE INFLAMMATIONAND
OEDEMA OF SOFTTISSUE
USES
 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

25. ALPHA CHYMOTRYPSIN
 PROTEOLYTIC ENZYME
 USES
FOR DISSOLVINGTHE SUSPENSORY LIGAMENT
OF LENS DURING INTRACAPSULAR
EXTRACTIONOF CATARACT
ADVERSE EFFECTS
TRANSIENT GLAUCOMA
WOUND DISRUPTION
RETINAL DAMAGE

26. 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.

27.  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.

28. COLLAGENASE
 DERIVED FROM FERMENTATIONOF
CL.HISTOLYTICUM
 ACTS ON DENATURED AND
UNDENATUREDCOLLAGEN
 USES
 DEBRIDEMENT OF DERMAL ULCERS AND
SEVERE BURNS

29. 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..

30.  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

31.  .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.

32. DEOXYRIBONUCLEASE
 DNA RELEASED FROM NEUTRPHIL
CONTRIBUTETOTHEVISCOSITY OF
SPUTUM IN CYSTIC FIBROSIS
 INHALED DEOXYRIBONUCLEASE CLEAVES
DNA HAS BEENTRIED IN PATIENTWITH
CYSTIC FIBROSIS

33. SERRATIOPEPTIDASE
 PROTEOLYTIC ENZYME
 DIGESTS NECROTICTISSUE ,CELL DEBRIS
,CELLULAR EXUDATE AND COAGULATED
BLOOD
 USED FOR THETREATMENT OF
INFLAMMATORY OEDEMA AND
HAEMATOMA

34. 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

35. 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

36.  . 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

37.  MPS II (Hunter syndrome)-THE ENZYME
DEFICIENT IS Iduronate sulfatase
 MPSVI and
 Glycogen storage disease type II.-THE
ENZYME DEFICIENT IS Acid maltase

38. 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

39.  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

40.  Phenylalanine ammonia-lyase-Treatment of
hyperphenylalaninemia